The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Abiraterone has multiple metabolic pathways and is an inhibitor of CYP2D6. Lenvatinib does not inhibit or induce this enzyme. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. There may be a risk of QT-prolongation with abiraterone. When abiraterone is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is a CYP3A4 and P-gp substrate. Lenvatinib does not inhibit or induce this pathway to a clinically significant effect.

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medications. If coadministration is required, administration of activated charcoal and lenvatinib should be separated by 4 hours. [Note: this interaction is not specific for lenvatinib but for any medication taken with activated charcoal.]

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Afatinib is mainly eliminated unchanged in the faeces.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Albiglutide is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by ubiquitous proteolytic enzymes. Albiglutide slows gastric emptying, but this is unlikely to have a clinically relevant effect on lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alectinib is metabolized by CYP3A4 to an active metabolite (M4), which is also metabolized by CYP3A4. Lenvatinib does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied. Alendronate is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, alendronate should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product. Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates.

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. Lenvatinib does not interact with this pathway. [Note, the European SmPC and US Prescribing Information for allopurinol recommend reduced dose in hepatic impairment.]

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Lenvatinib does not inhibit or induce CYPs or UGTs. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ambrisentan is metabolised 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 and OATP1B1. Lenvatinib does not inhibit or induce UGTs, CYPs or P-gp. Blood pressure should be well controlled prior to treatment with lenvatinib and should be regularly monitored during treatment. BP should be monitored after 1 week of treatment with lenvatinib, then every 2 weeks for the first 2 months, and monthly thereafter.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes or drug transporters are unlikely.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. Lenvatinib does not inhibit or induce these enzymes.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Apalutamide is metabolized by CYP2C8 and CYP3A4 and is a strong inducer of CYP3A4. Lenvatinib does not inhibit or induce CYPs or UGTs. Concentrations of lenvatinib may slightly decrease due to induction of CYP3A4 and P-gp. After coadministration with rifampicin, a strong CYP3A4 and P-gp inducer, lenvatinib AUC decreased by 18%. A similar effect may occur after coadministration with apalutamide. Therefore, no clinically relevant effect on lenvatinib exposure is expected. However, androgen deprivation treatment may prolong the QT interval.  Thus, if apalutamide is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Asciminib is metabolized by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Lenvatinib does not inhibit or induce CYPs or UGTs. Concentrations of lenvatinib may slightly increase due to weak inhibition of CYP3A4 by asciminib but this is unlikely to be clinically relevant. However, asciminib prolongs the QTc interval. When asciminib is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms. There may also be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticulo-endothelial system.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Atezolizumab is eliminated through catabolism. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. In vitro data suggest lenvatinib is a substrate for P-gp, BCRP and CYP3A4. Atezolizumab and bevacizumab are primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered, as per treatment protocols.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Atomoxetine is metabolized by CYP2D6 which is not affected by lenvatinib. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. There is a possible risk of QT interval prolongation with atomoxetine. When atomoxetine is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Lenvatinib does not inhibit or induce CYPs or UGTs. Avapritinib was shown to inhibit and induce CYP3A4 in vitro but the net effect in vivo has not been studied. A clinically relevant effect on lenvatinib is not expected. However, avapritinib may prolong the QTc interval. When avapritinib is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms. Moreover, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Axitinib is metabolized by CYP3A4. Lenvatinib does not inhibit or induce this enzyme.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bamlanivimab and etesevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Bamlanivimab and etesevimab are not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Belantamab mafodotin is a humanized monoclonal antibody conjugated to maleimidocaproyl monomethyl auristatin F (mcMMAF). The monoclonal antibody is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. mcMMAF has limited metabolic clearance. However, there may be risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib and belantamab mafodotin.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bendamustine is metabolized by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2. Lenvatinib does not inhibit or induce CYPs or UGTs. However, bendamustine has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. If bendamustine is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms. There may also be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300mg/m^2/day). Lenvatinib does not inhibit or induce CYPs or UGTs. Concentrations of lenvatinib may slightly decrease due to induction of CYP3A4. After coadministration with rifampicin, a strong CYP3A4 and P-gp inducer, lenvatinib AUC decreased by 18%. A similar effect may occur after coadministration with bexarotene. Therefore, no clinically relevant effect on lenvatinib exposure is expected. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Lenvatinib does not inhibit or induce CYPs or UGTs. Lenvatinib is metabolized by CYP3A4. Concentrations of lenvatinib may slightly increase due to weak inhibition of CYP3A4 but this is unlikely to be clinically relevant. However, androgen deprivation treatment may prolong the QT interval. Thus, if bicalutamide is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms.

Coadministration has not been studied. Bilastine is a substrate of P-gp. Lenvatinib does not inhibit or induce this pathway. However, bilastine prolongs the QTc interval. When bilastine is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Bisoprolol is also a substrate of P-gp. Lenvatinib does not interact with this metabolic or elimination pathway. Blood pressure should be well controlled prior to treatment with lenvatinib and should be regularly monitored during treatment. BP should be monitored after 1 week of treatment with lenvatinib, then every 2 weeks for the first 2 months, and monthly thereafter. [Note, the European SmPC for bisoprolol recommends a maximum of 10 mg in severe hepatic impairment whereas the US Prescribing Information recommends an initial 2.5 mg in hepatic impairment with caution in further dose titration.]

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bortezomib is mainly metabolized by CYP3A4 and CYP2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Lenvatinib does not inhibit or induce these enzymes. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. There may be a small risk of QT-prolongation with bortezomib. When bortezomib is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bosutinib is metabolized principally by CYP3A4. Lenvatinib does not inhibit or induce this enzyme. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered. Additionally, there may be a risk of QT-prolongation with bosutinib. When bosutinib is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brentuximab vedotin releases the active species MMAE within the tumour cell; MMAE is a substrate of CYP3A4, P-gp, and possibly CYP2D6. Due to multiple pathways, a clinically significant interaction is unlikely. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Brexpiprazole is predominantly metabolized by CYP3A4 and CYP2D6. Lenvatinib does not inhibit or induce CYPs or UGTs. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Brincidofovir is a prodrug converted to cidofovir, which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Unlike cidofovir, brincidofovir is not a substrate of OATs. Lenvatinib is not expected to interact with this pathway. However, the risk of haematological toxicity may be potentially increased as both lenvatinib and cidofovir can cause neutropenia. Closely monitor haematological parameters, as standard of care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bromperidol is a metabolized by CYP3A4. Lenvatinib does not inhibit or induce CYPs. However, as with other butyrophenones, there is a possible risk of QT interval prolongation with bromperidol. When bromperidol is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. Concurrent use of QT-prolonging drugs with bromperidol should be avoided. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

Coadministration has not been formally studied but based on current knowledge of the effect of vaccines on drug disposition a clinically significant interaction is considered unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Lenvatinib does not inhibit or induce CYPs.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Lenvatinib does not inhibit or induce this pathway to a clinically significant effect. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. There may be a small risk of QT-prolongation with capecitabine. When capecitabine is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Concomitant administration of lenvatinib and carboplatin had no significant impact on the pharmacokinetics of any of the substances. Carboplatin is excreted primarily by renal glomerular filtration and therefore there is little potential for a pharmacokinetic interaction.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Carfilzomib is extensively metabolised by peptidase and epoxide hydrolase, with minimal metabolism by CYP enzymes. Cases of QT prolongation with carfilzomib with been reported in clinical trials and post-marketing. When carfilzomib is coadministered with lenvatinib an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms. Furthermore, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Lenvatinib does not inhibit or induce CYPs or UGTs. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Casirivimab and imdevimab are IgG1 monoclonal antibodies and are likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Casirivimab and imdevimab are not metabolized by CYP enzymes. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.

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. Lenvatinib does not interact with this metabolic pathway. [Note, no dose adjustment is required in patients with normal hepatic function but a dose reduction of caspofungin daily dose to 35 mg is recommended for adults with moderate hepatic impairment. There is no clinical experience in adults with severe hepatic impairment.]

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes or drug transporters are unlikely.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other protein therapeutics, cetuximab is expected to be degraded into small peptides and amino acids via catabolic pathways.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorambucil is almost completely metabolized (little is known about chlorambucil metabolism in humans, most probably non-CYP mediated) and has extremely low urinary excretion.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is a substrate of CYPs 2D6 (major), 1A2, and 3A4 in vitro. Lenvatinib does not inhibit or induce CYPs. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. Caution is recommended in patients coadministered with a drug with a known risk of Torsade de Pointes. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cidofovir is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3 which are not expected to be affected by lenvatinib. However, the risk of haematological toxicity may be potentially increased as both lenvatinib and cidofovir can cause neutropenia. Closely monitor haematological parameters, as standard of care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Cisplatin is eliminated renally via OCT2 and MATE1. Lenvatinib does not inhibit or induce this pathway to a clinically significant effect.

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. Concentrations of lenvatinib may slightly increase due to inhibition of CYP3A4, but this is unlikely to be clinically relevant. Coadministration with ketoconazole, another strong CYP3A4 inhibitor, increased lenvatinib AUC by 15%. A similar effect may occur after coadministration with clofazimine. Both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for clofazimine; possible risk for lenvatinib) but the risk of QT interval prolongation is considered to be low as no significant pharmacokinetic interaction is expected.

Coadministration has not been studied. Cocaine is metabolized via multiple pathways including serum and hepatic cholinesterases, spontaneous hydrolysis, hepatic carboxylesterase and CYP3A4 to norcocaine. Lenvatinib does not interact with these pathways. However, the combination is not recommended. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. Cocaine prolongs the QT/c and has a known risk of Torsade de Pointes. If coadministration occurs, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when resolved to a QT interval <480 ms or baseline.

Coadministration has not been studied but may result in decreased concentrations of lenvatinib as absorption may be affected by insoluble complexes formed by the presence of cholestyramine. The clinical significance of these potential interactions is unknown but may result in a decreased efficacy of lenvatinib. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for lenvatinib, but for any medication taken with colestyramine.]

Coadministration has not been studied. The metabolism of conjugated estrogens is complex and involves CYP3A4 isoenzymes and glucuronidation in the liver. Lenvatinib does not inhibit or induce CYPs.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyclophosphamide is activated (major pathway) to 4-hydroxycyclophosphamide by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. Lenvatinib does not inhibit or induce CYPs.

Coadministration has not been studied but is contraindicated. Cyproterone acetate is metabolized by CYP3A4. Lenvatinib does not inhibit or induce CYPs or UGTs. Concentrations of lenvatinib may slightly increase due to inhibition of CYP3A4 by high dose cyproterone acetate (100 mg, three times daily) but this is unlikely to be clinically relevant. However, cyproterone acetate is hepatoxic and is contraindicated in previous or existing liver tumours, which are not due to metastases from carcinoma of the prostate. Additionally, androgen deprivation treatment may prolong the QT interval. Thus, if cyproterone acetate is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other protein therapeutics, daratumumab is expected to be degraded into small peptides and amino acids via catabolic pathways and is not anticipated to alter drug-metabolising enzymes.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dasatinib is metabolized by CYP3A4. Lenvatinib does not inhibit or induce this enzyme. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. There may be a risk of QT-prolongation with dasatinib. When dasatinib is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

Coadministration has not been studied. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Lenvatinib does not inhibit or induce these CYPs. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Lenvatinib does not inhibit or induce these CYPs. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. Lenvatinib does not inhibit or induce these CYPs. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate and moderate inducer of CYP3A4 at doses above 16 mg. After coadministration with rifampicin, a strong CYP3A4 inducer, lenvatinib AUC decreased by 18%. Therefore, no clinically relevant effect on lenvatinib exposure is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dienogest is a substrate of CYP3A4. Lenvatinib does not inhibit or induce these CYPs. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dinutuximab beta is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, there may be risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib and dinutuximab beta.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolutegravir is primarily metabolized by UGT1A1, with some contribution from CYP3A, and is an inhibitor of OCT2. Lenvatinib does not interact with these pathways.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dostarlimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Doxorubicin is mainly eliminated in the bile. Caution is advised due to possible cardiac (ECG abnormalities and sometimes arrhythmias) toxicities with doxorubicin. Monitoring of ECG is recommended if coadministered. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when is resolved to a QT interval <480 ms or baseline.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxylamine is metabolized primarily by CYP2D6, CYP1A2, and CYP2C9. Lenvatinib does not interact with these pathways.

Coadministration has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenvatinib does not inhibit or induce CYPs. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Estradiol is metabolised by CYP3A4, CYP1A2, and is glucuronidated. Lenvatinib does not interfere with these pathways.

Coadministration has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenvatinib does not inhibit or induce CYPs. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Lenvatinib does not inhibit or induce CYPs. Ethinylestradiol is mainly metabolized by hydroxylation with CYP3A4 and CYP2C9. However, as the effect of lenvatinib on contraceptive efficacy has not been investigated, the European product label for lenvatinib recommends the use of an additional contraceptive method, such as a barrier method.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by endogenous endopeptidases. Lenvatinib does not interfere with this metabolic pathway. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Durvalumab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, there may be risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib and durvalumab.

Coadministration has not been studied. MDMA is mainly metabolized by CYP2D6 which is not affected by lenvatinib. However, the combination is not recommended. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. MDMA has a possible risk of prolonging the QTc. If coadministration occurs, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when resolved to a QT interval <480 ms or baseline.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Elotuzumab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib and elotuzumab.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Elranatamab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, there may be risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction Is unlikely. Cobicistat is a strong inhibitor of CYP3A4. Concentrations of lenvatinib may slightly increase due to inhibition of CYP3A4, but this is unlikely to be clinically relevant. Coadministration with ketoconazole, another strong CYP3A4 inhibitor, increased lenvatinib AUC by 15%. A similar effect may occur after coadministration with elvitegravir/cobi/FTC/TAF.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction Is unlikely. Cobicistat is a strong inhibitor of CYP3A4. Concentrations of lenvatinib may slightly increase due to inhibition of CYP3A4, but this is unlikely to be clinically relevant. Coadministration with ketoconazole, another strong CYP3A4 inhibitor, increased lenvatinib AUC by 15%. A similar effect may occur after coadministration with elvitegravir/cobi/FTC/TDF.

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 excreted predominantly renally. Lenvatinib does not interact with this metabolic or elimination pathway.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Enzalutamide is primarily metabolized by CYP2C8 and is a strong inducer of CYP3A4. Lenvatinib does not inhibit or induce CYPs. Concentrations of lenvatinib may slightly decrease due to induction of CYP3A4. After coadministration with rifampicin, a strong CYP3A4 inducer, lenvatinib AUC decreased by 18%. A similar effect may occur after coadministration with enzalutamide. Therefore, no clinically relevant effect on lenvatinib exposure is expected. However, androgen deprivation treatment may prolong the QT interval. Thus, if enzalutamide is coadministered with lenvatinib, an additive or synergistic effect on QT-prolongation cannot be excluded. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when QT-prolongation is <480 ms.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Epcoritamab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. However, there may be risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib.

The clinical appropriateness of co-prescribing these medications has not been assessed. Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Epirubicin is glucuronidated by UGT2B7. Lenvatinib does not inhibit or induce UGTs. QT/QTc interval prolongation has been reported at a higher incidence in patients treated with lenvatinib than in patients treated with placebo. Caution is recommended in patients coadministered with a drug with a possible risk of Torsade de Pointes. If coadministration is necessary, clinical monitoring including ECG assessment is recommended. Lenvatinib should be withheld in the event of a QT interval >500 ms and resumed at a reduced dose when resolved to a QT interval <480 ms or baseline. Additionally, there may be a risk of additive haematological toxicity with coadministration. Routine monitoring of haematological parameters is recommended, as per standard care with lenvatinib. [Note: patients with severe hepatic impairment should not receive epirubicin.]