pharmacopeia
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/api/v1/drug/vemurafenib

Mechanism of action

Sourced from openFDA

Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms of BRAF serine- threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations.

BRAF Serine/Threonine KinaseCytochrome P450 1A2P-GlycoproteinProtein Kinase

Indications

Sourced from openFDA
  • ZELBORAF ® is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. ( 1.1 , 2.1 ) ZELBORAF ® is indicated for the treatment of patients with Erdheim- Chester Disease with BRAF V600 mutation.ICD-10: C43.9

Contraindications

Sourced from openFDA
  • None.contraindicated

Dosage & administration

Sourced from openFDA

Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with ZELBORAF. ( 2.1 ) Recommended dose: 960 mg orally twice daily taken approximately 12 hours apart with or without a meal. ( 2.2 ) 2.1 Patient Selection for Treatment of Melanoma Confirm the presence of BRAF V600E mutation in melanoma tumor specimens prior to initiation of treatment with ZELBORAF [see Warnings and Precautions (5.2) ] . Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dose The recommended dose of ZELBORAF is 960 mg (four 240 mg tablets) orally every 12 hours with or without a meal. A missed dose can be taken up to 4 hours prior to the next dose. Treat patients with ZELBORAF until disease progression or unacceptable toxicity occurs. Do not take an additional dose if vomiting occurs after ZELBORAF administration, but continue with the next scheduled dose. Do not crush or chew the tablets. 2.3 Dose Modifications For New Primary Cutaneous Malignancies: No dose modifications are recommended. For Other Adverse Reactions: Permanently discontinue ZELBORAF for any of the following: Grade 4 adverse reaction, first appearance (if clinically appropriate) or second appearance QTc prolongation > 500 ms and increased by > 60 ms from pre-treatment values [see Warnings and Precautions (5.5) ] Withhold ZELBORAF for NCI-CTCAE (v4.0) intolerable Grade 2 or greater adverse reactions.

Warnings & precautions

Sourced from openFDA

New Primary Cutaneous Malignancies: Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation of ZELBORAF. Manage with excision and continue treatment without dose adjustment. ( 5.1 ) New Non-Cutaneous Squamous Cell Carcinoma: Evaluate for symptoms or clinical signs of new non-cutaneous SCC before initiation of treatment and periodically during treatment. ( 5.1 ) Other Malignancies: Monitor patients receiving ZELBORAF closely for signs or symptoms of other malignancies ( 5.1 ). Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors ( 5.2 ). Serious Hypersensitivity Reactions including anaphylaxis and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome): Discontinue ZELBORAF for severe hypersensitivity reactions. ( 5.3 ) Severe Dermatologic Reactions, including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Discontinue ZELBORAF for severe dermatologic reactions. ( 5.4 ) QT Prolongation: Monitor ECG and electrolytes before and during treatment. Withhold ZELBORAF for QTc of 500 ms or greater. Correct electrolyte abnormalities and control for cardiac risk factors for QT prolongation. ( 5.5 ) Hepatotoxicity: Measure liver enzymes and bilirubin before initiating ZELBORAF and monitor monthly during treatment. ( 5.6 ) Photosensitivity: Advise patients to avoid sun exposure. ( 5.7 ) Serious Ophthalmologic Reactions: Monitor for signs and symptoms of uveitis. ( 5.8 ) Embryo-Fetal Toxicity: Can cause fetal harm.

Adverse reactions

Sourced from openFDA

The following adverse reactions are discussed in greater detail in other sections of the label: New Primary Malignancies [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Dermatologic Reactions [see Warnings and Precautions (5.4) ] QT Prolongation [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ] Photosensitivity [see Warnings and Precautions (5.7) ] Ophthalmologic Reactions [see Warnings and Precautions (5.8) ] Radiation Sensitization and Radiation Recall [see Warnings and Precautions (5.10) ] Renal Failure [see Warnings and Precautions (5.11) ] Dupuytren's Contracture and Plantar Fascial Fibromatosis [see Warnings and Precautions (5.12) ] Melanoma: Most common adverse reactions (≥ 30%) are arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma. ( 6.1 ) Erdheim-Chester Disease: Most common adverse reactions (>50%) are arthralgia, rash maculo-papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin papilloma. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

Use in specific populations

Sourced from openFDA

Lactation: Do not breastfeed while taking ZELBORAF. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of ZELBORAF in pregnant women to determine the drug-associated risk; however, placental transfer of vemurafenib to a fetus has been reported. Exposure to vemurafenib could not be achieved in animals at levels sufficient to fully address its potential toxicity in pregnant women. Advise pregnant women of the potential harm to a fetus. The estimated background risks of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Vemurafenib showed no evidence of developmental toxicity in rat fetuses at doses up to 250 mg/kg/day (approximately 1.3 times the clinical exposure at 960 mg twice daily based on AUC) or rabbit fetuses at doses up to 450 mg/kg/day (approximately 0.6 times the clinical exposure at 960 mg twice daily based on AUC). Fetal drug levels were 3–5% of maternal levels, indicating that vemurafenib has the potential to be transmitted from the mother to the developing fetus.

Pharmacokinetics

Sourced from openFDA
Metabolism
The pharmacokinetics of vemurafenib were determined in patients with BRAF mutation-positive metastatic melanoma following 15 days of 960 mg twice daily with dosing approximately 12 hours apart. The population pharmacokinetic analysis pooled data from 458 patients.

Overdosage

Sourced from openFDA

There is no information on overdosage of ZELBORAF.

Approval history

Sourced from openFDA
  • Aug 17, 2011NDANDA202429Hoffmann La Roche

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
11,910 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Rash1,54013%
  2. 2Death1,0608.9%
  3. 3Arthralgia1,0378.7%
  4. 4Fatigue1,0318.7%
  5. 5Off Label Use8567.2%
  6. 6Diarrhoea8236.9%
  7. 7Nausea8106.8%
  8. 8Disease Progression7666.4%
  9. 9Pyrexia7396.2%
  10. 10Alopecia5584.7%
  11. 11Decreased Appetite5324.5%
  12. 12Vomiting4744.0%
  13. 13Photosensitivity Reaction4123.5%
  14. 14Pruritus3863.2%
  15. 15Sunburn3733.1%

Literature

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Recent PubMed references pinned to Vemurafenib as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 168 ClinicalTrials.gov registrations naming Vemurafenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Frequently asked questions

How does Vemurafenib work?
Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms of BRAF serine- threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations.
What is Vemurafenib used for?
According to FDA labeling, Vemurafenib carries indications including: ZELBORAF ® is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. ( 1.1 , 2.1 ) ZELBORAF ® is indicated for the treatment of patients with Erdheim- Chester Disease with BRAF V600 mutation.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Vemurafenib?
Vemurafenib is classified as B-Raf serine-threonine kinase (BRAF) inhibitors, Kinase Inhibitor, BRAF Serine/Threonine Kinase Inhibitors, Cytochrome P450 1A2 Inhibitors, P-Glycoprotein Inhibitors, Protein Kinase Inhibitors, Cellular Proliferation Alteration.
What are the brand names for Vemurafenib?
Vemurafenib is marketed under brand names including Zelboraf.
What are the contraindications for Vemurafenib?
Vemurafenib labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.
Note. Data for vemurafenib is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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