lumacaftor/ivacaftor (Rx)

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 gene

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 gene

Contraindicated (33)

• bosentan

  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.

• carbamazepine

  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.

• cariprazine

  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.

• cobimetinib

  lumacaftor/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.

• dabrafenib

  dabrafenib 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.

• dexamethasone

  dexamethasone 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.

• doravirine

  lumacaftor/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.

• efavirenz

  efavirenz 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/grazoprevir

  lumacaftor/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.

• enzalutamide

  enzalutamide 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 acetate

  eslicarbazepine 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.

• etravirine

  etravirine 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.

• fosphenytoin

  fosphenytoin 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.

• fostemsavir

  lumacaftor/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 sulfate

  lumacaftor/ivacaftor will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lenacapavir

  lumacaftor/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.

• lonafarnib

  lumacaftor/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.

• lorlatinib

  lumacaftor/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.

• mavacamten

  lumacaftor/ivacaftor will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• mitotane

  mitotane 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.

• nafcillin

  nafcillin 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.

• nevirapine

  nevirapine 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.

• nirmatrelvir

  lumacaftor/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/ritonavir

  lumacaftor/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.

• oxcarbazepine

  oxcarbazepine 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.

• pentobarbital

  pentobarbital 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.

• phenobarbital

  phenobarbital 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.

• phenytoin

  phenytoin 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.

• primidone

  primidone 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.

• rifabutin

  rifabutin 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.

• rifampin

  rifampin 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.

• rifapentine

  rifapentine 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.

• St John's Wort

  St John's Wort 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.

Serious - Use Alternative (109)

• abemaciclib

  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.

• acalabrutinib

  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.

• adagrasib

  lumacaftor/ivacaftor will decrease the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• alfentanil

  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.

• alpelisib

  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.

• apalutamide

  apalutamide will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• avapritinib

  lumacaftor/ivacaftor will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• brigatinib

  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.

• cabozantinib

  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.

• carbamazepine

  carbamazepine will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ceritinib

  ceritinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chloramphenicol

  chloramphenicol will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chlorpropamide

  lumacaftor/ivacaftor will decrease the level or effect of chlorpropamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• clarithromycin

  lumacaftor/ivacaftor will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clonidine

  lumacaftor/ivacaftor will decrease the level or effect of clonidine 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.

• colchicine

  lumacaftor/ivacaftor will decrease the level or effect of colchicine 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.

• copanlisib

  lumacaftor/ivacaftor will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cyclosporine

  lumacaftor/ivacaftor will decrease the level or effect of cyclosporine 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.

• deflazacort

  lumacaftor/ivacaftor will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• dienogest/estradiol valerate

  lumacaftor/ivacaftor will decrease the level or effect of dienogest/estradiol valerate by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• dihydroergotamine

  lumacaftor/ivacaftor will decrease the level or effect of dihydroergotamine 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.

• disopyramide

  lumacaftor/ivacaftor will decrease the level or effect of disopyramide 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.

• duvelisib

  lumacaftor/ivacaftor will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• elacestrant

  lumacaftor/ivacaftor will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  lumacaftor/ivacaftor will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ergotamine

  lumacaftor/ivacaftor will decrease the level or effect of ergotamine 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.

• erythromycin base

  lumacaftor/ivacaftor will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  lumacaftor/ivacaftor will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  lumacaftor/ivacaftor will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  lumacaftor/ivacaftor will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethinylestradiol

  lumacaftor/ivacaftor will decrease the level or effect of ethinylestradiol by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• ethosuximide

  lumacaftor/ivacaftor will decrease the level or effect of ethosuximide 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.

• etonogestrel

  lumacaftor/ivacaftor will decrease the level or effect of etonogestrel by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• everolimus

  lumacaftor/ivacaftor will decrease the level or effect of everolimus 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.

• fedratinib

  lumacaftor/ivacaftor will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• fentanyl

  lumacaftor/ivacaftor will decrease the level or effect of fentanyl 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.

• fentanyl intranasal

  lumacaftor/ivacaftor will decrease the level or effect of fentanyl intranasal 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.

• fentanyl transdermal

  lumacaftor/ivacaftor will decrease the level or effect of fentanyl transdermal 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.

• fentanyl transmucosal

  lumacaftor/ivacaftor will decrease the level or effect of fentanyl transmucosal 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.

• fexinidazole

  lumacaftor/ivacaftor will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• finerenone

  lumacaftor/ivacaftor will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fostamatinib

  lumacaftor/ivacaftor will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ganaxolone

  lumacaftor/ivacaftor will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• glasdegib

  lumacaftor/ivacaftor will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glimepiride

  lumacaftor/ivacaftor will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• glipizide

  lumacaftor/ivacaftor will decrease the level or effect of glipizide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• glyburide

  lumacaftor/ivacaftor will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• infigratinib

  lumacaftor/ivacaftor will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• istradefylline

  lumacaftor/ivacaftor will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  lumacaftor/ivacaftor will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivosidenib

  lumacaftor/ivacaftor will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.
  
  ivosidenib will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ixazomib

  lumacaftor/ivacaftor will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• ketoconazole

  lumacaftor/ivacaftor will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• larotrectinib

  lumacaftor/ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• lefamulin

  lumacaftor/ivacaftor will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  lumacaftor/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.

• leniolisib

  lumacaftor/ivacaftor will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levoketoconazole

  lumacaftor/ivacaftor will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levonorgestrel intrauterine

  lumacaftor/ivacaftor will decrease the level or effect of levonorgestrel intrauterine by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• lorlatinib

  lorlatinib will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lumateperone

  lumacaftor/ivacaftor will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  lumacaftor/ivacaftor will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  lumacaftor/ivacaftor will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• midazolam

  lumacaftor/ivacaftor will decrease the level or effect of midazolam 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.

• midostaurin

  lumacaftor/ivacaftor will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mobocertinib

  lumacaftor/ivacaftor will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• naldemedine

  lumacaftor/ivacaftor will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• neratinib

  lumacaftor/ivacaftor will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• norethindrone

  lumacaftor/ivacaftor will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone acetate

  lumacaftor/ivacaftor will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone transdermal

  lumacaftor/ivacaftor will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• olutasidenib

  lumacaftor/ivacaftor will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• osimertinib

  lumacaftor/ivacaftor will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• pemigatinib

  lumacaftor/ivacaftor will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  lumacaftor/ivacaftor will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pimozide

  lumacaftor/ivacaftor will decrease the level or effect of pimozide 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.

• posaconazole

  lumacaftor/ivacaftor will decrease the level or effect of posaconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pralsetinib

  lumacaftor/ivacaftor will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• pretomanid

  lumacaftor/ivacaftor will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

• quinidine

  lumacaftor/ivacaftor will decrease the level or effect of quinidine 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.

• quinine

  lumacaftor/ivacaftor will decrease the level or effect of quinine 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.

• repaglinide

  lumacaftor/ivacaftor will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repaglinide is metabolized by CYP3A and CYP2C8. Lumacaftor /ivacaftor is a strong CYP3A4 inducer and may also induce CYP2C8.

• ribociclib

  lumacaftor/ivacaftor will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.
  
  ribociclib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rimegepant

  lumacaftor/ivacaftor will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ripretinib

  lumacaftor/ivacaftor will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

• rolapitant

  lumacaftor/ivacaftor will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

• selumetinib

  lumacaftor/ivacaftor will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  lumacaftor/ivacaftor will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  lumacaftor/ivacaftor will decrease the level or effect of sirolimus 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.

• sofosbuvir/velpatasvir

  lumacaftor/ivacaftor will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

• sonidegib

  lumacaftor/ivacaftor will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

• sotorasib

  lumacaftor/ivacaftor will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sparsentan

  lumacaftor/ivacaftor will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  lumacaftor/ivacaftor will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.

• tacrolimus

  lumacaftor/ivacaftor will decrease the level or effect of tacrolimus 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.

• tazemetostat

  lumacaftor/ivacaftor will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tivozanib

  lumacaftor/ivacaftor will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tolazamide

  lumacaftor/ivacaftor will decrease the level or effect of tolazamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• tolbutamide

  lumacaftor/ivacaftor will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• trabectedin

  lumacaftor/ivacaftor will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• triazolam

  lumacaftor/ivacaftor will decrease the level or effect of triazolam 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.

• tucatinib

  lumacaftor/ivacaftor will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.

• ubrogepant

  lumacaftor/ivacaftor will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  lumacaftor/ivacaftor will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

• valbenazine

  lumacaftor/ivacaftor will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

• venetoclax

  lumacaftor/ivacaftor will decrease the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of venetoclax with strong or moderate CYP3A inducers. Consider alternative treatment with agents that have less CYP3A induction.

• voclosporin

  lumacaftor/ivacaftor will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  lumacaftor/ivacaftor will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voxelotor

  lumacaftor/ivacaftor will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).
  
  voxelotor will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

Monitor Closely (121)

• ambrisentan

  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. .

• amiodarone

  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. .

• atazanavir

  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.

• atogepant

  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.

• belumosudil

  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.

• bortezomib

  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. .

• bosentan

  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. .

• brexpiprazole

  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.

• buprenorphine

  lumacaftor/ivacaftor will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine buccal

  lumacaftor/ivacaftor will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine subdermal implant

  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 injection

  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.

• bupropion

  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. .

• calcifediol

  lumacaftor/ivacaftor, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

• cannabidiol

  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.

• carbamazepine

  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.

• carisoprodol

  lumacaftor/ivacaftor, carisoprodol. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• carvedilol

  lumacaftor/ivacaftor, carvedilol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• celecoxib

  lumacaftor/ivacaftor, celecoxib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• citalopram

  lumacaftor/ivacaftor, citalopram. 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 citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of citalopram may be required to obtain desired therapeutic effect. Citalopram is a CYP3A and CYP2C19 substrate. Lumacaftor/ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.

• clarithromycin

  clarithromycin 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.

• clobazam

  lumacaftor/ivacaftor, clobazam. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• clomipramine

  lumacaftor/ivacaftor, clomipramine. affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• cobicistat

  cobicistat 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.

• conivaptan

  conivaptan 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.

• cyclophosphamide

  lumacaftor/ivacaftor, cyclophosphamide. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• dapsone

  lumacaftor/ivacaftor, dapsone. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• daridorexant

  lumacaftor/ivacaftor will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• darunavir

  darunavir 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.

• dexlansoprazole

  lumacaftor/ivacaftor, dexlansoprazole. 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 dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• diazepam

  lumacaftor/ivacaftor, diazepam. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• diazepam intranasal

  lumacaftor/ivacaftor will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diclofenac

  lumacaftor/ivacaftor, diclofenac. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• digoxin

  lumacaftor/ivacaftor, digoxin. P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Lumacaftor has the potential to both inhibit and induce P-gp. Additionally, a clinical study with ivacaftor monotherapy showed that ivacaftor is a weak inhibitor of P-gp.

• dronabinol

  lumacaftor/ivacaftor will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• efavirenz

  lumacaftor/ivacaftor, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• elagolix

  lumacaftor/ivacaftor will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF 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.

• escitalopram

  lumacaftor/ivacaftor, escitalopram. 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 escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of escitalopram may be required to obtain desired therapeutic effect. Escitalopram is a CYP3A and CYP2C19 substrate. Lumacaftor/ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.

• esomeprazole

  lumacaftor/ivacaftor, esomeprazole. 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 esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• estradiol vaginal

  lumacaftor/ivacaftor will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  lumacaftor/ivacaftor, etravirine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, etravirine. affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• flibanserin

  lumacaftor/ivacaftor will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

• fluoxetine

  lumacaftor/ivacaftor, fluoxetine. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• fluvastatin

  lumacaftor/ivacaftor, fluvastatin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• fosamprenavir

  fosamprenavir 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.

• fosphenytoin

  lumacaftor/ivacaftor, fosphenytoin. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, fosphenytoin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• gefitinib

  lumacaftor/ivacaftor will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

• glecaprevir/pibrentasvir

  lumacaftor/ivacaftor will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

• grapefruit

  grapefruit 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.

• guanfacine

  lumacaftor/ivacaftor will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• ibuprofen

  lumacaftor/ivacaftor will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

• ibuprofen IV

  lumacaftor/ivacaftor will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

• idelalisib

  idelalisib 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.

• ifosfamide

  lumacaftor/ivacaftor increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  lumacaftor/ivacaftor increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• imatinib

  imatinib 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, imatinib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• imipramine

  lumacaftor/ivacaftor, imipramine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• indinavir

  indinavir 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.

• irinotecan

  lumacaftor/ivacaftor, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• irinotecan liposomal

  lumacaftor/ivacaftor, irinotecan liposomal. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• isoniazid

  isoniazid 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.

• istradefylline

  istradefylline will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  itraconazole 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.

• ketamine

  lumacaftor/ivacaftor, ketamine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
  
  lumacaftor/ivacaftor, ketamine. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• ketoconazole

  ketoconazole 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.

• lacosamide

  lumacaftor/ivacaftor, lacosamide. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lansoprazole

  lumacaftor/ivacaftor, lansoprazole. 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 lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• levamlodipine

  lumacaftor/ivacaftor will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levoketoconazole

  levoketoconazole 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.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  lumacaftor/ivacaftor will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• lopinavir

  lopinavir 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.

• losartan

  lumacaftor/ivacaftor, losartan. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• medroxyprogesterone

  lumacaftor/ivacaftor will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

• mestranol

  lumacaftor/ivacaftor, mestranol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• methsuximide

  lumacaftor/ivacaftor, methsuximide. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• methylprednisolone

  lumacaftor/ivacaftor decreases levels of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of corticosteroids may be required for desired clinical effect.

• mifepristone

  mifepristone will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, monitor efficacy and adjust dosages as necessary

• modafinil

  lumacaftor/ivacaftor, modafinil. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• montelukast

  lumacaftor/ivacaftor, montelukast. 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 decreases levels of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dose adjustment for montelukast is recommended.

• nateglinide

  lumacaftor/ivacaftor, nateglinide. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• nefazodone

  nefazodone 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.

• nelfinavir

  nelfinavir 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, nelfinavir. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• nicardipine

  nicardipine 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.

• oliceridine

  lumacaftor/ivacaftor will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.

• omeprazole

  lumacaftor/ivacaftor, omeprazole. 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 omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• osilodrostat

  lumacaftor/ivacaftor will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

• ospemifene

  lumacaftor/ivacaftor, ospemifene. affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, ospemifene. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• pantoprazole

  lumacaftor/ivacaftor, pantoprazole. 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 pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• pentamidine

  lumacaftor/ivacaftor, pentamidine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• phenobarbital

  lumacaftor/ivacaftor, phenobarbital. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• phenytoin

  lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• pimavanserin

  lumacaftor/ivacaftor will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

• pitolisant

  lumacaftor/ivacaftor will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• polatuzumab vedotin

  lumacaftor/ivacaftor will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• posaconazole

  posaconazole 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.

• prednisone

  lumacaftor/ivacaftor decreases levels of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of corticosteroids may be required for desired clinical effect.

• progesterone micronized

  lumacaftor/ivacaftor, progesterone micronized. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• promethazine

  lumacaftor/ivacaftor, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• propofol

  lumacaftor/ivacaftor, propofol. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
  
  lumacaftor/ivacaftor, propofol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• quinidine

  quinidine 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.

• rabeprazole

  lumacaftor/ivacaftor, rabeprazole. 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 rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

• rifampin

  lumacaftor/ivacaftor, rifampin. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• ritonavir

  ritonavir 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.

• saquinavir

  saquinavir 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.

• selegiline

  lumacaftor/ivacaftor, selegiline. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• selexipag

  lumacaftor/ivacaftor will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• sertraline

  lumacaftor/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 SL

  lumacaftor/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.

• sulfadiazine

  lumacaftor/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. .

• sulfisoxazole

  lumacaftor/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. .

• tamoxifen

  lumacaftor/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. .

• tinidazole

  lumacaftor/ivacaftor will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  tipranavir 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.

• tofacitinib

  lumacaftor/ivacaftor, tofacitinib. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• torsemide

  lumacaftor/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. .

• trimethoprim

  lumacaftor/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. .

• trimipramine

  lumacaftor/ivacaftor, trimipramine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• voriconazole

  voriconazole 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.

• warfarin

  lumacaftor/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.

• zafirlukast

  lumacaftor/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. .

• zanubrutinib

  lumacaftor/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)

• acetazolamide

  acetazolamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  larotrectinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abemaciclib

  Serious - 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.

• acalabrutinib

  Serious - 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.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• adagrasib

  Serious - 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.

• alfentanil

  Serious - 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.

• alpelisib

  Serious - 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.

• ambrisentan

  Monitor 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. .

• amiodarone

  Monitor 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. .

• anastrozole

  Minor (1)anastrozole will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - 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.

• atazanavir

  Monitor 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.

• atogepant

  Monitor 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.

• avapritinib

  Serious - 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.

• belumosudil

  Monitor 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.

• bortezomib

  Monitor 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. .

• bosentan

  Contraindicated (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. .

• brexpiprazole

  Monitor 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.

• brigatinib

  Serious - 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.

• buprenorphine

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine buccal

  Monitor 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 implant

  Monitor 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 injection

  Monitor 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.

• bupropion

  Monitor 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. .

• cabozantinib

  Serious - 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.

• calcifediol

  Monitor 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.

• cannabidiol

  Monitor 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.

• carbamazepine

  Contraindicated (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.

• cariprazine

  Contraindicated (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.

• carisoprodol

  Monitor Closely (1)lumacaftor/ivacaftor, carisoprodol. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• carvedilol

  Monitor Closely (1)lumacaftor/ivacaftor, carvedilol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• celecoxib

  Monitor Closely (1)lumacaftor/ivacaftor, celecoxib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• ceritinib

  Serious - Use Alternative (1)ceritinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chlorpropamide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of chlorpropamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• citalopram

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of citalopram may be required to obtain desired therapeutic effect. Citalopram is a CYP3A and CYP2C19 substrate. Lumacaftor/ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.
  
  lumacaftor/ivacaftor, citalopram. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• clarithromycin

  Monitor Closely (1)clarithromycin 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clobazam

  Monitor Closely (1)lumacaftor/ivacaftor, clobazam. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• clomipramine

  Monitor Closely (1)lumacaftor/ivacaftor, clomipramine. affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• clonidine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of clonidine 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.

• cobicistat

  Monitor Closely (1)cobicistat 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.

• cobimetinib

  Contraindicated (1)lumacaftor/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.

• colchicine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of colchicine 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.

• conivaptan

  Monitor Closely (1)conivaptan 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.

• copanlisib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cyclophosphamide

  Monitor Closely (1)lumacaftor/ivacaftor, cyclophosphamide. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .Minor (1)cyclophosphamide will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of cyclosporine 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.

• dabrafenib

  Contraindicated (1)dabrafenib 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.

• dapsone

  Monitor Closely (1)lumacaftor/ivacaftor, dapsone. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• daridorexant

  Monitor Closely (1)lumacaftor/ivacaftor will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

• darunavir

  Monitor Closely (1)darunavir 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.

• deflazacort

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• dexamethasone

  Contraindicated (1)dexamethasone 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.

• dexlansoprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, dexlansoprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• diazepam

  Monitor Closely (1)lumacaftor/ivacaftor, diazepam. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• diazepam intranasal

  Monitor Closely (1)lumacaftor/ivacaftor will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diclofenac

  Monitor Closely (1)lumacaftor/ivacaftor, diclofenac. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• dienogest/estradiol valerate

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of dienogest/estradiol valerate by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• digoxin

  Monitor Closely (1)lumacaftor/ivacaftor, digoxin. P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Lumacaftor has the potential to both inhibit and induce P-gp. Additionally, a clinical study with ivacaftor monotherapy showed that ivacaftor is a weak inhibitor of P-gp.

• dihydroergotamine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of dihydroergotamine 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.

• disopyramide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of disopyramide 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.

• doravirine

  Contraindicated (1)lumacaftor/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.

• dronabinol

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• duvelisib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• efavirenz

  Contraindicated (1)efavirenz 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, efavirenz. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• elacestrant

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elbasvir/grazoprevir

  Contraindicated (1)lumacaftor/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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF 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.

• enzalutamide

  Contraindicated (1)enzalutamide 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.

• erdafitinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ergotamine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ergotamine 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.

• erythromycin base

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of escitalopram may be required to obtain desired therapeutic effect. Escitalopram is a CYP3A and CYP2C19 substrate. Lumacaftor/ivacaftor is a strong inducer of CYP3A and has the potential to induce CYP2C19.
  
  lumacaftor/ivacaftor, escitalopram. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• eslicarbazepine acetate

  Contraindicated (1)eslicarbazepine 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.

• esomeprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, esomeprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• estradiol vaginal

  Monitor Closely (1)lumacaftor/ivacaftor will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethinylestradiol

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ethinylestradiol by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• ethosuximide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ethosuximide 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.

• etonogestrel

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of etonogestrel by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• etravirine

  Contraindicated (1)etravirine 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 (2)lumacaftor/ivacaftor, etravirine. affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .
  
  lumacaftor/ivacaftor, etravirine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• everolimus

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of everolimus 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.

• fedratinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• fentanyl

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fentanyl 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.

• fentanyl intranasal

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fentanyl intranasal 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.

• fentanyl transdermal

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fentanyl transdermal 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.

• fentanyl transmucosal

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fentanyl transmucosal 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.

• fexinidazole

  Serious - Use Alternative (1)lumacaftor/ivacaftor will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• finerenone

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

• fluoxetine

  Monitor Closely (1)lumacaftor/ivacaftor, fluoxetine. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• fluvastatin

  Monitor Closely (1)lumacaftor/ivacaftor, fluvastatin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• fosamprenavir

  Monitor Closely (1)fosamprenavir 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.

• fosphenytoin

  Contraindicated (1)fosphenytoin 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 (2)lumacaftor/ivacaftor, fosphenytoin. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, fosphenytoin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• fostamatinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fostemsavir

  Contraindicated (1)lumacaftor/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.

• ganaxolone

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• gefitinib

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

• glasdegib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glecaprevir/pibrentasvir

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

• glimepiride

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of glimepiride by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• glipizide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of glipizide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• glyburide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• grapefruit

  Monitor Closely (1)grapefruit 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.

• guanfacine

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• ibuprofen

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

• ibuprofen IV

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

• idelalisib

  Monitor Closely (1)idelalisib 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.

• ifosfamide

  Monitor Closely (2)lumacaftor/ivacaftor increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  lumacaftor/ivacaftor increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• imatinib

  Monitor Closely (2)imatinib 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, imatinib. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• imipramine

  Monitor Closely (1)lumacaftor/ivacaftor, imipramine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• indinavir

  Monitor Closely (1)indinavir 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.

• infigratinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  Monitor Closely (1)lumacaftor/ivacaftor, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• irinotecan liposomal

  Monitor Closely (1)lumacaftor/ivacaftor, irinotecan liposomal. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• isavuconazonium sulfate

  Contraindicated (1)lumacaftor/ivacaftor will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isoniazid

  Monitor Closely (1)isoniazid 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.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  Monitor Closely (1)itraconazole 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (2)ivosidenib will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  lumacaftor/ivacaftor will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ixazomib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• ketamine

  Monitor Closely (2)lumacaftor/ivacaftor, ketamine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
  
  lumacaftor/ivacaftor, ketamine. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• ketoconazole

  Monitor Closely (1)ketoconazole 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lacosamide

  Monitor Closely (1)lumacaftor/ivacaftor, lacosamide. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lansoprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, lansoprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• larotrectinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-livesMinor (1)larotrectinib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lefamulin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  Serious - Use Alternative (1)lumacaftor/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.

• lenacapavir

  Contraindicated (1)lumacaftor/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.

• leniolisib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levamlodipine

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levoketoconazole

  Monitor Closely (1)levoketoconazole 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levonorgestrel intrauterine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of levonorgestrel intrauterine by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• lonafarnib

  Contraindicated (1)lumacaftor/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.

• lopinavir

  Monitor Closely (1)lopinavir 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.

• lorlatinib

  Contraindicated (1)lumacaftor/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.Serious - Use Alternative (1)lorlatinib will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• losartan

  Monitor Closely (1)lumacaftor/ivacaftor, losartan. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lumateperone

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• mavacamten

  Contraindicated (1)lumacaftor/ivacaftor will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• medroxyprogesterone

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Contraceptirve failure possible. Use alternative if available.

• mestranol

  Monitor Closely (1)lumacaftor/ivacaftor, mestranol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• methsuximide

  Monitor Closely (1)lumacaftor/ivacaftor, methsuximide. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• methylprednisolone

  Monitor Closely (1)lumacaftor/ivacaftor decreases levels of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of corticosteroids may be required for desired clinical effect.

• midazolam

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of midazolam 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.

• midostaurin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  Monitor Closely (1)mifepristone will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, monitor efficacy and adjust dosages as necessary

• mitotane

  Contraindicated (1)mitotane 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.

• mobocertinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Monitor Closely (1)lumacaftor/ivacaftor, modafinil. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• montelukast

  Monitor Closely (2)lumacaftor/ivacaftor, montelukast. 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 decreases levels of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dose adjustment for montelukast is recommended.

• nafcillin

  Contraindicated (1)nafcillin 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.

• naldemedine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• nateglinide

  Monitor Closely (1)lumacaftor/ivacaftor, nateglinide. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• nefazodone

  Monitor Closely (1)nefazodone 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.

• nelfinavir

  Monitor Closely (2)nelfinavir 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, nelfinavir. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• neratinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• nevirapine

  Contraindicated (1)nevirapine 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.

• nicardipine

  Monitor Closely (1)nicardipine 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.

• nirmatrelvir

  Contraindicated (1)lumacaftor/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/ritonavir

  Contraindicated (1)lumacaftor/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.

• norethindrone

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone acetate

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone transdermal

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• oliceridine

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.

• olutasidenib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omeprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, omeprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• osilodrostat

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.

• osimertinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• ospemifene

  Monitor Closely (2)lumacaftor/ivacaftor, ospemifene. affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, ospemifene. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• oxcarbazepine

  Contraindicated (1)oxcarbazepine 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.

• pantoprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, pantoprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• pemigatinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pentamidine

  Monitor Closely (1)lumacaftor/ivacaftor, pentamidine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• pentobarbital

  Contraindicated (1)pentobarbital 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.

• pexidartinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenobarbital

  Contraindicated (1)phenobarbital 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, phenobarbital. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• phenytoin

  Contraindicated (1)phenytoin 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 (2)lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
  
  lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• pimavanserin

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

• pimozide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pimozide 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.

• pitolisant

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• polatuzumab vedotin

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• posaconazole

  Monitor Closely (1)posaconazole 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of posaconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pralsetinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• prednisone

  Monitor Closely (1)lumacaftor/ivacaftor decreases levels of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. A higher dose of corticosteroids may be required for desired clinical effect.

• pretomanid

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers.

• primidone

  Contraindicated (1)primidone 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.

• progesterone micronized

  Monitor Closely (1)lumacaftor/ivacaftor, progesterone micronized. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• promethazine

  Monitor Closely (1)lumacaftor/ivacaftor, promethazine. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• propofol

  Monitor Closely (2)lumacaftor/ivacaftor, propofol. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
  
  lumacaftor/ivacaftor, propofol. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• quinidine

  Monitor Closely (1)quinidine 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.Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of quinidine 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.

• quinine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of quinine 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.

• rabeprazole

  Monitor Closely (2)lumacaftor/ivacaftor will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.
  
  lumacaftor/ivacaftor, rabeprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• repaglinide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Repaglinide is metabolized by CYP3A and CYP2C8. Lumacaftor /ivacaftor is a strong CYP3A4 inducer and may also induce CYP2C8.

• ribociclib

  Serious - Use Alternative (2)ribociclib will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  lumacaftor/ivacaftor will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

• rifabutin

  Contraindicated (1)rifabutin 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.

• rifampin

  Contraindicated (1)rifampin 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, rifampin. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• rifapentine

  Contraindicated (1)rifapentine 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.

• rimegepant

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ripretinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

• ritonavir

  Monitor Closely (1)ritonavir 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.

• rolapitant

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

• saquinavir

  Monitor Closely (1)saquinavir 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.

• selegiline

  Monitor Closely (1)lumacaftor/ivacaftor, selegiline. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

• selexipag

  Monitor Closely (1)lumacaftor/ivacaftor will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• selumetinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sertraline

  Monitor Closely (2)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.
  
  lumacaftor/ivacaftor, sertraline. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• siponimod

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sirolimus 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.

• sofosbuvir/velpatasvir

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

• sonidegib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

• sotorasib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sparsentan

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• St John's Wort

  Contraindicated (1)St John's Wort 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.

• stiripentol

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.

• sufentanil SL

  Monitor Closely (1)lumacaftor/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.

• sulfadiazine

  Monitor Closely (1)lumacaftor/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. .

• sulfisoxazole

  Monitor Closely (1)lumacaftor/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. .

• tacrolimus

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of tacrolimus 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.

• tamoxifen

  Monitor Closely (1)lumacaftor/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. .

• tazemetostat

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tinidazole

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir 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.

• tivozanib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tofacitinib

  Monitor Closely (1)lumacaftor/ivacaftor, tofacitinib. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• tolazamide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of tolazamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• tolbutamide

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Sulfonylureas are CYP2C9 substrates. Lumacaftor/ivacaftor has the potential to induce CYP2C9.

• torsemide

  Monitor Closely (1)lumacaftor/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. .

• trabectedin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• triazolam

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of triazolam 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.

• trimethoprim

  Monitor Closely (1)lumacaftor/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. .

• trimipramine

  Monitor Closely (1)lumacaftor/ivacaftor, trimipramine. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• tucatinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.

• ubrogepant

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• upadacitinib

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

• valbenazine

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

• venetoclax

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of venetoclax with strong or moderate CYP3A inducers. Consider alternative treatment with agents that have less CYP3A induction.

• voclosporin

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Monitor Closely (4)voriconazole 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 will decrease the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  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. .

• voxelotor

  Serious - Use Alternative (2)lumacaftor/ivacaftor will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).
  
  voxelotor will increase the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (1)lumacaftor/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.

• zafirlukast

  Monitor Closely (1)lumacaftor/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. .

• zanubrutinib

  Monitor Closely (1)lumacaftor/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.