Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Talazoparib

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%). Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Alendronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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 alendronate before taking any other oral medicinal product.

Description:

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No Interaction Expected

Talazoparib

Alfentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes extensive CYP3A4 metabolism. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Alfuzosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. Aliskiren is also a substrate of P-gp. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

Alosetron

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 data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Alprazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

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No Interaction Expected

Talazoparib

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is metabolized by glucuronidation via UGTs 1A3, 1A9 and 2B7 and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs, UGTs or P-gp.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OCTs.

Description:

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Potential Interaction

Talazoparib

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Amiodarone is metabolised by CYP3A4 and CYP2C8 and is an inhibitor of CYP2C9 (moderate), CYP3A4 and P-gp (strong). The major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYPs 3A4 (weak), 2C9 (moderate), 2D6 (moderate), 2C19 (weak), 1A1 (strong), 2B6 (moderate) and P-gp (strong). Talazoparib concentrations may increase due to P-gp inhibition. After coadministration with itraconazole (a strong P-gp inhibitor), talazoparib exposure increased by approximately 45% and an increase in rate of talazoparib dose reductions was observed. A similar effect may occur after coadministration with amiodarone. Therefore, if coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of amiodarone 3-5 half-lives after discontinuation of amiodarone. Furthermore, although a thorough QT study has not been performed, talazoparib and amiodarone potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG. Note: due to the long half-life of amiodarone, interactions can be observed for several months after discontinuation of amiodarone.

Description:

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No Interaction Expected

Talazoparib

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). Talazoparib is unlikely to interact with this elimination pathway.

Description:

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Potential Interaction

Talazoparib

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and amitriptyline potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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Potential Weak Interaction

Talazoparib

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Talazoparib is unlikely to interact with this elimination pathway. However, the European SPC for amphotericin B states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension and so monitoring may be required.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway. 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.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Antacids are not metabolised by CYPs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

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No Interaction Expected

Talazoparib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not inhibit or induce CYPs, P-gp or BCRP.

Description:

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No Interaction Expected

Talazoparib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. During treatment, aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Talazoparib does not interact with these metabolic pathways.

Description:

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No Interaction Expected

Talazoparib

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Asenapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 (minor) and 2D6 (minor)). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

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Potential Interaction

Talazoparib

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. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and astemizole potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Talazoparib does not inhibit or induce CYPs, P-gp or OATP1B1.

Description:

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Potential Weak Interaction

Talazoparib

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Talazoparib does not interact with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

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Potential Interaction

Talazoparib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce P-gp or MRP2. Azithromycin is also an inhibitor of P-gp and may increase talazoparib exposure. However, the clinical relevance of P-gp inhibition by azithromycin is unknown. If coadministration is unavoidable, monitor closely for talazoparib toxicity and adjust dose based on tolerability. Monitor talazoparib plasma concentrations, if available. Furthermore, although a thorough QT study has not been performed, talazoparib and azithromycin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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Potential Interaction

Talazoparib

Bedaquiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bedaquiline is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and bedaquiline potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

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. In vitro data indicate that bendroflumethiazide inhibits these renal transporters, but a clinically significant interaction is unlikely in the range of observed clinical concentrations. Talazoparib does not interact with this metabolic pathway and does not inhibit or induce OATs.

Description:

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Potential Interaction

Talazoparib

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and bepridil potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

Betamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Talazoparib

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosentan is a substrate and weak inducer of CYP3A4 and CYP2C9. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Budesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

Buprenorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

Buspirone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce OATs.

Description:

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Potential Interaction

Talazoparib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Carbamazepine is also an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6, UGT1A1 and P-gp (moderate). Talazoparib concentrations may decrease due to P-gp induction by carbamazepine. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

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No Interaction Expected

Talazoparib

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 CYPs 2C9 and 1A2. Talazoparib does not inhibit or induce CYPs or UGTs. Carvedilol is also an inhibitor of P-gp and may increase talazoparib concentrations. However, the clinical relevance of P-gp inhibition is unknown. After coadministration with weak/moderate P-gp inhibitors (e.g. diltiazem), talazoparib exposure increased by approximately 8%, which is considered to not be clinically relevant.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OATs or MATEs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib

Description:

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No Interaction Expected

Talazoparib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly glucuronidated. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong) and CYP2D6 (weak). Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

Chlordiazepoxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolised by CYP3A4 but does not inhibit or induce cytochromes. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

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Potential Interaction

Talazoparib

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and chlorpromazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

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No Interaction Expected

Talazoparib

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. 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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

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No Interaction Expected

Talazoparib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclosporin is a substrate of CYP3A4 and P-gp and also inhibits CYP3A4 and OATP1B1. Talazoparib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not interact with this metabolic pathway. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

Potential Interaction

Talazoparib

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. It is also metabolised and partially cleared through the bile and intestine. Ciprofloxacin is also a weak-moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Talazoparib does not interact with this metabolic or elimination pathway. However, although a thorough QT study has not been performed, talazoparib and ciprofloxacin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Do Not Coadminister

Talazoparib

Cisapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Cisapride is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. Coadministration of cisapride with other drugs that prolong the QTc interval, such as talazoparib, should be avoided. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and citalopram potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied and should be approached with caution. Clarithromycin is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. Clarithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Clarithromycin may increase talazoparib concentrations due to P-gp inhibition. After coadministration with itraconazole (a strong P-gp inhibitor), talazoparib exposure increased by approximately 45% and an increase in rate of talazoparib dose reductions was observed. A similar effect may occur after coadministration with clarithromycin. Therefore, if coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of clarithromycin 1 day after discontinuation of clarithromycin. Furthermore, although a thorough QT study has not been performed, talazoparib and clarithromycin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolised by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Talazoparib

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. Talazoparib does not interact with this metabolic or elimination pathway. However, although a thorough QT study has not been performed, talazoparib and clofazimine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. 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. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and clomipramine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Clopidogrel is also an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and of CYP2C9 (in vitro) at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Clorazepate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Oxazepam is mainly glucuronidated. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Talazoparib does not inhibit or induce CYPs. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered. Furthermore, although a thorough QT study has not been performed, talazoparib and clozapine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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). Codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. The metabolite morphine is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs, UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is metabolised by CYP3A4 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is transported via P-gp and is renally excreted. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Desipramine is metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and desipramine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Desogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate of CYP3A4. Talazoparib does not inhibit or induce CYPs. Dexamethasone has also been described as a weak inducer of CYP3A4. However, the clinical relevance of this interaction is not known as CYP3A4 induction by dexamethasone has not yet been established. Talazoparib is not metabolised by CYP3A4.

Description:

See Summary

No Interaction Expected

Talazoparib

Dextropropoxyphene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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). Morphine is also a substrate of P-gp. Talazoparib does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Diazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Temazepam is mainly glucuronidated. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs of UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Digoxin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is eliminated renally via OATP4C1 and P-gp. Talazoparib does not inhibit or induce OATP4C1 or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Dihydrocodeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diltiazem is metabolised by CYP3A4 and CYP2D6. Diltiazem is also a moderate inhibitor of CYP3A4 and an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition is unknown. Diltiazem may increase talazoparib concentrations due to P-gp inhibition. After coadministration with weak/moderate P-gp inhibitors (e.g. diltiazem), talazoparib exposure increased by approximately 8%, which is considered to not be clinically relevant.

Description:

See Summary

Potential Interaction

Talazoparib

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Diphenhydramine is also a weak inhibitor of CYP2D6. Talazoparib does not interact with this metabolic pathway. However, although a thorough QT study has not been performed, talazoparib and diphenhydramine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

Potential Interaction

Talazoparib

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 in the urine. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and disopyramide potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. 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%). Talazoparib does not inhibit or induce CYPs or UGTs. However, although a thorough QT study has not been performed, talazoparib and dolasetron potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Domperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Domperidone is mainly metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and domperidone potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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 disposition of talazoparib, or to be affected if coadministered with talazoparib.

Description:

See Summary

No Interaction Expected

Talazoparib

Doxazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolised mainly by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Doxepin and nordoxepin are both metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Dronabinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Drospirenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolised to a minor extent via CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway. 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

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Dutasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Dydrogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or P-gp. Erythromycin is also an inhibitor of CYP3A4 (moderate) and P-gp. Talazoparib concentrations may increase due to P-gp inhibition by erythromycin. After coadministration with itraconazole (a strong P-gp inhibitor), talazoparib exposure increased by approximately 45% and an increase in rate of talazoparib dose reductions was observed. A similar effect may occur after coadministration with erythromycin. If coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of erythromycin approximately 12 hours after discontinuation of erythromycin. Furthermore, although a thorough QT study has not been performed, talazoparib and erythromycin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and escitalopram potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole is also an inhibitor of CYP2C19. Talazoparib does not interact with this metabolic pathway. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

No Interaction Expected

Talazoparib

Estazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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%). Talazoparib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Etonogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway. 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

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famotidine is excreted via OAT1/OAT3. Talazoparib does not inhibit or induce OATs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

No Interaction Expected

Talazoparib

Felodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Fentanyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine is a substrate of P-gp. Talazoparib does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Finasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Potential Interaction

Talazoparib

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and flecainide potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

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). Talazoparib does not interact with this metabolic or elimination pathway. However, although a thorough QT study has not been performed, talazoparib and fluconazole potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Flucytosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Talazoparib does not interact with this elimination pathway. However, 5-FU binds to the enzyme thymidylate synthase resulting in DNA damage. This mechanism occurs in all fast-dividing cells including bone marrow cells, resulting in haematological toxicity. Talazoparib also induces haematological toxicity which could be enhanced by the use of flucytosine. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

Fludrocortisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolised in the liver to inactive metabolites, possibly via CYP3A. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Flunitrazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Fluoxetine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Talazoparib

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fluphenazine is metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and fluphenazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Flurazepam

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 flurazepam is most likely CYP-mediated. Talazoparib is unlikely to interact with this unspecified metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Fluticasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Fluvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolised by CYP2C9 (75%) and to a lesser extent by CYP3A4 (20%) and CYP2C8 (5%). Fluvastatin also potentially inhibits CYP2C9. However, the clinical relevance of CYP2C9 inhibition is unknown. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Furthermore, talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. During treatment, aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Talazoparib does not interact with these metabolic pathways.

Description:

See Summary

Potential Interaction

Talazoparib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Talazoparib does not interact with this metabolic pathway. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Talazoparib does not inhibit or induce CYPs. Phenytoin is also a potent inducer of CYP3A4, UGT and P-gp. Talazoparib concentrations may decrease due to P-gp induction by phenytoin. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs or OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Gemfibrozil is also 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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Gestodene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Glibenclamide (Glyburide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. However, although a thorough QT study has not been performed, talazoparib and granisetron potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Grapefruit juice is known to inhibit CYP3A4 enzymes. Talazoparib is not metabolised by CYP3A4.

Description:

See Summary

No Interaction Expected

Talazoparib

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

No Interaction Expected

Talazoparib

Griseofulvin

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 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. Talazoparib does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Talazoparib does not inhibit or induce CYPs or UGTs. However, although a thorough QT study has not been performed, talazoparib and haloperidol potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Hydralazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Hydrocortisone (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydroxyurea is metabolised in the liver and cleared via the lungs and kidneys. Talazoparib is unlikely to interact with this metabolic or elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

Potential Interaction

Talazoparib

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. Talazoparib does not interact with this metabolic pathway. However, although a thorough QT study has not been performed, talazoparib and hydroxyzine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant 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

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

Potential Interaction

Talazoparib

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Iloperidone is metabolised by CYP3A4 and CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and iloperidone potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and imipramine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Indapamide is extensively metabolised by CYP450s. 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. Talazoparib does not inhibit or induce CYPs or OATs. However, although a thorough QT study has not been performed, talazoparib and indapamide potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Potential Weak Interaction

Talazoparib

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Interleukin-2 is mainly eliminated by glomerular filtration. Talazoparib is unlikely to interact with this elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce UGTs or CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Isosorbide dinitrate

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 that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and should be approached with caution. Itraconazole is primarily metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Concentrations of talazoparib will increase due to P-gp inhibition by itraconazole. In patients with advanced solid tumours (n=19), coadministration of talazoparib (0.5mg single dose) and itraconazole (100mg twice daily) increased exposure of talazoparib by approximately 45%. Therefore, if coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of itraconazole 5-9 days after discontinuation of itraconazole.

Description:

See Summary

Potential Interaction

Talazoparib

Ivabradine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ivabradine is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and ivabradine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ketoconazole is a substrate of CYP3A4. Talazoparib does not inhibit or induce CYPs. Ketoconazole is also an inhibitor of CYP3A4 (strong) and P-gp. After coadministration with itraconazole (a strong P-gp inhibitor), talazoparib exposure increased by approximately 45% and an increase in rate of talazoparib dose reductions was observed. A similar effect may occur after coadministration with ketoconazole. Therefore, if coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of ketoconazole 24-40 hours after discontinuation of ketoconazole. Furthermore, although a thorough QT study has not been performed, talazoparib and ketoconazole potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. Coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Lacidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Talazoparib does not inhibit or induce CYPs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

No Interaction Expected

Talazoparib

Lercanidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is mainly metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Levofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Levofloxacin is renally eliminated mainly by glomerular filtration and active secretion (possibly OCT2). Talazoparib is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and levofloxacin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and levomepromazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Levonorgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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 and is a weak inhibitor of CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this unspecified metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Lithium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. 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. However, although a thorough QT study has not been performed, talazoparib and lithium potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Do Not Coadminister

Talazoparib

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. If coadministration is judged clinically necessary, use with extreme caution since generalised infections can occur.

Description:

See Summary

No Interaction Expected

Talazoparib

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is mainly metabolised by CYP3A4 and CYP2C8 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Loratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Macitentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Magnesium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Medroxyprogesterone (depot)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Metamizole

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Talazoparib

Metformin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance 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. Talazoparib does not inhibit or induce OCTs or MATEs.

Description:

See Summary

Potential Interaction

Talazoparib

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Methadone is demethylated by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and methadone potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, closely monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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 talazoparib, or to be affected if coadministered with talazoparib.

Description:

See Summary

No Interaction Expected

Talazoparib

Methylprednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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 the CYP450 system (mainly CYP2D6). Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. 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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Miconazole is extensively metabolized by the liver. Miconazole is also an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Midazolam (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Talazoparib

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%). Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Mometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Morphine is also a substrate of P-gp. Talazoparib does not inhibit or induce UGTs or P-gp.

Description:

See Summary

Do Not Coadminister

Talazoparib

Moxifloxacin

Quality of Evidence: Low

Summary:

Coadministration has not been studied but should be avoided. Moxifloxacin is predominantly glucuronidated by UGT1A1. Talazoparib does not inhibit or induce UGTs. However, the product labels for moxifloxacin contraindicate its use in the presence of other drugs that prolong the QT interval, such as talazoparib. Therefore coadministration should be avoided. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Talazoparib does not interact with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Nateglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nefazodone is metabolised mainly by CYP3A4 and is also a strong inhibitor of CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Nicardipine is also a weak inhibitor of CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Nifedipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Nisoldipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Nitrendipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolised mainly by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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%). Talazoparib does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Norelgestromin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Norgestimate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Norgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4 and is glucuronidated to a minor extent. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

Potential Interaction

Talazoparib

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Nortriptyline is metabolised mainly by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and nortriptyline potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Potential Interaction

Talazoparib

Ofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ofloxacin is renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Talazoparib is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and ofloxacin potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Talazoparib does not interact with this metabolic pathway. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

Potential Interaction

Talazoparib

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Ondansetron is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. However, although a thorough QT study has not been performed, talazoparib and ondansetron potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cystolic enzymes. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Palonosetron is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Talazoparib does not inhibit or induce CYPs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Paroxetine is also an inhibitor of CYP2D6 (strong) and CYP2C9. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Due to the risk of additive haematological toxicity, haematological parameters should be monitored of coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not inhibit or induce CYPs or FMO3.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Perphenazine is metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and perphenazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Pethidine (Meperidine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Talazoparib

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Talazoparib does not inhibit or induce CYPs. Phenytoin is also a potent inducer of CYP3A4, UGT and P-gp. Talazoparib concentrations may decrease due to P-gp induction by phenytoin. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Do Not Coadminister

Talazoparib

Pimozide

Quality of Evidence: Low

Summary:

Coadministration has not been studied but should be avoided. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Talazoparib does not inhibit or induce CYPs. However, the product labels for pimozide contraindicate its use in the presence of other drugs that prolong the QT interval, such as talazoparib.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and pipotiazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Pitavastatin is also a substrate of OATP1B1. Talazoparib does not inhibit or induce CYPs, UGTS or OATP1B1.

Description:

See Summary

Potential Interaction

Talazoparib

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Posaconazole is also a strong inhibitor of CYP3A4. Talazoparib does not interact with this metabolic pathway. However, although a thorough QT study has not been performed, talazoparib and posaconazole potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Prasugrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Prednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism via CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Prednisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolised by CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and prochlorperazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Interaction

Talazoparib

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Promethazine is metabolised by CYP2D6. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and promethazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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). Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Prucalopride is also a substrate of P-gp. Talazoparib does not inhibit or induce P-gp and is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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

No Interaction Expected

Talazoparib

Quetiapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

Potential Interaction

Talazoparib

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 also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. Quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Talazoparib concentrations may increase due to P-gp inhibition by quinidine. After coadministration with weak/moderate P-gp inhibitors (e.g. diltiazem), talazoparib exposure increased by approximately 8% which is considered to not be clinically relevant. However, although a thorough QT study has not been performed, talazoparib and quinidine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Talazoparib does not inhibit or induce CYPs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranitidine is excreted via OAT1/OAT3. Talazoparib does not inhibit or induce OATs. In a popPK analysis it was observed that gastric acid reducing agents including proton pump inhibitors and H2 antagonists did not have a clinically significant effect on talazoparib absorption.

Description:

See Summary

Potential Interaction

Talazoparib

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 a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. Ranolazine is also a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Talazoparib concentrations may increase due to P-gp inhibition. After coadministration with weak/moderate P-gp inhibitors (e.g. diltiazem), talazoparib exposure increased by approximately 8%, which is considered to not be clinically relevant. However, although a thorough QT study has not been performed, talazoparib and ranolazine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. Coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Reboxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolised by CYP3A4. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4, but in vivo data showed no inhibitory effect on CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Potential Interaction

Talazoparib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Rifabutin is metabolised by CYP3A and via deacetylation. Talazoparib does not interact with this metabolic pathway. Rifabutin is also a strong CYP3A4 and P-gp inducer. Talazoparib concentrations may decrease due to P-gp induction by rifabutin. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

Potential Interaction

Talazoparib

Rifampicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Talazoparib concentrations may decrease due to P-gp induction by rifampicin. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

Potential Interaction

Talazoparib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8 and P-gp inducer. Talazoparib concentrations may decrease due to P-gp induction by rifapentine. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Risperidone is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Rivaroxaban is also a substrate of P-gp and BCRP. Talazoparib does not inhibit or induce CYPs, P-gp or BCRP and is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce OATP1B1 or BCRP.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolised by CYP3A4. The systemic exposure of salmeterol is low and talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Do Not Coadminister

Talazoparib

Sertindole

Quality of Evidence: Low

Summary:

Coadministration has not been studied but should be avoided. Sertindole is metabolised by CYP2D6 and CYP3A4. Talazoparib does not inhibit or induce CYPs. However, the product labels for sertindole contraindicate its use in the presence of other drugs that prolong the QT interval, such as talazoparib.

Description:

See Summary

No Interaction Expected

Talazoparib

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Sildenafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolised by CYP3A4. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Talazoparib does not inhibit or induce CYPs, BCRP or OATP1B1.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce these transporters or CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Sotalol

Quality of Evidence: Low

Summary:

Coadministration has not been studied but is not recommended. Sotalol is excreted unchanged via renal elimination. Talazoparib is unlikely to interact with this elimination pathway. The product labels for sotalol advise extreme caution if given with other drugs that prolong the QT interval, such as sotalol. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this unspecified metabolic pathway.

Description:

See Summary

Potential Interaction

Talazoparib

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. St John’s wort is a P-gp and CYP3A4 inducer. Talazoparib concentrations may decrease due to P-gp inhibition. The clinical relevance of this interaction is unknown. Therefore, if coadministration is unavoidable, closely monitor talazoparib efficacy. Monitor talazoparib plasma concentrations, if available, and adjust dose accordingly.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Sulpiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. Talazoparib is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and sulpiride potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

Potential Weak Interaction

Talazoparib

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tacrolimus is metabolised mainly by CYP3A4. 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. Talazoparib does not interact with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Talazoparib

Tadalafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Tamsulosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Talazoparib does not inhibit or induce CYPs and is unlikely to interact with this elimination pathway. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Talazoparib concentrations may increase due to P-gp inhibition. However, the clinical relevance of P-gp inhibition by telithromycin is unknown. After coadministration with weak/moderate P-gp inhibitors (e.g. diltiazem), talazoparib exposure increased by approximately 8% which is considered to not be clinically relevant.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Talazoparib

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and CYP2C19. Terbinafine is also a moderate-strong inhibitor of CYP2D6. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Do Not Coadminister

Talazoparib

Thioridazine

Quality of Evidence: Low

Summary:

Coadministration has not been studied but should be avoided. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, the product labels for thioridazine contraindicate its use in the presence of other drugs that prolong the QT interval, such as talazoparib.

Description:

See Summary

Potential Interaction

Talazoparib

Tiapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tiapride is excreted largely unchanged in urine. Talazoparib is unlikely to interact with this elimination pathway. However, although a thorough QT study has not been performed, talazoparib and tiapride potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ticagrelor is a substrate and mild inhibitor of CYP3A4. Ticagrelor is also a substrate of P-gp. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

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. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and tolterodine potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs or OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolised by CYPs 3A4, 2B6, and 2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Talazoparib

Trazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Trazodone is primarily metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs. However, although a thorough QT study has not been performed, talazoparib and trazodone potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Triamcinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamcinolone is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Triazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolised by CYP3A4. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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 CYPs 3A4, 1A2 and 2C9). 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. Sulfamethoxazole is a weak inhibitor of CYP2C9. Talazoparib does not interact with these metabolic or elimination pathways.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Tropisetron is metabolised mainly by CYP2D6. Tropisetron is also a substrate of P-gp. Talazoparib does not inhibit or induce CYPs or P-gp. However, although a thorough QT study has not been performed, talazoparib and tropisetron potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ulipristal is mainly metabolised by CYP3A4 and to a lesser extent CYP1A2 and CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Valproic acid is also an inhibitor of CYP2C9. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Talazoparib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). After coadministration with itraconazole (a strong P-gp inhibitor), talazoparib exposure increased by approximately 45% and an increase in rate of talazoparib dose reductions was observed. A similar effect may occur after coadministration with verapamil. Therefore, if coadministration is unavoidable, reduce the talazoparib dose by 0.25 mg. Closely monitor talazoparib toxicity and, if available, talazoparib plasma concentrations. Increase the talazoparib dose to the dose used prior to initiation of verapamil 28-40 hours after discontinuation of verapamil.

Description:

See Summary

No Interaction Expected

Talazoparib

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 and is a substrate of P-gp. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

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

Potential Interaction

Talazoparib

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Talazoparib does not interact with this metabolic pathway. However, although a thorough QT study has not been performed, talazoparib and voriconazole potentially cause QTc interval prolongation. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor ECG.

Description:

See Summary

No Interaction Expected

Talazoparib

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4. S-warfarin (more potent) is metabolised by CYP2C9. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Talazoparib

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolised by aldehyde oxidase and to a lesser extent by CYP3A4. Talazoparib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Talazoparib

Ziprasidone

Quality of Evidence: Low

Summary:

Coadministration has not been studied but should be avoided. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Talazoparib does not inhibit or induce CYPs. However, the product labels for ziprasidone contraindicate its use in the presence of other drugs that prolong the QT interval, such as talazoparib.

Description:

See Summary

No Interaction Expected

Talazoparib

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. Talazoparib is unlikely to interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Talazoparib

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 1A2. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Zopiclone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C8. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zotepine is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Talazoparib does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Talazoparib

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolised by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4) and glucuronidation. Talazoparib does not inhibit or induce CYPs or UGTs.

Description:

See Summary