BRAF V600 inhibitor Pregnancy: Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to determine the drug-associated risk, but placental transfer of vemurafenib to a fetus has been reported and fetal drug levels were 3–5% of maternal levels in animals. Advise pregnant women of the potential harm to a fetus.

Vemurafenib (Specialist drug)

Brand names: Zelboraf

Vemurafenib is an oral kinase inhibitor used to treat BRAF V600 mutation-positive unresectable or metastatic melanoma.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 960 mg (four 240 mg tablets)

Route: Oral — with or without a meal; do not crush or chew the tablets

Frequency: Every 12 hours (twice daily), until disease progression or unacceptable toxicity occurs

No UK SPC (eMC) record was fetched — this draft is distilled from the US prescribing information for ZELBORAF (label date 2025-12-01) and must be verified against the UK SPC. Confirm the presence of a BRAF V600E mutation in tumour specimens before initiating treatment. MISSED DOSE: a missed dose can be taken up to 4 hours prior to the next dose; do not take an additional dose if vomiting occurs after administration, but continue with the next scheduled dose. DOSE MODIFICATION: no dose modification is recommended for new primary cutaneous malignancies. Withhold for NCI-CTCAE (v4.0) intolerable Grade 2 or greater adverse reactions; on recovery to Grade 0–1 restart at 720 mg twice daily for a first appearance of intolerable Grade 2 or Grade 3 reactions, or 480 mg twice daily for a second appearance of Grade 2 (if intolerable) or Grade 3 reactions or a first appearance of a Grade 4 reaction (if clinically appropriate). Do not dose reduce below 480 mg twice daily. Permanently discontinue for a Grade 4 adverse reaction (first appearance if clinically appropriate, or second appearance) or for QTc prolongation >500 ms that is also increased by >60 ms from pre-treatment values. CYP3A4 INDUCERS: avoid concomitant strong CYP3A4 inducers; if unavoidable, increase the ZELBORAF dose by 240 mg (one tablet) as tolerated, and resume the previous dose two weeks after the inducer is discontinued. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established. Vemurafenib was studied in 6 adolescent patients aged 15 to 17 years with unresectable or metastatic BRAF V600-mutant melanoma; a maximum tolerated dose was not reached with doses up to 960 mg twice daily, no new safety signals were observed, and steady-state exposure was generally similar to adults. Verify any under-18 use against a children's formulary. Indications in the fetched label are BRAF V600E-mutant melanoma and Erdheim-Chester disease.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None stated — the US label section 4 Contraindications reads 'None'

Side effects

Arthralgia (most common, ≥30% in melanoma)
Rash (including maculo-papular rash) and skin papilloma
Alopecia and fatigue
Photosensitivity reaction and pruritus
Nausea; labelled serious reactions include new primary cutaneous and non-cutaneous malignancies, severe hypersensitivity including anaphylaxis and DRESS, Stevens-Johnson syndrome and toxic epidermal necrolysis, QT prolongation, hepatotoxicity, ophthalmologic reactions, radiation sensitisation and recall, renal failure, and Dupuytren's contracture/plantar fascial fibromatosis

Interactions

Strong CYP3A4 inhibitors — increase vemurafenib plasma concentrations and may lead to increased toxicity; avoid co-administration, and consider a vemurafenib dose reduction if unavoidable and clinically indicated
Strong CYP3A4 inducers (e.g. phenytoin, carbamazepine, rifampin) — decrease vemurafenib plasma concentrations and may reduce efficacy; avoid and replace with alternative drugs where possible, or if unavoidable increase the vemurafenib dose by 240 mg (one tablet) as tolerated
CYP1A2 substrates with a narrow therapeutic window — vemurafenib can increase their concentrations; avoid concomitant use, or monitor closely for toxicity and consider reducing the dose of the CYP1A2 substrate

Clinical monograph

How it works

It selectively inhibits the mutated BRAF V600 kinase, blocking constitutive signalling through the MAPK pathway that drives tumour growth.

Prescribing in practice

Confirm a validated BRAF V600 mutation before starting, as the drug is ineffective and may stimulate tumours in BRAF wild-type disease.
Cutaneous squamous cell carcinomas and other secondary skin lesions can develop, requiring dermatological surveillance.
It prolongs the QT interval and is a specialist oncology medicine initiated under expert supervision.

Monitoring

Perform regular dermatological skin assessments, ECG and electrolyte checks, and monitor liver function throughout treatment.

Counselling the patient

Avoid sun exposure and use high-factor broad-spectrum sun protection because of marked photosensitivity.
Report any new skin lumps, warty growths or changing moles without delay.
Seek urgent advice for fever, rash with blistering, or eye problems.

Evidence & guidelines

Approval followed the BRIM-3 trial demonstrating improved survival versus dacarbazine in BRAF V600-positive melanoma.

Reference: NICE TA269; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways