CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor. ketoconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.lapatinibMonitor Closely (3)lapatinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor. lapatinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification. ivacaftor increases levels of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.larotrectinibSerious - Use Alternative (1)ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)larotrectinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lefamulinMonitor Closely (1)ivacaftor will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.lemborexantSerious - Use Alternative (1)ivacaftor will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.lenacapavirMonitor Closely (2)lenacapavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates. lenacapavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.letermovirMonitor Closely (1)letermovir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.levamlodipineMonitor Closely (1)ivacaftor will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.levoketoconazoleMonitor Closely (2)levoketoconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification. levoketoconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.lidocaineMonitor Closely (2)ivacaftor increases levels of lidocaine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index. ivacaftor increases effects of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lomustineMonitor Closely (1)lomustine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .lonafarnibContraindicated (1)ivacaftor will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated. Serious - Use Alternative (1)lonafarnib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.loperamideMonitor Closely (1)ivacaftor increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.lopinavirMonitor Closely (2)lopinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor. lopinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.loratadineMonitor Closely (1)ivacaftor increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.lorlatinibMonitor Closely (2)lorlatinib will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. lorlatinib will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lovastatinMonitor Closely (1)ivacaftor increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.lurbinectedinSerious - Use Alternative (1)ivacaftor will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.maravirocMonitor Closely (1)ivacaftor increases levels of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.mavacamtenMonitor Closely (1)ivacaftor will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose. mefloquineMonitor Closely (1)ivacaftor increases levels of mefloquine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.methimazoleMonitor Closely (1)methimazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .methoxsalenMonitor Closely (1)methoxsalen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .methylprednisoloneMonitor Closely (1)ivacaftor increases levels of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.metronidazoleMonitor Closely (2)metronidazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor. metronidazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.micafunginMonitor Closely (1)micafungin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .midazolam intranasalSerious - Use Alternative (1)ivacaftor will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.mifepristoneMonitor Closely (1)mifepristone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.Serious - Use Alternative (1)mifepristone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.mitomycinMonitor Closely (1)ivacaftor increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.mitotaneMonitor Closely (1)mitotane decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.Serious - Use Alternative (1)mitotane will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.mitoxantroneMonitor Closely (1)mitoxantrone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .mobocertinibSerious - Use Alternative (1)ivacaftor will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.morphineMonitor Closely (1)ivacaftor increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.nafcillinSerious - Use Alternative (2)nafcillin decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold). nafcillin will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.naldemedineMonitor Closely (1)ivacaftor increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.nefazodoneMonitor Closely (2)nefazodone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor. nefazodone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.nelfinavirMonitor Closely (3)ivacaftor increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index. nelfinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification. nelfinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.netupitant/palonosetronMonitor Closely (2)netupitant/palonosetron will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor. netupitant/palonosetron will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.nevirapineSerious - Use Alternative (2)nevirapine will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. nevirapine, ivacaftor. Other (see comment). Avoid or Use Alternate Drug. Comment: Nevirapine decreases levels of ivacaftor by CYP enzyme induction; whereas, ivacaftor increases levels of efavirenz by inhibiting CYP3A4.nicardipineMonitor Closely (1)nicardipine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.nilotinibMonitor Closely (1)ivacaftor increases levels of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.nintedanibMonitor Closely (1)ivacaftor increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .nirmatrelvir/ritonavirMonitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dosage of ivacaftor, elexacaftor/tezacaftor/ivacaftor, or tezacaftor/ivacaftor if coadministered.nizatidineMonitor Closely (1)nizatidine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .norgestrelMonitor Closely (1)ivacaftor will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects olanzapineMonitor Closely (1)olanzapine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .oliceridineMonitor Closely (1)ivacaftor will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant