Zelboraf_pi_sept_2013_for_ppt_fa

PRESCRIBING INFORMATION
severe hypersensitivity reactions occur; these may (CYP2C9), CYP2C8 substrates or CYP2B6 substrates include Stevens-Johnson syndrome, generalised rash, (e.g. bupropion). May affect pharmacokinetics of ZELBORAF (vemurafenib)
erythema or hypotension. Ophthalmologic reactions: medicines transported by P-gp. A wash out period Serious reactions have been reported; monitor patients of ≥8 days recommended between vemurafenib and Indication: As monotherapy for the treatment of routinely. QT prolongation: Exposure-dependent QT initiation of a new therapy. Fertility/pregnancy/
adult patients with BRAF V600 mutation-positive prolongation has been observed and may lead to an lactation: Women of childbearing potential should
unresectable or metastatic melanoma. Dosage and increased risk of ventricular arrhythmias including use effective contraception during treatment and
Administration: Confirm BRAF V600 mutation-positive
Torsade de Pointes. Treatment not recommended in for at least 6 months afterwards. Vemurafenib might tumour status by a validated test prior to treatment. patients with uncorrectable electrolyte abnormalities decrease efficacy of hormonal contraceptives. No data Treat until disease progression or the development of (including magnesium), long QT syndrome or who are in pregnant or lactating women. Side effects: See
unacceptable toxicity. Recommended dose is 960mg taking medicines known to prolong the QT interval. SPC for full details. Very common: arthralgia, fatigue, (4 tablets of 240mg) twice daily. Vemurafenib may be ECG and electrolytes (including magnesium) should be rash, photosensitivity reaction, nausea, alopecia, taken with or without food, but consistent intake of both monitored before treatment with vemurafenib, after one pruritus, and cuSCC. Serious or potentially serious: daily doses on an empty stomach should be avoided. month of treatment and after dose modification. Further Hypersensitivity reactions, including anaphylaxis Swallow tablets whole with water. If a dose is missed, monitoring recommended (particularly in patients with and Stevens-Johnson syndrome; QT prolongation; it can be taken up to 4 hours prior to the next dose moderate-severe hepatic impairment) monthly for first ophthalmologic reactions including uveitis, iritis to maintain the twice daily regimen. Both doses should 3 months and then 3 monthly thereafter, more frequently and retinal vein occlusion. Legal category: POM.
not be taken at the same time. Vomiting – continue if clinically indicated. Initiation of vemurafenib is not Presentation: 56 film-coated tablets (Aluminium/
treatment as usual. Management of symptomatic recommended in patients with QTc >500ms. If during adverse drug reactions or QTc prolongation may Aluminium blisters). Basic NHS price: £1750.00
treatment the QTc >500ms, temporarily interrupt and require dose reduction, temporary interruption and/or correct electrolyte abnormalities (including magnesium); for 56 tablets. MA Number: EU/1/12/751/001.
treatment discontinuation – refer to SPC. Dose reduction control cardiac risk factors for QT prolongation MA holder: Roche Registration Ltd., 6 Falcon Way,
for cutaneous squamous cell carcinoma (cuSCC) is (e.g. congestive heart failure, bradyarrythmias). Re- Shire Park, Welwyn Garden City, AL7 1TW, UK. not recommended. Adjustments to <480mg twice initiate treatment once the QTc <500ms, and at a RXUKMEDI00153. daily are not recommended. Contra-indications:
lower dose as per SPC. Permanently discontinue Date of preparation: September 2013.
Hypersensitivity to the active substance or to any of the vemurafenib if the QTc increase is both >500ms and excipients. Precautions and warnings: CuSCC and
>60ms change from pre-treatment values. Liver injury: new primary malignant melanoma: cuSCC (including Monitor transaminases, alkaline phosphatase and keratoacanthoma or mixed keratoacanthoma subtype) bilirubin before initiation and monthly during treatment, additional monitoring. Reporting suspected and new primary malignant melanoma have been or as clinically indicated. Hepatic impairment: No adverse reactions after authorisation of reported; cases of non-cuSCC have been reported. adjustment to starting dose needed. Patients with Evaluate prior to and monitor routinely while on moderate to severe hepatic impairment may have therapy. Excise any suspicious skin lesions, and increased exposure; monitor closely and be aware of It al ows continued monitoring of the benefit/ obtain dermatopathologic evaluation; treat as per local accumulation. Renal impairment: Mild or moderate – no risk balance of the medicinal product.
standard of care. Examine patient monthly during and adjustment of starting dose needed. Severe impairment for 6 months after treatment. In patients who develop – use with caution and monitor closely. Photosensitivity: cuSCC or new primary malignant melanoma, continue Has been reported; avoid sun exposure and protect treatment without dose adjustment. Monitoring should against sunburn. Concurrent administration with found at www.mhra.gov.uk/yellowcard
continue for 6 months following discontinuation of ipilimumab: Hepatotoxicity reported. Combination vemurafenib or until initiation of another anti-neoplastic not recommended. Interactions: Vemurafenib may
therapy. Patients should inform their physician upon increase plasma exposure of drugs metabolised by the occurrence of any skin changes. Hypersensitivity CYP1A2 and decrease that of those metabolised by reaction: Serious hypersensitivity reactions, including CYP3A4. The efficacy of contraceptive pills metabolised anaphylaxis have been reported. Vemurafenib by CYP3A4 used with vemurafenib might be decreased. treatment should be permanently discontinued if Exercise caution when co-administered with warfarin

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