cobimetinib (Rx)

Melanoma

Indicated for unresectable or metastatic melanoma in patients with a BRAF V600E or V600K mutation, in combination with vemurafenib

60 mg PO qDay for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity

Vemurafenib: 960 mg PO BID on days 1-28 of an every 28-day cycle

Histiocytic Neoplasms

Indicated as a single agent for adults with histiocytic neoplasms

60 mg PO qDay for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity

Dosage Modifications

New primary malignancies (cutaneous and noncutaneous): No dosage modification required

Avoid concurrent use of cobimetinib and strong or moderate CYP3A inducers including but not limited to carbamazepine, efavirenz, phenytoin, rifampin, and St. John’s Wort

Hepatic impairment

• Mild-to-severe (Child-Pugh A to C): No dosage adjustment necessary

Renal impairment

• Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
• Severe (CrCl <30 mL/min): Safety and efficacy not established

Coadministration with CYP3A inhibitors

• Do not take strong or moderate CYP3A inhibitors while taking cobimetinib
• If concurrent short-term (≤14 days) use of moderate CYP3A inhibitors is unavoidable for patients taking cobimetinib 60 mg, reduce dose to 20 mg; after the moderate CYP3A inhibitor is discontinued, resume previous cobimetinib dose
• Use an alternative to a strong or moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily)

Dose reductions

• First dose reduction: 40 mg PO qDay
• Second dose reduction: 20 mg PO qDay
• Subsequent modification: Permanently discontinue cobimetinib if unable to tolerate 20-mg dose

Hemorrhage

• Grade 3: Withhold cobimetinib for up to 4 wk; if improved to grade 0 or 1, resume at the next lower dose level; permanently discontinue if not improved within 4 wk
• Grade 4: Permanently discontinue

Cardiomyopathy

• Asymptomatic

  • Definition: Absolute decrease in LVEF from baseline of >10% and less than institutional lower limit of normal (LLN) Withhold cobimetinib for 2 wk; repeat LVEF
  • Resume at next lower dose if all of the following are present: LVEF is ≥LLN and absolute decrease from baseline LVEF is ≤10%
  • Permanently discontinue if any of the following are present: LVEF is 10%

• Symptomatic LVEF decrease from baseline

  • Withhold cobimetinib for 4 wk; repeat LVEF
  • Resume at next lower dose if all of the following are present:
  • Symptoms resolve and LVEF is ≥LLN and absolute decrease from baseline LVEF is ≤10%
  • Permanently discontinue if any of the following are present:
  • Symptoms persist, or LVEF is 10%

Dermatologic reactions

• Grade 2 (intolerable) or grades 3 or 4: Withhold or reduce dose

Retinopathy or retinal vein occlusion

• Serous retinopathy: Withhold for up to 4 wk; if signs and symptoms improve, resume at the next lower dose level; permanently discontinue if not improved or symptoms recur at the lower dose within 4 wk
• Retinal vein occlusion: Permanently discontinue

Hepatoxicity

• First occurrence grade 4: Withhold for up to 4 wk; if improved to grade 0 or 1, resume at the next lower dose level; permanently discontinue if not improved within 4 wk
• Recurrent grade 4: Permanently discontinue

Rhabdomyolysis and elevated CPK

• Grade 4 creatine phosphokinae (CPK) elevation or any CPK elevation plus myalgia: Withhold for up to 4 wk; if improved to ≤grade 3, resume at the next lower dose level; permanently discontinue if not improved within 4 wk

Photosensitivity

• Grade 2 (intolerable), grades 3 or 4: Withhold for up to 4 wk; if improved to grade 0 or 1, resume at the next lower dose level; permanently discontinue if not improved within 4 wk

Other adverse events

• Grade 2 (intolerable) adverse reactions or any grade 3

  • Withhold for up to 4 wk; if improved to grade 0 or 1, resume at the next lower dose level; permanently discontinue if not improved within 4 wk

• First occurrence of any grade 4 adverse reaction

  • Withhold until adverse reaction improves to grade 0 or 1 and then resume at the next lower dose level, OR
  • Permanently discontinue

• Recurrent grade 4 adverse reaction

  • Permanently discontinue

Dosage Considerations

Melanoma

• Confirm presence of BRAF V600E or V600K mutation in tumor specimens before initiating cobimetinib with vemurafenib
• See information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma

Safety and efficacy not established

Contraindicated (46)

• armodafinil

  armodafinil will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• atazanavir

  atazanavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• bosentan

  bosentan will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• carbamazepine

  carbamazepine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• clarithromycin

  clarithromycin will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• clobazam

  clobazam will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• cobicistat

  cobicistat will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• conivaptan

  conivaptan will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• dabrafenib

  dabrafenib will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• darunavir

  darunavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• dexamethasone

  dexamethasone will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• efavirenz

  efavirenz will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• enzalutamide

  enzalutamide will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• etravirine

  etravirine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• fosamprenavir

  fosamprenavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• fosphenytoin

  fosphenytoin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• grapefruit

  grapefruit will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• idelalisib

  idelalisib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• imatinib

  imatinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• indinavir

  indinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• isoniazid

  isoniazid will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lopinavir

  lopinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• mitotane

  mitotane will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nafcillin

  nafcillin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nefazodone

  nefazodone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• nelfinavir

  nelfinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• nevirapine

  nevirapine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nicardipine

  nicardipine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• pentobarbital

  pentobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• phenobarbital

  phenobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• phenytoin

  phenytoin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• posaconazole

  posaconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• primidone

  primidone will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• quinidine

  quinidine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• rifabutin

  rifabutin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• rifampin

  rifampin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• rifapentine

  rifapentine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• ritonavir

  ritonavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• saquinavir

  saquinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• St John's Wort

  St John's Wort will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• tipranavir

  tipranavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• voriconazole

  voriconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

Serious - Use Alternative (47)

• abametapir

  abametapir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• aminolevulinic acid oral

  aminolevulinic acid oral, cobimetinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  cobimetinib, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amiodarone

  amiodarone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• amobarbital

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

• apalutamide

  apalutamide will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  aprepitant will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• bicalutamide

  bicalutamide will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• ceritinib

  ceritinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• chloramphenicol

  chloramphenicol will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ciprofloxacin

  ciprofloxacin will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• crizotinib

  crizotinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• cyclosporine

  cyclosporine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• diltiazem

  diltiazem will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (=14 days) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce cobimetinib dose to 20 mg. After discontinuing the moderate CYP3A inhibitor, resume cobimetinib 60 mg. In patients who are already receiving reduced cobimetinib doses due to adverse reactions, avoid moderate CYP3A4 and use alternative therapy.

• doxycycline

  doxycycline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• dronedarone

  dronedarone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin base

  erythromycin base will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin stearate

  erythromycin stearate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• fexinidazole

  fexinidazole will increase the level or effect of cobimetinib 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.

• fluconazole

  fluconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• fosaprepitant

  fosaprepitant will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• haloperidol

  haloperidol will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• iloperidone

  iloperidone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• itraconazole

  itraconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• ivosidenib

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

• ketoconazole

  ketoconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lapatinib

  lapatinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• levoketoconazole

  levoketoconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lidocaine

  lidocaine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• lonafarnib

  lonafarnib will increase the level or effect of cobimetinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lorlatinib

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

• methyl aminolevulinate

  cobimetinib, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• metronidazole

  metronidazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• netupitant/palonosetron

  netupitant/palonosetron will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• palifermin

  palifermin increases toxicity of cobimetinib 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.

• ribociclib

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

• schisandra

  schisandra will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• secobarbital

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

• sertraline

  sertraline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• tetracycline

  tetracycline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• ticagrelor

  ticagrelor will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• tucatinib

  tucatinib will increase the level or effect of cobimetinib 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.

• verapamil

  verapamil will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• voxelotor

  voxelotor will increase the level or effect of cobimetinib 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.

• zileuton

  zileuton will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

Monitor Closely (17)

• belzutifan

  belzutifan will decrease the level or effect of cobimetinib 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.

• cenobamate

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

• cholera vaccine

  cobimetinib decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• dengue vaccine

  cobimetinib 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.

• duvelisib

  duvelisib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

• elagolix

  elagolix will decrease the level or effect of cobimetinib 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.

• encorafenib

  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.

• fedratinib

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

• istradefylline

  istradefylline will increase the level or effect of cobimetinib 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.

• lenacapavir

  lenacapavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• mifepristone

  mifepristone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If short-term coadministration (14 days or less) of mifepristone necessary, reduce dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of mifepristone, resume cobimetinib at previous dose; use alternative to mifepristone in patients who are already taking a reduced dose of cobimetinib (20-40 mg daily)

• ponesimod

  ponesimod and cobimetinib 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.

• rucaparib

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

• siponimod

  siponimod and cobimetinib 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.

• stiripentol

  stiripentol, cobimetinib. 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.

• tazemetostat

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

• tecovirimat

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

Minor (4)

• acetazolamide

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

• anastrozole

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

• cyclophosphamide

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

• larotrectinib

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

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• acetazolamide

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

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, cobimetinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)cobimetinib, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amiodarone

  Serious - Use Alternative (1)amiodarone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• amobarbital

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

• anastrozole

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

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  Serious - Use Alternative (1)aprepitant will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• armodafinil

  Contraindicated (1)armodafinil will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• atazanavir

  Contraindicated (1)atazanavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of cobimetinib 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.

• bicalutamide

  Serious - Use Alternative (1)bicalutamide will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• bosentan

  Contraindicated (1)bosentan will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• carbamazepine

  Contraindicated (1)carbamazepine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• cenobamate

  Monitor Closely (1)cenobamate will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Serious - Use Alternative (1)ceritinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cholera vaccine

  Monitor Closely (1)cobimetinib decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• ciprofloxacin

  Serious - Use Alternative (1)ciprofloxacin will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• clarithromycin

  Contraindicated (1)clarithromycin will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• clobazam

  Contraindicated (1)clobazam will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• cobicistat

  Contraindicated (1)cobicistat will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• conivaptan

  Contraindicated (1)conivaptan will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• crizotinib

  Serious - Use Alternative (1)crizotinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• cyclophosphamide

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

• cyclosporine

  Serious - Use Alternative (1)cyclosporine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• dabrafenib

  Contraindicated (1)dabrafenib will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• darunavir

  Contraindicated (1)darunavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• dengue vaccine

  Monitor Closely (1)cobimetinib 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.

• dexamethasone

  Contraindicated (1)dexamethasone will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• diltiazem

  Serious - Use Alternative (1)diltiazem will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (=14 days) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce cobimetinib dose to 20 mg. After discontinuing the moderate CYP3A inhibitor, resume cobimetinib 60 mg. In patients who are already receiving reduced cobimetinib doses due to adverse reactions, avoid moderate CYP3A4 and use alternative therapy.

• doxycycline

  Serious - Use Alternative (1)doxycycline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• dronedarone

  Serious - Use Alternative (1)dronedarone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

• efavirenz

  Contraindicated (1)efavirenz will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• elagolix

  Monitor Closely (1)elagolix will decrease the level or effect of cobimetinib 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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Contraindicated (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• encorafenib

  Monitor Closely (1)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.

• enzalutamide

  Contraindicated (1)enzalutamide will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• erythromycin base

  Serious - Use Alternative (1)erythromycin base will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin lactobionate

  Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• erythromycin stearate

  Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• eslicarbazepine acetate

  Contraindicated (1)eslicarbazepine acetate will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• etravirine

  Contraindicated (1)etravirine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of cobimetinib 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.

• fluconazole

  Serious - Use Alternative (1)fluconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• fosamprenavir

  Contraindicated (1)fosamprenavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• fosaprepitant

  Serious - Use Alternative (1)fosaprepitant will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• fosphenytoin

  Contraindicated (1)fosphenytoin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• grapefruit

  Contraindicated (1)grapefruit will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• haloperidol

  Serious - Use Alternative (1)haloperidol will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• idelalisib

  Contraindicated (1)idelalisib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• iloperidone

  Serious - Use Alternative (1)iloperidone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• imatinib

  Contraindicated (1)imatinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• indinavir

  Contraindicated (1)indinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• isoniazid

  Contraindicated (1)isoniazid will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Serious - Use Alternative (1)itraconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  Serious - Use Alternative (1)ketoconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lapatinib

  Serious - Use Alternative (1)lapatinib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• larotrectinib

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

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• levoketoconazole

  Serious - Use Alternative (1)levoketoconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lidocaine

  Serious - Use Alternative (1)lidocaine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of cobimetinib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lopinavir

  Contraindicated (1)lopinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• lorlatinib

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

• lumacaftor/ivacaftor

  Contraindicated (1)lumacaftor/ivacaftor will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• methyl aminolevulinate

  Serious - Use Alternative (1)cobimetinib, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• metronidazole

  Serious - Use Alternative (1)metronidazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• mifepristone

  Monitor Closely (1)mifepristone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If short-term coadministration (14 days or less) of mifepristone necessary, reduce dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of mifepristone, resume cobimetinib at previous dose; use alternative to mifepristone in patients who are already taking a reduced dose of cobimetinib (20-40 mg daily)

• mitotane

  Contraindicated (1)mitotane will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nafcillin

  Contraindicated (1)nafcillin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nefazodone

  Contraindicated (1)nefazodone will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• nelfinavir

  Contraindicated (1)nelfinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• netupitant/palonosetron

  Serious - Use Alternative (1)netupitant/palonosetron will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• nevirapine

  Contraindicated (1)nevirapine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• nicardipine

  Contraindicated (1)nicardipine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• oxcarbazepine

  Contraindicated (1)oxcarbazepine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• palifermin

  Serious - Use Alternative (1)palifermin increases toxicity of cobimetinib 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.

• pentobarbital

  Contraindicated (1)pentobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• phenobarbital

  Contraindicated (1)phenobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• phenytoin

  Contraindicated (1)phenytoin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• ponesimod

  Monitor Closely (1)ponesimod and cobimetinib 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.

• posaconazole

  Contraindicated (1)posaconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• primidone

  Contraindicated (1)primidone will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• quinidine

  Contraindicated (1)quinidine will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• ribociclib

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

• rifabutin

  Contraindicated (1)rifabutin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• rifampin

  Contraindicated (1)rifampin will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• rifapentine

  Contraindicated (1)rifapentine will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• ritonavir

  Contraindicated (1)ritonavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• saquinavir

  Contraindicated (1)saquinavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• schisandra

  Serious - Use Alternative (1)schisandra will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• secobarbital

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

• sertraline

  Serious - Use Alternative (1)sertraline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• siponimod

  Monitor Closely (1)siponimod and cobimetinib 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.

• St John's Wort

  Contraindicated (1)St John's Wort will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• stiripentol

  Monitor Closely (1)stiripentol, cobimetinib. 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.

• tazemetostat

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

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• tetracycline

  Serious - Use Alternative (1)tetracycline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• ticagrelor

  Serious - Use Alternative (1)ticagrelor will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• tipranavir

  Contraindicated (1)tipranavir will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of cobimetinib 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.

• verapamil

  Serious - Use Alternative (1)verapamil will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

• voriconazole

  Contraindicated (1)voriconazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of cobimetinib 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.

• zileuton

  Serious - Use Alternative (1)zileuton will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).