CYP2C8 inhibitors.sertralinelumacaftor/ivacaftor, sertraline. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .lumacaftor/ivacaftor will decrease the level or effect of sertraline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of sertraline may be required to obtain desired therapeutic effect. Sertraline is a substrate of CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP2B6. Lumacaftor/ivacaftor is a strong inducer of CYP3A and lumacaftor has the potential to induce CYP2C19, CYP2C9, CYP2D6, and CYP2B6.sufentanil SLlumacaftor/ivacaftor decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.sulfadiazinelumacaftor/ivacaftor, sulfadiazine. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .sulfisoxazolelumacaftor/ivacaftor, sulfisoxazole. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .tamoxifenlumacaftor/ivacaftor, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .tinidazolelumacaftor/ivacaftor will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirtipranavir increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.tofacitiniblumacaftor/ivacaftor, tofacitinib. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .torsemidelumacaftor/ivacaftor, torsemide. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .trimethoprimlumacaftor/ivacaftor, trimethoprim. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .trimipraminelumacaftor/ivacaftor, trimipramine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .voriconazolevoriconazole increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.lumacaftor/ivacaftor, voriconazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .lumacaftor/ivacaftor, voriconazole. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .lumacaftor/ivacaftor will decrease the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.warfarinlumacaftor/ivacaftor will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inducers of these isoenzymes and adjust warfarin dose if needed. zafirlukastlumacaftor/ivacaftor, zafirlukast. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .zanubrutiniblumacaftor/ivacaftor will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. Minor (4)acetazolamideacetazolamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.anastrozoleanastrozole will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclophosphamidecyclophosphamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.larotrectiniblarotrectinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.abemaciclibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.acalabrutinibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.acetazolamideMinor (1)acetazolamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.adagrasibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.alfentanilSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.alpelisibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.ambrisentanMonitor Closely (1)lumacaftor/ivacaftor, ambrisentan. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .amiodaroneMonitor Closely (1)lumacaftor/ivacaftor, amiodarone. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .anastrozoleMinor (1)anastrozole will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.apalutamideSerious - Use Alternative (1)apalutamide will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.atazanavirMonitor Closely (1)atazanavir increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.atogepantMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.avapritinibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.belumosudilMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.bortezomibMonitor Closely (1)lumacaftor/ivacaftor, bortezomib. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .bosentanContraindicated (1)bosentan will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.Monitor Closely (1)lumacaftor/ivacaftor, bosentan. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .brexpiprazoleMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.brigatinibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.buprenorphineMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.buprenorphine buccalMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.buprenorphine subdermal implantMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.buprenorphine, long-acting injectionMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.bupropionMonitor Closely (1)lumacaftor/ivacaftor, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .cabozantinibSerious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.calcifediolMonitor Closely (1)lumacaftor/ivacaftor, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.cannabidiolMonitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.carbamazepineContraindicated (1)carbamazepine will decrease the level or effect of lumacaftor/ivacaftor by aldehyde dehydrogenase inhibition. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.Serious - Use Alternative (1)carbamazepine will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.cariprazineContraindicated (1)lumacaftor/ivacaftor will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.carisoprodolMonitor Closely (1)lumacaftor/ivacaftor,