AdultPediatricDosage Forms & Strengths lumacaftor/ivacaftor tablet 200mg/125mg Cystic Fibrosis Indicated for cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene 2 tablets PO q12hr (each tablet containing 200 mg/125 mg [ie, 400 mg/250 mg per dose]); take with fat-containing food Dosage Modifications Hepatic impairment Mild (Child-Pugh A): Dosage adjustment not required Moderate (Child-Pugh B): Reduce dose to 2 tablets in the morning and 1 tablet in the evening (ie, lumacaftor 600 mg/ivacaftor 375 mg per day) Severe (Child-Pugh C) Not studied, but exposure is systemic and expected to be higher than moderate impairment Use with caution at a maximum dose of 1 tablet in the morning and 1 tablet in the evening (ie, lumacaftor 400 mg/ivacaftor 250 mg per day), or less, after weighing the risks and benefits of treatment Increased liver enzymes ALT or AST >5 x ULN (not associated with elevated bilirubin): Interrupt dosing ALT or AST >3 x ULN associated with elevated bilirubin >3 x ULN: Interrupt dosing Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing Coadministration with CYP3A inhibitors Initiating CYP3A inhibitor in patients already taking lumacaftor/ivacaftor: No dosage adjustment required Initiating lumacaftor/ivacaftor in patients currently taking a strong CYP3A inhibitor: Reduce lumacaftor/ivacaftor dose to 1 tablet daily for the first week of treatment; following this period, continue with the recommended daily dose If lumacaftor/ivacaftor is interrupted for >1 week and then reinitiated while taking a strong CYP3A inhibitor, reduce lumacaftor/ivacaftor dose to 1 tablet daily for the first week of treatment; following this period, continue with the recommended daily dose Dosing Considerations Efficacy and safety have not been established in patients with CF other than those homozygous for the F508del mutation If genotype unknown, use an FDA-cleared CF mutation test to detect the presence of the F508del mutation on both alleles of the CFTR geneDosage Forms & Strengths lumacaftor/ivacaftor tablet 100mg/125mg 200mg/125mg oral granules (75mg/94mg)/packet (100mg/125mg)/packet (150mg/188mg)/packet Cystic Fibrosis Indicated for cystic fibrosis (CF) in patients aged ≥1 year who are homozygous for the F508del mutation in the CFTR gene <1 years: Safety and efficacy not established 1 to <2 years 7 to <9 kg: 75 mg/94 mg oral granule packet PO q12hr 9 to <14 kg: 100 mg/125 mg oral granule packet PO q12hr ≥14 kg: 150 mg/188 mg oral granule packet PO q12hr 2-5 years <14 kg: 100 mg/125 mg oral granule packet PO q12hr ≥14 kg: 150 mg/188 mg oral granule packet PO q12hr 6-11 years: 2 tablets PO q12hr (each tablet containing 100 mg/125 mg [ie, 200 mg/250 mg per dose]) ≥12 years: 2 tablets PO q12hr (each tablet containing 200 mg/125 mg [ie, 400 mg/250 mg per dose]) Take doses with fat-containing food (see Administration) Dosage Modifications Hepatic impairment Mild (Child-Pugh A): Dosage adjustment not required Moderate (Child-Push B) aged 1 to <2 years Oral granules 7 to >9 kg: 75 mg/94 mg-packet in the morning and 75 mg/94 mg-packet every other evening 9 to <14 kg: 100 mg/125 mg-packet in the morning and 100 mg/125 mg-packet every other evening ≥14 kg: 150 mg/188 mg-packet in the morning and 150 mg/188 mg-packet every other evening Moderate (Child-Pugh B) aged 2-5 years Oral granules <14 kg: 100 mg/125 mg-packet in the morning and 100 mg/125 mg-packet every other evening ≥14 kg: 150 mg/188 mg-packet in the morning and 150 mg/188 mg-packet every other evening Moderate (Child-Pugh B) aged 6-11 years 100 mg/125 mg-tablets: Reduce dose to 2 tablets in the morning and 1 tablet in the evening Moderate (Child-Pugh B) aged ≥12 years 200 mg/125 mg-tablets: Reduce to 2 tablets in the morning and 1 tablet in the evening Severe (Child-Pugh C) aged 1 to <2 years Oral granules 7 to <9 kg: 75 mg/94 mg-packet in the morning and no dose in the evening 9 to <14 kg: 100 mg/125 mg-packet in the morning and no dose in the evening ≥14 kg: 150 mg/188 mg-packet in the morning and no dose in the evening Severe (Child-Pugh C) aged 2-5 years Oral granules <14 kg: 100 mg/125 mg-packet in the morning and no dose in the evening ≥14 kg: 150 mg/188 mg-packet in the morning and no dose in the evening Severe (Child-Pugh C) aged 6-11 years 100 mg/125 mg-tablets: 1 tablet PO q12hr (or less frequently) Severe (Child-Pugh C) aged ≥12 years 200 mg/125 mg-tablets: 1 tablet PO q12hr (or less frequently) Increased liver enzymes ALT or AST >5 x ULN (not associated with elevated bilirubin): Interrupt dosing ALT or AST >3 x ULN associated with elevated bilirubin >3 x ULN: Interrupt dosing Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing Coadministration with CYP3A inhibitors Initiating CYP3A inhibitor in patients already taking lumacaftor/ivacaftor: No dosage adjustment required Initiating lumacaftor/ivacaftor in patients currently taking strong CYP3A inhibitor Reduce lumacaftor/ivacaftor dose for first week of treatment based on age 1-5 years: 1 packet every other day ≥6 years: 1 tablet qDay Following this one-week period, resume recommended daily dosage If lumacaftor/ivacaftor interrupted for >1 week and then reinitiated while taking strong CYP3A inhibitor Reduce lumacaftor/ivacaftor dose for first week of treatment reinitiation as follows 1-5 years: 1 packet every other day ≥6 years: 1 tablet qDay Following this one-week period, resume recommended daily dosage Dosing Considerations Efficacy and safety have not been established in patients with CF other than those homozygous for the F508del mutation If genotype unknown, use an FDA-cleared CF mutation test to detect the presence of the F508del mutation on both alleles of the CFTR geneInteraction CheckerEnter a drug name and lumacaftor/ivacaftorNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (33)bosentanbosentan 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.carbamazepinecarbamazepine 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.cariprazinelumacaftor/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.cobimetiniblumacaftor/ivacaftor will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.dabrafenibdabrafenib 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.dexamethasonedexamethasone 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.doravirinelumacaftor/ivacaftor will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine. efavirenzefavirenz 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.elbasvir/grazoprevirlumacaftor/ivacaftor will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.enzalutamideenzalutamide 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.eslicarbazepine acetateeslicarbazepine acetate 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.etravirineetravirine 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.fosphenytoinfosphenytoin 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.fostemsavirlumacaftor/ivacaftor will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.isavuconazonium sulfatelumacaftor/ivacaftor will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.lenacapavirlumacaftor/ivacaftor will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lenacapavir with strong CYP3A inducers is contraindicated. lonafarniblumacaftor/ivacaftor, lonafarnib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate that is contraindicated with strong or moderate CYP3A4 inhibitors or inducers. Lumacaftor/ivacaftor is both a CYP3A4 inhibitor and an inducer.lorlatiniblumacaftor/ivacaftor will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.mavacamtenlumacaftor/ivacaftor will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.mitotanemitotane 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.nafcillinnafcillin 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.nevirapinenevirapine 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.nirmatrelvirlumacaftor/ivacaftor will decrease the level or effect of nirmatrelvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.nirmatrelvir/ritonavirlumacaftor/ivacaftor will decrease the level or effect of nirmatrelvir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.oxcarbazepineoxcarbazepine 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.pentobarbitalpentobarbital 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.phenobarbitalphenobarbital 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.phenytoinphenytoin will decrease the level or effect of lumacaftor/ivacaftor