Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Sotorasib

Acarbose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Acenocoumarol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Acetylsalicylic acid (Aspirin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGTs, major UGT1A6). Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Agomelatine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2 (90%), with a small proportion metabolised by CYP2C9 and CYP2C19 (10%). Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Alendronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Alendronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, alendronic acid should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronic acid before taking any other oral medicinal product.

Description:

See Summary

Potential Interaction

Sotorasib

Alfentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Alfentanil undergoes extensive CYP3A4 metabolism. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor alfentanil efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Alfuzosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Alfuzosin is metabolised by CYP3A. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor alfuzosin efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. Aliskiren is also a substrate of P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of aliskiren. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with aliskiren. Monitoring for aliskiren toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Allopurinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Allopurinol is also an inhibitor of xanthine oxidase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Alosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of alosetron efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Alprazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Alprazolam is mainly metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor alprazolam efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Aluminium hydroxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aluminium hydroxide is not metabolised.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ambrisentan is metabolized by glucuronidation via UGT1A3, UGT1A9 and UGT2B7 and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Concentrations of ambrisentan may increase due to P-gp inhibition by sotorasib but concentrations of ambrisentan may also decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on ambrisentan exposure. Monitoring for ambrisentan efficacy and toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Amikacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Amiloride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Amiodarone is metabolised by CYP3A4 and CYP2C8. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYP3A4 (weak), CYP2C9 (moderate), CYP2D6 (moderate), CYP2C19 (weak), CYP1A1 (strong), CYP2B6 (moderate) and P-gp (strong). Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and thus, concentrations of sotorasib may increase after coadministration with amiodarone. Coadministration should be avoided. Note: due to the long half-life of amiodarone, interactions can be observed for several months after discontinuation of amiodarone.

Description:

See Summary

No Interaction Expected

Sotorasib

Amisulpride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolised and is primarily eliminated renally (possibly via OCT). Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of amitriptyline efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Amlodipine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor amlodipine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Amoxicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Sotorasib does not interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Ampicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion. About 20-40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60-80% is excreted in the urine within 6 hours. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Anidulafungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperatures. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Antacids are not metabolised by CYPs. However, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by antacids reduces its bioavailability. Coadministration is not recommended. If coadministration is necessary, sotorasib should be administered at the moment at which acid secretion is less inhibited, and that is 2 hours before a new dose of the antacid. Monitor sotorasib plasma levels, if available.

Description:

See Summary

Do Not Coadminister

Sotorasib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Apixaban is a substrate of P-gp and BCRP and is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Concentrations of apixaban may decrease due to CYP3A4 induction by sotorasib but concentrations of apixaban may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on apixaban exposure. If coadministration is unavoidable, monitor closely for apixaban toxicity and efficacy and anti-Xa concentrations, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied is not recommended. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4 (not clinically relevant), CYP2C9 and UGT. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor aprepitant efficacy. Monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor aripiprazole efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Asenapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 (minor) and 2D6 (minor)). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of asenapine efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor astemizole efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Atenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Concentrations of atorvastatin may increase due to P-gp inhibition by sotorasib but concentrations of atorvastatin may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on atorvastatin exposure. Monitoring of atorvastatin efficacy and toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines by xanthine oxidase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2 and concentrations may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with azithromycin. Azithromycin is also an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition by azithromycin is unknown. Monitoring for both sotorasib and azithromycin toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Beclometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450 but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Bedaquiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bedaquiline is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor bedaquiline efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Bendroflumethiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%) and excreted unchanged in the urine (30%) via OAT1 and OAT3. Sotorasib does not interact with this metabolic or elimination pathway. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically significant interaction is unlikely in the range of observed clinical concentrations. Sotorasib is not transported by OATs.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of bepridil efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Betamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Betamethasone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of betamethasone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Bezafibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of a bezafibrate dose is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Bisacodyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor bisoprolol efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bosentan is a substrate of CYP3A4 and CYP2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, bosentan is a weak inducer of CYP3A4 and CYP2C9. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by bosentan. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A decrease in sotorasib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no CYP3A4 induction potential is recommended. Monitor sotorasib plasma levels, if available. Monitoring of bosentan efficacy should also be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bromazepam undergoes oxidative biotransformation. Interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of bromazepam efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Budesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Budesonide is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of budesonide efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Buprenorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of buprenorphine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Bupropion

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolised by CYP2B6 and is a strong inhibitor of CYP2D6, which does not affect sotorasib.

Description:

See Summary

Potential Interaction

Sotorasib

Buspirone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Buspirone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor buspirone efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Calcium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcium is eliminated through faeces, urine and sweat. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Candesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Capreomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Captopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1. Sotorasib does not inhibit or induce OATs.

Description:

See Summary

Do Not Coadminister

Sotorasib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, carbamazepine is an inducer of CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong), CYP1A2 (weak), CYP2B6, UGT1A1 and P-gp. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp and concentrations may decrease due to CYP3A4 and P-gp induction by carbamazepine. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with carbamazepine. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additional metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Sotorasib does not inhibit or induce these UGTs or CYPs. Carvedilol is also an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition by carvedilol is unknown. Although sotorasib is a P-gp substrate, a clinically relevant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Caspofungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Cefalexin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1 and concentrations may increase due to MATE1 inhibition by sotorasib. After coadministration of sotorasib and metformin, a MATE1/2 substrate, no relevant effect on metformin exposure or antihyperglycemic effects were identified. Therefore, no relevant effect on cefalexin exposure is expected.

Description:

See Summary

No Interaction Expected

Sotorasib

Cefazolin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Cefixime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefixime is renally excreted predominantly by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Cefotaxime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolised by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Ceftazidime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftazidime is excreted predominantly by renal glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Ceftriaxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Celecoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolised by CYP2C9. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Sotorasib

Cetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. In vitro data indicate that cetirizine is also an inhibitor of OCT2. Sotorasib is not transported by OCT2.

Description:

See Summary

Do Not Coadminister

Sotorasib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Chloramphenicol is predominantly glucuronidated. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong) and CYP2D6 (weak). Sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by chloramphenicol. Coadministration is contraindicated. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the absorbed concentrations are unlikely to cause a clinically significant interaction.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Chlordiazepoxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chlordiazepoxide is extensively metabolised by CYP3A4 and does not inhibit or induce cytochromes. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of chlordiazepoxide efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Chlorphenamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2, Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Chlortalidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by sotorasib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments.

Description:

See Summary

Potential Interaction

Sotorasib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ciclosporin is a substrate of CYP3A4 and P-gp. Concentrations of ciclosporin may increase due to P-gp inhibition by sotorasib but concentrations of ciclosporin may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on ciclosporin exposure. Furthermore, ciclosporin inhibits CYP3A4 and OATP1B1. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by ciclosporin. Coadministration is not recommended. If coadministration cannot be avoided, monitor sotorasib toxicity and plasma levels, if available. Closely monitor ciclosporin efficacy and toxicity, and ciclosporin plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Cilazapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Cimetidine is metabolised by CYP450 enzymes. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Cimetidine is also a weak inhibitor of CYPs 3A4, 1A2, 2D6 and 2C19. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to weak CYP3A4 inhibition by cimetidine. Monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is metabolised and partially cleared through the bile and intestine. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by ciprofloxacin. Coadministration is not recommended. If coadministration cannot be avoided, monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Cisapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Cisapride is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor cisapride efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of citalopram efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Clarithromycin is metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong) and P-gp. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and thus, sotorasib concentrations may increase. Clarithromycin concentrations may also decrease due to CYP3A4 induction by sotorasib. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Clavulanic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolised (likely non-CYP mediated pathway) and excreted in the urine by glomerular filtration. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Clemastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolised in the liver via CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Interaction

Sotorasib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Clindamycin is metabolised by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by clindamycin. Coadministration is not recommended. If coadministration is unavoidable, closely monitor clindamycin efficacy and also monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Clobetasol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of clobetasol.

Description:

See Summary

Potential Interaction

Sotorasib

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Clofazimine is largely excreted unchanged in the faeces. In vitro data suggest that clofazimine is a CYP3A4 inhibitor. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by clofazimine. Coadministration is not recommended. If coadministration cannot be avoided, monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Clofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolysed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Clomipramine and desmethylclomipramine are metabolised by CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of clomipramine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Clonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in the form of the unchanged parent drug (40-60% of the dose). Clonidine is also a weak inhibitor of OCT2. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of the active metabolite may increase when combined with sotorasib. Monitoring for clopidogrel toxicity should be considered. Moreover, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and of CYP2C9 (in vitro) at high concentrations, which does not affect sotorasib. The clinical relevance of CYP2C9 inhibition is unknown.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Clorazepate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of clorazepate efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Cloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of clozapine efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Morphine is further metabolized by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). The metabolite, morphine, is a substrate of P-gp and morphine concentrations may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with morphine. Additionally, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of codeine efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Colchicine is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of colchicine may increase due to P-gp inhibition by sotorasib but concentrations of colchicine may decrease due to CYP3A4 induction by sotorasib. Monitoring for both colchicine toxicity and efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Cycloserine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dabigatran is transported via P-gp and is renally excreted. Sotorasib is an inhibitor of P-gp and may increase concentrations of dabigatran. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with dabigatran. Monitor dabigatran toxicity and plasma concentrations / ECT/dTT, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Dapsone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP450 enzymes. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Do Not Coadminister

Sotorasib

Desogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dexamethasone is a substrate of CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, dexamethasone has been described as a weak inducer of CYP3A4 and could possibly decrease sotorasib plasma concentrations. However, the clinical relevance of this interaction is not known as CYP3A4 induction by dexamethasone has not yet been established. Monitoring of dexamethasone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dextropropoxyphene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dextropropoxyphene is mainly metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of dextropropoxyphene efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diamorphine is rapidly metabolised by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Additionally, morphine is a substrate of P-gp and concentrations may increase due to inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with diamorphine. Monitoring for diamorphine toxicity should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Diazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of diazepam efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Diclofenac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9. Sotorasib does not inhibit or induce these UGTs or CYPs.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Digoxin

Quality of Evidence: Low

Summary:

Coadministration has been studied and care should be taken. Digoxin is eliminated renally via OATP4C1 and P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of digoxin. In healthy volunteers (n=14), coadministration of sotorasib (single dose of 960 mg) and digoxin (multiple doses of 0.5 mg) increased digoxin AUC by 21%. Monitoring for digoxin toxicity and plasma levels should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dihydrocodeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of dihydrocodeine efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Diltiazem is metabolised by CYP3A4 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, diltiazem is an inhibitor of CYP3A4 (moderate) and P-gp. However, the clinical relevance of P-gp inhibition by diltiazem is unknown. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by diltiazem. Coadministration is not recommended. If coadministration cannot be avoided, monitor for sotorasib toxicity and plasma levels, if available, and closely monitor diltiazem efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Moreover, diphenhydramine is a weak inhibitor of CYP2D6. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Dipyridamole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Sotorasib does not inhibit or induce UGTs.

Description:

See Summary

Potential Interaction

Sotorasib

Disopyramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor disopyramide efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Concentrations may increase due to CYP3A4 inhibition by sotorasib, but this is unlikely to be relevant.

Description:

See Summary

Potential Interaction

Sotorasib

Domperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Domperidone is mainly metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor domperidone efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Dopamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. There is little potential for dopamine to affect the disposition of sotorasib, or to be affected if coadministered with sotorasib.

Description:

See Summary

Potential Interaction

Sotorasib

Doxazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Doxazosin is metabolised mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor doxazosin efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolised to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolised by CYP2D6. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Doxycycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Between 40-60% of an administered dose can be accounted for in the urine. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dronabinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of dronabinol efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Drospirenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Drospirenone is metabolised to a minor extent via CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Dulaglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by endogenous endopeptidases. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See Summary

No Interaction Expected

Sotorasib

Duloxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolised by CYP2D6 and CYP1A2. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Dutasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dutasteride is mainly metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of dutasteride efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Dydrogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied care should be taken. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Concentrations of edoxaban may decrease due to CYP3A4 induction by sotorasib but concentrations of edoxaban may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on edoxaban exposure. Monitoring for edoxaban toxicity and efficacy, and anti-Xa concentrations, if available, should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Eltrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1 and UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Enalapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Enoxaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is predominantly renally excreted. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Eprosartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eprosartan is largely excreted in bile and urine as unchanged drug. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Ertapenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Erythromycin is a substrate of CYP3A4 and P-gp and concentrations may alter due to CYP3A4 induction and P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. The combined effect of CYP3A induction and P-gp inhibition on erythromycin is unknown. Monitor for erythromycin efficacy and toxicity. Moreover, erythromycin is an inhibitor of CYP3A4 (moderate) and P-gp. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and concentrations of sotorasib may increase. Coadministration is not recommended. If coadministration cannot be avoided, monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of escitalopram efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, esomeprazole is also an inhibitor of CYP2C19. Sotorasib is not metabolised by CYP2C19. However, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by esomeprazole reduces its bioavailability. Coadministration of sotorasib and omeprazole decreased the steady-state AUC of sotorasib by 42%. Coadministration is contraindicated. If coadministration cannot be avoided, sotorasib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability, but this has not been assessed in a clinical study. Closely monitor esomeprazole efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Estazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor estazolam efficacy.

Description:

See Summary

Do Not Coadminister

Sotorasib

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Ethambutol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolised by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and urine (50%). Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Ethionamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolised in the liver; animal studies suggest involvement of flavin-containing monooxygenases. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Etonogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Etonogestrel is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Potential Interaction

Sotorasib

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of everolimus may increase due to P-gp inhibition but concentrations of everolimus may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on everolimus exposure. Closely monitor everolimus efficacy and toxicity, and everolimus plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Exenatide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See Summary

No Interaction Expected

Sotorasib

Ezetimibe

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Sotorasib does not inhibit or induce UGTs.

Description:

See Summary

Potential Interaction

Sotorasib

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Famotidine is excreted via OAT1/OAT3. Sotorasib does not interact with this elimination pathway. The bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by famotidine reduces its bioavailability. Coadministration is not recommended. If coadministration is necessary, sotorasib should be administered at the moment at which acid secretion is less inhibited, and that is 2 hours before a new dose of famotidine. Monitor sotorasib plasma levels, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Felodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Felodipine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor felodipine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Fenofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolysed to an active metabolite, fenofibric acid. In vitro data suggest that fenofibric acid inhibits OAT3. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Fentanyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fentanyl undergoes extensive CYP3A4 metabolism. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor fentanyl efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fexofenadine is a substrate of P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of fexofenadine. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with fexofenadine. Monitoring for fexofenadine toxicity should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Finasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Finasteride is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of finasteride efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Fish oils

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is described as a CYP3A4 inducer. However, the mechanism and clinical relevance of this interaction is unknown. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by flucloxacillin. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A decrease in sotorasib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no CYP3A4 induction potential is recommended.

Description:

See Summary

Potential Interaction

Sotorasib

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fluconazole is cleared primarily by renal excretion and is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by fluconazole. Coadministration is not recommended. If coadministration cannot be avoided, monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Flucytosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Sotorasib does not interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Fludrocortisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fludrocortisone is metabolised in the liver to inactive metabolites, possibly via CYP3A. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of fludrocortisone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Flunitrazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of flunitrazepam efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Fluoxetine is also a strong inhibitor of CYP2D6 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of fluoxetine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Flurazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. The metabolism of flurazepam is most likely CYP-mediated. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of flurazepam efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Fluticasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluticasone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of fluticasone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Fluvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluvastatin is mainly metabolised by CYP2C9 (75%) and to a lesser extent by CYP3A4 (20%) and CYP2C8 (5%). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of fluvastatin efficacy should be considered. Moreover, fluvastatin potentially inhibits CYP2C9, but the clinical relevance of CYP2C9 inhibition is unknown. Sotorasib is not metabolised by CYP2C9.

Description:

See Summary

Potential Interaction

Sotorasib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and 2D6 (weak). Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by fluvoxamine. Coadministration is not recommended. If coadministration cannot be avoided, monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Fondaparinux

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Formoterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation. As multiple CYP450 and UGT enzymes catalyse the transformation the potential for a pharmacokinetic interaction is low.

Description:

See Summary

Potential Interaction

Sotorasib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4 (not clinically relevant), CYP2C9 and UGT. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to moderate CYP3A4 inhibition by sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor fosaprepitant efficacy. Monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Do Not Coadminister

Sotorasib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Phenytoin is also a potent inducer of CYP3A4, UGT and P-gp. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp and concentrations may decrease due to CYP3A4 and P-gp induction by fosphenytoin. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with fosphenytoin. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. In vitro data indicate that furosemide is also an inhibitor of the renal transporters OAT1/OAT3. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Gabapentin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gabapentin is cleared mainly by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Gemfibrozil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Moreover, gemfibrozil is an inhibitor of CYP2C8 (strong), OATP1B1 and OAT3. In vitro data indicate gemfibrozil to be a strong inhibitor of CYP2C9 but in vivo data showed no clinically relevant effect on CYP2C9. Sotorasib does not interact with this metabolic pathway

Description:

See Summary

No Interaction Expected

Sotorasib

Gentamicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gentamicin is eliminated unchanged predominantly via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Gestodene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Glibenclamide (Glyburide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of glibenclamide efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Gliclazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C19. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Glimepiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glimepiride is mainly metabolised by CYP2C9. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Sotorasib

Glipizide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is mainly metabolised by CYP2C9. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of granisetron may increase due to P-gp inhibition by sotorasib but concentrations may also decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on granisetron exposure. Monitoring for granisetron efficacy and toxicity should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Grapefruit juice is known to inhibit CYP3A4 enzymes. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by grapefruit juice. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Green tea

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

Potential Interaction

Sotorasib

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs, such as sotorasib. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by griseofulvin. A decrease in sotorasib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no CYP3A4 induction potential is recommended. Monitor sotorasib plasma levels, if available.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of haloperidol efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Heparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydralazine is metabolised via primary oxidative metabolism and acetylation. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to weak CYP3A4 inhibition by hydralazine. Monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Hydrochlorothiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Therefore, monitoring of hydrocodone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Hydrocortisone (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydrocortisone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of hydrocortisone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Hydrocortisone (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of hydrocortisone.

Description:

See Summary

No Interaction Expected

Sotorasib

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Sotorasib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Sotorasib

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyurea is metabolised in the liver and cleared via the lungs and kidneys. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Hydroxyzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor hydroxyzine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ibandronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid.

Description:

See Summary

No Interaction Expected

Sotorasib

Ibuprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Iloperidone is metabolised by CYP3A4 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor iloperidone efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Imipenem/Cilastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and to a lesser extent by active tubular secretion. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of imipramine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolised by CYP450s. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by sotorasib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Insulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Ipratropium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Irbesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Iron supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Isoniazid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Isosorbide dinitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of isosorbide dinitrate efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Itraconazole is primarily metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, sotorasib is metabolised by CYP3A4 and is an in vitro substrate of P-gp. Concentrations of sotorasib may increase due to P-gp and CYP3A4 inhibition by itraconazole. Coadministration is contraindicated.

Description:

See Summary

Potential Interaction

Sotorasib

Ivabradine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ivabradine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor ivabradine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Kanamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Kanamycin is eliminated unchanged predominantly via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Ketoconazole is a substrate of CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, ketoconazole is an inhibitor of CYP3A4 (strong) and P-gp. Sotorasib is metabolised by CYP3A4 and is an in vitro substrate of P-gp. Concentrations of sotorasib may increase due to P-gp and CYP3A4 inhibition by ketoconazole. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Labetalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated (via UGT1A1 and UGT2B7). Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Lacidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Lacidipine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of lacidipine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Lactulose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by lansoprazole reduces its bioavailability. Coadministration of sotorasib and omeprazole decreased the steady-state AUC of sotorasib by 42%. Coadministration is contraindicated. If coadministration cannot be avoided, sotorasib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability. However, this has not been assessed in a clinical study. Closely monitor lansoprazole efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Lercanidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Lercanidipine is mainly metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor lercanidipine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Levocetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Levofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levofloxacin is renally eliminated mainly by glomerular filtration and active secretion (possibly OCT2). Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Do Not Coadminister

Sotorasib

Levonorgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Do Not Coadminister

Sotorasib

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Sotorasib

Levothyroxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolised by deiodination (by enzymes of deiodinase family) and glucuronidation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of lidocaine efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is also a substrate of P-gp. Concentrations of linagliptin may decrease due to CYP3A4 induction by sotorasib, but this is unlikely to be clinically relevant. However, concentrations of linagliptin may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with linagliptin. Furthermore, linagliptin is a weak inhibitor of CYP3A4. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to weak CYP3A4 inhibition by linagliptin. Monitor for sotorasib toxicity and plasma levels, if available. Monitoring for linagliptin toxicity should also be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Linezolid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linezolid undergoes non-CYP mediated metabolism. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Liraglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Liraglutide is degraded by endogenous endopeptidases.

Description:

See Summary

No Interaction Expected

Sotorasib

Lisinopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisinopril is eliminated unchanged renally via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Lithium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate. Therefore, no pharmacokinetic interaction is expected.

Description:

See Summary

No Interaction Expected

Sotorasib

Live vaccines

Quality of Evidence: Very Low

Summary:

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. However, since sotorasib is not an immunosuppressant drug, no additional unwanted effects are expected.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Loperamide is mainly metabolised by CYP3A4 and CYP2C8 and is a substrate of P-gp. Concentrations of loperamide may increase due to P-gp inhibition but concentrations of loperamide may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on loperamide exposure. Monitoring for both loperamide efficacy and toxicity should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Loratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Loratadine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of loratadine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Lorazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorazepam undergoes non-CYP-mediated elimination. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Lormetazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Losartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

Potential Interaction

Sotorasib

Lovastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor lovastatin efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Macitentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor macitentan efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Magnesium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Magnesium is eliminated in the kidney, mainly by glomerular filtration. Sotorasib does not interact with this elimination pathway. However, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by magnesium reduces its bioavailability. Coadministration is not recommended. If coadministration is necessary, sotorasib should be administered at the moment at which acid secretion is less inhibited, and that is 2 hours before a new dose of magnesium. Monitor sotorasib plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Maprotiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Do Not Coadminister

Sotorasib

Medroxyprogesterone (depot)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Medroxyprogesterone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Do Not Coadminister

Sotorasib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Sotorasib

Mefenamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefenamic acid is metabolised by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Sotorasib does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Sotorasib

Megestrol acetate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Megestrol acetate is mainly eliminated in the urine. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Meropenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney with in vitro data suggesting it is a substrate of the renal transporters OAT3>OAT1. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Mesalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolised to N-acetyl-mesalazine by N-acetyltransferase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Metamizole is metabolised in serum and excreted via urine (90%) and faeces (10%). Metamizole is an inducer of CYP3A4. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by metamizole. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with metamizole. A decrease in sotorasib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no CYP3A4 induction potential is recommended. If coadministration cannot be avoided, monitor sotorasib plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Metformin

Quality of Evidence: Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Metformin is mainly eliminated unchanged in the urine and is a substrate of OCT1, OCT2, OCT3, MATE1 and MATE2K. Concentrations of metformin may increase due to MATE1 inhibition by sotorasib. However, in healthy volunteers (n=13), coadministration of sotorasib (multiple doses of 960 mg) and metformin (multiple doses of 850 mg) resulted in no relevant effect on metformin exposure and no antihyperglycemic effects were identified.

Description:

See Summary

Potential Interaction

Sotorasib

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Methadone is demethylated by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor methadone efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Methyldopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged and as the mono-O-sulfate conjugate. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Methylphenidate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolised by CYP450s to a clinically relevant extent and does not inhibit or induce CYP450s. Therefore, there is little potential for methylphenidate to affect disposition of sotorasib, or to be affected if coadministered with sotorasib.

Description:

See Summary

Potential Interaction

Sotorasib

Methylprednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Methylprednisolone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor methylprednisolone efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Metoclopramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolised by CYP450 system (mainly CYP2D6). Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Metolazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metolazone is largely excreted unchanged in the urine. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by sotorasib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Metoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Metronidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metronidazole is eliminated via glomerular filtration. Elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, ciclosporin) with metronidazole. However, metronidazole did not increase concentrations of several CYP3A probe drugs (e.g. midazolam, alprazolam). Thus, a clinically relevant effect on sotorasib exposure is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mexiletine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of mianserin efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Miconazole is extensively metabolized by the liver. Moreover, miconazole is an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Sotorasib is metabolised by CYP3A4 and concentrations may increase due to strong CYP3A4 inhibition by miconazole. Coadministration is contraindicated. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinically relevant interaction is expected.

Description:

See Summary

Potential Interaction

Sotorasib

Midazolam (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Midazolam is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor midazolam efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Sotorasib

Milnacipran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of mirtazapine efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Mometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mometasone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of mometasone efficacy should be considered. Note: No clinically relevant interaction are expected with the topical use of mometasone.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of montelukast efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Additionally, morphine is a substrate of P-gp and concentrations may increase due to inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with morphine. Monitoring of morphine toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Moxifloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Sotorasib does not inhibit or induce UGT1A1.

Description:

See Summary

No Interaction Expected

Sotorasib

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Nadroparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nadroparin is excreted renally by a nonsaturable mechanism. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Nandrolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nandrolone is metabolised in the liver by alpha-reductase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Naproxen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Sotorasib does not inhibit or induce these UGTs or CYPs.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Nateglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of nateglinide efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Nebivolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Do Not Coadminister

Sotorasib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Nefazodone is metabolised mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Furthermore, nefazodone is a strong inhibitor of CYP3A4. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to strong CYP3A4 inhibition by nefazodone. Coadministration is contraindicated.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, nicardipine is a weak inhibitor of CYP3A4. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to weak CYP3A4 inhibition by nicardipine. Monitoring of nicardipine efficacy should be considered. Monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Nicotinamide (Niacinamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolised by xanthine oxidase and aldehyde oxidase, which are not affected by sotorasib.

Description:

See Summary

Potential Interaction

Sotorasib

Nifedipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Nifedipine is metabolised mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor nifedipine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Nimesulide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nimesulide is extensively metabolised in the liver following multiple pathways including CYP2C9. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Nisoldipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Nisoldipine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor nisoldipine efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Nitrendipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nitrendipine is extensively metabolised mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of nitrendipine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Nitrofurantoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolised in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Norelgestromin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Norethisterone (Norethindrone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Norgestimate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

Do Not Coadminister

Sotorasib

Norgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4 and is glucuronidated to a minor extent. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolised mainly by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Nystatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant. Therefore, no drug interactions are expected.

Description:

See Summary

No Interaction Expected

Sotorasib

Ofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Olanzapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolised mainly by CYP1A2 (major) and CYP2D6, but also by glucuronidation (UGT1A4). Sotorasib does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Sotorasib

Olmesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Omeprazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and is contraindicated. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19, which does not affect sotorasib. Moreover, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by omeprazole reduces its bioavailability. In healthy volunteers (n=14), coadministration of sotorasib (multiple doses of 960 mg) and omeprazole (40 mg once daily for 6 days) decreased the steady-state AUC of sotorasib by 42%. Coadministration is contraindicated. If coadministration cannot be avoided, sotorasib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability. However, this has not been assessed in a clinical study. Closely monitor omeprazole efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Ondansetron is also a substrate of P-gp. Concentrations of ondansetron may increase due to P-gp inhibition by sotorasib but concentrations of ondansetron may also decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on ondansetron exposure. Monitoring for ondansetron efficacy and toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Oxazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by oxcarbazepine. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with oxcarbazepine. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Oxprenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised via glucuronidation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor oxycodone efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of paliperidone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Palonosetron is also a substrate of P-gp. Concentrations of palonosetron may increase due to P-gp inhibition by sotorasib but concentrations of palonosetron may also decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on palonosetron exposure. Monitoring for palonosetron efficacy and toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Pamidronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pamidronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by pantoprazole reduces its bioavailability. Coadministration of sotorasib and omeprazole decreased the steady-state AUC of sotorasib by 42%. Coadministration is contraindicated. If coadministration cannot be avoided, sotorasib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability. However, this has not been assessed in a clinical study. Closely monitor pantoprazole efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Para-aminosalicylic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1, and 2B15), sulfation, and to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Concentrations of paracetamol may increase due to CYP3A4 inhibition by sotorasib, but this is unlikely to be clinically relevant.

Description:

See Summary

No Interaction Expected

Sotorasib

Paroxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolised by CYP2D6. Moreover, paroxetine is an inhibitor of CYP2D6 (strong) and CYP2C9. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

No Interaction Expected

Sotorasib

Penicillins

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Perazine is mainly metabolised by CYPs 1A2, 3A4 and 2C19, and to a lesser extent by CYPs 2C9, 2D6 and 2E1, with oxidation via FMO3. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor perazine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Periciazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Perindopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolised to other inactive metabolites. Elimination occurs predominantly via the urine. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Pethidine (Meperidine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pethidine is metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of pethidine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Phenelzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolised by oxidation via monoamine oxidase and to a lesser extent by acetylation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. Phenobarbital is also a strong inducer of CYP3A4, CYP2C9, CYP2C8 and UGTs. Sotorasib is metabolised by CYP3A4 and concentrations may decrease due to CYP3A4 induction by phenobarbital. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with phenobarbital. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

Do Not Coadminister

Sotorasib

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. If coadministration is unavoidable, closely monitor phenprocoumon efficacy and INR/PT, if available.

Description:

See Summary

Do Not Coadminister

Sotorasib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Phenytoin is a strong inducer of CYP3A4, UGT and P-gp. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp and concentrations may decrease due to CYP3A4 and P-gp induction by phenytoin. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with phenytoin. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Phytomenadione (Vitamin K)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An in vitro study found that the only CYP450 enzyme involved in phytomenadione metabolism was CYP4F2. Sotorasib does not inhibit or induce CYP4F2.

Description:

See Summary

Potential Interaction

Sotorasib

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor pimozide efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Pindolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring for pioglitazone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Sotorasib

Piroxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolised by CYP2C9. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Sotorasib

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Moreover, pitavastatin is a substrate of OATP1B1. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of posaconazole. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with posaconazole. Moreover, posaconazole is a strong inhibitor of CYP3A4. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to strong CYP3A4 inhibition by posaconazole. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on limited data available an interaction appears unlikely. Potassium is eliminated renally. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Prasugrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. Concentrations of prasugrel may decrease and concentrations of the active metabolite may increase due to CYP3A4 induction by sotorasib. If coadministration is unavoidable, closely monitor for prasugrel toxicity with a thrombocytes aggregation test, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Pravastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pravastatin is minimally metabolised via CYP enzymes and is a substrate of OATP1B1. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Prazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin is extensively metabolised, primarily by demethylation and conjugation. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Prednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prednisolone undergoes hepatic metabolism via CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of prednisolone efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Prednisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of prednisone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Pregabalin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pregabalin is cleared mainly by glomerular filtration (90% as unchanged drug). Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Sotorasib does not inhibit or induce CYP2D6 or CYP2C19.

Description:

See Summary

No Interaction Expected

Sotorasib

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolised by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of propafenone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolised by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Additionally, prucalopride is a substrate of P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of prucalopride. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with prucalopride. Monitoring for prucalopride toxicity should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Pyrazinamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolised by xanthine oxidase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Pyridoxine (Vitamin B6)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

Potential Interaction

Sotorasib

Quetiapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Quetiapine is primarily metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor quetiapine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Quinapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinapril is de-esterified to the active metabolite quinaprilat which is eliminated primarily by renal excretion via OAT3. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is a substrate of P-gp. Concentrations may decrease due to CYP3A4 induction and increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on quinidine exposure. Monitoring for quinidine efficacy and toxicity should be considered. Moreover, quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp. Therefore, concentrations of sotorasib may increase. Coadministration is not recommended. If coadministration cannot be avoided, monitor for sotorasib toxicity and plasma levels, if available.

Description:

See Summary

Do Not Coadminister

Sotorasib

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration is contraindicated. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by rabeprazole reduces its bioavailability. Coadministration of sotorasib and omeprazole decreased the steady-state AUC of sotorasib by 42%. Coadministration is contraindicated. If coadministration cannot be avoided, sotorasib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability. However, this has not been assessed in a clinical study. Closely monitor rabeprazole efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Ramipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolised to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ranitidine is excreted via OAT1/OAT3. Sotorasib does not interact with this elimination pathway. However, the bioavailability of sotorasib is pH-dependent and, thus, an increase in gastric pH by ranitidine reduces its bioavailability. Coadministration is not recommended. If coadministration is necessary, sotorasib should be administered at the moment at which acid secretion is less inhibited, and that is 2 hours before a new dose of ranitidine. Monitor sotorasib plasma levels, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ranolazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Concentrations of ranolazine may increase due to P-gp inhibition by sotorasib but concentrations may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on ranolazine exposure. Moreover, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of sotorasib may increase due to weak CYP3A4 inhibition and P-gp inhibition by ranolazine. Selection of an alternative concomitant medication with no CYP3A4 or P-gp inhibition potential is recommended. Monitor sotorasib toxicity and plasma levels, if available. Monitoring for ranolazine efficacy and toxicity should also be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Reboxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Reboxetine is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor reboxetine efficacy. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Thus, no clinically relevant effect on sotorasib exposure is expected.

Description:

See Summary

No Interaction Expected

Sotorasib

Repaglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolised by CYP2C8 and CYP3A4, with clinical data indicating it is a substrate of the hepatic transporter OATP1B1. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Retinol (Vitamin A)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver but retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Riboflavin (Vitamin B2)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

Do Not Coadminister

Sotorasib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifabutin is metabolised by CYP3A4 and via deacetylation. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Moreover, rifabutin is a strong CYP3A4 and P-gp inducer. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and concentrations may decrease. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with rifabutin. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

Do Not Coadminister

Sotorasib

Rifampicin

Quality of Evidence: Low

Summary:

Coadministration has been studied and is contraindicated. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and concentrations may decrease. In healthy volunteers (n=14), coadministration of sotorasib (multiple doses of 960 mg) and rifampicin (multiple doses of 600 mg) decreased the steady-state AUC of sotorasib by 51%. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

Do Not Coadminister

Sotorasib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8 and P-gp inducer. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and concentrations may decrease. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Rifaximin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Furthermore, risperidone is a substrate of P-gp. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Concentrations of risperidone may also increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on risperidone exposure. Monitoring for both risperidone toxicity and efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Moreover, rivaroxaban is a substrate of P-gp and BCRP. Concentrations of rivaroxaban may decrease due to CYP3A4 induction by sotorasib but concentrations of rivaroxaban may increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on rivaroxaban exposure. If coadministration is unavoidable, monitor closely for rivaroxaban toxicity and efficacy and anti-Xa concentrations, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Rosiglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP2C9. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Sotorasib

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosuvastatin is largely excreted unchanged in the faeces via OATP1B1 and is a substrate of BCRP. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Salbutamol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolised to the inactive salbutamol-4’-O-sulphate. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Salmeterol is metabolised by CYP3A4. The systemic exposure of salmeterol is low. However, concentrations may decrease due to CYP3A4 induction by sotorasib. Monitoring of salmeterol efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Concentrations of saxagliptin may also increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on saxagliptin exposure. Coadministration is not recommended. If coadministration is unavoidable, closely monitor saxagliptin efficacy and toxicity.

Description:

See Summary

No Interaction Expected

Sotorasib

Senna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant interactions are known.

Description:

See Summary

Potential Interaction

Sotorasib

Sertindole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Sertindole is metabolised by CYP2D6 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor sertindole efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of sertraline efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Sildenafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor sildenafil efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Simvastatin is metabolised by CYP3A4. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor simvastatin efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of sirolimus may increase due to P-gp inhibition by sotorasib but concentrations may decrease due to CYP3A4 induction by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on sirolimus exposure. Closely monitor sirolimus efficacy and toxicity, and sirolimus plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Sitagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, and P-gp) and metabolism by CYP3A4 represents a minor metabolic pathway. Sitagliptin concentrations may increase due to P-gp inhibition by sotorasib but may also decrease due to CYP3A4 induction by sotorasib. However, this is unlikely to be clinically relevant.

Description:

See Summary

No Interaction Expected

Sotorasib

Sodium nitroprusside

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Sotalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is excreted unchanged via renal elimination. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Spectinomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spectinomycin is predominantly eliminated unchanged in the kidneys via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Spironolactone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spironolactone is partly metabolised by the flavin containing monooxygenases. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Stanozolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol undergoes hepatic metabolism. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. St John’s wort is a P-gp and CYP3A4 inducer. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of sotorasib may decrease due to CYP3A4 and P-gp induction by St John’s Wort. Coadministration of sotorasib and rifampicin, a strong CYP3A4 inducer, decreased the steady-state AUC of sotorasib by 51%. A similar effect may occur after coadministration with St John’s Wort. A decrease in sotorasib exposure can lead to decreased efficacy. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Streptokinase

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Streptomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is eliminated by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Sulfadiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Sotorasib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Sotorasib

Sulpiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tacrolimus is metabolised mainly by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Tacrolimus is also an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to CYP3A4 inhibition by tacrolimus. Selection of an alternative concomitant medication with no CYP3A4 inhibition potential is recommended. Monitor for sotorasib toxicity and plasma levels, if available. If coadministration is unavoidable, closely monitor tacrolimus efficacy and plasma concentrations, if available.

Description:

See Summary

Potential Interaction

Sotorasib

Tadalafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tadalafil is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor tadalafil efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Tamsulosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor tamsulosin efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Tazobactam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is excreted as unchanged drug (approximately 80%) and inactive metabolite (approximately 20%) in the urine. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. However, the clinical relevance of P-gp inhibition is unknown. Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp, and concentrations may increase due to strong CYP3A4 inhibition by telithromycin. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Telmisartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Temazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and CYP2C19. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of terbinafine efficacy should be considered. Terbinafine is also a moderate-strong inhibitor of CYP2D6, which does not affect sotorasib.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Testosterone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of testosterone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Tetracycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracycline is eliminated unchanged primarily by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Theophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolised by CYP1A2. Sotorasib does not inhibit or induce CYP1A2.

Description:

See Summary

No Interaction Expected

Sotorasib

Thiamine (Vitamin B1)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of thioridazine efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Tiapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiapride is excreted largely unchanged in urine. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Sotorasib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Ticagrelor is a substrate of CYP3A4 and P-gp. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Concentrations of ticagrelor may also increase due to P-gp inhibition by sotorasib. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. It is unknown what the combined effect of P-gp inhibition and CYP3A induction is on ticagrelor exposure. If coadministration is unavoidable, monitor closely for ticagrelor toxicity and efficacy and anti-Xa concentrations, if available. Ticagrelor is also a weak inhibitor of CYP3A4 and may increase concentrations of sotorasib. Monitor sotorasib toxicity and plasma levels, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Timolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Sotorasib does not inhibit or induce CYP2D6. Note: the systemic absorption of timolol after ocular administration is low.

Description:

See Summary

No Interaction Expected

Sotorasib

Tinzaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Sotorasib does not inhibit or induce these CYPs.

Description:

See Summary

Potential Interaction

Sotorasib

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 playing a minor role. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor tolterodine efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Torasemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolised mainly by CYP2C9. Furthermore, OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tramadol is metabolised by CYPs 3A4, 2B6, and 2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of tramadol efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Trandolapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trandolapril is hydrolysed to trandolaprilat. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Tranexamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tranexamic acid is mainly cleared by glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Tranylcypromine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tranylcypromine is hydroxylated and acetylated. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Trazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Trazodone is primarily metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor trazodone efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Triamcinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Triamcinolone is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of triamcinolone efficacy should be considered.

Description:

See Summary

Potential Interaction

Sotorasib

Triazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Triazolam is metabolised by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor triazolam efficacy.

Description:

See Summary

No Interaction Expected

Sotorasib

Trimethoprim/Sulfamethoxazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. To a lesser extent (approximately 30%), trimethoprim is metabolised by CYP enzymes (in vitro data suggest CYP3A4, CYP1A2 and CYP2C9) and concentrations may increase due to CYP3A4 inhibition by sotorasib, but this is unlikely to be relevant. Sulfamethoxazole is metabolised by CYP2C9. Furthermore, trimethoprim is a weak CYP2C8 inhibitor and in vitro data also suggest that trimethoprim is an inhibitor of OCT2 and MATE1, which does not affect sotorasib. Sulfamethoxazole is a weak inhibitor of CYP2C9, which does not affect sotorasib.

Description:

See Summary

No Interaction Expected

Sotorasib

Trimipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolised mainly by CYP2D6. Sotorasib does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tropisetron is metabolised mainly by CYP2D6. Tropisetron is also a substrate of P-gp. Sotorasib is an inhibitor of P-gp and may increase concentrations of tropisetron. Coadministration of a single dose sotorasib and digoxin, a P-gp substrate, increased the AUC of digoxin by 21%. A similar effect may occur with tropisetron. Monitoring for tropisetron toxicity should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Ulipristal is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration should be avoided.

Description:

See Summary

No Interaction Expected

Sotorasib

Valproic acid (Valproate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valproic acid is primarily metabolized by glucuronidation (50%) and mitochondrial beta-oxidation (30-40%). To a lesser extent (10%), valproic acid is metabolized by CYP2C9 and CYP2C19. In addition, valproic acid is an inhibitor of CYP2C9. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Valsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valsartan is eliminated unchanged mostly through biliary excretion. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Vancomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vancomycin is excreted unchanged via glomerular filtration. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of venlafaxine efficacy should be considered.

Description:

See Summary

Do Not Coadminister

Sotorasib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Sotorasib is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations of sotorasib may increase due to moderate CYP3A4 inhibition by verapamil. Coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Sotorasib

Vildagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vildagliptin is inactivated via non-CYP mediated hydrolysis. Sotorasib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Sotorasib

Vitamin E

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See Summary

Do Not Coadminister

Sotorasib

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Sotorasib is metabolised by CYP3A4 and concentrations may increase due to strong CYP3A4 inhibition by voriconazole. Coadministration is contraindicated.

Description:

See Summary

Do Not Coadminister

Sotorasib

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. S-warfarin (more potent) is metabolised by CYP2C9. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. If coadministration is unavoidable, monitor R-warfarin efficacy closely and INR/PT, if available.

Description:

See Summary

No Interaction Expected

Sotorasib

Xipamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 90% of xipamide is excreted in the urine, mainly as unchanged drug (~50%) and glucuronides (30%). OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Sotorasib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Zaleplon is mainly metabolised by aldehyde oxidase and to a lesser extent by CYP3A4. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of zaleplon efficacy should be considered

Description:

See Summary

Potential Weak Interaction

Sotorasib

Ziprasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of ziprasidone efficacy should be considered.

Description:

See Summary

No Interaction Expected

Sotorasib

Zoledronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zoledronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Sotorasib does not interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Sotorasib

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Zolpidem is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 1A2. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor zolpidem efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Zopiclone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Zopiclone is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C8. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor zopiclone efficacy.

Description:

See Summary

Potential Interaction

Sotorasib

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Zotepine is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Coadministration is not recommended. If coadministration is unavoidable, closely monitor zotepine efficacy.

Description:

See Summary

Potential Weak Interaction

Sotorasib

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Zuclopenthixol is metabolised by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4). Sotorasib has potential to cause drug interactions due to time-dependent inhibition of CYP3A and induction of CYP3A. According to the EU and US product labels, concentrations of CYP3A substrates may decrease when combined with sotorasib. Monitoring of zuclopenthixol efficacy should be considered.

Description:

See Summary