Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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). Topotecan does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Topotecan

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%). Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Topotecan 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

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. After coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with aluminium hydroxide.

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Interaction

Topotecan

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Amiodarone is metabolised by CYP3A4 and CYP2C8. Topotecan does not inhibit or induce CYPs. 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). After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with amiodarone. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction for topotecan may also be required.

Description:

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No Interaction Expected

Topotecan

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 renally eliminated (possibly via OCT). Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Topotecan

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amphotericin B is not appreciably metabolised but is eliminated to a large extent in the bile. Topotecan does not interfere with this metabolic or 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. Monitoring may be required.

Description:

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No Interaction Expected

Topotecan

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. Topotecan 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

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. After coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with antacids.

Description:

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No Interaction Expected

Topotecan

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is a substrate of P-gp and BCRP, and is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Topotecan does not inhibit or induce CYPs, P-gp or BCRP.

Description:

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No Interaction Expected

Topotecan

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Topotecan does not inhibit or induce CYPs. During treatment, aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Topotecan concentrations may decrease due to UGT induction. However, no clinically significant effect on topotecan exposure is expected as glucuronidation is only a minor metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs, P-gp or OATP1B1.

Description:

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Potential Weak Interaction

Topotecan

Azathioprine

Quality of Evidence: Very Low

Summary:

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

Description:

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Potential Weak Interaction

Topotecan

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Topotecan is unlikely to interfere with this elimination pathway. Azithromycin is also an inhibitor of P-gp but the clinical relevance of P-gp inhibition by azithromycin is unknown. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by azithromycin. Monitoring for topotecan toxicity should be considered.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this pathway.

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

Bosentan

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using the intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce OATs.

Description:

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Potential Interaction

Topotecan

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Carbamazepine is also an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6, UGT1A1 and P-gp (moderate). Topotecan is substrate for P-gp and concentrations may decrease due to induction of P-gp by carbamazepine. The clinical relevance of this interaction is unknown. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor closely for topotecan efficacy. A dose increment for topotecan should be considered.

Description:

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Potential Weak Interaction

Topotecan

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additional metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Topotecan does not inhibit or induce CYPs or UGTs. Carvedilol is also an inhibitor of P-gp, but the clinical relevance of P-gp inhibition by carvedilol is unknown. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by carvedilol. Monitoring for topotecan toxicity should be considered.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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 renally eliminated unchanged by glomerular filtration and tubular secretion via OAT1 and MATE1. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this pathway.

Description:

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No Interaction Expected

Topotecan

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly glucuronidated. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYPs 3A4 (strong), 2C19 (strong) and 2D6 (weak). Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Interaction

Topotecan

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not be studied but should be approached with caution. Ciclosporin is a substrate of CYP3A4 and P-gp. Topotecan does not inhibit or induce CYPs or P-gp. Ciclosporin also inhibits CYP3A4, P-gp and OATP1B1. After coadministration of orally administered topotecan with cyclosporine A exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cimetidine is metabolised by CYP450 enzymes. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Cimetidine is also a weak inhibitor of CYPs 3A4, 1A2, 2D6 and 2C19. Topotecan does not interact with this pathway. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with cimetidine.

Description:

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No Interaction Expected

Topotecan

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is metabolised and partially cleared through the bile and intestine. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Topotecan is unlikely to interfere with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Topotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Topotecan

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clarithromycin is metabolised by CYP3A4. Topotecan does not inhibit or induce CYPs. Clarithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by clarithromycin. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with clarithromycin. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may also be required.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Clindamycin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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

No Interaction Expected

Topotecan

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces. In vitro data suggest that clofazimine is a CYP3A4 inhibitor. Topotecan is unlikely to interact with this elimination or metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Topotecan

Clomipramine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Clopidogrel

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Topotecan

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Topotecan does not inhibit or induce CYPs. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Topotecan

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 a substrate of P-gp. Topotecan does not inhibit or induce CYPs, UGTs or P-gp. Furthermore, in a population study using intravenous administration of topotecan, morphine did not appear to have a clinically significant effect on topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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 renally excreted via glomerular filtration. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Desogestrel

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate of CYP3A4. Topotecan does not inhibit or induce CYPs. Dexamethasone has also been described as a weak inducer of CYP3A4. However, the clinical relevance of this interaction is not known and the induction of CYP3A4 by dexamethasone has not yet been established. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs or P-gp. Furthermore, in a population study using intravenous administration of topotecan, morphine did not appear to have a clinically significant effect on topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs or CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated via OATP4C1 and P-gp. Topotecan does not inhibit or induce OATP4C1 or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs or CYPs.

Description:

See Summary

Potential Weak Interaction

Topotecan

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diltiazem is metabolised by CYP3A4 and CYP2D6. Topotecan does not inhibit or induce CYPs. Diltiazem is also an inhibitor of CYP3A4 (moderate) and P-gp, but the clinical relevance of P-gp inhibition by diltiazem is unknown. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by diltiazem. Monitoring for topotecan toxicity should be considered.

Description:

See Summary

No Interaction Expected

Topotecan

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 a weak inhibitor of CYP2D6. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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%). Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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 topotecan, or to be affected if coadministered with topotecan.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Doxepin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan 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

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Drospirenone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan 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

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Dydrogesterone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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). Topotecan does not inhibit or induce CYPs or UGTs

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated (possibly via OATs). Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Topotecan

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Erythromycin is a substrate of CYP3A4 and P-gp. Topotecan does not inhibit or induce CYPs or P-gp. Erythromycin is also an inhibitor of CYP3A4 (moderate) and P-gp. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by erythromycin. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with erythromycin. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may also be required.

Description:

See Summary

No Interaction Expected

Topotecan

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole is also an inhibitor of CYP2C19. Topotecan does not interact with this pathway. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with esomeprazole.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Estradiol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Etonogestrel

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Topotecan

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with exenatide renal elimination. 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

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce OATs. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with famotidine.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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 renally eliminated unchanged. Topotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin has been described as a CYP3A4 inducer. Topotecan is unlikely to interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is cleared primarily by renal excretion and is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Topotecan does not interact with this pathway.

Description:

See Summary

Potential Weak Interaction

Topotecan

Flucytosine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Fluoxetine is also a strong inhibitor of CYP2D6 and CYP2C19. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and 2D6 (weak). Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 predominantly renally eliminated. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Formoterol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Topotecan does not interact with this metabolic pathway. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Topotecan does not inhibit or induce CYPs. During treatment, aprepitant is a moderate inhibitor of CYP3A4. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Topotecan concentrations maybe decrease due to UGT induction. However, no clinically significant effect on topotecan exposure is expected as glucuronidation is only a minor metabolic pathway.

Description:

See Summary

Potential Interaction

Topotecan

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Topotecan does not interact with this metabolic pathway. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Topotecan does not inhibit or induce CYPs. Phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Topotecan concentrations may decrease due to UGT and P-gp induction. In a case report, coadministration with phenytoin decreased topotecan lactone (an active component of topotecan) exposure by approximately 60% on day 1 compared to topotecan alone; On day 2 and 5 no clinically relevant difference in topotecan lactone exposure was observed. Phenytoin decreased total topotecan exposure by approximately 53% on day 1; no clinically relevant effect was observed on day 2 and 5. Coadministration is not recommended. If coadministration is unavoidable, closely monitor topotecan efficacy. A dose increment of topotecan should be considered.

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated unchanged (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. Topotecan is unlikely to interfere with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Gestodene

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp. Moreover, in a population study using intravenous administration of topotecan, granisetron did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Grapefruit juice is known to inhibit CYP3A4 enzymes. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Green tea

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs. Topotecan is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydralazine is metabolised via primary oxidative metabolism and acetylation. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 but 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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Topotecan

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Topotecan 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

Topotecan

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. Topotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or OATs.

Description:

See Summary

No Interaction Expected

Topotecan

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Topotecan

Interferon alpha

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Topotecan

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Topotecan

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Itraconazole is primarily metabolised by CYP3A4. Topotecan does not inhibit or induce CYPs. Itraconazole is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Topotecan is a substrate of BCRP and P-gp and concentrations may increase due to P-gp and BCRP inhibition. After coadministration of elacridar, a P-gp and BCRP inhibitor, topotecan lactone (an active component of topotecan) and total topotecan exposure increased by approximately 2.5-fold. A similar effect may occur after coadministration with itraconazole. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may be required.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Topotecan

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ketoconazole is a substrate of CYP3A4. Topotecan does not inhibit or induce CYPs. Ketoconazole is also an inhibitor of CYP3A4 (strong) and P-gp. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition of P-gp by ketoconazole. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with ketoconazole. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may be required.

Description:

See Summary

No Interaction Expected

Topotecan

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). Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Topotecan does not inhibit or induce CYPs. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with lansoprazole.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Levonorgestrel

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is also a substrate of P-gp and is a weak inhibitor of CYP3A4. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated unchanged via glomerular filtration. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Lithium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Do Not Coadminister

Topotecan

Live vaccines

Quality of Evidence: Very Low

Summary:

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. If coadministration is judged clinically necessary, use with extreme caution since generalised infections can occur.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Medroxyprogesterone (depot)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway. Moreover, in a population study using the intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Metamizole is metabolised in serum and excreted via urine (90%) and faeces (10%). Metamizole is also an inducer of CYP3A4. Topotecan is unlikely to interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 OCT1/2/3, MATE1 and MATE2K. Topotecan does not inhibit or induce OCTs or MATEs.

Description:

See Summary

No Interaction Expected

Topotecan

Methadone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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 topotecan, or to be affected if coadministered with topotecan.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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). Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan 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).

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Miconazole

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs or P-gp. Furthermore, in a population study using intravenous administration of topotecan, morphine did not appear to have a clinically significant effect on topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Topotecan

Mycophenolate

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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%). Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Nefazodone

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Nicardipine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

Norelgestromin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Norethisterone (Norethindrone)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Norgestimate

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

Norgestrel

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Topotecan does not interact with this pathway. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with omeprazole.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp. Moreover, in a population study using intravenous administration of topotecan, ondansetron did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Topotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Topotecan does not inhibit or induce CYPs. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with pantoprazole.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Weak Interaction

Topotecan

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is mainly metabolised by CYPs 1A2, 3A4 and 2C19, and to a lesser extent by CYPs 2C9, 2D6 and 2E1, with oxidation via FMO3. Topotecan does not inhibit or induce CYPs or FMO3.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. Topotecan does not inhibit or induce CYPs. Phenobarbital is also a strong inducer of CYPs 3A4, 2C9, 2C8 and UGTs. Topotecan concentrations may decrease due to UGT induction. However, no clinically significant effect on topotecan exposure is expected as glucuronidation is only a minor metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Topotecan

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Topotecan does not inhibit or induce CYPs. Phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Topotecan concentrations may decrease due to UGT and P-gp induction. In a case report, coadministration with phenytoin decreased topotecan lactone (an active component of topotecan) exposure by approximately 60% on day 1 compared to topotecan alone; On day 2 and 5 no clinically relevant difference in topotecan lactone exposure was observed. Phenytoin decreased total topotecan exposure by approximately 53% on day 1; no clinically relevant effect was observed on day 2 and 5. Coadministration is not recommended. If coadministration is unavoidable, closely monitor topotecan efficacy. A dose increment of topotecan should be considered.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs, UGTs or OAP1B1.

Description:

See Summary

No Interaction Expected

Topotecan

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Posaconazole is also a strong inhibitor of CYP3A4. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Potassium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

Prochlorperazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Propranolol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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 renally eliminated, partly by active secretion by renal transporters. Prucalopride is also a substrate of P-gp. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Topotecan

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is also a substrate of P-gp. Topotecan does not inhibit or induce CYPs or P-gp. Quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Topotecan is a substrate of P-gp and concentrations may increase due to inhibition of P-gp. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with quinidine. Therefore, coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction for topotecan may also be required.

Description:

See Summary

No Interaction Expected

Topotecan

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Topotecan does not inhibit or induce CYPs. Moreover, after coadministration of ranitidine with orally administered topotecan, no clinically relevant effect on topotecan exposure was observed. Therefore, no clinically relevant effect due to gastric pH elevation is expected when topotecan is coadministered with rabeprazole.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Ranitidine is excreted via OAT1/OAT3. Topotecan does not inhibit or induce OATs. Furthermore, in patients with solid tumours (n=13), coadministration of ranitidine (150mg twice daily for 4 days) with orally administered topotecan (2.3mg/m2 i.v. daily), had no clinically relevant effect on topotecan exposure.

Description:

See Summary

Potential Interaction

Topotecan

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ranolazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Topotecan does not inhibit or induce CYPs or P-gp. Moreover, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by ranolazine. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with ranolazine. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may be required.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Riboflavin (Vitamin B2)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Topotecan

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Rifabutin is metabolised by CYP3A4 and via deacetylation. Topotecan does not interact with this metabolic pathway. Rifabutin is also a strong CYP3A4 and P-gp inducer. Topotecan is a substrate of P-gp and concentrations may decrease due to P-gp induction by rifabutin. As the clinical relevance of this interaction is unknown, coadministration is not recommended. If coadministration is unavoidable, closely monitor topotecan efficacy. A dose increment of topotecan should be considered.

Description:

See Summary

Potential Interaction

Topotecan

Rifampicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Topotecan is a substrate of P-gp and concentrations may decrease due to P-gp induction by rifampicin. As the clinical relevance of this interaction is unknown, coadministration is not recommended. If coadministration is unavoidable, closely monitor topotecan efficacy. A dose increment of topotecan should be considered.

Description:

See Summary

Potential Interaction

Topotecan

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8 and P-gp inducer. Topotecan is a substrate of P-gp and concentrations may decrease due to P-gp induction by rifapentine. As the clinical relevance of this interaction is unknown, coadministration is not recommended. If coadministration is unavoidable, closely monitor topotecan efficacy. A dose increment of topotecan should be considered.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosuvastatin is largely excreted unchanged in the faeces via OATP1B1 and is a substrate of BCRP. Topotecan does not inhibit or induce OATP1B1 or BCRP.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Furthermore, topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Topotecan

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

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

Sertraline

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs, BCRP or OATP1B1.

Description:

See Summary

Potential Weak Interaction

Topotecan

Sirolimus

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Topotecan

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

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this unspecified metabolic pathway. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

See Summary

Do Not Coadminister

Topotecan

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. St John’s wort is a P-gp and CYP3A4 inducer. Topotecan is a substrate of P-gp and concentrations may decrease due to P-gp induction. As the clinical relevance of this interaction is unknown, coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Topotecan

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tacrolimus is metabolised mainly by CYP3A4. Tacrolimus is also an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Topotecan does not interact with this pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Topotecan

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Topotecan does not inhibit or induce CYPs. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Topotecan is a substrate of P-gp and concentrations may increase due to P-gp inhibition by telithromycin. After coadministration of elacridar, a P-gp and BCRP inhibitor, topotecan lactone (an active component of topotecan) and total topotecan exposure increased by approximately 2.5-fold. A similar effect may occur after coadministration with telithromycin. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may also be required.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Topotecan

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. Topotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Topotecan

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

Ticagrelor

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or OATs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs. Moreover, in a population study using intravenous administration of topotecan, corticosteroids did not appear to have a clinically significant effect on total topotecan exposure.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with these metabolic or elimination pathways.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

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No Interaction Expected

Topotecan

Ulipristal

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Topotecan

Valproic acid (Valproate)

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

Venlafaxine

Quality of Evidence: Very Low

Summary:

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

Description:

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Potential Interaction

Topotecan

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Topotecan does not inhibit or induce CYPs. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Topotecan is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by verapamil. After coadministration of orally administered topotecan with cyclosporine A, a P-gp inhibitor, exposure of topotecan lactone (an active component of topotecan) increased 2-fold and total topotecan exposure increased 2.5-fold. A similar effect may occur after coadministration with verapamil. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for topotecan toxicity. A dose reduction of topotecan may be required.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs or P-gp.

Description:

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No Interaction Expected

Topotecan

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:

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No Interaction Expected

Topotecan

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Voriconazole is metabolised by CYP2C19 (major) and to a lesser extent by CYP3A4 and CYP2C9. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Topotecan does not interact with this pathway.

Description:

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No Interaction Expected

Topotecan

Warfarin

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Topotecan

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. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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). Topotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Topotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Topotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Topotecan

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. Topotecan does not interact with this metabolic pathway.

Description:

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