elexacaftor/tezacaftor/ivacaftor (Rx)

Brand and Other Names:Trikafta
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Dosing & Uses

AdultPediatric

Dosage 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
    • Administer two elexacaftor/tezacaftor/ivacaftor qAM and omit evening ivacaftor
  • Day 2
    • Administer one elexacaftor/tezacaftor/ivacaftor qAM and omit evening ivacaftor
  • 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
    • Alternate daily dose between 2 fixed-dose tablets qAM and 1 ivacaftor 150-mg tablet qAM
    • Do not take an evening dose
  • Strong CYP3A inhibitors
    • Take 2 fixed-dose tablets PO twice weekly, ~3-4 days apart
    • Do not take an evening dose

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

Cystic Fibrosis

Indicated for cystic fibrosis in children aged ≥6 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

<6 years:

  • Not established

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 ~12 hr apart
  • ≥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 hr apart

≥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; ~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
    • Administer two elexacaftor/tezacaftor/ivacaftor qAM and omit evening ivacaftor
  • Day 2
    • Administer one elexacaftor/tezacaftor/ivacaftor qAM and omit evening ivacaftor
  • 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
    • Alternate daily dose between 2 fixed-dose tablets qAM and 1 ivacaftor 150-mg tablet qAM
    • Do not take an evening dose
  • Strong CYP3A inhibitors
    • Take 2 fixed-dose tablets PO twice weekly, ~3-4 days apart
    • Do not take an evening dose

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
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Interactions

Interaction Checker

and elexacaftor/tezacaftor/ivacaftor

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            Contraindicated (1)

            • lonafarnib

              ivacaftor will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            Serious - Use Alternative (55)

            • abametapir

              abametapir 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.

            • amobarbital

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

            • apalutamide

              apalutamide 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.

            • apalutamide

              apalutamide 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.

            • avapritinib

              ivacaftor 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.

            • bosentan

              bosentan 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).

            • butabarbital

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

            • carbamazepine

              carbamazepine 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).

            • butalbital

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

            • carbamazepine

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

            • chloramphenicol

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

            • cimetidine

              ivacaftor 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.

            • colchicine

              ivacaftor 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. .

            • dabigatran

              ivacaftor 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.

            • dabrafenib

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

            • dexamethasone

              dexamethasone 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).

            • efavirenz

              efavirenz 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 .

            • enzalutamide

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

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

            • eslicarbazepine acetate

              eslicarbazepine 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)

            • etravirine

              etravirine 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).

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

            • fexinidazole

              fexinidazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              fexinidazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosphenytoin

              fosphenytoin 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).

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

            • grapefruit

              grapefruit increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid grapefruit, grapefruit juice, or Seville oranges while taking ivacaftor.

              grapefruit will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of tezacaftor with grapefruit juice, which contains 1 or more components that moderately inhibit CYP3A, may increase exposure of tezacaftor. Avoid food containing grapefruit or Seville oranges.

            • infigratinib

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

            • ivosidenib

              ivosidenib will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ivosidenib

              ivosidenib will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lemborexant

              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.

            • lonafarnib

              lonafarnib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • lurbinectedin

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

            • midazolam intranasal

              ivacaftor will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • mifepristone

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

            • mitotane

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

            • mobocertinib

              ivacaftor will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • nafcillin

              nafcillin decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

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

            • nevirapine

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

              nevirapine, ivacaftor. Other (see comment). Avoid or Use Alternate Drug. Comment: Nevirapine decreases levels of ivacaftor by CYP enzyme induction; whereas, ivacaftor increases levels of efavirenz by inhibiting CYP3A4.

            • oxcarbazepine

              oxcarbazepine 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).

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

            • pemigatinib

              ivacaftor will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pentobarbital

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

            • pentobarbital

              pentobarbital 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).

            • pexidartinib

              ivacaftor will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • phenobarbital

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

              phenobarbital 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).

            • phenytoin

              phenytoin 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).

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

            • primidone

              primidone 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).

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

            • rifabutin

              rifabutin 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).

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

            • rifampin

              rifampin 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).

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

            • rifapentine

              rifapentine 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).

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

            • rimegepant

              ivacaftor will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • St John's Wort

              St John's Wort will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • secobarbital

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

            • selumetinib

              ivacaftor will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • siponimod

              ivacaftor will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • St John's Wort

              St John's Wort 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).

            • tazemetostat

              ivacaftor will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • tucatinib

              tucatinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              tucatinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • voxelotor

              voxelotor will increase the level or effect of 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.

              voxelotor will increase the level or effect of tezacaftor 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 (216)

            • acetaminophen

              acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • acetaminophen IV

              acetaminophen IV increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • acetaminophen rectal

              acetaminophen rectal increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • acetazolamide

              acetazolamide increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • aliskiren

              ivacaftor increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • alvimopan

              ivacaftor increases levels of alvimopan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ambrisentan

              ivacaftor increases levels of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • amiodarone

              amiodarone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              ivacaftor increases levels of amiodarone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              amiodarone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • amitriptyline

              ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • aprepitant

              aprepitant will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • anastrozole

              anastrozole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • armodafinil

              armodafinil increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • atazanavir

              atazanavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              atazanavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • atogepant

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

            • berotralstat

              tezacaftor increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              elexacaftor increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • atorvastatin

              ivacaftor increases levels of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • azelastine

              azelastine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • belzutifan

              belzutifan will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • bendamustine

              ivacaftor increases levels of bendamustine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • betamethasone

              betamethasone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • betamethasone topical

              betamethasone topical increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • betrixaban

              ivacaftor increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • bicalutamide

              bicalutamide will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              bicalutamide increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Reduce ivacaftor dose to 150 mg once daily when coadministered with moderate CYP3A4 inhibitors.

            • budesonide

              ivacaftor increases levels of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • cenobamate

              cenobamate will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • carvedilol

              ivacaftor increases levels of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • cenobamate

              cenobamate will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              ivacaftor increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              ceritinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ceritinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • clarithromycin

              clarithromycin will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • chlorzoxazone

              chlorzoxazone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • cimetidine

              cimetidine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification. .

            • ciprofloxacin

              ivacaftor increases levels of ciprofloxacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              ciprofloxacin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • clarithromycin

              clarithromycin will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • clemastine

              clemastine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • clozapine

              clozapine will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              clozapine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • cobicistat

              cobicistat will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              cobicistat will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • conivaptan

              conivaptan will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              conivaptan will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • crizotinib

              crizotinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              crizotinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • crofelemer

              crofelemer increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclosporine

              cyclosporine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • cyclosporine

              cyclosporine will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. 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.

            • dabrafenib

              dabrafenib will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • danazol

              danazol increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • darunavir

              darunavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              darunavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • daunorubicin

              ivacaftor increases levels of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • desipramine

              desipramine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • desipramine

              desipramine will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • desloratadine

              ivacaftor increases levels of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • desvenlafaxine

              desvenlafaxine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • dexamethasone

              ivacaftor increases levels of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • dexmedetomidine

              dexmedetomidine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • diazepam intranasal

              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

              diclofenac increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • diclofenac topical

              diclofenac topical increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • digoxin

              ivacaftor increases levels of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • diltiazem

              diltiazem will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When tezacaftor/ivacaftor is combined with moderate CYP3A4 inhibitors, administer tezacaftor/ivacaftor (100 mg/150 mg) in the morning, every other day. Administer ivacaftor 150 mg alonein the evening, every other day, on alternate days from tezacaftor/ivacaftor.

              diltiazem will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • disulfiram

              disulfiram increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • doxycycline

              doxycycline will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • docetaxel

              ivacaftor increases levels of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • doxorubicin

              ivacaftor increases levels of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • dronedarone

              dronedarone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              dronedarone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • drospirenone

              drospirenone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • duvelisib

              duvelisib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • duvelisib

              duvelisib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • edoxaban

              ivacaftor will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

            • efavirenz

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

            • elagolix

              elagolix decreases levels of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              elagolix decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              ivacaftor increases levels of eletriptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • encorafenib

              encorafenib, tezacaftor. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • encorafenib

              encorafenib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • entrectinib

              ivacaftor will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • erythromycin base

              erythromycin base will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              erythromycin base will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • erythromycin ethylsuccinate

              ivacaftor increases levels of erythromycin ethylsuccinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              erythromycin ethylsuccinate will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              erythromycin ethylsuccinate will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              ivacaftor increases levels of erythromycin lactobionate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              erythromycin lactobionate will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              erythromycin stearate will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              ivacaftor increases levels of erythromycin stearate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • estradiol

              ivacaftor increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • fedratinib

              fedratinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • etoposide

              ivacaftor increases levels of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • everolimus

              ivacaftor increases levels of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • fedratinib

              fedratinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • fexofenadine

              ivacaftor increases levels of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • finerenone

              ivacaftor will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fluconazole

              fluconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              fluconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • fluoxetine

              fluoxetine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • fluvoxamine

              fluvoxamine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dose when coadministered with a moderate CYP3A4 inhibitor

            • fluvastatin

              fluvastatin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • fluvoxamine

              fluvoxamine will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with CYP3A4 inhibitors; see ivacaftor prescribing information for precise dosage information

            • fosamprenavir

              fosamprenavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of fosamprenavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              fosamprenavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • fostamatinib

              fostamatinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • haloperidol

              haloperidol will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • glecaprevir/pibrentasvir

              ivacaftor will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • glyburide

              ivacaftor increases levels of glyburide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              glyburide increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • haloperidol

              haloperidol will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • hydralazine

              hydralazine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • hydrocortisone

              ivacaftor increases levels of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • idelalisib

              idelalisib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              idelalisib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • iloperidone

              iloperidone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              iloperidone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • imatinib

              imatinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              imatinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • indinavir

              indinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              indinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • irbesartan

              irbesartan increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • isoniazid

              isoniazid will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • irinotecan

              ivacaftor increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • irinotecan liposomal

              ivacaftor increases levels of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • isavuconazonium sulfate

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

            • isoniazid

              isoniazid will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • istradefylline

              istradefylline will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. 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. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              istradefylline will increase the level or effect of tezacaftor 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 will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              itraconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivermectin

              ivacaftor increases levels of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ketoconazole

              ketoconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • ketoconazole

              ketoconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • lapatinib

              lapatinib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              lapatinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • larotrectinib

              larotrectinib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • lopinavir

              lopinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • lefamulin

              ivacaftor will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • letermovir

              letermovir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • levamlodipine

              ivacaftor will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • lidocaine

              ivacaftor increases levels of lidocaine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              ivacaftor increases effects of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lomustine

              lomustine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • loperamide

              ivacaftor increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • lopinavir

              lopinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • loratadine

              ivacaftor increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • lorlatinib

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

              lorlatinib will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              ivacaftor increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • metronidazole

              metronidazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • maraviroc

              ivacaftor increases levels of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • mefloquine

              ivacaftor increases levels of mefloquine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • methimazole

              methimazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • methoxsalen

              methoxsalen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • methylprednisolone

              ivacaftor increases levels of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • metronidazole

              metronidazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • micafungin

              micafungin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • mifepristone

              mifepristone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • mitomycin

              ivacaftor increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • mitotane

              mitotane decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • mitoxantrone

              mitoxantrone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • morphine

              ivacaftor increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • naldemedine

              ivacaftor increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

            • nefazodone

              nefazodone will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              nefazodone will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • nelfinavir

              ivacaftor increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              nelfinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              nelfinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              netupitant/palonosetron will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • nicardipine

              nicardipine will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • nilotinib

              ivacaftor increases levels of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • nintedanib

              ivacaftor increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .

            • nizatidine

              nizatidine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • olanzapine

              olanzapine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • oliceridine

              ivacaftor will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • ondansetron

              ivacaftor increases levels of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • orphenadrine

              orphenadrine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • oxybutynin

              oxybutynin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • oxybutynin topical

              oxybutynin topical increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • oxybutynin transdermal

              oxybutynin transdermal increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • paclitaxel

              ivacaftor increases levels of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • paclitaxel protein bound

              ivacaftor increases levels of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • paroxetine

              paroxetine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • pazopanib

              ivacaftor increases levels of pazopanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • pentamidine

              pentamidine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • pilocarpine

              pilocarpine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • posaconazole

              ivacaftor increases levels of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              posaconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              posaconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • pravastatin

              ivacaftor increases levels of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              pravastatin increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • prednisone

              ivacaftor increases levels of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • progesterone intravaginal gel

              progesterone intravaginal gel increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • progesterone micronized

              progesterone micronized increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • propofol

              propofol increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • quinidine

              ivacaftor increases levels of quinidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ranolazine

              ivacaftor increases levels of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ribociclib

              ribociclib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ribociclib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • rifampin

              ivacaftor increases levels of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ritonavir

              ritonavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • rifaximin

              ivacaftor increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • rimegepant

              ivacaftor will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • risperidone

              ivacaftor increases levels of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              risperidone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • ritonavir

              ritonavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • rucaparib

              rucaparib will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              rucaparib will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • saquinavir

              saquinavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              saquinavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              ivacaftor increases levels of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • saxagliptin

              ivacaftor increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • schisandra

              schisandra will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • selegiline

              selegiline increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • sertraline

              sertraline will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              sertraline will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • silodosin

              ivacaftor increases levels of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • stiripentol

              stiripentol, tezacaftor. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • simvastatin

              ivacaftor increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • sirolimus

              ivacaftor increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • sitagliptin

              ivacaftor increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • stiripentol

              stiripentol will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • sulconazole

              sulconazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • tacrolimus

              ivacaftor increases levels of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • talazoparib

              ivacaftor will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • tamoxifen

              tamoxifen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • tazemetostat

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

              tazemetostat will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              tecovirimat will decrease the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • temsirolimus

              ivacaftor increases levels of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • tetracycline

              tetracycline will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • teniposide

              ivacaftor increases levels of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • testosterone

              ivacaftor increases levels of testosterone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

              testosterone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • testosterone buccal system

              testosterone buccal system increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • testosterone topical

              testosterone topical increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • tipranavir

              tipranavir will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              tipranavir will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

            • tolvaptan

              ivacaftor increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • verapamil

              verapamil will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • topotecan

              ivacaftor increases levels of topotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • tranylcypromine

              tranylcypromine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • valproic acid

              valproic acid increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • venetoclax

              ivacaftor increases levels of venetoclax by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • verapamil

              verapamil will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • vinblastine

              ivacaftor increases levels of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • vincristine

              ivacaftor increases levels of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • vincristine liposomal

              ivacaftor increases levels of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • voclosporin

              ivacaftor will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

            • voriconazole

              voriconazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

              voriconazole will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • zafirlukast

              zafirlukast increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • zanubrutinib

              ivacaftor will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            • ziprasidone

              ziprasidone increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            Minor (0)

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              Adverse Effects

              >10%

              Headache (17%)

              Upper respiratory tract infection (16%)

              Abdominal pain (14%)

              Diarrhea (13%)

              1-10%

              Rash (10%)

              Increased ALT (10%)

              Increased AST (9%)

              Increased BUN (9%)

              Nasal congestion (9%)

              Rhinorrhea (8%)

              Rhinitis (7%)

              Influenza (7%)

              Sinusitis (5%)

              Increased bilirubin (5%)

              2 to <5%

              • Flatulence
              • Abdominal distension
              • Conjunctivitis
              • Pharyngitis
              • Respiratory tract infection
              • Tonsillitis
              • Urinary tract infection
              • Increased C-reactive protein
              • Hypoglycemia
              • Dizziness
              • Dysmenorrhea
              • Acne
              • Eczema
              • Pruritus
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              Warnings

              Contraindications

              None

              Cautions

              Noncongenital lens opacities reported with ivacaftor-containing regimens; other risk factors were present in some cases (eg, corticosteroid use, radiation exposure); a possible risk attributable to treatment with ivacaftor cannot be excluded

              Hormonal contraceptives may play a role in occurrence of rash; for patients taking hormonal contraceptives who develop rash, consider interrupting therapy and hormonal contraceptives; following the resolution of rash, consider resuming therapy without the hormonal contraceptives; if rash does not recur, resumption of hormonal contraceptives can be considered

              Elevated transaminases and hepatic injury

              • Elevated liver transaminases and bilirubin levels observed; liver failure leading to transplantation reported in a patient with cirrhosis and portal hypertension while receiving treatment
              • Avoid use in patients with pre-existing advanced liver disease (eg, as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless benefits expected to outweigh risks; if used in these patients, they should be closely monitored after initiation of treatment
              • In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including patients without a history of pre-existing liver disease
              • Measure levels before initiating, q3Months during first year, and annually thereafter; consider more frequent monitoring for those with history of hepatic disease; interrupt dosing for significant elevations

              Drug interaction overview

              • CYP3A inhibitors or inducers
                • Coadministration with moderate or strong CYP3A inhibitors increases systemic exposure of elexacaftor/tezacaftor/ivacaftor; dosage adjustment is required if coadministered
                • Coadministration with strong CYP3A inducers is not recommended; ivacaftor systemic exposure is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease if coadministered with a strong CYP3A inducer
              • Potential for elexacaftor/tezacaftor/ivacaftor to affect other drugs
                • Ivacaftor may inhibit CYP2C9; monitor INR if coadministered with warfarin; caution with other CYP2C9 substrates (eg, glimepiride, glipizide)
                • Coadministration of ivacaftor or tezacaftor/ivacaftor with digoxin, a sensitive P-gp substrate, increased digoxin AUC by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor
                • Elexacaftor and its active metabolite (M23-ELX) inhibit uptake by OATP1B1 and OATP1B3 in vitro; coadministration may increase exposures of drugs that are substrates of these transporters (eg, statins, glyburide, nateglinide, repaglinide)
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              Pregnancy & Lactation

              Pregnancy

              Human data are limited and incomplete from clinical trials on the use of elexacaftor/tezacaftor/ivacaftor or its individual components in pregnant women to inform a drug-associated risk

              Although there are no animal reproduction studies with the concomitant administration of elexacaftor, tezacaftor, and ivacaftor, separate reproductive and developmental studies were conducted with each active component in pregnant rats and rabbits

              Animal data

              • In animal embryofetal development studies, oral administration of elexacaftor to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse developmental effects at doses that produced maternal exposures up to ~2 times the exposure at the maximum recommended human dose (MRHD) in rats and 4 times the MRHD in rabbits

              Lactation

              No data are available regarding the presence of elexacaftor, tezacaftor, or ivacaftor in human milk, the effects on the breastfed infant, or the effects on milk production.

              Elexacaftor, tezacaftor, and ivacaftor are excreted into the milk of lactating rats

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Elexacaftor and tezacaftor bind to different sites on the cystic fibrosis transmembrane conductance regulator (CFTR) protein and have an additive effect in facilitating the cellular processing and trafficking of F508del-CFTR to increase the amount of CFTR protein delivered to the cell surface compared with either molecule alone

              Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface

              Absorption

              Absolute bioavailability

              • Elexacaftor: 80%
              • Tezacaftor: Not determined
              • Ivacaftor: Not determined

              Peak plasma time

              • Elexacaftor: 6 hr
              • Tezacaftor: 3 hr
              • Ivacaftor: 4 hr

              Peak plasma concentration

              • Elexacaftor: 8.7 mcg/ml
              • Tezacaftor: 6.8 mcg/mL
              • Ivacaftor: 1.2 mcg/mL

              AUC

              • Elexacaftor: 162 mcg⋅h/mL
              • Tezacaftor: 94.5 mcg⋅h/mL
              • Ivacaftor: 11.7 mcg⋅h/mL

              Time to steady-state

              • Elexacaftor: Within 14 days
              • Tezacaftor: Within 8 days
              • Ivacaftor: Within 3-5 days

              Distribution

              Protein bound

              • Elexacaftor: >99%
              • Tezacaftor: ~99%
              • Ivacaftor: ~99%

              Vd

              • Elexacaftor: 53.7 L
              • Tezacaftor: 82 L
              • Ivacaftor: 293 L

              Metabolism

              Elexacaftor

              • Primary pathway: CYP3A4/5
              • Active metabolite: M23-ELX
              • Metabolite potency relative to parent: Similar

              Tezacaftor

              • Primary pathway: CYP3A4/5
              • Active metabolite: M1-TEZ
              • Metabolite potency relative to parent: Similar

              Ivacaftor

              • Primary pathway: CYP3A4/5
              • Active metabolite: M1-IVA
              • Metabolite potency relative to parent: ~1/6

              Elimination

              Half-life

              • Elexacaftor: 29.8 hr
              • Tezacaftor: 17.4 hr
              • Ivacaftor: 15 hr

              Clearance

              • Elexacaftor: 1.18 L/hr
              • Tezacaftor: 0.79 L/hr
              • Ivacaftor: 10.2 L/hr

              Excretion

              • Elexacaftor: Feces (87.3%; primarily as metabolites); urine (0.23%)
              • Tezacaftor: Feces (72%; unchanged or as M2-TEZ); urine (14%; 0.79% unchanged)
              • Ivacaftor: Feces (87.8%); urine (6.6%)

              Pharmacogenomics

              CFTR gene mutations that produce CFTR protein and are responsive to ivacaftor

              • 3141del9, 546insCTA
              • A46D, A120T, A234D, A349V, A455E, A1006E, A1067T
              • D110E, D110H, D192G, D443Y, D4437;G576A;R668C, D579G, D614G, D836Y, D924N, D979V, D1152H, D1270N
              • E56K, E60K, E92K, E116K, E193K, E403D, E588V, E822K
              • F191V, F311del, F311L, F508C, F508C;S1251N, F508del, F575Y, F1016S, F1052V, F1074L, F1099L
              • G27R, G85E, G126D, G178E, G178R, G194R, G194V, G314E, G463V, G480C, G551D, G551S, G576A, G576A;R668C, G970D, G1061R, G1069R, G1244E, G1249R, G1349D
              • H939R, H199Y, H939R, H1054D, H1085P, H1085R, H1375P
              • I148T, I175V, I336K, I502T, I601F, I618T I807M, I980K, I1027T, I1139V, I1269N, I1366N
              • K1060T
              • L15P, L165S, L206W, L320V, L346P, L453S, L967S, L997F, L1077P, L1324P, L1335P, L1480P
              • M152V, M265R, M952I, M952T, M1101K
              • P5L, P67L, P205S, P574H
              • Q98R, Q237E, Q237H, Q359R, Q1291R
              • R31L, R74W, R74W;D1270N, R74W;V201M, R74W;V201M;D127N, R75Q, R117C, R117G, R117H, R117L, R117P, R170H, R258G, R334L, R334Q, R347H, R347L, R347P, R352Q, R352W, R553Q, R668C, R751L, R792G, R933G, R1066H, R1070Q, R1070W, R1162L, R1283M, R1283S
              • S13F, S341P, S364P, S492F S549N, S549R, S737F, S589N, S737F, S912L, S945L, S977F, S1159F, S1159P, S1251N, S1255P
              • T338I, T1036N, T1053I
              • V201M, V232D, V456F, V562I, V754M, V1153E, V1240G, V1293G
              • W361R, W1098C, W1282R
              • Y109N, Y161D, Y161S, Y563N, Y1014C, Y1032C
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              Administration

              Oral Administration

              Swallow tablets whole; do not chew, crush, or split

              Take with fat-containing food (eg, meals or snacks prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, or meats)

              Missed dose

              • ≤6 hr since missing a morning or evening dose: Take missed dose as soon as possible and continue on the original schedule
              • >6 hr since a missed morning dose: Take missed dose as soon as possible and NOT take the evening dose; the next scheduled morning dose should be taken at the usual time
              • >6 hr since a missed evening dose: Do NOT take the missed dose; the next scheduled morning dose should be taken at the usual time
              • Morning and evening doses should not be taken at the same time

              Storage

              Store at 68-77ºF (20-25ºC); excursions permitted to 59-86ºF (15-30ºC)

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.