Dosing & Uses
Dosage Forms & Strengths
tablet
- 240mg
Malignant Melanoma
Indicated for treatment of unresectable or metastatic melanoma with BRAF-V600E mutation as detected by an FDA-approved test
960 mg (4 x 240 mg tablets) PO q12hr (administer approximately 12 hr apart)
See also Administration
Erdheim-Chester Disease
Indicated for the treatment of Erdheim-Chester Disease (ECD) with BRAF V600 mutation
960 mg (4 x 240 mg tablets) PO q12hr (administer approximately 12 hr apart)
See also Administration
Dosage Modifications
New primary cutaneous malignancies: No dose modifications necessary
Do not dose reduce to below 480 mg q12hr
Recommended dosage modifications for other adverse events (AE)
Permanently discontinue treatment
- Grade 4 AE, first appearance (if clinically appropriate) or second appearance
- QTc prolongation >500 ms and increased by >60 ms from pretreatment values
Withhold treatment for intolerable Grade ≥2
- First appearance of intolerable Grade 2 or Grade 3 AE: Restart and reduced dose to 720 mg PO q12hr upon recovery to Grade 0–1
- Second appearance of Grade 2 (if intolerable) or Grade 3 adverse reactions or for first appearance of Grade 4 adverse reaction (if clinically appropriate): Restart and reduced dose to 480 mg PO q12hr upon recovery to Grade 0–1
Concomitant use of strong CYP3A4 inducers
- Avoid concomitant use of strong CYP3A4 inducers with vemurafenib
- If concomitant use of a strong CYP3A4 inducer is unavoidable, increase vemurafenib dose by 240 mg (one tablet) as tolerated
- After discontinuation of a strong CYP3A4 inducer for 2 weeks, resume vemurafenib dose that was taken prior to initiating the strong CYP3A4 inducer
Renal Impairment
- Mild-to-moderate: No dose adjustment required
- Severe: Appropriate dose not established
Hepatic impairment
- Mild-to-moderate: No dose adjustment required
- Severe: Appropriate dose not established
Dosing Considerations
Limitation of use
- Not recommended for use with wild-type BRAF melanoma
Orphan Designations
Thyroid cancer: Treatment of anaplastic thyroid carcinoma and advanced papillary thyroid cancer whose tumors harbor a BRAF V600 mutation
Non-small cell lung cancer (NSCLC) with BRAF V600E mutation
Sponsor
- Genentech, Inc; 1 DNA Way, M/S 241B; South San Francisco, CA 94080-4990
<18 years: Safety and efficacy not established
No dosage adjustments are required for geriatric patients
During clinical trials, 28% of patients were aged 65 yr or older
Elderly patients may be more likely to experience some adverse reactions, including cutaneous squamous cell carcinoma, nausea, decreased appetite, peripheral edema, keratoacanthoma and atrial fibrillation
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (4)
- goserelin
goserelin increases toxicity of vemurafenib by QTc interval. Contraindicated. Increases risk of torsades de pointes.
- lefamulin
lefamulin will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.
- leuprolide
leuprolide increases toxicity of vemurafenib by QTc interval. Contraindicated. Increases risk of torsades de pointes.
- saquinavir
saquinavir will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
Serious - Use Alternative (183)
- abametapir
abametapir will increase the level or effect of vemurafenib 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.
- adagrasib
adagrasib, vemurafenib. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
- alfuzosin
alfuzosin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- alpelisib
vemurafenib will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.
- aminolevulinic acid oral
aminolevulinic acid oral, vemurafenib. 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
vemurafenib, 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
vemurafenib and amiodarone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Amiodarone may also increase vemurafenib levels.
- amisulpride
amisulpride and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
- amitriptyline
vemurafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- amoxapine
vemurafenib and amoxapine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- anagrelide
anagrelide and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of vemurafenib 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.
- apomorphine
vemurafenib and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- aripiprazole
aripiprazole and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- arsenic trioxide
vemurafenib and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- artemether
artemether and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- artemether/lumefantrine
vemurafenib and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- asenapine
vemurafenib and asenapine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- asenapine transdermal
asenapine transdermal and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- atazanavir
atazanavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atomoxetine
atomoxetine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- azithromycin
vemurafenib and azithromycin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- buprenorphine
buprenorphine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine buccal
buprenorphine buccal and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine subdermal implant
buprenorphine subdermal implant and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine transdermal
buprenorphine transdermal and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
ceritinib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - chloramphenicol
chloramphenicol will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chlorpromazine
vemurafenib and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- ciprofloxacin
vemurafenib and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- citalopram
vemurafenib and citalopram both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- clarithromycin
vemurafenib and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Clarithromycin may also increase levels of vemurafenib.
clarithromycin will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - clomipramine
vemurafenib and clomipramine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- clozapine
clozapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- cobicistat
cobicistat will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- colchicine
vemurafenib increases levels of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid use of colchicine with P-gp inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment. .
- conivaptan
conivaptan will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dabrafenib
dabrafenib will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darolutamide
darolutamide will increase the level or effect of vemurafenib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- darunavir
darunavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dasatinib
vemurafenib and dasatinib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- degarelix
vemurafenib and degarelix both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- desflurane
desflurane and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- desipramine
vemurafenib and desipramine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- dexamethasone
dexamethasone decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dofetilide
vemurafenib and dofetilide both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- dolasetron
vemurafenib and dolasetron both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- donepezil
donepezil and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- dronedarone
vemurafenib and dronedarone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Dronedarone may also increase vemurafenib levels.
- droperidol
vemurafenib and droperidol both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- edoxaban
vemurafenib will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended
- efavirenz
efavirenz will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
efavirenz and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. - eliglustat
eliglustat and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- encorafenib
encorafenib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Encorafenib is associated with dose-dependent QTc interval prolongation. Avoid with drugs known to prolong QT interval.
- entrectinib
vemurafenib and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.
- enzalutamide
enzalutamide will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- eribulin
eribulin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin base
vemurafenib and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Erythromycin may also increase vemurafenib levels.
- erythromycin ethylsuccinate
vemurafenib and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Erythromycin may also increase vemurafenib levels.
- erythromycin lactobionate
vemurafenib and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Erythromycin may also increase vemurafenib levels.
- erythromycin stearate
vemurafenib and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Erythromycin may also increase vemurafenib levels.
- escitalopram
vemurafenib and escitalopram both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
escitalopram increases toxicity of vemurafenib by QTc interval. Avoid or Use Alternate Drug. - eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
fexinidazole will increase the level or effect of vemurafenib 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. - fingolimod
fingolimod and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- flecainide
vemurafenib increases levels of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP2D6 substrate drug. Combination may increase risk QT prolongation.
- fluconazole
vemurafenib and fluconazole both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- fluoxetine
vemurafenib and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- fosamprenavir
fosamprenavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- foscarnet
vemurafenib and foscarnet both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- fosphenytoin
fosphenytoin decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- gemifloxacin
vemurafenib and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- gilteritinib
gilteritinib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- glasdegib
vemurafenib and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.
- granisetron
granisetron and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- haloperidol
vemurafenib and haloperidol both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- histrelin
histrelin increases toxicity of vemurafenib by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- hydroxyzine
hydroxyzine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- ibutilide
vemurafenib and ibutilide both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- idelalisib
idelalisib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- iloperidone
vemurafenib and iloperidone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- imatinib
imatinib increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- indapamide
vemurafenib and indapamide both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- indinavir
indinavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- inotuzumab
inotuzumab and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- isoflurane
isoflurane and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- isoniazid
isoniazid increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- isradipine
vemurafenib and isradipine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- itraconazole
itraconazole increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
itraconazole and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. - ivosidenib
ivosidenib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
ivosidenib will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs. - ketoconazole
ketoconazole increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lapatinib
vemurafenib and lapatinib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Lapatinib may also increase vemurafenib levels.
- lasmiditan
lasmiditan increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
lasmiditan increases levels of vemurafenib by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates. - levofloxacin
vemurafenib and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- levoketoconazole
levoketoconazole increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lithium
lithium and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
vemurafenib and lopinavir both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
lopinavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - lumefantrine
vemurafenib and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- macimorelin
macimorelin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.
- maprotiline
vemurafenib and maprotiline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- mefloquine
vemurafenib and mefloquine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Mefloquine may also increase vemurafenib levels.
mefloquine increases toxicity of vemurafenib by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents. - methadone
vemurafenib and methadone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- methyl aminolevulinate
vemurafenib, methyl aminolevulinate. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.
- mifepristone
mifepristone will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mirtazapine
mirtazapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- mobocertinib
mobocertinib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.
- moxifloxacin
vemurafenib and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- nefazodone
nefazodone increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nelfinavir
nelfinavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nicardipine
nicardipine increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nilotinib
vemurafenib and nilotinib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Nilotinib may also increase vemurafenib levels.
- nortriptyline
vemurafenib and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- octreotide
vemurafenib and octreotide both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- ofloxacin
vemurafenib and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- olanzapine
olanzapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- ondansetron
ondansetron and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias. Alterations in ondansetron concentrations may occur with concomitant use.
- oxaliplatin
oxaliplatin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- oxcarbazepine
oxcarbazepine decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ozanimod
vemurafenib increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .
- pacritinib
vemurafenib will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- palifermin
palifermin increases toxicity of vemurafenib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- paliperidone
vemurafenib and paliperidone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- panobinostat
vemurafenib and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.
- pazopanib
vemurafenib and pazopanib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Pazopanib may also increase levels of vemurafenib.
- pentamidine
vemurafenib and pentamidine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- phenobarbital
phenobarbital decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pimavanserin
pimavanserin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. Coadministration may increase the risk of QT prolongation and cardiac arrhythmia.
- pitolisant
vemurafenib and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.
- posaconazole
vemurafenib and posaconazole both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Posaconazole may also increase levels of vemurafenib.
posaconazole will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. - primaquine
primaquine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- procainamide
vemurafenib increases levels of procainamide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP2D6 substrate drug. Combination may increase risk QT prolongation.
- propafenone
vemurafenib and propafenone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- protriptyline
vemurafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- quetiapine
vemurafenib and quetiapine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- quinine
vemurafenib and quinine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- ranolazine
vemurafenib and ranolazine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Ranolazine may also increase vemurafenib levels.
- ribociclib
ribociclib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
ribociclib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - rifabutin
rifabutin decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rimegepant
vemurafenib will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
vemurafenib will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP. - riociguat
vemurafenib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
- risperidone
vemurafenib and risperidone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- ritonavir
vemurafenib and ritonavir both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
ritonavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - romidepsin
vemurafenib and romidepsin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Romidepsin may also increase vemurafenib levels.
- saquinavir
vemurafenib and saquinavir both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Saquinavir may also increase levels of vemurafenib.
- sertraline
sertraline and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- sevoflurane
sevoflurane and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- siponimod
siponimod and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- solifenacin
solifenacin and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- sotalol
vemurafenib and sotalol both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- sotorasib
sotorasib will decrease the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- St John's Wort
St John's Wort decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sunitinib
vemurafenib and sunitinib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- tacrolimus
tacrolimus and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- talazoparib
vemurafenib will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.
- telavancin
vemurafenib and telavancin both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- tepotinib
tepotinib will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- tetrabenazine
tetrabenazine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- thioridazine
vemurafenib increases levels of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP2D6 substrate drug. Combination may increase risk QT prolongation.
- thiothixene
vemurafenib and thiothixene both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- tipranavir
tipranavir increases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- topotecan
vemurafenib will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance
- toremifene
vemurafenib and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- trimipramine
vemurafenib and trimipramine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- triptorelin
triptorelin increases toxicity of vemurafenib by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.
- tucatinib
tucatinib will increase the level or effect of vemurafenib 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.
- umeclidinium bromide/vilanterol inhaled
vemurafenib increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
- vandetanib
vemurafenib and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- vardenafil
vemurafenib and vardenafil both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- venetoclax
vemurafenib will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.
- vilanterol/fluticasone furoate inhaled
vemurafenib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
- voriconazole
vemurafenib and voriconazole both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Voriconazole may also increase levels of vemurafenib.
- vorinostat
vemurafenib and vorinostat both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
- voxelotor
voxelotor will increase the level or effect of vemurafenib 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.
- ziprasidone
vemurafenib and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.
Monitor Closely (124)
- abiraterone
abiraterone increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- acalabrutinib
acalabrutinib increases levels of vemurafenib by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
- albuterol
albuterol and vemurafenib both increase QTc interval. Use Caution/Monitor.
- alfuzosin
vemurafenib and alfuzosin both increase QTc interval. Use Caution/Monitor.
- aliskiren
vemurafenib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- apalutamide
apalutamide will decrease the level or effect of vemurafenib by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.
- arformoterol
arformoterol and vemurafenib both increase QTc interval. Use Caution/Monitor.
- atogepant
vemurafenib will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
vemurafenib increases levels of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bedaquiline
vemurafenib and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely
- berotralstat
vemurafenib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.
vemurafenib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.
berotralstat will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered. - betrixaban
vemurafenib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
- bosentan
bosentan will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- carbamazepine
carbamazepine decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- carvedilol
vemurafenib increases levels of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ceritinib
vemurafenib increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cetirizine
vemurafenib increases levels of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- chloroquine
chloroquine increases toxicity of vemurafenib by QTc interval. Use Caution/Monitor.
- cholera vaccine
vemurafenib 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.
- crizotinib
crizotinib and vemurafenib both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.
- cyclosporine
cyclosporine increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
vemurafenib increases levels of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - dabigatran
vemurafenib will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min
- daunorubicin
vemurafenib increases levels of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dengue vaccine
vemurafenib 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.
- desloratadine
vemurafenib increases levels of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- deutetrabenazine
vemurafenib and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
deutetrabenazine and vemurafenib both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation). - dexamethasone
vemurafenib increases levels of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- digoxin
vemurafenib increases levels of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- diltiazem
vemurafenib increases levels of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- docetaxel
vemurafenib increases levels of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dofetilide
dofetilide increases toxicity of vemurafenib by QTc interval. Use Caution/Monitor.
- doxepin
doxepin and vemurafenib both increase QTc interval. Use Caution/Monitor.
- doxorubicin
vemurafenib increases levels of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- duvelisib
duvelisib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
vemurafenib will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
vemurafenib will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib. - elagolix
elagolix will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix decreases levels of vemurafenib 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. - eliglustat
eliglustat increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- encorafenib
encorafenib, vemurafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
encorafenib will increase the level or effect of vemurafenib by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. - etoposide
vemurafenib increases levels of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- everolimus
vemurafenib increases levels of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fexofenadine
vemurafenib increases levels of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fosamprenavir
vemurafenib increases levels of fosamprenavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fosphenytoin
fosphenytoin decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fostamatinib
fostamatinib will increase the level or effect of vemurafenib by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
fostamatinib will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp/BCRP substrate drugs. Monitor for toxicities of P-gp/BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib. - fostemsavir
fostemsavir will increase the level or effect of vemurafenib by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.
vemurafenib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir. - gadobenate
gadobenate and vemurafenib both increase QTc interval. Use Caution/Monitor.
- gemtuzumab
vemurafenib and gemtuzumab both increase QTc interval. Use Caution/Monitor.
- glecaprevir/pibrentasvir
vemurafenib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.
glecaprevir/pibrentasvir will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
glecaprevir/pibrentasvir will increase the level or effect of vemurafenib by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates. - grapefruit
grapefruit increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- imatinib
vemurafenib increases levels of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- indinavir
vemurafenib increases levels of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ipilimumab
ipilimumab, vemurafenib. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Grade 3 increases in transaminases and bilirubin observed in a majority of patients when coadministered.
- irinotecan
vemurafenib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- irinotecan liposomal
vemurafenib increases levels of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- isavuconazonium sulfate
vemurafenib will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of vemurafenib 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.
istradefylline will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - itraconazole
itraconazole increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ketoconazole
ketoconazole increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir 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.
- lenvatinib
vemurafenib and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.
- levoketoconazole
levoketoconazole increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lofexidine
vemurafenib and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.
- lonafarnib
lonafarnib will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- loperamide
vemurafenib increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loratadine
vemurafenib increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lorlatinib
lorlatinib will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lovastatin
vemurafenib increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mifepristone
mifepristone, vemurafenib. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.
- mitomycin
vemurafenib increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mitotane
mitotane decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nafcillin
nafcillin will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- naldemedine
vemurafenib increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.
- nelfinavir
nelfinavir increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
vemurafenib increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nicardipine
nicardipine increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nintedanib
vemurafenib increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .
- osilodrostat
osilodrostat and vemurafenib both increase QTc interval. Use Caution/Monitor.
- osimertinib
osimertinib and vemurafenib both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.
- oteseconazole
oteseconazole will increase the level or effect of vemurafenib by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- oxaliplatin
oxaliplatin will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.
- ozanimod
ozanimod and vemurafenib both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
- paclitaxel
vemurafenib increases levels of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paclitaxel protein bound
vemurafenib increases levels of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pasireotide
vemurafenib and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.
- phenytoin
phenytoin decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pravastatin
vemurafenib increases levels of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- quinidine
vemurafenib and quinidine both increase QTc interval. Modify Therapy/Monitor Closely. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended. Quinidine may also increase vemurafenib levels.
- regorafenib
regorafenib will increase the level or effect of vemurafenib by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.
- rifampin
vemurafenib increases levels of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
rifampin decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - rifaximin
vemurafenib increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ritonavir
ritonavir increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
vemurafenib increases levels of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - rivaroxaban
vemurafenib increases levels of rivaroxaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- safinamide
safinamide will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.
- sarecycline
sarecycline will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- saxagliptin
vemurafenib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- selexipag
vemurafenib will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.
- selpercatinib
selpercatinib increases toxicity of vemurafenib by QTc interval. Use Caution/Monitor.
- silodosin
vemurafenib increases levels of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- siponimod
siponimod and vemurafenib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sirolimus
vemurafenib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sitagliptin
vemurafenib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sorafenib
sorafenib and vemurafenib both increase QTc interval. Use Caution/Monitor.
- St John's Wort
St John's Wort decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- stiripentol
stiripentol, vemurafenib. 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.
stiripentol will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.
stiripentol will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered. - tafamidis
tafamidis will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tafamidis meglumine
tafamidis meglumine will increase the level or effect of vemurafenib by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tamoxifen
tamoxifen increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
vemurafenib will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tecovirimat
tecovirimat will decrease the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- teniposide
vemurafenib increases levels of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- theophylline
vemurafenib decreases levels of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP1A2 substrate drug.
- tizanidine
vemurafenib increases levels of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP1A2 substrate drug.
- tolvaptan
vemurafenib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- triclabendazole
triclabendazole and vemurafenib both increase QTc interval. Use Caution/Monitor.
- tucatinib
tucatinib will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- ubrogepant
vemurafenib will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dose adjustment is recommended with concomitant use of ubrogepant and moderate and weak CYP3A4 inducers. (see Dosage Modifications)
- valbenazine
valbenazine and vemurafenib both increase QTc interval. Use Caution/Monitor.
- verapamil
verapamil increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
vemurafenib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - vinblastine
vemurafenib increases levels of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine
vemurafenib increases levels of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine liposomal
vemurafenib increases levels of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- voclosporin
voclosporin, vemurafenib. Either increases effects of the other by QTc interval. Use Caution/Monitor.
- voriconazole
voriconazole will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (4)
- acetazolamide
acetazolamide will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10% (All Grades)
Arthralgia (82%)
Maculopapular rash (59%)
Alopecia (55%) Fatigue (55%)
Skin papilloma (55%)
QT prolongation (55%)
Hyperkeratosis (50%)
Diarrhea (50%)
Dry skin (45%)
Seborrheic keratosis (41%)
Photosensitivity reaction (41%)
Palmar-plantar erythrodysesthesia syndrome (41%)
Pruritus (36%) SCC of skin (36%)
Peripheral sensory neuropathy (36%)
Cough (36%) Hypertension (36%)
Nausea (32%)
Actinic keratosis (32%)
Keratosis pilaris (32%)
Rash papular (23%)
Vomiting (23%)
Melanocytic nevus (23%)
Sunburn (23%)
Keratoacanthoma (<20%)
Dupuytren’s contracture (<20%)
>10% (Grade 3 or 4)
SCC of skin (36%)
Hypertension (23%)
Arthralgia (14%)
1-10% (Grades 3 or 4)
Elevated AST (9.1%)
Actinic keratosis (5%)
Fatigue (5%)
QT prolongation (5%)
Elevated alkaline phosphatase (4.5%)
Postmarketing Reports
Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Progression of pre-existing chronic myelomonocytic leukemia with NRAS mutation
Skin and subcutaneous tissue disorders: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Blood and lymphatic systems disorder: Neutropenia
Injury, poisoning and procedural complications: Radiation sensitization and recall
Gastrointestinal disorders: Pancreatitis
Renal and urinary disorders: Acute interstitial nephritis, acute tubular necrosis
Musculoskeletal and connective tissue disorders: Dupuytren’s contracture and plantar fascial fibromatosis
Warnings
Contraindications
None
Cautions
Anaphylaxis and other serious hypersensitivity reactions reported during treatment and upon reinitiation, including generalized rash and erythema, hypotension, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); permanently discontinue
Severe dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis reported; discontinue treatment
Elevated liver enzymes may occur; monitor liver enzymes and bilirubin before treatment initiation and then monthly or as clinically indicated
Liver injury leading to functional hepatic impairment, including coagulopathy or other organ dysfunction, can occur with vemurafenib
Mild-to-moderate photosensitivity reported; advise patients to avoid sun exposure and wear protective clothing and use a broad spectrum UVA/UVB sunscreen and lip balm (SPF >30) when outdoors
Serious ophthalmologic reactions, including uveitis, iritis, blurry vision, photophobia, and retinal vein occlusion reported
Based on mechanism of action, can cause fetal harm when administered to pregnant women; avoid use during pregnancy and use effective contraception (see Pregnancy
Severe cases of radiation sensitization and recall reported
Renal failure, including acute interstitial nephritis and acute tubular necrosis reported; measure serum creatinine before initiation of therapy and periodically during treatment
Dupuytren’s contracture and plantar fascial fibromatosis reported; majority of cases, mild to moderate, but severe disabling cases of Dupuytren’s contracture also reported
BRAF mutation test required to confirm eligibility for treatment; has not been studied with wild-type BRAF melanoma
New primary malignancies
- Cutaneous squamous cell carcinomas (cuSCC) and keratoacanthoma occurred in 24% of patients
- Unresectable or metastatic melanoma, new primary malignant melanoma occurred in 2.1% of patients
- Perform dermatologic evaluations prior to treatment initiation and q2Months while on therapy
- Manage with excision and continue treatment without dose adjustment; consider monitoring for 6 months following discontinuation of treatment
- Noncutaneous squamous cell carcinomas (non-cuSCC) of the head and neck can; monitor for signs or symptoms of new non-cuSCC
- Based on mechanism of action, vemurafenib may promote malignancies associated with activation of RAS through mutation or other mechanisms; monitor for signs or symptoms of other malignancies
- Cases of myeloid neoplasms amongst patients with Erdheim-Chester disease (ECD) reported, including in patients who have received therapy; monitoring complete blood count in ECD patients with co-existing myeloid malignancies recommended
QT prolongation
- Concentration-dependent QT prolongation reported
- Do not start treatment in patients with uncorrectable electrolyte abnormalities, QTc >500 ms, or long QT syndrome, or in patients who are taking medication associated with QT prolongation
- Monitor ECG and electrolytes before treatment initiation and after dose modification
- Monitor ECGs at day 15, monthly during the first 3 months of treatment, and then q3Months thereafter, or more often as clinically indicated
- If the QTc exceeds 500 ms, temporarily interrupt treatment, correct electrolyte abnormalities, and control for cardiac risk factors for QT prolongation (see Dosage Modifications)
- Permanently discontinue if QTc interval remains >500 ms and increased >60 ms from pretreatment values after controlling cardiac risk factors for QT prolongation (eg, electrolyte abnormalities, congestive heart failure, and bradyarrhythmias)
Drug interactions overview
- Vemurafenib is a CYP3A4 substrate and CYP1A2 inhibitor
- Avoid coadministration of vemurafenib with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, saquinavir, ritonavir, indinavir, nelfinavir, voriconazole) and replace and use alternative drugs when possible
- Avoid coadministration with strong CYP3A4 inducers; if unavoidable, increase vemurafenib dose (see Dosage Modifications)
- Avoid concomitant use of vemurafenib with drugs having a narrow therapeutic window that are predominantly metabolized by CYP1A2; coadministration of vemurafenib with tizanidine, a sensitive CYP1A2 substrate, increased tizanidine systemic exposure by 4.7-fold
- Avoid concurrent use of P-gp substrates known to have narrow therapeutic window; if medication use is unavoidable, consider dose reduction of P-gp substrates with narrow therapeutic indices
- Increases in transaminases and bilirubin occurred in a majority of patients who are concurrently using ipilimumab and vemurafenib
Pregnancy & Lactation
Pregnancy
There are no available data on the use of vemurafenib in pregnant women to determine the drug-associated risk
Based on mechanism of action, therapy can cause fetal harm when administered to pregnant women; advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the final dose
Lactation
There is no information available regarding presence of vemurafenib in human milk, effects on breastfed infant, or effects on milk production; because of potential for serious adverse reactions in breastfed infant, including malignancy, severe dermatologic reactions, QT prolongation, hepatotoxicity, photosensitivity, and ophthalmologic toxicity, advise women not to breastfeed during treatment and for 2 weeks after 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
Inhibitor of some mutated forms of BRAF serine-threonine kinase, including BRAF-V600E
Also inhibits other kinases in vitro (eg, CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, FGR) at similar concentrations
Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation
Absorption
Bioavailability: Not determined
Peak Plasma Time: 3 hr
Peak Plasma Concentration: 62 mcg/mL
AUC: 610 mcg•h/mL
Steady state, twice daily regimen: 15-22 days
Distribution
Protein Bound: >99% to human albumin and alpha-1 acid glycoprotein plasma proteins
Vd: 106 L (66% inter-patient variability)
Metabolism
Mean data showed that vemurafenib and its metabolites represented 95% and 5% of the components in plasma, respectively
Metabolized by CYP3A4
Moderate CYP1A2 inhibitor, weak CYP2D6 inhibitor, and a CYP3A4 inducer
Substrate and an inhibitor of the efflux transporter P-glycoprotein
Elimination
Half-life: 57 hr (range 30-120 hr)
Total body clearance: 31 L/day (32% inter-patient variability)
Excretion, following 960 mg dose: Feces (94%), urine (1%)
Pharmacogenomics
Vemurafenib is indicated only for patients with melanoma who have the V600E mutation of the BRAF gene (50% of patients with melanoma have this type of BRAF mutation, which does not occur in normal cells)
Genetic test
- Vemurafenib approved with companion diagnostic test known as the cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems)
Administration
Oral Administration
Take in morning and evening approximately 12 hr apart
May take with or without food
Swallow whole with a glass of water; do not chew or crush
If a dose is missed, it can be taken up to 4 hr prior to the next dose to maintain the twice daily regimen; do not take both doses at the same time
Do not take an additional dose if vomiting occurs after administration, but continue with the next scheduled dose
Duration of treatment is until disease progression occurs or unacceptable toxicity occurs
Storage
Store at room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
Store in the original container with the lid tightly closes
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Zelboraf oral - | 240 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
vemurafenib oral
VEMURAFENIB - ORAL
(VEM-ue-RAF-e-nib)
COMMON BRAND NAME(S): Zelboraf
USES: Vemurafenib is used to treat a type of skin cancer (melanoma). It is also used to treat a rare type of blood cell cancer called Erdheim-Chester disease. These cancer cells have a certain type of abnormal "BRAF" gene. Vemurafenib works by slowing the growth of certain cancer cells. It belongs to a class of drugs known as kinase inhibitors.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking vemurafenib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually twice daily about 12 hours apart. Swallow whole with a glass of water. Do not crush or chew this medication. If you vomit after taking your dose, do not take an extra dose of this medication. Take the next dose of the medication at the regularly scheduled time.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Tell your doctor if your condition lasts or gets worse.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.
SIDE EFFECTS: Hair loss, dry skin, headache, nausea, vomiting, diarrhea, swelling of ankles/feet/hands, or joint/muscle pain may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Vemurafenib may cause other types of skin cancer (such as cutaneous squamous cell carcinoma and melanoma) that usually does not spread to other parts of the body. (See also Notes section.) Tell your doctor right away if you have any skin changes including: new wart, skin sore, change in size/color of a mole, skin bump that bleeds or does not heal.Rarely, vemurafenib may also cause or worsen other types of cancer (such as non-cutaneous squamous cell carcinomas of the head and neck; cancers with RAS mutations, such as certain types of leukemias). Consult your doctor for more details.Get medical help right away if you have any very serious side effects, including: eye pain/swelling/redness, vision changes (such as blurred vision, blind spot/shadows in the center of your vision, sensitivity to light), fast/irregular heartbeat, severe dizziness, fainting, liver problems (symptoms such as loss of appetite, extreme tiredness, stomach/abdominal pain, dark urine, yellowing eyes/skin), pain/trouble swallowing, heartburn, signs of kidney problems (such as change in the amount of urine, pink/bloody urine).Vemurafenib can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rash that could be a sign of a severe reaction. Tell your doctor right away if you develop any rash.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking vemurafenib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: radiation therapy.Vemurafenib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using vemurafenib, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using vemurafenib safely.This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially skin changes, nausea, decreased appetite, swelling of ankles/feet/hands, and QT prolongation (see above).Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using vemurafenib. Vemurafenib may harm an unborn baby. Ask about reliable forms of birth control while using this medication and for 2 weeks after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of possible risk to the infant, breast-feeding while using this medication and for 2 weeks after stopping treatment is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: ipilimumab.Many drugs besides vemurafenib may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, quinidine, procainamide, sotalol, and certain antipsychotic medications (such as pimozide, thioridazine, ziprasidone), among others.Other medications can affect the removal of vemurafenib from your body, which may affect how vemurafenib works. Examples include azole antifungals (such as ketoconazole, itraconazole), macrolide antibiotics (such as clarithromycin), nefazodone, HIV protease inhibitors (such as atazanavir), ritonavir, St. John's wort, telithromycin, among others.Vemurafenib can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include caffeine, warfarin, among others.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as BRAF testing, liver function tests, kidney function tests, EKG, blood mineral levels) should be done before you start taking this medication and while you are taking it. Keep all appointments as it is important to have regular skin exams (such as every 2 months) while taking and for up to 6 months after stopping treatment with vemurafenib. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is within 4 hours of your next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature. Keep this medication in the original container away from light and moisture. Do not store in the bathroom. Keep all medication away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised January 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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