Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of acenocoumarol. However, no clinically relevant effect on acenocoumarol exposure is expected.

Description:

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No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Letrozole

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%). Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of agomelatine. However, no clinically relevant effect on agomelatine exposure is expected.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway. Although no pharmacokinetic interaction is expected, alendronic acid should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronic acid before taking any other oral medicinal product.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Letrozole

Allopurinol

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

Aluminium hydroxide

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase ambrisentan concentrations. However, since CYP2C19 is a minor pathway, no clinically relevant effect on ambrisentan exposure is expected.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs.

Description:

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No Interaction Expected

Letrozole

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiodarone is metabolised by CYP3A4 and CYP2C8. Letrozole does not inhibit or induce CYP3A4 or CYP2C8. Moreover, 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). Concentrations of letrozole may increase due to CYP3A4 inhibition. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with amiodarone.

Description:

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No Interaction Expected

Letrozole

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). Letrozole is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Letrozole

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of amitriptyline. As the clinical relevance of this interaction is unknown, monitoring for amitriptyline toxicity may be required.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Letrozole

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. Letrozole is unlikely to interfere 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

Letrozole

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. Letrozole is unlikely to interfere 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

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this unspecified metabolic pathway.

Description:

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Potential Weak Interaction

Letrozole

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of apixaban. As the clinical relevance of this interaction is unknown, monitoring for apixaban toxicity and anti-Xa levels may be required.

Description:

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Potential Weak Interaction

Letrozole

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase aprepitant concentrations. Since CYP2C19 is a minor pathway, no clinically relevant effect on aprepitant exposure is expected. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase letrozole concentrations. The clinical relevance of this interaction is unknown. Monitoring for letrozole toxicity may be required. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of letrozole may decrease due to CYP3A4 induction, but this is not considered to be clinically relevant.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or CYP2D6.

Description:

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No Interaction Expected

Letrozole

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)). Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

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No Interaction Expected

Letrozole

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Letrozole does not inhibit or induce these CYPs.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4, P-gp or OATP1B1.

Description:

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No Interaction Expected

Letrozole

Azathioprine

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Letrozole

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Azithromycin is also an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition by azithromycin is unknown. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Letrozole

Bedaquiline

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Letrozole

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Letrozole does not inhibit or induce CYP2D6 or CYP3A4.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs and is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Letrozole

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bosentan is a substrate and weak inducer of CYP3A4 and CYP2C9. Letrozole does not inhibit or induce CYP3A4 or CYP2C9. However, letrozole concentrations may decrease due to induction of CYP3A4 by bosentan. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy may be required.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2B6 in vitro and may increase concentrations of bupropion. However, no clinically relevant effect on bupropion exposure is expected.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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Potential Weak Interaction

Letrozole

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Letrozole does not inhibit or induce these CYPs. Carbamazepine is also an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6, UGT1A1 and P-gp (moderate). Letrozole is metabolised by CYP3A4 and concentrations may decrease due to induction by carbamazepine. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy may be required.

Description:

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No Interaction Expected

Letrozole

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. Carvedilol is also an inhibitor of P-gp, but the clinical relevance of P-gp inhibition is unknown. Letrozole does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Letrozole

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chloramphenicol is predominantly glucuronidated. Letrozole does not inhibit or induce UGTs. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYPs 3A4 (strong), 2C19 (strong) and 2D6 (weak). Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the absorbed concentrations are unlikely to cause a clinically significant interaction.

Description:

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No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

Chlorpromazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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Potential Weak Interaction

Letrozole

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ciclosporin is a substrate of CYP3A4 and P-gp and also inhibits CYP3A4 and OATP1B1. Letrozole does not inhibit or induce CYP3A4 or P-gp. However, letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Cimetidine is metabolised by CYP450 enzymes. Letrozole is an inhibitor of CYP2A6 and CYP2C19 in vitro, but since multiple CYP enzymes are involved in cimetidine metabolism, no clinically relevant effect on cimetidine exposure is expected. 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. Letrozole concentrations may increase due to inhibition of CYP3A4. However, after coadministration with cimetidine, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%).

Description:

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Potential Weak Interaction

Letrozole

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Letrozole is unlikely to interfere with this metabolic or elimination pathway. However, ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Cisapride

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Letrozole

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of letrozole. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Letrozole

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clarithromycin is metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4. Clarithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Letrozole

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clindamycin is metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4. In vitro data suggest clindamycin is also a CYP3A4 inhibitor and may increase concentrations of letrozole. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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 Weak Interaction

Letrozole

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clofazimine is largely excreted unchanged in the faeces. Letrozole is unlikely to interfere with this elimination pathway. In vitro data suggest that clofazimine is also a CYP3A4 inhibitor and may increase concentrations of letrozole. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway and does not inhibit or induce OATs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Clomipramine and desmethylclomipramine are both metabolised by CYP2D6. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of clomipramine. As the clinical relevance of this interaction is unknown, monitoring for clomipramine toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of clopidogrel. As the clinical relevance of this interaction is unknown, monitoring for clopidogrel toxicity, in addition to thrombocyte aggregation tests may be required. Moreover, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and of CYP2C9 (in vitro) at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Letrozole is not metabolised by these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Letrozole is an inhibitor of CYP2C19 in vitro and may increase clozapine concentrations. However, no clinically relevant effect on clozapine exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs, UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

Desipramine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Do Not Coadminister

Letrozole

Desogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with desogestrel is contraindicated as desogestrel could interfere with the pharmacological action of letrozole. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of desogestrel. However, no clinically relevant effect on desogestrel exposure is expected.

Description:

See Summary

Potential Weak Interaction

Letrozole

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dexamethasone is a substrate of CYP3A4. Letrozole does not inhibit or induce CYP3A4. Dexamethasone has also been described as a weak inducer of CYP3A4 and could possibly decrease letrozole plasma concentrations. However, the clinical relevance of this interaction is not known as the induction of CYP3A4 by dexamethasone has not yet been established. Monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase diazepam concentrations. However, since diazepam has a broad therapeutic index, no clinically relevant effect on diazepam exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce OATP4C1 or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diltiazem is metabolised by CYP3A4 and CYP2D6. Letrozole does not inhibit or induce CYP3A4 or CYP2D6. Diltiazem is also an inhibitor of CYP3A4 (moderate) and P-gp, but the clinical relevance of P-gp inhibition is unknown. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Diphenhydramine is also weak inhibitor of CYP2D6. Letrozole is an inhibitor of CYP2C19 in vitro and may increase diphenhydramine concentrations. However, no clinically relevant effect on diphenhydramine exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

Disopyramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Letrozole does not inhibit or induce CYP3A4 and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Domperidone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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 letrozole, or to be affected if coadministered with letrozole.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Weak Interaction

Letrozole

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of doxepin. As the clinical relevance of this interaction is unknown, monitoring for doxepin toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway. Between 40-60% of an administered dose can be accounted for in the urine.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9 or CYP3A4.

Description:

See Summary

Do Not Coadminister

Letrozole

Drospirenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with drospirenone is contraindicated as drospirenone could interfere with the pharmacological action of letrozole. Drospirenone is metabolised to a minor extent via CYP3A4. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole 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

Letrozole

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. Letrozole does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Do Not Coadminister

Letrozole

Dydrogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with dydrogesterone is contraindicated as dydrogesterone could interfere with the pharmacological action of letrozole. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce CYP2C8, CYP1A2 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Erythromycin is a substrate of CYP3A4 and P-gp. Letrozole does not inhibit or induce CYP3A4 or P-gp. Erythromycin is also an inhibitor of CYP3A4 (moderate) and P-gp. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Letrozole

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of escitalopram. As the clinical relevance of this interaction is unknown, monitoring for escitalopram toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Letrozole

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase esomeprazole concentrations. As the clinical relevance of this interaction is unknown, monitoring for esomeprazole toxicity may be required. Esomeprazole is also an inhibitor of CYP2C19. Letrozole is not metabolised by CYP2C19.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Do Not Coadminister

Letrozole

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with estradiol is contraindicated as estradiol could interfere with the pharmacological action of letrozole. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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%). Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with ethinylestradiol is contraindicated as ethinylestradiol could interfere with the pharmacological action of letrozole. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Etonogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with etonogestrel is contraindicated as etonogestrel could interfere with the pharmacological action of letrozole. Etonogestrel is metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere 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

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

Fish oils

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Flecainide

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Letrozole

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Letrozole is unlikely to interfere with this elimination pathway. Flucloxacillin is also described as a CYP3A4 inducer and may decrease letrozole concentrations. However, the mechanism and clinical relevance of this interaction is unknown. Monitoring of letrozole efficacy may be required.

Description:

See Summary

Potential Weak Interaction

Letrozole

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluconazole is cleared primarily by renal excretion. Letrozole is unlikely to interfere with this elimination pathway. Fluconazole is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Flucytosine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase flunitrazepam concentrations. However, since flunitrazepam has a broad therapeutic index, no clinically relevant effect on flunitrazepam exposure is expected.

Description:

See Summary

Potential Weak Interaction

Letrozole

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Fluoxetine is also a strong inhibitor of CYP2D6 and CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of fluoxetine. As the clinical relevance of this interaction is unknown, monitoring for fluoxetine toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Fluphenazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this unspecified metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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, but the clinical relevance of CYP2C9 inhibition is unknown. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Letrozole does not inhibit or induce CYP2D6 or CYP1A2. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and 2D6 (weak). Letrozole concentrations may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 and CYP2A6 in vitro and may increase formoterol concentrations. However, as multiple CYP450 and UGT enzymes catalyse the transformation the potential for a pharmacokinetic interaction is low.

Description:

See Summary

Potential Weak Interaction

Letrozole

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Letrozole does not interact with this metabolic pathway. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase aprepitant concentrations. Since CYP2C19 is a minor pathway, no clinically relevant effect on aprepitant exposure is expected. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase letrozole concentrations. The clinical relevance of this interaction is unknown. Monitoring for letrozole toxicity may be required. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of letrozole may decrease due to CYP3A4 induction, but this is not considered to be clinically relevant.

Description:

See Summary

Potential Weak Interaction

Letrozole

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Letrozole does not interact with this metabolic pathway. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase phenytoin concentrations. Monitoring for phenytoin toxicity and, if available, phenytoin plasma concentrations may be required. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Letrozole concentrations may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Gestodene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with gestodene is contraindicated as gestodene could interfere with the pharmacological action of letrozole. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase gestodene concentrations. However, since CYP2C19 is a minor pathway, no clinically relevant effect on gestodene exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of gliclazide. However, no clinically relevant effect on gliclazide exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

Granisetron

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Letrozole

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Grapefruit juice is known to inhibit CYP3A4 enzymes and may increase letrozole concentrations. The clinical relevance of this interaction is unknown. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor closely for letrozole toxicity.

Description:

See Summary

No Interaction Expected

Letrozole

Green tea

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Letrozole

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Letrozole is unlikely to interfere with this elimination pathway. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs, such as letrozole. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Letrozole concentrations may increase due to inhibition of CYP3A4. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with hydralazine.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6 or CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Hydroxyzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway. 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

Letrozole

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. Letrozole does not inhibit or induce CYP2C9, CYP2C8 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

Iloperidone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of imipramine. As the clinical relevance of this interaction is unknown, monitoring for imipramine toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolised by CYP450s. OAT1/3 are the major transporters of loop and thiazide diuretics. 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. Letrozole does not interact with this metabolic pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Interferon alpha

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce UGTs or CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Weak Interaction

Letrozole

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Itraconazole is primarily metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4. Itraconazole is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Ivabradine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ketoconazole is a substrate of CYP3A4. Letrozole does not inhibit or induce CYP3A4. Ketoconazole is also an inhibitor of CYP3A4 (strong) and P-gp. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase lansoprazole concentrations. As the clinical relevance of this interaction is unknown, monitoring for lansoprazole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Levofloxacin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Levomepromazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Do Not Coadminister

Letrozole

Levonorgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with levonorgestrel is contraindicated as levonorgestrel could interfere with the pharmacological action of letrozole. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

Do Not Coadminister

Letrozole

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Coadministration of levonorgestrel with letrozole is contraindicated as levonorgestrel may increase the risk of developing a hormone sensitive tumour. However, the use of levonorgestrel as emergency contraception is a relative contraindication due to the risk of a pregnancy while having a hormone sensitive tumour. Therefore, the following information is applicable: Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP1A2 or CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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 for P-gp. Letrozole does not inhibit or induce CYP3A4 or P-gp. However, linagliptin is a weak inhibitor of CYP3A4 and may increase letrozole concentrations. After coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this unspecified metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Lithium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. However, letrozole is not an immunosuppressant, immunomodulatory or bone marrow toxic drug. Therefore, no pharmacodynamic interaction is expected with live vaccines.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this unspecified metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase macitentan concentrations. However, since CYP2C19 is a minor pathway, no clinically relevant effect on macitentan exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

Do Not Coadminister

Letrozole

Medroxyprogesterone (depot)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with medroxyprogesterone is contraindicated as medroxyprogesterone could interfere with the pharmacological action of letrozole. Medroxyprogesterone is metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Do Not Coadminister

Letrozole

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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%). Letrozole is unlikely to interfere with this metabolic or elimination pathway. However, metamizole is an inducer of CYP3A4 and may decrease letrozole concentrations. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce OCTs or MATEs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and care should be taken. Methadone is demethylated by CYP3A4. Letrozole does not inhibit or induce CYP3A4. However, in healthy females (n=15) coadministration of methadone (2 mg single dose) and letrozole (2.5 mg daily for 11 days) increased methadone exposure by 23%. This is not expected to be clinically relevant but monitoring for methadone toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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 letrozole, or to be affected if coadministered with letrozole.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway. 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). Letrozole concentrations may increase due to CYP3A4 inhibition, however no clinically relevant effect is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Miconazole is extensively metabolized by the liver. Letrozole is unlikely to interfere with this unspecified metabolic pathway. Moreover, miconazole is an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinically relevant interaction is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Letrozole

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%). Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

Moxifloxacin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Letrozole does not inhibit or induce UGTs or OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9, CYP1A2 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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%). Letrozole does not inhibit or induce CYP2C9 or CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

Potential Weak Interaction

Letrozole

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nefazodone is metabolised mainly by CYP3A4. Letrozole does not inhibit or induce CYP3A4. Nefazodone is also a strong CYP3A4 inhibitor and may increase concentrations of letrozole. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs. Nicardipine is also a weak inhibitor of CYP3A4 and may increase letrozole concentrations. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with nicardipine.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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%). Letrozole does not inhibit or induce UGTs and is unlikely to interfere with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Norelgestromin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with norelgestromin is contraindicated as norelgestromin could interfere with the pharmacological action of letrozole. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

Do Not Coadminister

Letrozole

Norethisterone (Norethindrone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with norethisterone is contraindicated as norethisterone could interfere with the pharmacological action of letrozole. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Norgestimate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with norgestimate is contraindicated as norgestimate could interfere with the pharmacological action of letrozole. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Letrozole is unlikely to interfere with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Letrozole

Norgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with norgestrel is contraindicated as norgestrel could interfere with the pharmacological action of letrozole. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4 and is glucuronidated to a minor extent. Letrozole does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

Nortriptyline

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Nystatin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Ofloxacin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase omeprazole concentrations. As the clinical relevance of this interaction is unknown, monitoring for omeprazole toxicity may be required. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Letrozole is not metabolised by these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

Ondansetron

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Letrozole does not interact with this metabolic pathway. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Letrozole concentrations may decrease due to induction of CYP3A4. However, the clinical relevance of this interaction is unknown. Monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A or CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Letrozole is an inhibitor of CYP2C19 in vitro and may increase pantoprazole concentrations. As the clinical relevance of this interaction is unknown, monitoring for pantoprazole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole does not inhibit or induce these CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase perazine concentrations. As the clinical relevance of this interaction is unknown, monitoring for perazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Perphenazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2B6 in vitro and may increase concentrations of pethidine. However, no clinically relevant effect on pethidine exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of phenobarbital. Monitoring for phenobarbital toxicity and, if available, phenobarbital concentrations may be required. Phenobarbital is also a strong inducer of CYPs 3A4, 2C9, 2C8 and UGTs. Letrozole concentrations may decrease due to induction of CYP3A4. However, the clinical relevance of this interaction is unknown. Monitoring of letrozole efficacy may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9 or CYP3A4.

Description:

See Summary

Potential Weak Interaction

Letrozole

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Letrozole is an inhibitor of CYP2C19 in vitro and may increase phenytoin concentrations. Monitoring for phenytoin toxicity and, if available, phenytoin concentrations may be required. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Letrozole concentrations may decrease due to induction of CYP3A4. However, the clinical relevance of this interaction is unknown. Monitoring of letrozole efficacy may also be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP4F2.

Description:

See Summary

No Interaction Expected

Letrozole

Pimozide

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6 and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

Pipotiazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs, UGTs or OATP1B1.

Description:

See Summary

Potential Weak Interaction

Letrozole

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Letrozole does not inhibit or induce UGTs or P-gp. Moreover, posaconazole is a strong inhibitor of CYP3A4 and may increase letrozole concentrations. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Potassium is eliminated renally. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2B6 and CYP2C19 in vitro and may increase concentrations of prasugrel. However, no clinically relevant effect on prasugrel exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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). Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Letrozole is an inhibitor of CYP2C19 and may increase prochlorperazine concentrations. As the clinical relevance of this interaction is unknown, monitoring for prochlorperazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

Promethazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

Potential Weak Interaction

Letrozole

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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). Letrozole is an inhibitor of CYP2C19 and may increase propranolol concentrations. As the clinical relevance of this interaction is unknown, monitoring for propranolol toxicity and blood pressure may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is also a substrate of P-gp. Letrozole does not inhibit or induce these CYPs or P-gp. Furthermore, quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Concentrations of letrozole may increase due to CYP3A4 inhibition. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with quinidine.

Description:

See Summary

Potential Weak Interaction

Letrozole

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase rabeprazole concentrations. As the clinical relevance of this interaction is unknown, monitoring for rabeprazole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranolazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Letrozole does not inhibit or induce CYP3A4, CYP2D6 or P-gp. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Letrozole concentrations may increase due to inhibition of CYP3A4. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with ranolazine.

Description:

See Summary

No Interaction Expected

Letrozole

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. Therefore, CYP3A4 inhibition by reboxetine is unlikely to affect letrozole exposure.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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 Weak Interaction

Letrozole

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rifabutin is metabolised by CYP3A4 and via deacetylation. Letrozole does not inhibit or induce CYP3A4 or P-gp. Rifabutin is also a strong CYP3A4 and P-gp inducer. Letrozole concentrations may decrease due to CYP3A4 induction. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Letrozole

Rifampicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Letrozole concentrations may decrease due to CYP3A4 induction. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy should be considered.

Description:

See Summary

Potential Weak Interaction

Letrozole

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8 and P-gp inducer. Letrozole concentrations may decrease due to CYP3A4 induction. As the clinical relevance of this interaction is unknown, monitoring of letrozole efficacy should be considered.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6, CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs, P-gp or BCRP and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C8 or CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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 for BCRP. Letrozole does not inhibit or induce OATP1B1 or BCRP.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Moreover, letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Letrozole

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

No Interaction Expected

Letrozole

Sertindole

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Letrozole

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of sertraline. As the clinical relevance of this interaction is unknown, monitoring for sertraline toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4, OATP1B1 or BCRP.

Description:

See Summary

No Interaction Expected

Letrozole

Sirolimus

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce OAT3, OATP4C1, P-gp or CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Sotalol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this unspecified metabolic pathway.

Description:

See Summary

Potential Interaction

Letrozole

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. St John’s wort is a P-gp and CYP3A4 inducer. Letrozole concentrations may decrease due to CYP3A4 induction. The clinical relevance of this interaction is unknown. Therefore, coadministration is not recommended. If coadministration is unavoidable, closely monitor letrozole efficacy.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

Sulpiride

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tacrolimus is metabolised mainly by CYP3A4. Letrozole does not inhibit or induce 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. Therefore, no clinically relevant effect on letrozole exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Letrozole does not inhibit or induce CYP3A4. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp, but the clinical relevance of P-gp inhibition by telithromycin is unknown. Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase terbinafine concentrations. However, no clinically relevant effect on terbinafine exposure is expected.

Description:

See Summary

Do Not Coadminister

Letrozole

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with testosterone is contraindicated as testosterone is a precursor of estradiol and could, therefore, potentially interfere with the pharmacological action of letrozole. Testosterone is metabolised by CYP3A4. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP1A2.

Description:

See Summary

No Interaction Expected

Letrozole

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

No Interaction Expected

Letrozole

Thioridazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

Tiapride

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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 of CYP3A4 and P-gp. Letrozole does not inhibit or induce CYP3A4 or P-gp. Ticagrelor is also a mild inhibitor of CYP3A4 and may increase concentrations of letrozole. However, after coadministration with cimetidine, a weak and unspecific CYP3A4 inhibitor, no clinically relevant effect on letrozole exposure was observed (AUC decreased 8%). Therefore, no clinically relevant effect on letrozole exposure is expected after coadministration with ticagrelor.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase tolbutamide concentrations. However, no clinically relevant effect on tolbutamide exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 playing a minor role. Letrozole does not inhibit or induce CYP3A4 or CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2C9 or OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2B6 in vitro and may increase concentrations of tramadol. However, no clinically relevant effect on tramadol exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Trazodone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with these metabolic or elimination pathways.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6.

Description:

See Summary

No Interaction Expected

Letrozole

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tropisetron is metabolised mainly by CYP2D6. Tropisetron is also a substrate of P-gp. Letrozole does not inhibit or induce CYP2D6 or P-gp.

Description:

See Summary

Do Not Coadminister

Letrozole

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Letrozole is used for hormone-sensitive tumours. Coadministration with ulipristal is contraindicated as ulipristal could interfere with the pharmacological action of letrozole. Ulipristal is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of valproic acid. However, no clinically relevant effect on valproic acid exposure is expected. In addition, valproic acid is an inhibitor of CYP2C9. Letrozole is not metabolised by CYP2C9.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Letrozole

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of venlafaxine. As the clinical relevance of this interaction is unknown, monitoring for venlafaxine toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Letrozole

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Letrozole does not inhibit or induce these CYPs. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Letrozole concentrations may increase due to CYP3A4 inhibition. As the clinical relevance of this interaction is unknown, monitoring for letrozole toxicity may be required.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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 Weak Interaction

Letrozole

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. Letrozole is an inhibitor of CYP2C19 in vitro and may increase concentrations of voriconazole. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Letrozole concentrations may increase due to CYP3A4 inhibition. The clinical relevance of this interaction is unknown. Monitoring for letrozole and voriconazole toxicity may be required. Monitoring of voriconazole plasma concentrations should also be considered, if available.

Description:

See Summary

No Interaction Expected

Letrozole

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and 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. Letrozole does not inhibit or induce these CYPs. In healthy males (n=14), coadministration of warfarin (25 mg single dose) and letrozole (2.5 mg daily for 15 days) produced AUC ratios for R-warfarin and S-warfarin of 1.00 and 1.01, respectively. The ratio for prothrombin time was 1.04. Letrozole therefore has no clinically relevant effect on warfarin exposure or prothrombin time.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Letrozole

Ziprasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Letrozole does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole is an inhibitor of CYP2C19 in vitro and may increase zolpidem concentrations. However, no clinically relevant effect on zolpidem exposure is expected.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP3A4 or CYP2C8.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce these CYPs.

Description:

See Summary

No Interaction Expected

Letrozole

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. Letrozole does not inhibit or induce CYP2D6, CYP3A4 or UGTs.

Description:

See Summary