Dosing & Uses
Dosage Forms & Strengths
tablet
- 20 mg
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (46)
- 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.
Adverse Effects
Adverse reactions are listed for all grades, unless otherwise stated
Data listed below are based on combination of cobimetinib plus vemurafenib
>10%
Increased creatinine (99.6%)
Increased CPK (79%)
Increased AST (73%)
Lymphopenia (73%)
Increased alkaline phosphatase (71%)
Anemia (69%)
Increased ALT (68%)
Hypophosphatemia (68%)
Increased GGT (65%)
Diarrhea (60%)
Photosensitivity (46%)
Hypoalbuminemia (42%)
Nausea (41%)
Hyponatremia (38%)
Pyrexia (28%)
Hyperkalemia (26%)
Hypokalemia (25%)
Hypocalcemia (24%)
Vomiting (24%)
Thrombocytopenia (18%)
Acneiform dermatitis (16%)
Hypertension (15%)
Vision impaired (15%)
Alopecia (15%)
Stomatitis (14%)
Hemorrhage (13%)
Chorioretinopathy (13%)
Retinal detachment (12%)
Hyperkeratosis (11%)
Grades 3-4
- Increased GGT (21%)
- Increased CPK (14%)
- Hypophosphatemia (12%)
- Increased ALT (11%)
1-10%
Chills (10%)
Erythema (10%)
Grades 3-4
- Lymphopenia (10%)
- Increased AST (8%)
- Increased alkaline phosphatase (7%)
- Hyponatremia (6%)
- Diarrhea (6%)
- Hypokalemia (4.5%), Hyperkalemia (2.9%)
- Photosensitivity (4%)
- Hypertension (4%)
- Increased creatinine (3.3%)
- Anemia (2.5)
- Acneiform dermatitis (2%)
- Pyrexia (2%)
- Retinal detachment (2%)
- Nausea (1%) Vomiting (1%)
- Stomatitis (1%) Hemorrhage (1%)
<1%
Grades 3-4
- Vision impaired
- Chorioretinopathy
- Hypoalbuminemia
- Hypocalcemia
Postmarketing Reports
Respiratory, thoracic, and mediastinal disorders: Hypoxia, pulmonary edema, and respiratory failure
Eye disorders: Vision blurred, retinal vascular disorder, and retinopathy
Nervous system disorders: Headache
Warnings
Contraindications
None
Cautions
Refer to the Dosage Modification section for instructions on withholding, decreasing, or permanently discontinuing cobimetinib in the event of adverse reactions
New primary malignancies can occur; monitor for new malignancies prior to initiation of therapy, while on therapy, and for up to 6 months following the last dose (see Dosage Modifications)
May cause severe dermatologic reactions; monitor for severe rashes; interrupt, reduce dose, or discontinue therapy if it occurs (see Dosage Modifications)
Serous retinopathy and retinal vein occlusion reported; perform an ophthalmological evaluation at regular intervals and for any visual disturbances; if serous retinopathy diagnosed, interrupt therapy until visual symptoms improve (see Dosage Modifications)
Hepatotoxicity reported; monitor liver laboratory tests monthly during treatment and as clinically indicated; (see Dosage Modifications)
Monitor CPK periodically and as clinically indicated for signs and symptoms of rhabdomyolysis (see Dosage Modifications)
Severe photosensitivity may occur; advise patients to avoid sun exposure (see Dosage Modifications)
Can cause fetal harm; advise females of reproductive potential of the potential risk to a fetus and to use effective contraception
Cardiomyopathy
- Risk of cardiomopathy is increased in patients receiving cobimetinib with vemurafenib compared with vemurafenib as a single agent; safety has not been established in patients with decreased LVEF; evaluate LVEF before treatment, after 1 month of treatment, then q3 months thereafter during treatment (see Dosage Modifications)
- Of the patients with decreased LVEF, all had dose interruption and/or reduction and none required permanent discontinuation
- Decreased LVEF resolved to above the LLN or within 10% of baseline in 60% of patients receiving this drug with a median time to resolution of 31 days (range: 13 days to 126 days)
Hemorrhage
- Major hemorrhagic events reported; monitor for signs and symptoms of bleeding (see Dosage Modifications)
- Gastrointestinal tract hemorrhage, reproductive system hemorrhage, and hematuria also occurred at a higher incidence in patients receiving the drug in combination with vemurafenib compared with patients receiving vemurafenib alone
- Withhold therapy for Grade 3 hemorrhagic events; if improved to Grade 0 or 1 within 4 weeks, resume therapy at a lower dose level
Drug interactions overview
- Coadministration with itraconazole (a strong CYP3A4 inhibitor) increased cobimetinib systemic exposure by 6.7-fold
- Avoid coadministration with moderate or strong CYP3A4 inhibitors or inducers; if unable to avoid short-term use of moderate CYP3A4 inhibitors, reduce cobimetinib dose (see Dosage Modifications)
- Coadministration with a strong CYP3A inducer may decrease cobimetinib systemic exposure by more than 80% and reduce its efficacy
- Also see Dosage Modification
Pregnancy
Pregnancy
Based on findings from animal reproduction studies and its mechanism of action, cobimetinib can cause fetal harm when administered to a pregnant woman
In animal reproduction studies, oral administration of cobimetinib in pregnant rats during organogenesis was teratogenic and embryotoxic at exposures (AUC) that were 0.9- to 1.4-times those observed in humans at the recommended human dose of 60 mg
Advise pregnant women of the potential risk to a fetus
Contraception: Advise females of reproductive potential to use effective contraception during treatment with and for 2 weeks after the final dose
Infertility: Based on findings in animals, cobimetinib may reduce fertility in females and males of reproductive potential
Lactation
Unknown if distributed in human breast milk
Because of the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment and for 2 weeks after the final dose
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.Pharmacology
Mechanism of Action
Reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2
MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation
BRAF V600E and K mutations result in constitutive activation of the BRAF pathway, which includes MEK1 and MEK2
Cobimetinib and vemurafenib target 2 different kinases in the RAS/RAF/MEK/ERK pathway; compared with either drug alone, coadministration resulted in increased apoptosis in vitro and reduced tumor growth in mouse implantation models of tumor cell lines harboring BRAF V600E mutations
Cobimetinib also prevented vemurafenib-mediated growth enhancement of a wild-type BRAF tumor cell line in an in vivo mouse implantation model
Absorption
Bioavailability: 46%
Peak plasma time: 2.4 hr
Peak plasma concentration: 273 ng/mL
AUC: 4340 ng·h/mL
Distribution
Protein bound: 95%
Vd: 806 L
Metabolism
CYP3A oxidation and UGT2B7 glucuronidation are the major metabolic pathways for cobimetinib
Elimination
Half-life: 44 hr
Clearance: 13.8 L/hr
Excretion: 76% feces (6.6% unchanged); 17.8% urine (1.6% unchanged)
Administration
Instructions
May take with or without food
Missed or vomited dose: Resume dosing with the next scheduled dose
Storage
Store at room temperature below 30°C (86°F)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Cotellic oral - | 20 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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