Zelboraf 240 mg film-coated tablets.
Each tablet contains 240 mg of vemurafenib (as a co-precipitate of vemurafenib and hypromellose acetate succinate).
For the full list of excipients, see section 6.1.
Film-coated tablet (tablet).
Pinkish white to orange white, oval, biconvex film-coated tablets of approximately 19 mm, with 'VEM' engraved on one side.
Vemurafenib is indicated in monotherapy for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma (see section 5.1).
Treatment with vemurafenib should be initiated and supervised by a qualified physician experienced in the use of anticancer medicinal products.
Before taking vemurafenib, patients must have BRAF V600 mutation-positive tumour status confirmed by a validated test (see sections 4.4 and 5.1).
Posology
The recommended dose of vemurafenib is 960 mg (4 tablets of 240 mg) twice daily (equivalent to a total daily dose of 1,920 mg). Vemurafenib may be taken with or without food, but consistent intake of both daily doses on an empty stomach should be avoided (see section 5.2).
Duration of treatment
Treatment with vemurafenib should continue until disease progression or the development of unacceptable toxicity (see tables 1 and 2 below).
Missed doses
If a dose is missed, it can be taken up to 4 hours prior to the next dose to maintain the twice daily regimen. Both doses should not be taken at the same time.
Vomiting
In case of vomiting after vemurafenib administration the patient should not take an additional dose of the medicinal product but the treatment should be continued as usual.
Posology adjustments
Management of adverse drug reactions or QTc prolongation may require dose reduction, temporary interruption and/or treatment discontinuation (see tables 1 and 2). Posology adjustments resulting in a dose below 480 mg twice daily are not recommended.
In the event the patient develops Cutaneous Squamous Cell Carcinoma (cuSCC), it is recommended to continue the treatment without modifying the dose of vemurafenib (see sections 4.4 and 4.8).
Table 1: Dose modification schedule based on the grade of any AEs
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Grade (CTC-AE) (a)
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Recommended dose modification
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Grade 1 or Grade 2 (tolerable)
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Maintain vemurafenib at a dose of 960 mg twice daily.
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Grade 2 (intolerable) or Grade 3
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1st occurrence of any grade 2 or 3 AE
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Interrupt treatment until grade 0 – 1. Resume dosing at 720 mg twice daily (or 480 mg twice daily if the dose has already been lowered).
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2nd occurrence of any grade 2 or 3 AE or persistence after treatment interruption
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Interrupt treatment until grade 0 – 1. Resume dosing at 480 mg twice daily (or discontinue permanently if the dose has already been lowered to 480 mg twice daily).
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3rd occurrence of any grade 2 or 3 AE or persistence after 2nd dose reduction
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Discontinue permanently.
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Grade 4
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1st occurrence of any grade 4 AE
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Discontinue permanently or interrupt vemurafenib treatment until grade 0 – 1.
Resume dosing at 480 mg twice daily (or discontinue permanently if the dose has already been lowered to 480 mg twice daily).
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2nd occurrence of any grade 4 AE or persistence of any grade 4 AE after 1st dose reduction
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Discontinue permanently.
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(a) The intensity of clinical adverse events graded by the Common Terminology Criteria for Adverse Events v4.0 (CTC-AE).
Exposure-dependent QT prolongation was observed in an uncontrolled, open-label phase II study in previously treated patients with metastatic melanoma. Management of QTc prolongation may require specific monitoring measures (see section 4.4).
Table 2: Dose modification schedule based on prolongation of the QT interval
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QTc value
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Recommended dose modification
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QTc>500 ms at baseline
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Treatment not recommended.
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QTc increase meets values of both >500 ms and >60 ms change from pre-treatment values
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Discontinue permanently.
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1st occurrence of QTc>500 ms during treatment and change from pre-treatment value remains <60 ms
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Temporarily interrupt treatment until QTc decreases below 500 ms.
See monitoring measures in section 4.4.
Resume dosing at 720 mg twice daily (or 480 mg twice daily if the dose has already been lowered).
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2nd occurrence of QTc>500 ms during treatment and change from pre-treatment value remains <60 ms
|
Temporarily interrupt treatment until QTc decreases below 500 ms.
See monitoring measures in section 4.4.
Resume dosing at 480 mg twice daily (or discontinue permanently if the dose has already been lowered to 480 mg twice daily).
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3rd occurrence of QTc>500 ms dur |
