Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639, Grenzach-Wyhlen, Germany
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).
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).
Treatment with vemurafenib should continue until disease progression or the development of unacceptable toxicity (see tables 1 and 2 below).
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.
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.
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 Adverse Events (AEs):
| Grade (CTC-AE)a | Recommended dose modification |
|---|---|
| Grade 1 or Grade 2 (tolerable) | Maintain vemurafenib at a dose of 960 mg twice daily. |
| Grade 2 (intolerable) or Grade 3 | |
| 1st occurrence of any grade 2 or 3 AE | 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). |
| 2nd occurrence of any grade 2 or 3 AE or persistence after treatment interruption | 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). |
| 3rd occurrence of any grade 2 or 3 AE or persistence after 2nd dose reduction | Discontinue permanently. |
| Grade 4 | |
| 1st occurrence of any grade 4 AE | 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). |
| 2nd occurrence of any grade 4 AE or persistence of any grade 4 AE after 1st dose reduction | Discontinue permanently. |
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:
| QTc value | Recommended dose modification |
|---|---|
| QTc>500 ms at baseline | Treatment not recommended. |
| QTc increase meets values of both >500 ms and >60 ms change from pre-treatment values | Discontinue permanently. |
| 1st 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 720 mg twice daily (or 480 mg twice daily if the dose has already been lowered). |
| 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). |
| 3rd occurrence of QTc>500 ms during treatment and change from pre-treatment value remains <60 ms | Discontinue permanently. |
No special dose adjustment is required in patients aged >65 years old.
Limited data are available in patients with renal impairment. A risk for increased exposure in patients with severe renal impairment cannot be excluded. Patients with severe renal impairment should be closely monitored (see sections 4.4 and 5.2).
Limited data are available in patients with hepatic impairment. As vemurafenib is cleared by the liver, patients with moderate to severe hepatic impairment may have increased exposure and should be closely monitored (see sections 4.4 and 5.2).
The safety and efficacy of vemurafenib in children less than 18 years old have not been established. Currently available data are described in sections 4.8, 5.1, and 5.2, but no recommendation on a posology can be made.
The safety and efficacy of vemurafenib has not been established in non-Caucasian patients. No data are available.
Vemurafenib is for oral use. The tablets are to be swallowed whole with water. They should not be chewed or crushed.
There is no specific antidote for overdose of vemurafenib. Patients who develop adverse reactions should receive appropriate symptomatic treatment. No cases of overdose have been observed with vemurafenib in clinical trials. In case of suspected overdose, vemurafenib should be withheld and supportive care initiated.
Shelf life: 3 years.
Store in the original package in order to protect from moisture.
Aluminium/Aluminium perforated unit dose blisters.
Pack-size: 56 × 1 film-coated tablets (7 blisters of 8 × 1 tablet)
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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