AdultPediatricDosage Forms & Strengths elexacaftor/tezacaftor/ivacaftor fixed-dose tablet copackaged with ivacaftor tablet 100mg/50mg/75mg plus ivacaftor 150 mg Cystic Fibrosis Indicated for cystic fibrosis in patients who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population If genotype unknown, use FDA-cleared CF mutation test to confirm presence of at least one F508del mutation or a mutation that is responsive based on in vitro data 2 fixed-dose tablets (elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg) PO qAM and 1 ivacaftor 150-mg tablet PO qPM; ~12 hr apart Dosage Modifications Renal impairment Mild or moderate (eGFR 30 to <90 mL/min/1.73 m2): No dosage adjustment required Severe (eGFR <30 mL/min/1.73 m2) or ESRD: Use caution Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Moderate (Child-Pugh B): Not recommended unless benefit exceeds risk; if used administer as follows Day 1 2 tab (100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor) qAM; no evening dose of ivacaftor tablet Day 2 1 tab (100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor qAM; no evening dose of ivacaftor tablet Continue alternating Day 1 and Day 2 dosing thereafter Monitor liver function tests Severe (Child-Pugh C): Do not use Coadministration with moderate or strong CYP3A inhibitors Moderate CYP3A inhibitors Day 1: 2 tab (100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor) qAM Day 2: 1 tab 150 mg ivacaftor qAM No evening dose of ivacaftor tablet Strong CYP3A inhibitors 2 tab (100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor) qAM twice a week; approximately 3-4 days apart No evening dose of ivacaftor tablet Elevated liver function tests Interrupt therapy ALT or AST >5x ULN, or ALT or AST >3x ULN with bilirubin >2x ULN Consider benefits and risks of resuming treatment following resolution of transaminase elevations Dosing Considerations Laboratory monitoring Assess liver function tests (ALT, AST, and bilirubin) for all patients before initiating, q3Months during the first year, and annually thereafter For patients with history of hepatobiliary disease or liver function test elevations, consider more frequent monitoring Dosage Forms & Strengths elexacaftor/tezacaftor/ivacaftor fixed-dose tablet copackaged with ivacaftor tablet 100mg/50mg/75mg plus ivacaftor 150 mg oral granules 80mg/40mg/60mg plus unit-dose ivacaftor 59.5 mg 100mg/50mg/75mg plus unit-dose ivacaftor 75 mg Cystic Fibrosis Indicated for cystic fibrosis in children aged ≥2 years who have at least 1 F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population If genotype unknown, use FDA-cleared CF mutation test to confirm presence of at least one F508del mutation or a mutation that is responsive based on in vitro data NOTE: Morning and evening should be taken ~12 hr apart ≥2 to <6 years <14 kg: 1 packet containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg oral granules qAM and 1 packet containing ivacaftor 59.5 mg oral granules PO qPM ≥14 kg: 1 packet containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg oral granules qAM and 1 packet containing ivacaftor 75 mg oral granules PO qPM 6 to <12 years <30 kg: 2 tab each containing 50 mg elexacaftor/ 25 mg tezacaftor/ 37.5 mg ivacaftor qAM and 1 ivacaftor 75-mg tab PO qPM ≥30 kg: 2 tab each containing 100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor qAM and 1 ivacaftor 150-mg tab PO qPM ≥12 years 2 fixed-dose tablets (elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg) PO qAM and 1 ivacaftor 150-mg tablet PO qPM Dosage Modifications Renal impairment Mild or moderate (eGFR 30 to <90 mL/min/1.73 m2): No dosage adjustment required Severe (eGFR <30 mL/min/1.73 m2) or ESRD: Use caution Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Moderate (Child-Pugh B): Not recommended unless benefit exceeds risk; if used administer as follows NOTE: No evening ivacaftor tablet dose for all ages ≥2 to <6 years and <14 kg Weekly schedule Days 1-3, 5-6: 1 packet containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg oral granules qAM Days 4 and 7: No dose ≥2 to <6 years and ≥14 kg Weekly schedule Days 1-3, 5-6: 1 packet containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg oral granules qAM Days 4 and 7: No dose ≥6 to <12 years and <30 kg Alternating daily schedule Day 1: 2 tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) qAM Day 2: 1 tablet of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg qAM ≥6 to <12 years and ≥30 kg Alternating daily schedule Day 1: 2 tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) qAM Day 2: 1 tablet elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg qAM ≥12 years Alternating daily schedule Day 1: 2 tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) qAM Day 2: 1 tablet elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg qAM Severe (Child-Pugh C): Do not use Coadministration with moderate CYP3A inhibitors Alternating daily dose schedules as follows NOTE: No evening ivacaftor tablet dose for all ages ≥2 to <6 years and <14 kg Day 1: 1 packet containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg qAM Day 2: 1 packet containing ivacaftor 59.5 mg oral granules qAM ≥2 to <6 years and ≥14 kg Day 1: 1 packet containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg qAM Day 2: 1 packet containing ivacaftor 75 mg oral granules qAM ≥6 to <12 years and <30 kg Day 1: 2 tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg qAM Day 2: 1 tablet of ivacaftor 75 mg qAM ≥6 years and ≥30 kg Day 1: 2 tablets elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) qAM Day 2: 1 tablet of ivacaftor 150 mg qAM Coadministration with strong CYP3A inhibitors Twice weekly dosing NOTE: No evening ivacaftor tablet dose for all ages ≥2 to <6 years and <14 kg 1 packet containing elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg in AM twice a week, ~3-4 days apart ≥2 to <6 years and ≥14 kg 1 packet containing elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg in AM twice a week, ~3-4 days apart ≥6 to <12 years and <30 kg 2 tablets of elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg (total dose of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in AM twice a week, ~3-4 days apart ≥6 and ≥30 kg 2 tablets of elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (total dose of elexacaftor 200 mg/tezacaftor 100 mg/ivacaftor 150 mg) in AM twice a week, ~3-4 days apart Elevated liver function tests Interrupt therapy ALT or AST >5x ULN, or ALT or AST >3x ULN with bilirubin >2x ULN Consider benefits and risks of resuming treatment following resolution of transaminase elevations Dosing Considerations Laboratory monitoring Assess liver function tests (ALT, AST, and bilirubin) for all patients before initiating, q3Months during the first year, and annually thereafter For patients with history of hepatobiliary disease or liver function test elevations, consider more frequent monitoring Interaction CheckerEnter a drug name and elexacaftor/tezacaftor/ivacaftorNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (1)lonafarnibivacaftor will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated. Serious - Use Alternative (62)abametapirabametapir increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.abametapir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.amobarbitalamobarbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.apalutamideapalutamide will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.apalutamideapalutamide will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.avapritinibivacaftor will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.bosentanbosentan will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.bosentan decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).butabarbitalbutabarbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.carbamazepinecarbamazepine decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).butalbitalbutalbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.carbamazepinecarbamazepine will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.chloramphenicolchloramphenicol will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.cimetidineivacaftor increases levels of cimetidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.colchicineivacaftor increases levels of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid use of colchicine with P-gp inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment. .dabigatranivacaftor increases levels of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min.dabrafenibdabrafenib will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.dexamethasonedexamethasone will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.dexamethasone decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).efavirenzefavirenz will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.efavirenz, ivacaftor. Other (see comment). Avoid or Use Alternate Drug. Comment: Efavirenz decreases levels of ivacaftor by CYP enzyme induction; whereas, ivacaftor increases levels of efavirenz by inhibiting CYP3A4 .elacestrantivacaftor will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.enzalutamideenzalutamide will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.enzalutamideenzalutamide will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.eslicarbazepine acetateeslicarbazepine acetate will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.eslicarbazepine acetate will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold)etravirineetravirine decreases levels of ivacaftor by affecting hepatic/intestinal enzyme