vemurafenib(vem-u-raf-e-nib ) ,
Pregnancy Category: D
Pharmacologic: kinase inhibitors
Pharmacologic: kinase inhibitors
genetic implication Treatment of unresectable or metastatic melanoma with BRAF V600Emutation.
Inhibits mutated forms of the enzyme kinase. Inhibits proliferation that occurs in conjunction with activated BRAF proteins.
Decreased spread of melanoma.
Absorption: Some absorption follows oral administration, bioavailability is not known.
Protein Binding: >99%.
Metabolism and Excretion: Mostly metabolized by the liver (mostly by the CYP3A4 enzyme system), 1% eliminated in urine.
Half-life: 57 hr (range 30–120 hr).
Time/action profile (blood levels)
|PO||unknown||3 hr||12 hr|
Contraindicated in: Obstetric: Should not be used during pregnancy, may cause fetal harm; Lactation: Breast feeding should be avoided; None noted.
Use Cautiously in: Pre-existing severe hepatic or renal impairment; Geriatric: Increased risk of cutaneous squamous cell carcinoma, nausea, decreased appetite, peripheral edema, keratoacanthoma and atrial fibrillation;Concurrent use of stong inducers/inhibitors of the the CYP3A4 enzyme system or drugs that are substrates of CYP3A4, CYP1A2 or CYP2D6 enzyme systems; monitoring of effects and necessary dose adjustments may be necessary; Obstetric: Patients with child-bearing potential; Pediatric: safe and effective use in children <18 yr has not been established.
Adverse Reactions/Side Effects
Central nervous system
- fatigue (most frequent)
- weakness (most frequent)
Ear, Eye, Nose, Throat
- retinal vein occlusion
- QTc prolongation (life-threatening)
- peripheral edema (most frequent)
- hepatotoxicity (life-threatening)
- ↓ appetite
- stevens-johnson syndrome (life-threatening)
- toxic epidermal necrolysis (life-threatening)
- alopecia (most frequent)
- dry skin (most frequent)
- rash(↑ in females) (most frequent)
- pruritus (most frequent)
- rash (most frequent)
- photosensitivity (↑ in females) (most frequent)
- skin papilloma (most frequent)
- keratocanthoma (↑ in males)
- ↑ creatinine (↑ in females)
- arthralgia(↑ in females) (most frequent)
- myalgia (most frequent)
- back pain
- musculoskeletal pain
- hypersensitivity reactions including anaphylaxis
- fever (most frequent)
Drug-Drug interactionConcurrent use with agents with narrow therapeutic indices that are metabolized by the CYP1A2 enzyme systems not recommended. Consider dose ↓ of substrates.Strong CYP3A inhibitors, including atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole may ↑ levels and effects; avoid concurrent use.Strong inducers of CYP3A4 including carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine may ↓ levels and effectiveness; avoid concurrent use.May ↑ risk of bleeding with warfarin.Concurrent use with ipilimumab may ↑ risk of hepatotoxicity
Oral (Adults) 960 mg twice daily. Treatment should continue until unacceptable toxicity or disease progression occurs.
Tablets: 240 mg
- Perform dermatologic evaluation prior to initiation and every 2 mo during therapy. Excise any suspicious lesions, send for dermapathologic evaluation, and treat with standard care. Continue monitoring for 6 mo following discontinuation of therapy.
- Monitor ECG 15 days after initiation of therapy, monthly during first 3 mo, every 3 mo thereafter, and more often if clinically indicated.
- Monitor for hypersensitivity reactions (rash, erythema, hypotension). Permanently discontinue therapy if severe reaction occurs.
- Monitor for signs and symptoms of uveitis periodically during therapy. May require treatment with steroid and mydriatic ophthalmic drops.
- Assess patient for rash (mild to moderate rash usually occurs in the 2nd wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis), therapy must be discontinued immediately.
- Lab Test Considerations: Monitor serum potassium, magnesium, and calcium before starting therapy and after dose modification.
- Monitor AST, ALT, alkaline phosphatase, and bilirubin before starting therapy, monthly during therapy, and as clinically indicated. May require dose reduction, treatment interruption or discontinuation.
Potential Nursing DiagnosesImpaired skin integrity (Indications)
- Oral: Administer (four 240 mg tablets) twice daily, without regard to food. Take first dose in the morning with second dose about 12 hrs later. Swallow tablets whole, do not crush or chew.
- Adverse reactions or QTc prolongation may occur requiring dose modification. If Grade 1 or 2 (tolerable) occur, maintain dose at 960 mg twice daily. If Grade 2 (Intolerable) or Grade 3, 1st appearance occurs, interrupt therapy until Grade 0–1. Resume dosing at 720 mg twice daily. If 2nd appearance, interrupt therapy until Grade 0–1. Resume dosing at 480 mg twice daily. If 3rd appearance, discontinue permanently. If Grade 4, 1st appearance occurs, discontinue permanently or interrupt therapy until Grade 0–1. Resume dosing at 480 twice daily. If 2nd appearance, discontinue permanently. Doses below 480 mg twice daily are not recommended.
- Instruct patient to take venurafenib as directed. Take missed doses as soon as remembered up to 4 hrs before next dose; do not double dose.
- genetic implication Inform patient that assessment of BRAF mutation is required for selection of patients.
- Instruct patient to stop taking vemurafenib and notify health care professional immediately if signs and symptoms of allergic reaction (rash or redness all over body; feeling faint; difficulty breathing or swallowing; throat tightness or hoarseness; fast heartbeat; swelling of face, lips, or tongue) or severe skin reactions (blisters on skin; blisters or sores in mouth; peeling of skin, fever, redness or swelling of face, hands, or soles of feet) occur.
- Advise patient to wear broad spectrum UVA/UVB sunscreen, lip balm (SPF ≥30) and protective clothing, and to avoid sun exposure to prevent photosensitivity reactions. Severe photosensitivity reactions may require dose modifications.
- Advise patient to notify health care professional if signs and symptoms of liver dysfunction (yellow skin or whites of eyes; feeling tired; urine turns dark or brown; nausea or vomiting; loss of appetite; pain on right side of stomach) or eye problems (eye pain, swelling, or redness; blurred vision; vision changes) occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Inform patient that regular assessments of skin and assessments for signs and symptoms of other malignancies must be done during and for up to 6 mo after therapy. Advise patient to notify health care professional immediately if any changes in skin occur.
- Advise women of childbearing potential and men to use appropriate contraceptive measures during and for at least 2 mo after discontinuation of vemurafenib, and to avoid breast feeding.
- Decreased spread of melanoma.
Drug Guide, © 2015 Farlex and Partners
vemurafenibAn experimental drug which counters the V600E mutation of B-Raf in the B-Raf/MEK/ERK cell-signalling pathway, which controls cell division, differentiation and apoptosis. Vemurafenib disrupts V600E mutated B-Raf, which blocks apoptosis, allowing apoptosis to continue forward, which is effective for managing melanomas with the V600E mutation.
Segen's Medical Dictionary. © 2012 Farlex, Inc. All rights reserved.