encorafenib (Rx)

Brand and Other Names:Braftovi

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 75mg

Melanoma

Indicated in combination with binimetinib for unresectable or metastatic melanoma in patients with a BRAF V600E or V600K mutation, as detected by an FDA-approved test

450 mg PO qDay in combination with binimetinib

Continue until disease progression or unacceptable toxicity

See binimetinib drug monograph for recommended dosing information

Non-Small Cell Lung Cancer

Indicated in combination with binimetinib for unresectable or metastatic non-small cell lung cancer (NSCLC) in patients with a BRAF V600E mutation, as detected by an FDA-approved test

450 mg PO qDay in combination with binimetinib

Continue until disease progression or unacceptable toxicity

See binimetinib drug monograph for recommended dosing information

Metastatic Colorectal Cancer

Indicated in combination with cetuximab for metastatic colorectal cancer (CRC) in patients with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy

300 mg PO qDay in combination with cetuximab

Continue until disease progression or unacceptable toxicity

See cetuximab drug monograph for recommended dosing information

Dosage Modifications

Recommended dose reductions for encorafenib for adverse reactions

  • Melanoma or NSCLC
    • If binimetinib is withheld, reduce encorafenib to a maximum dose of 300 mg/day until binimetinib is resumed
    • First dose reduction: 300 mg PO qDay
    • Second dose reduction: 225 mg PO qDay
    • Unable to tolerate 225 mg PO qDay: Permanently discontinue
  • Metastatic colorectal cancer
    • If cetuximab is discontinued, discontinue encorafenib
    • First dose reduction: 225 mg PO qDay
    • Second dose reduction: 150 mg PO qDay
    • Unable to tolerate 150 mg PO qDay: Permanently discontinue

New primary malignancies

  • Noncutaneous RAS mutation-positive malignancies: Permanently discontinue

Uveitis

  • Grade 1 or 2 (no response to specific ocular therapy), or Grade 3 uveitis: Withhold for up to 6 weeks; if uveitis resolves, resume at same or reduced dose; permanently discontinue if uveitis does not improve
  • Grade 4: Permanently discontinue

Cardiomyopathy

  • Symptomatic congestive heart failure or absolute decrease in left ventricular ejection fraction (LVEF) >20% from baseline that is also below LLN
  • Reduce by 1 dose level if
    • LVEF improves to at least institutional LLN and absolute decrease to ≤10% compared to baseline, continue encorafenib at reduced dose
    • No improvement, withhold until improves to at least institutional LLN and absolute decrease to ≤10% compared to baseline and then resume at reduced dose or reduce dose an additional dose level

QT prolongation

  • QTcF >500 ms and ≤60 ms increase from baseline: Withhold until QTcF ≤500 ms, then resume at reduced dose; if >1 recurrence, permanently discontinue
  • QTcF >500 ms and >60 ms increase from baseline: Permanently discontinue

Hepatotoxicity

  • Grade 2 AST or ALT increased: Maintain dose; if no improvement within 4 weeks, withhold until improves to Grade <1 or baseline and then resume at same dose

  • Grade 3 or 4 AST or ALT increased
    • First occurrence Grade 3: Withhold for up to 4 weeks; if improves to Grade <1 or baseline, resume at reduced dose; if no improvement, permanently discontinue
    • First occurrence Grade 4: Permanently discontinue or withhold for up to 4 weeks; if improves to Grade <1 or to baseline, resume at reduced dose; if no improvement, permanently discontinue
    • Recurrent Grade 3: Consider permanently discontinuing
    • Recurrent Grade 4: Permanently discontinue

Dermatologic

  • Grade 2: If no improvement within 2 weeks, withhold until Grade 0-1; resume at same dose
  • Grade 3: Withhold until Grade <1; resume at same dose if first occurrence or reduce dose if recurrent
  • Grade 4: Permanently discontinue

Other adverse reactions, including hemorrhage

  • Recurrent Grade 2 or first occurrence of any Grade 3: Withhold for up to 4 weeks; if improves to Grade <1 or baseline, resume at reduced dose; if no improvement, permanently discontinue
  • First occurrence of any Grade 4: Permanently discontinue OR withhold for up to 4 weeks; if improves to Grade <1 or baseline, resume at reduced dose; if no improvement, permanently discontinue
  • Recurrent Grade 3: Consider permanently discontinuing
  • Recurrent Grade 4: Permanently discontinue

Coadministered strong or moderate CYP3A4 inhibitors

  • Avoid concurrent use of strong or moderate CYP3A4 inhibitors during treatment
  • Planned dose is based on the recommendations for dose reductions for adverse effects
  • After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose
  • Moderate CYP3A4 inhibitors
    • Planned dose (encorafenib 450 mg/day): Reduce to 225 mg/day
    • Planned dose (encorafenib 300 mg/day): Reduce to 150 mg/day
    • Planned dose (encorafenib 150 mg or 225 mg/day): Reduce to 75 mg/day
  • Strong CYP3A4 inhibitors
    • Planned dose (encorafenib 450 mg/day): Reduce to 150 mg/day
    • Planned dose (encorafenib 150, 225, or 300 mg/day): Reduce to 75 mg/day

Hepatic impairment

  • Mild (Child-Pugh A): No dose adjustment required
  • Moderate-to-severe (Child-Pugh B or C): No recommended dose established

Renal impairment

  • Mild-to-moderate (CrCl 30 to <90 mL/min): No dose adjustment required
  • Severe (CrCl <30 mL/min): A recommended dose has not been established

Dosing Considerations

Melanoma: Confirm presence of a BRAF V600E or V600K mutation in tumor specimens before initiating

NSCLC or CRC: Confirm presence of a BRAF V600E mutation in tumor specimens before initiating

NSCLC: If no mutation is detected in a plasma specimen, test tumor tissue

Information on FDA-approved tests for the detection of BRAF V600E or V600K mutations is available at: http://www.fda.gov/CompanionDiagnostics

Limitations of use

  • Not indicated for melanoma in patients with wild-type BRAF melanoma or wild-type BRAF CRC

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and encorafenib

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            Contraindicated (8)

            • doravirine

              encorafenib will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

            • dronedarone

              encorafenib and dronedarone both increase QTc interval. Contraindicated.

            • elagolix

              encorafenib will increase the level or effect of elagolix by Other (see comment). Contraindicated.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Monitor if isavuconazonium (a CYP3A4 substrate) is coadministered with encorafenib (a CYP3A4 inhibitor and inducer).

              encorafenib, isavuconazonium sulfate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Monitor if isavuconazonium (a CYP3A4 substrate) is coadministered with encorafenib (a CYP3A4 inhibitor and inducer).

            • lonafarnib

              encorafenib, lonafarnib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate that is contraindicated with strong or moderate CYP3A4 inhibitors or inducers. Encorafenib is both a CYP3A4 inhibitor and an inducer.

            • mavacamten

              encorafenib decreases levels of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pacritinib

              encorafenib, pacritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Encorafenib (a CYP3A4 inhibitor and inducer) may increase or decrease levels of pacritinib.

            • voriconazole

              encorafenib and voriconazole both increase QTc interval. Contraindicated.

            Serious - Use Alternative (232)

            • adagrasib

              adagrasib, encorafenib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

            • alfuzosin

              alfuzosin and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • amiodarone

              encorafenib and amiodarone both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • amisulpride

              encorafenib and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

            • amitriptyline

              encorafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • anagrelide

              encorafenib and anagrelide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • apalutamide

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

            • apomorphine

              apomorphine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • aprepitant

              aprepitant will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • aripiprazole

              aripiprazole and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • arsenic trioxide

              encorafenib and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • artemether

              encorafenib and artemether both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • asenapine

              encorafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine transdermal

              asenapine transdermal and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • atomoxetine

              atomoxetine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • avapritinib

              encorafenib, avapritinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate or strong CYP3A4 inhibitors. If coadministration of avapritinib with a moderate inhibitor cannot be avoided, reduce avapritinib starting dose (see drug monograph Dosage Modifications).

            • bedaquiline

              bedaquiline and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • bosentan

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

            • buprenorphine

              encorafenib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine buccal

              buprenorphine buccal and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine transdermal

              buprenorphine transdermal and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • capivasertib

              encorafenib, capivasertib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib may inhibit or induce CYP3A. .

            • carbamazepine

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

            • ceritinib

              ceritinib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

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

            • chloramphenicol

              chloramphenicol will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • chlorpromazine

              encorafenib and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

            • ciprofloxacin

              encorafenib and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              encorafenib and citalopram both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • clarithromycin

              clarithromycin will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              clarithromycin and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • clomipramine

              encorafenib and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • clozapine

              clozapine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • cobicistat

              cobicistat will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • conivaptan

              conivaptan will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use with CYP3A4 substrates. Delay initiation of drugs metabolized by CYP3A4 for at least 7 days following the discontinuation of conivaptan.

            • crizotinib

              crizotinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              crizotinib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • cyclosporine

              cyclosporine will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • dabrafenib

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

            • daridorexant

              encorafenib, daridorexant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib, a CYP3A4 inducer and inhibitor, may increase or decrease daridorexant levels.

            • darunavir

              darunavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • dasatinib

              dasatinib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • degarelix

              degarelix and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • desflurane

              desflurane and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • desipramine

              encorafenib and desipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • dienogest/estradiol valerate

              encorafenib will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Encorafenib can cause fetal harm. Advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • diltiazem

              diltiazem will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • disopyramide

              encorafenib and disopyramide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • dofetilide

              encorafenib and dofetilide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

              dofetilide increases toxicity of encorafenib by QTc interval. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • donepezil

              donepezil and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • doxepin

              doxepin and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • dronedarone

              dronedarone will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • droperidol

              encorafenib and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • efavirenz

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

              efavirenz and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

              encorafenib and efavirenz both increase QTc interval. Avoid or Use Alternate Drug.

            • elacestrant

              encorafenib, elacestrant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib inhibits and induces CYP3A4. Avoid with sensitive CYP3A4 substrates.

            • eliglustat

              encorafenib and eliglustat both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • entrectinib

              encorafenib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

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

            • enzalutamide

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

            • eribulin

              encorafenib and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

              eribulin and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              erythromycin base will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram increases toxicity of encorafenib by QTc interval. Avoid or Use Alternate Drug.

            • ethinylestradiol

              encorafenib will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Since encorafenib can cause fetal harm, advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • etrasimod

              etrasimod, encorafenib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod. .

            • etravirine

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

            • fedratinib

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

            • fexinidazole

              fexinidazole and encorafenib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of encorafenib 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.

            • finerenone

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

            • fingolimod

              fingolimod and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • flecainide

              encorafenib and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

            • fluconazole

              fluconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and fluconazole both increase QTc interval. Contraindicated.

            • fluoxetine

              encorafenib and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • fluvoxamine

              encorafenib and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

            • fosamprenavir

              fosamprenavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • fosaprepitant

              fosaprepitant will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • foscarnet

              encorafenib and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

            • fosphenytoin

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

            • fostamatinib

              fostamatinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • fruquintinib

              encorafenib will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.

            • ganaxolone

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

            • gemifloxacin

              encorafenib and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • gemtuzumab

              encorafenib and gemtuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • gilteritinib

              encorafenib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              encorafenib and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • goserelin

              encorafenib and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

            • granisetron

              encorafenib and granisetron both increase QTc interval. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • haloperidol

              encorafenib and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • histrelin

              encorafenib and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              encorafenib and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

              hydroxychloroquine sulfate and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxyzine

              encorafenib and hydroxyzine both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              encorafenib and ibutilide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • idelalisib

              idelalisib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • iloperidone

              iloperidone will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and iloperidone both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • imatinib

              imatinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • imipramine

              encorafenib and imipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • indinavir

              indinavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • infigratinib

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

            • inotuzumab

              encorafenib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • isoflurane

              encorafenib and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • itraconazole

              itraconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

            • ketoconazole

              ketoconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce encorafenib dose to 150 mg/day if current dose is 450 mg/day and 75 mg/day if current dose is 150-300mg/day. After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • lapatinib

              encorafenib and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • lefamulin

              lefamulin and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • lemborexant

              encorafenib, lemborexant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with drugs that may inhibit or induce CYP3A.

            • lenacapavir

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

              lenacapavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the current encorafenib dose. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume encorafenib dose that was taken before initiating the CYP3A4 inhibitor.

            • leniolisib

              encorafenib, leniolisib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib, an inhibitor and inducer of CYP3A4, may either increase or decrease leniolisib systemic exposure .

            • lenvatinib

              encorafenib and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • letermovir

              letermovir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • leuprolide

              encorafenib and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

            • levofloxacin

              encorafenib and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • levoketoconazole

              levoketoconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce encorafenib dose to 150 mg/day if current dose is 450 mg/day and 75 mg/day if current dose is 150-300mg/day. After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • levonorgestrel intrauterine

              encorafenib will decrease the level or effect of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Since encorafenib can cause fetal harm, advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              encorafenib will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Encorafenib can cause fetal harm. Advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • levonorgestrel transdermal

              encorafenib will decrease the level or effect of levonorgestrel transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Since encorafenib can cause fetal harm, advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • lithium

              encorafenib and lithium both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              encorafenib and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              lopinavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and lopinavir both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • lorlatinib

              encorafenib will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with moderate CYP3A inducers. If unable to avoid, monitor ALT, AST, and bilirubin as recommended.

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

            • lumateperone

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

            • lumefantrine

              encorafenib and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • lurbinectedin

              encorafenib, lurbinectedin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lurbinectedin is a CYP3A4 substrate. Coadministration with encorafenib (a CYP3A4 inhibitor and inducer) may increase or decrease plasma levels. Monitor for lurbinectedin toxicities or possible decreases in efficacy.

            • macimorelin

              encorafenib and macimorelin both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • maprotiline

              encorafenib and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

            • mefloquine

              encorafenib and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

            • methadone

              encorafenib and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • midostaurin

              encorafenib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • mifepristone

              mifepristone will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and mifepristone both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • mirtazapine

              encorafenib and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

            • mitotane

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

            • mobocertinib

              encorafenib 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.

              mobocertinib and encorafenib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • moxifloxacin

              encorafenib and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • nafcillin

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

            • nefazodone

              nefazodone will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • nelfinavir

              nelfinavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • nilotinib

              nilotinib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and nilotinib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • nirmatrelvir

              nirmatrelvir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration owing to potential risk of serious adverse events (eg, QT interval prolongation).

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration owing to potential risk of serious adverse events (eg, QT interval prolongation).

            • nirogacestat

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

            • nortriptyline

              encorafenib and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide

              encorafenib and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • ofloxacin

              encorafenib and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • olanzapine

              encorafenib and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • olutasidenib

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

            • omaveloxolone

              encorafenib, omaveloxolone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Encorafenib may increase or decrease systemic exposure of omeveloxolone. .

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • ondansetron

              encorafenib and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.

            • osimertinib

              encorafenib and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.

            • oxaliplatin

              encorafenib and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

            • palbociclib

              palbociclib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • palifermin

              palifermin increases toxicity of encorafenib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

            • paliperidone

              encorafenib and paliperidone both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • panobinostat

              encorafenib and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.

            • pasireotide

              encorafenib and pasireotide both increase QTc interval. Avoid or Use Alternate Drug.

            • pazopanib

              encorafenib and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pemigatinib

              encorafenib, pemigatinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pemigatinib (a CYP3A4 substrate) with encorafenib (a CYP3A4 inducer and inhibitor) may increase or decrease plasma levels or effects of pemigatinib.

            • pentamidine

              encorafenib and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • pexidartinib

              encorafenib, pexidartinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of pexidartinib (a CYP3A4 substrate) with encorafenib (a CYP3A4 inducer and inhibitor) may increase or decrease plasma levels or effects of pexidartinib.

            • phenobarbital

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

            • phenytoin

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

            • pimavanserin

              encorafenib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • pimozide

              encorafenib and pimozide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • pirtobrutinib

              encorafenib will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).

            • pitolisant

              encorafenib and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              encorafenib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • posaconazole

              posaconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and posaconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • pretomanid

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

            • primaquine

              encorafenib and primaquine both increase QTc interval. Avoid or Use Alternate Drug.

            • primidone

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

            • procainamide

              encorafenib and procainamide both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • promazine

              encorafenib and promazine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • promethazine

              encorafenib and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

            • propafenone

              encorafenib and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

            • protriptyline

              encorafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • quetiapine

              encorafenib and quetiapine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • quinidine

              encorafenib and quinidine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • quinine

              encorafenib and quinine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • quizartinib

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

            • ranolazine

              encorafenib and ranolazine both increase QTc interval. Avoid or Use Alternate Drug.

            • repotrectinib

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

            • ribociclib

              ribociclib will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and ribociclib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

              ribociclib increases toxicity of encorafenib by QTc interval. Avoid or Use Alternate Drug.

            • rifabutin

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

            • rifampin

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

            • rifapentine

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

            • rilpivirine

              encorafenib and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • rimegepant

              encorafenib, rimegepant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a CYP3A4 substrate) with drugs that both inhibit and induce CYP3A4 (eg, encorafenib).

            • risperidone

              encorafenib and risperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • romidepsin

              encorafenib and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

              encorafenib and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • schisandra

              schisandra will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • selumetinib

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

            • sertraline

              encorafenib and sertraline both increase QTc interval. Avoid or Use Alternate Drug.

            • sevoflurane

              encorafenib and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • siponimod

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

              encorafenib and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • solifenacin

              encorafenib and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

            • sorafenib

              encorafenib and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • sotalol

              encorafenib and sotalol both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • sulbactam/durlobactam

              encorafenib will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

            • sunitinib

              encorafenib and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tacrolimus

              encorafenib and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

            • tazemetostat

              encorafenib, tazemetostat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate and strong CYP3A4 inhibitors or inducers.

            • telavancin

              encorafenib and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

            • tetrabenazine

              encorafenib and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • thioridazine

              encorafenib and thioridazine both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • tipranavir

              tipranavir will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • toremifene

              encorafenib and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • trazodone

              encorafenib and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • trimipramine

              encorafenib and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • triptorelin

              encorafenib and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of encorafenib 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.

            • vandetanib

              encorafenib and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • vardenafil

              encorafenib and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

            • vemurafenib

              encorafenib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            • venlafaxine

              encorafenib and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.

            • verapamil

              verapamil will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • voclosporin

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

            • vonoprazan

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

            • voriconazole

              voriconazole will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • vorinostat

              encorafenib and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

            • voxelotor

              encorafenib, voxelotor. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Encorafenib may inhibit or induce CYP3A4. If unable to avoid, monitor carefully and adjust dose according to adverse effects or efficacy.

              voxelotor will increase the level or effect of encorafenib 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.

            • zanubrutinib

              encorafenib will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            • zavegepant intranasal

              encorafenib will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. OATP1B3 inhibitors may result in a significant increase in systemic exposure of zavegepant (an OATP1B3 substrate).

            • ziprasidone

              encorafenib and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.

            Monitor Closely (347)

            • abemaciclib

              encorafenib, abemaciclib. 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.

            • abiraterone

              encorafenib, abiraterone. 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.

            • acalabrutinib

              encorafenib, acalabrutinib. 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.

            • ado-trastuzumab emtansine

              encorafenib, ado-trastuzumab emtansine. 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.

            • albuterol

              albuterol and encorafenib both increase QTc interval. Use Caution/Monitor.

            • alfentanil

              encorafenib, alfentanil. 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.

            • alfuzosin

              encorafenib, alfuzosin. 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.

              encorafenib and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • alpelisib

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

              encorafenib will increase the level or effect of alpelisib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • alprazolam

              encorafenib, alprazolam. 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.

            • ambrisentan

              encorafenib will increase the level or effect of ambrisentan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • amiodarone

              encorafenib, amiodarone. 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.

            • amlodipine

              encorafenib, amlodipine. 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.

            • apalutamide

              encorafenib, apalutamide. 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.

            • apixaban

              encorafenib, apixaban. 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.

            • apremilast

              encorafenib, apremilast. 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.

            • aprepitant

              encorafenib, aprepitant. 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.

            • arformoterol

              arformoterol and encorafenib both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              encorafenib, aripiprazole. 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.

            • armodafinil

              encorafenib, armodafinil. 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.

            • atazanavir

              encorafenib, atazanavir. 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.

            • atogepant

              encorafenib, atogepant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor if atogepant (a CYP3A4 substrate) is coadministered with encorafenib (a CYP3A4 inhibitor and inducer).

              encorafenib will increase the level or effect of atogepant by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • atorvastatin

              encorafenib, atorvastatin. 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.

              encorafenib will increase the level or effect of atorvastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • avanafil

              encorafenib, avanafil. 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.

            • axitinib

              encorafenib, axitinib. 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.

            • azithromycin

              azithromycin increases toxicity of encorafenib by QTc interval. Use Caution/Monitor.

            • bedaquiline

              encorafenib, bedaquiline. 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.

            • belumosudil

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

            • belzutifan

              belzutifan will decrease the level or effect of encorafenib 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.

            • benzhydrocodone/acetaminophen

              encorafenib, benzhydrocodone/acetaminophen. 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.

            • benzphetamine

              encorafenib, benzphetamine. 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.

            • bortezomib

              encorafenib, bortezomib. 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.

            • bosentan

              encorafenib, bosentan. 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.

              encorafenib will increase the level or effect of bosentan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • bosutinib

              encorafenib, bosutinib. 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.

            • brentuximab vedotin

              encorafenib, brentuximab vedotin. 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.

            • brexpiprazole

              encorafenib, brexpiprazole. 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.

            • brigatinib

              encorafenib, brigatinib. 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.

            • bromocriptine

              encorafenib, bromocriptine. 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.

            • budesonide

              encorafenib, budesonide. 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.

            • buprenorphine

              encorafenib, buprenorphine. 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.

            • buprenorphine subdermal implant

              encorafenib, buprenorphine subdermal implant. 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.

            • buprenorphine transdermal

              encorafenib, buprenorphine transdermal. 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.

            • buspirone

              encorafenib, buspirone. 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.

            • cabozantinib

              encorafenib, cabozantinib. 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.

            • calcifediol

              encorafenib, calcifediol. 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.

            • calcitriol

              encorafenib, calcitriol. 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.

            • carbamazepine

              encorafenib, carbamazepine. 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.

            • cariprazine

              encorafenib, cariprazine. 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.

            • caspofungin

              encorafenib will increase the level or effect of caspofungin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • cenobamate

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

            • ceritinib

              encorafenib, ceritinib. 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.

            • chlordiazepoxide

              encorafenib, chlordiazepoxide. 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.

            • chloroquine

              encorafenib, chloroquine. 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.

              chloroquine increases toxicity of encorafenib by QTc interval. Use Caution/Monitor.

            • chlorothiazide

              encorafenib will increase the level or effect of chlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • cilostazol

              encorafenib, cilostazol. 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.

            • cimetidine

              encorafenib will increase the level or effect of cimetidine by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • citalopram

              encorafenib, citalopram. 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.

            • clarithromycin

              encorafenib, clarithromycin. 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.

            • clonazepam

              encorafenib, clonazepam. 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.

            • clorazepate

              encorafenib, clorazepate. 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.

            • cobicistat

              encorafenib, cobicistat. 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.

            • cobimetinib

              encorafenib, cobimetinib. 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.

            • colchicine

              encorafenib, colchicine. 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.

            • conivaptan

              encorafenib, conivaptan. 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.

            • conjugated estrogens

              encorafenib, conjugated estrogens. 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.

            • copanlisib

              encorafenib, copanlisib. 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.

            • crizotinib

              encorafenib, crizotinib. 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.

            • cyclosporine

              encorafenib, cyclosporine. 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.

            • cyproheptadine

              encorafenib, cyproheptadine. 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.

            • dabrafenib

              encorafenib, dabrafenib. 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.

            • dantrolene

              encorafenib, dantrolene. 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.

            • dapsone

              encorafenib, dapsone. 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.

            • darifenacin

              encorafenib, darifenacin. 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.

            • darunavir

              encorafenib, darunavir. 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.

            • dasatinib

              encorafenib, dasatinib. 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.

            • daunorubicin

              encorafenib will increase the level or effect of daunorubicin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • deflazacort

              encorafenib, deflazacort. 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.

            • dengue vaccine

              encorafenib decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

            • deutetrabenazine

              encorafenib and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

            • dexamethasone

              encorafenib, dexamethasone. 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.

            • diazepam

              encorafenib, diazepam. 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.

            • diazepam intranasal

              encorafenib, diazepam intranasal. Other (see comment). Use Caution/Monitor. Comment: Coadministration may either increase or decrease diazepam elimination.

            • digoxin

              encorafenib will increase the level or effect of digoxin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • dihydroergotamine

              encorafenib, dihydroergotamine. 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.

            • dihydroergotamine inhaled

              encorafenib, dihydroergotamine inhaled. 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.

            • dihydroergotamine intranasal

              encorafenib, dihydroergotamine intranasal. 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.

            • diltiazem

              encorafenib, diltiazem. 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.

            • dipyridamole

              encorafenib will increase the level or effect of dipyridamole by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • disopyramide

              encorafenib, disopyramide. 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.

            • docetaxel

              encorafenib, docetaxel. 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.

            • doxorubicin

              encorafenib, doxorubicin. 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.

            • doxorubicin liposomal

              encorafenib, doxorubicin liposomal. 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.

            • dronedarone

              encorafenib, dronedarone. 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.

            • duvelisib

              duvelisib will increase the level or effect of encorafenib 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.

            • efavirenz

              encorafenib, efavirenz. 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.

            • elagolix

              elagolix will decrease the level or effect of encorafenib 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.

            • elbasvir/grazoprevir

              encorafenib, elbasvir/grazoprevir. 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.

              encorafenib will increase the level or effect of elbasvir/grazoprevir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • eletriptan

              encorafenib, eletriptan. 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.

            • eliglustat

              encorafenib, eliglustat. 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.

            • eluxadoline

              encorafenib will increase the level or effect of eluxadoline by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • elvitegravir

              encorafenib, elvitegravir. 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.

            • enalapril

              encorafenib will increase the level or effect of enalapril by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • enzalutamide

              encorafenib, enzalutamide. 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.

            • eplerenone

              encorafenib, eplerenone. 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.

            • ergoloid mesylates

              encorafenib, ergoloid mesylates. 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.

            • erlotinib

              encorafenib, erlotinib. 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.

            • erythromycin base

              encorafenib, erythromycin base. 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.

              encorafenib will increase the level or effect of erythromycin base by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • erythromycin ethylsuccinate

              encorafenib, erythromycin ethylsuccinate. 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.

              encorafenib will increase the level or effect of erythromycin ethylsuccinate by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • erythromycin lactobionate

              encorafenib, erythromycin lactobionate. 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.

              encorafenib will increase the level or effect of erythromycin lactobionate by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • erythromycin stearate

              encorafenib, erythromycin stearate. 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.

              encorafenib will increase the level or effect of erythromycin stearate by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • escitalopram

              encorafenib, escitalopram. 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.

            • estradiol

              encorafenib, estradiol. 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.

            • estrogens conjugated synthetic

              encorafenib, estrogens conjugated synthetic. 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.

            • estrogens esterified

              encorafenib, estrogens esterified. 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.

            • estropipate

              encorafenib, estropipate. 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.

            • eszopiclone

              encorafenib, eszopiclone. 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.

            • ethinylestradiol

              encorafenib will increase the level or effect of ethinylestradiol by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ethosuximide

              encorafenib, ethosuximide. 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.

            • etoposide

              encorafenib, etoposide. 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.

            • etravirine

              encorafenib, etravirine. 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.

            • everolimus

              encorafenib, everolimus. 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.

            • exemestane

              encorafenib, exemestane. 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.

            • ezetimibe

              encorafenib will increase the level or effect of ezetimibe by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • fedratinib

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

            • felbamate

              encorafenib, felbamate. 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.

            • felodipine

              encorafenib, felodipine. 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.

            • fentanyl

              encorafenib, fentanyl. 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.

            • fentanyl intranasal

              encorafenib, fentanyl intranasal. 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.

            • fentanyl transdermal

              encorafenib, fentanyl transdermal. 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.

            • fentanyl transmucosal

              encorafenib, fentanyl transmucosal. 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.

            • fexofenadine

              encorafenib will increase the level or effect of fexofenadine by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • fluphenazine

              encorafenib and fluphenazine both increase QTc interval. Use Caution/Monitor.

            • flurazepam

              encorafenib, flurazepam. 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.

            • fluvastatin

              encorafenib will increase the level or effect of fluvastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • formoterol

              encorafenib and formoterol both increase QTc interval. Use Caution/Monitor.

            • fosamprenavir

              encorafenib, fosamprenavir. 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.

            • fosaprepitant

              encorafenib, fosaprepitant. 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.

            • fostamatinib

              encorafenib, fostamatinib. 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.

            • fostemsavir

              encorafenib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gadobenate

              encorafenib and gadobenate both increase QTc interval. Use Caution/Monitor.

            • gefitinib

              encorafenib, gefitinib. 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.

            • gepirone

              encorafenib will increase the level or effect of gepirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce gepirone dose by 50% when used concomitantly with a moderate CYP3A4 inhibitor.

              gepirone and encorafenib both increase QTc interval. Modify Therapy/Monitor Closely.

            • glecaprevir/pibrentasvir

              encorafenib, glecaprevir/pibrentasvir. 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.

              encorafenib will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • glyburide

              encorafenib will increase the level or effect of glyburide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • guanfacine

              encorafenib, guanfacine. 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.

            • haloperidol

              encorafenib, haloperidol. 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.

            • hydrocodone

              encorafenib, hydrocodone. 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.

            • hydroxyprogesterone caproate (DSC)

              encorafenib, hydroxyprogesterone caproate (DSC). 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.

            • ibrutinib

              encorafenib, ibrutinib. 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.

            • idelalisib

              encorafenib, idelalisib. 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.

            • imatinib

              encorafenib, imatinib. 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.

              encorafenib will increase the level or effect of imatinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP and OATP1B3 inhibitor) may increase the concentration and toxicities of BCRP and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • indacaterol, inhaled

              encorafenib and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.

            • indinavir

              encorafenib, indinavir. 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.

            • irinotecan

              encorafenib, irinotecan. 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.

              encorafenib will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • irinotecan liposomal

              encorafenib, irinotecan liposomal. 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.

            • isosorbide dinitrate

              encorafenib, isosorbide dinitrate. 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.

            • isosorbide mononitrate

              encorafenib, isosorbide mononitrate. 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.

            • isradipine

              encorafenib, isradipine. 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.

            • istradefylline

              istradefylline will increase the level or effect of encorafenib 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.

            • ivacaftor

              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.

            • ixabepilone

              encorafenib, ixabepilone. 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.

            • ixazomib

              encorafenib, ixazomib. 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.

            • ketamine

              encorafenib, ketamine. 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.

            • ketoconazole

              encorafenib, ketoconazole. 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.

            • lansoprazole

              encorafenib, lansoprazole. 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.

            • lapatinib

              encorafenib, lapatinib. 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.

              encorafenib will increase the level or effect of lapatinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ledipasvir/sofosbuvir

              encorafenib will increase the level or effect of ledipasvir/sofosbuvir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • leflunomide

              encorafenib will increase the level or effect of leflunomide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • lenvatinib

              encorafenib will increase the level or effect of lenvatinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • letermovir

              encorafenib will increase the level or effect of letermovir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • levalbuterol

              encorafenib and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levamlodipine

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

            • levoketoconazole

              encorafenib, levoketoconazole. 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.

            • levomilnacipran

              encorafenib, levomilnacipran. 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.

            • levonorgestrel oral

              encorafenib, levonorgestrel oral. 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.

            • lidocaine

              encorafenib, lidocaine. 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.

            • linagliptin

              encorafenib, linagliptin. 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.

            • lomitapide

              encorafenib, lomitapide. 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.

            • lopinavir

              encorafenib, lopinavir. 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.

            • losartan

              encorafenib, losartan. 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.

            • lovastatin

              encorafenib, lovastatin. 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.

              encorafenib will increase the level or effect of lovastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • lumefantrine

              encorafenib, lumefantrine. 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.

            • lurasidone

              encorafenib, lurasidone. 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.

            • macimorelin

              encorafenib, macimorelin. 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.

            • macitentan

              encorafenib, macitentan. 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.

            • maraviroc

              encorafenib, maraviroc. 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.

            • marijuana

              encorafenib, marijuana. 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.

            • medroxyprogesterone

              encorafenib, medroxyprogesterone. 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.

            • mefloquine

              encorafenib, mefloquine. 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.

            • mestranol

              encorafenib, mestranol. 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.

            • metaxalone

              encorafenib, metaxalone. 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.

            • methadone

              encorafenib, methadone. 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.

            • methotrexate

              encorafenib will increase the level or effect of methotrexate by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • methylergonovine

              encorafenib, methylergonovine. 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.

            • methylprednisolone

              encorafenib, methylprednisolone. 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.

            • midazolam

              encorafenib, midazolam. 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.

            • midostaurin

              encorafenib, midostaurin. 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.

            • mifepristone

              encorafenib, mifepristone. 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.

            • mirtazapine

              encorafenib, mirtazapine. 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.

            • mitoxantrone

              encorafenib will increase the level or effect of mitoxantrone by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • modafinil

              encorafenib, modafinil. 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.

            • momelotinib

              encorafenib increases toxicity of momelotinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1/B3 inhibitor increases momelotinib (OATP1B1/B3 subtrate) plasma concentrations, which may increase the risk of adverse reactions with momelotinib.

            • naldemedine

              encorafenib, naldemedine. 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.

            • naloxegol

              encorafenib, naloxegol. 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.

            • nefazodone

              encorafenib, nefazodone. 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.

            • nelfinavir

              encorafenib, nelfinavir. 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.

            • netupitant/palonosetron

              encorafenib, netupitant/palonosetron. 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.

            • nevirapine

              encorafenib, nevirapine. 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.

            • nicardipine

              encorafenib, nicardipine. 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.

            • nifedipine

              encorafenib, nifedipine. 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.

            • nilotinib

              encorafenib, nilotinib. 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.

            • nimodipine

              encorafenib, nimodipine. 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.

            • nisoldipine

              encorafenib, nisoldipine. 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.

            • norethindrone

              encorafenib, norethindrone. 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.

            • norgestrel

              encorafenib will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods

            • olaparib

              encorafenib, olaparib. 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.

            • oliceridine

              encorafenib 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.

            • olmesartan

              encorafenib will increase the level or effect of olmesartan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • olodaterol inhaled

              encorafenib and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

            • omeprazole

              encorafenib, omeprazole. 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.

            • ondansetron

              encorafenib, ondansetron. 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.

            • osilodrostat

              osilodrostat and encorafenib both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              encorafenib, osimertinib. 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.

              encorafenib will increase the level or effect of osimertinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ospemifene

              encorafenib, ospemifene. 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.

            • oxycodone

              encorafenib, oxycodone. 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.

            • ozanimod

              ozanimod and encorafenib both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

              encorafenib will increase the level or effect of ozanimod by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • paclitaxel

              encorafenib, paclitaxel. affecting hepatic enzyme CYP2E1 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.

              encorafenib will increase the level or effect of paclitaxel by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • paclitaxel protein bound

              encorafenib, paclitaxel protein bound. 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.

            • palbociclib

              encorafenib, palbociclib. 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.

            • palovarotene

              encorafenib will increase the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of palovarotene, a CYP3A substrate, with moderate CYP3A inhibitors. If unavoidable, reduce palovarotene dose by 50%.

            • panobinostat

              encorafenib, panobinostat. 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.

            • pantoprazole

              encorafenib will increase the level or effect of pantoprazole by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • pazopanib

              encorafenib, pazopanib. 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.

              encorafenib will increase the level or effect of pazopanib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • perampanel

              encorafenib, perampanel. 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.

            • perphenazine

              encorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

            • pimavanserin

              encorafenib, pimavanserin. 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.

            • pitavastatin

              encorafenib will increase the level or effect of pitavastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • ponatinib

              encorafenib, ponatinib. 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.

            • pravastatin

              encorafenib will increase the level or effect of pravastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • praziquantel

              encorafenib, praziquantel. 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.

            • primaquine

              encorafenib, primaquine. 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.

            • prochlorperazine

              encorafenib and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

            • progesterone intravaginal gel

              encorafenib, progesterone intravaginal gel. 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.

            • progesterone micronized

              encorafenib, progesterone micronized. 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.

            • quetiapine

              encorafenib, quetiapine. 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.

            • quinidine

              encorafenib, quinidine. 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.

            • quinine

              encorafenib, quinine. 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.

            • quizartinib

              quizartinib, encorafenib. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

            • rabeprazole

              encorafenib, rabeprazole. 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.

            • ranolazine

              encorafenib, ranolazine. 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.

            • regorafenib

              encorafenib, regorafenib. 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.

            • repaglinide

              encorafenib, repaglinide. 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.

              encorafenib will increase the level or effect of repaglinide by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • revefenacin

              encorafenib will increase the level or effect of revefenacin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ribociclib

              encorafenib, ribociclib. 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.

            • rifabutin

              encorafenib, rifabutin. 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.

            • rifampin

              encorafenib will increase the level or effect of rifampin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • riociguat

              encorafenib, riociguat. 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.

              encorafenib will increase the level or effect of riociguat by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ripretinib

              encorafenib will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avoided, increase dosing frequency from recommended dose of 150 mg once daily to 150 mg twice daily during co-administration period; monitor for clinical response and tolerability

            • ritonavir

              encorafenib, ritonavir. 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.

            • rivaroxaban

              encorafenib, rivaroxaban. 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.

            • roflumilast

              encorafenib, roflumilast. 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.

            • rolapitant

              encorafenib, rolapitant. 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.

            • romidepsin

              encorafenib, romidepsin. 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.

            • ropivacaine

              encorafenib, ropivacaine. 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.

            • rosuvastatin

              encorafenib will increase the level or effect of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • rucaparib

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

            • ruxolitinib

              encorafenib, ruxolitinib. 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.

            • ruxolitinib topical

              encorafenib, ruxolitinib topical. 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.

            • salmeterol

              encorafenib, salmeterol. 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.

              encorafenib and salmeterol both increase QTc interval. Use Caution/Monitor.

            • saquinavir

              encorafenib, saquinavir. 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.

            • saxagliptin

              encorafenib, saxagliptin. 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.

            • selexipag

              encorafenib will increase the level or effect of selexipag by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • selpercatinib

              selpercatinib increases toxicity of encorafenib by QTc interval. Use Caution/Monitor.

            • selumetinib

              encorafenib will increase the level or effect of selumetinib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • sildenafil

              encorafenib, sildenafil. 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.

            • simvastatin

              encorafenib, simvastatin. 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.

              encorafenib will increase the level or effect of simvastatin by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • siponimod

              siponimod and encorafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • sirolimus

              encorafenib, sirolimus. 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.

            • sofosbuvir

              encorafenib will increase the level or effect of sofosbuvir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • solifenacin

              encorafenib, solifenacin. 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.

            • sonidegib

              encorafenib, sonidegib. 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.

            • sorafenib

              encorafenib, sorafenib. 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.

            • sparsentan

              encorafenib will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

            • stiripentol

              stiripentol, encorafenib. 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.

              encorafenib will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor closely if stiripentol is coadministered with a moderate CYP3A4 inducer.

            • sufentanil

              encorafenib, sufentanil. 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.

            • sufentanil SL

              encorafenib, sufentanil SL. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with encorafenib, a CYP3A4 inhibitor and inducer, may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression. Encorafenib may also induce sufentanil, and thereby reduce levels and efficacy.

            • sulfasalazine

              encorafenib will increase the level or effect of sulfasalazine by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • sunitinib

              encorafenib, sunitinib. 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.

            • suvorexant

              encorafenib, suvorexant. 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.

            • tacrolimus

              encorafenib, tacrolimus. 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.

            • tacrolimus ointment

              encorafenib, tacrolimus ointment. 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.

            • tadalafil

              encorafenib, tadalafil. 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.

            • talazoparib

              encorafenib will increase the level or effect of talazoparib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • tamoxifen

              encorafenib, tamoxifen. 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.

            • tamsulosin

              encorafenib, tamsulosin. 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.

            • tasimelteon

              encorafenib, tasimelteon. 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.

            • tazemetostat

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

            • telmisartan

              encorafenib will increase the level or effect of telmisartan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • temsirolimus

              encorafenib, temsirolimus. 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.

            • teniposide

              encorafenib, teniposide. 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.

            • tenofovir AF

              encorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • tenofovir DF

              encorafenib will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • tetracycline

              encorafenib, tetracycline. 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.

            • tezacaftor

              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.

            • theophylline

              encorafenib, theophylline. 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.

            • tiagabine

              encorafenib, tiagabine. 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.

            • ticlopidine

              encorafenib, ticlopidine. 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.

            • tinidazole

              encorafenib, tinidazole. 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.

            • tipranavir

              encorafenib, tipranavir. 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.

            • tivozanib

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

            • tofacitinib

              encorafenib, tofacitinib. 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.

            • tolterodine

              encorafenib, tolterodine. 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.

            • tolvaptan

              encorafenib, tolvaptan. 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.

            • topotecan

              encorafenib will increase the level or effect of topotecan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • toremifene

              encorafenib, toremifene. 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.

            • trabectedin

              encorafenib, trabectedin. 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.

            • tramadol

              encorafenib, tramadol. 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.

            • trazodone

              encorafenib, trazodone. 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.

            • triazolam

              encorafenib, triazolam. 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.

            • triclabendazole

              triclabendazole and encorafenib both increase QTc interval. Use Caution/Monitor.

            • trifluoperazine

              encorafenib and trifluoperazine both decrease QTc interval. Use Caution/Monitor.

            • trimethoprim

              encorafenib, trimethoprim. 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.

            • trimipramine

              encorafenib, trimipramine. 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.

            • troglitazone

              encorafenib will increase the level or effect of troglitazone by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 inhibitor) may increase the concentration and toxicities of OATP1B1 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ubrogepant

              encorafenib will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is recommended with concomitant use of ubrogepant and moderate and weak CYP3A4 inducers. (see Dosage Modifications)

              encorafenib will increase the level or effect of ubrogepant by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • ulipristal

              encorafenib, ulipristal. 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.

            • umeclidinium bromide/vilanterol inhaled

              encorafenib and umeclidinium bromide/vilanterol inhaled both decrease QTc interval. Use Caution/Monitor.

            • valbenazine

              encorafenib, valbenazine. 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.

              valbenazine and encorafenib both increase QTc interval. Use Caution/Monitor.

            • valsartan

              encorafenib will increase the level or effect of valsartan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • vandetanib

              encorafenib, vandetanib. 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.

            • vardenafil

              encorafenib, vardenafil. 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.

            • velpatasvir

              encorafenib, velpatasvir. 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.

              encorafenib will increase the level or effect of velpatasvir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • vemurafenib

              encorafenib, vemurafenib. 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.

              encorafenib will increase the level or effect of vemurafenib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • venetoclax

              encorafenib, venetoclax. 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.

            • venlafaxine

              encorafenib, venlafaxine. 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.

            • verapamil

              encorafenib, verapamil. 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.

            • vilanterol/fluticasone furoate inhaled

              encorafenib and vilanterol/fluticasone furoate inhaled both increase QTc interval. Use Caution/Monitor.

            • vilazodone

              encorafenib, vilazodone. 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.

            • vinblastine

              encorafenib, vinblastine. 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.

            • vincristine

              encorafenib, vincristine. 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.

            • vincristine liposomal

              encorafenib, vincristine liposomal. 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.

            • vinorelbine

              encorafenib, vinorelbine. 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.

            • voclosporin

              voclosporin, encorafenib. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • vortioxetine

              encorafenib, vortioxetine. 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.

            • voxilaprevir

              encorafenib, voxilaprevir. 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.

              encorafenib will increase the level or effect of voxilaprevir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1, OATP1B3, and BCRP inhibitor) may increase the concentration and toxicities of OATP1B1, OATP1B3, and BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. Screen reader support enabled.

            • warfarin

              encorafenib, warfarin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Warfarin serum concentrations may be increased or decreased. Encorafenib it both an inhibitor and inducer of CYP3A4. The less potent R-enantiomer of warfarin is a substrate of CYP3A4.

            • zolpidem

              encorafenib, zolpidem. 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.

            • zonisamide

              encorafenib, zonisamide. 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.

            Minor (6)

            • acetazolamide

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

            • anastrozole

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

            • cyclophosphamide

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

            • erdafitinib

              encorafenib will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. If a moderate CYP3A4 inducer must be coadministered, administer 8-mg/day dose initially, with potential to increase to 9 mg/day based on serum phosphate levels on Days 14-21 and tolerability. If a moderate CYP3A4 inducer must be coadministered after the initial dose increase period based on serum phosphate levels and tolerability, increase erdafitinib dose up to 9 mg. When a moderate inducer discontinued, continue erdafitinib at same dose, in absence of drug-related toxicity.

            • larotrectinib

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

            • nitrofurantoin

              encorafenib will increase the level or effect of nitrofurantoin by Other (see comment). Minor/Significance Unknown. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

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            Adverse Effects

            >10% (Melanoma)

            All grades

            • Fatigue (43%)
            • Nausea (41%)
            • Vomiting (30%)
            • Abdominal pain (28%)
            • Arthralgia (26%)
            • Myopathy (23%)
            • Hyperkeratosis (23%)
            • Constipation (22%)
            • Rash (22%)
            • Headache (22%)
            • Hemorrhage (19%)
            • Pyrexia (18%)
            • Dry skin (16%)
            • Dizziness (15%)
            • Alopecia (14%)
            • Pruritus (13%)
            • Peripheral neuropathy (12%)
            • Pain in extremity (11%)

            >10% (mCRC)

            All grades

            • Fatigue (51%)
            • Anemia (34%)
            • Nausea (34%)
            • Diarrhea (33%)
            • Dermatitis acneiform (32%)
            • Abdominal pain (30%)
            • Decreased appetite (27%)
            • Arthralgia (27%)
            • Rash (26%)
            • Lymphopenia (24%)
            • Vomiting (21%)
            • Headache (20%)
            • Hypomagnesemia (19%)
            • Hemorrhage (19%)
            • Peripheral neuropathy (19%)
            • Increased alkaline phosphatase (18%)
            • Pyrexia (17%)
            • Increased AST/ALT (15-17%)
            • Constipation (15%)
            • Myopathy (15%)
            • Melanocytic nevus (14%)
            • Pruritus (14%)
            • Increased aPTT (13%)
            • Insomnia (13%)
            • Dry skin (13%)
            • Hypokalemia (12%)
            • Hyponatremia (11%)

            1-10% (Melanoma)

            All grades

            • Facial paresis (<10%)
            • Pancreatitis (<10%)
            • Panniculitis (<10%)
            • Drug hypersensitivity (<10%)

            Grade 3 or 4

            • Abdominal pain (4%)
            • Pyrexia (4%)
            • Fatigue (3%)
            • Hemorrhage (3%)
            • Dizziness (3%)
            • Vomiting (2%)
            • Nausea (2%)
            • Headache (2%)
            • Pruritus (1%)
            • Rash (1%)
            • Hyperkeratosis (1%)
            • Peripheral neuropathy (1%)
            • Pain in extremity (1%)
            • Arthralgia (1%)

            1-10% (mCRC)

            All grades

            • Pancreatitis (<10%)
            • Pain in extremity (10%)

            Grade 3 or 4

            • Fatigue (7%)
            • Increased alkaline phosphatase (4%)
            • Abdominal pain (4%)
            • Hypokalemia (3%)
            • Diarrhea (2%)
            • Hyponatremia (2%)
            • Hemorrhage (2%)
            • Peripheral neuropathy (1%)
            • Increased AST (1%)
            • Dermatitis acneiform (1%)
            • Arthralgia (1%)
            • Myopathy (1%)
            • Decreased appetite (1%)
            • Vomiting (1%)
            • Nausea (1%)
            • Pyrexia (1%)
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            Warnings

            Contraindications

            None

            Cautions

            Confirm evidence of BRAF V600E or V600K mutation prior to initiating treatment; in vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells, which are exposed to BRAF inhibitors; not indicated for wild-type BRAF melanoma

            Hemorrhage can occur; hemorrhagic events include GI, hemorrhoidal, rectal, and intracranial hemorrhage and hematochezia

            Uveitis (eg, iritis, iridocyclitis) reported; assess for visual symptoms at each visit; perform an ophthalmologic evaluation regularly and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings

            Dose-dependent QTc interval prolongation reported; monitor patients who already have or who are at significant risk of developing QTc prolongation (eg, patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure, those taking medications associated with QT prolongation); correct hypokalemia and hypomagnesemia prior to and during administration

            Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman

            Grade 3 or 4 dermatologic reactions occurred in 21% of patients treated with encorafenib as a single agent compared with 2% of patients treated with encorafenib in combination with binimetinib

            Refer to the binimetinib or cetuximab prescribing information for additional risk information that applies to combination use treatment

            New primary malignancies

            • New primary malignancies, cutaneous and noncutaneous, observed
            • Cutaneous squamous cell carcinoma
              • In the COLUMBUS trial, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA) and basal cell carcinoma, in addition to skin papilloma, occurred in patients who received encorafenib in combination with binimetinib
              • Perform dermatologic evaluations before initiating treatment, q2months during treatment, and for up to 6 months following discontinuation of treatment
              • Manage suspicious skin lesions with excision and dermatopathologic evaluation
              • Dose modification is not recommended for new primary cutaneous malignancies
            • Noncutaneous malignancies
              • Based on its mechanism of action, encorafenib may promote malignancies associated with activation of RAS through mutation or other mechanisms
              • Monitor for signs and symptoms of noncutaneous malignancies
              • Discontinue treatment for RAS mutation-positive noncutaneous malignancies

            Cardiomyopathy

            • Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, reported
            • Evidence of cardiomyopathy (decreased in LVEF below the institutional LLN with an absolute decreased in LVEF≥10% below baseline as detected by echocardiography or MUGA) occurred in 7% of patients receiving encorafenib plus binimetinib
            • Assess ejection fraction by echocardiogram or MUGA scan before initiating, 1 month after initiating treatment, and every 2-3 months during treatment
            • Safety of encorafenib in combination with binimetinib not established in patients with baseline ejection fraction that is either <50% or below the institutional LLN
            • Closely monitor patients with cardiovascular risk factors

            Drug interaction overview

            • Reversible inhibitor of UGT1A1, CYP1A2, CYP2B6, CYP2C8/9, CYP2D6, and CYP3A, and a time-dependent inhibitor of CYP3A4 at clinically relevant plasma concentrations
            • Inhibitor of OATP1B1, OATP1B3, and BCRP
            • Induces CYP2B6, CYP2C9, and CYP3A4 at clinically relevant plasma concentrations
            • Substrate of CYP3A4 and P-glycoprotein (P-gp)
            • Strong or moderate CYP3A4 inhibitors
              • Avoid coadministration
              • Strong or moderate CYP3A4 inhibitor increases encorafenib plasma concentrations and the risk of toxicities
              • If coadministration unavoidable, modify dose as recommended
            • Strong or moderate CYP3A4 inducers
              • Avoid coadministration
              • Strong or moderate CYP3A4 inducer may decrease encorafenib plasma concentrations and efficacy
            • Sensitive CYP3A4 substrates
              • Coadministration with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents
              • Encorafenib can decrease concentrations and efficacy of hormonal contraceptives; avoid hormonal contraceptives
            • Drugs that prolong the QT interval
              • Avoid use with drugs known to prolong QT/QTc
              • Encorafenib is associated with dose-dependent QTc interval prolongation
            • OATP1B1, OATP1B3, or BCRP substrates
              • Closely monitor signs and symptoms of toxicities of OATP1B1, OATP1B3, or BCRP substrates; consider dosage adjustment of these substrates
              • Encorafenib can result in increased concentrations of OATP1B1, OATP1B3, or BCRP substrates, and may increase toxicity of these agents
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            Pregnancy

            Pregnancy

            Based on its mechanism of action, fetal harm may occur when administered to pregnant women

            There are no available clinical data on the use of encorafenib during pregnancy

            Advise pregnant women of the potential risk to a fetus

            Animal data

            • In animal reproduction studies, encorafenib produced embryo-fetal developmental changes in rats and rabbits and was an abortifacient in rabbits at doses greater than or equal to those resulting in exposures ~26 (in the rat) and 178 (in the rabbit) times the human exposure at the clinical dose of 450 mg, with no clear findings at lower doses

            Contraception

            • Verify the pregnancy status of females of reproductive potential prior to initiating treatment
            • Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the final dose
            • Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking encorafenib and binimetinib (see Drug Interactions)

            Infertility

            • Based on findings in male rats at doses ~13 times the human exposure at the 450-mg clinical dose, use of encorafenib may impact fertility in males

            Lactation

            The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

            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

            Kinase inhibitor that targets BRAF V600E

            This pathway regulates several key cellular activities, including proliferation, differentiation, survival, and angiogenesis; inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma

            Encorafenib and binimetinib target 2 different kinases in the RAS/RAF/MEK/ERK pathway; compared with either drug alone, coadministration resulted in greater antiproliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice

            Additionally, the combination of encorafenib and binimetinib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone

            Absorption

            Peak plasma time: 2 hr

            At least 86% of the dose is absorbed

            Effect of Food

            • Administration of a single dose of encorafenib 100 mg (0.2 times the recommended dose) with a high-fat, high-calorie meal (composed of ~150 calories from protein, 350 calories from carbohydrates, and 500 calories from fat) decreased the mean peak plasma concentration by 36% with no effect on AUC

            Distribution

            Protein bound: 86%

            Vd: 164 L

            Metabolism

            Primary metabolic pathway is N-dealkylation, with CYP3A4 as the main contributor (83%) to total oxidative clearance of encorafenib in human liver microsomes, followed by CYP2C19 (16%) and CYP2D6 (1%)

            Elimination

            Half-life: 3.5 hr

            Clearance: 14 L/hr (day 1); 32 L/hr (steady-state)

            Excretion, single 100-mg dose: Feces 47% (5% unchanged); urine 47% (2% unchanged)

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            Administration

            Oral Administration

            May take with or without food

            Missed dose: Do not take a missed dose within 12 hr of the next scheduled dose

            Vomiting: Do not take an additional dose if vomiting occurs following administration, but continue with the next scheduled dose

            Storage

            Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

            Dispense in original bottle and protect from moisture

            Capsules are moisture sensitive; advise patients to store encorafenib in the original bottle with desiccant and to keep the cap of the bottle tightly closed

            Do not remove the desiccants from the bottle

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Braftovi oral
            -
            75 mg capsule
            Braftovi oral
            -
            50 mg capsule

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

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

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each 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.