Ophthalmologic reactions

Serious ophthalmologic reactions, including uveitis, iritis and retinal vein occlusion, have been reported. Monitor patients routinely for ophthalmologic reactions.

Cutaneous Squamous Cell Carcinoma (cuSCC)

Cases of cuSCC (which include those classified as keratoacanthoma or mixed keratoacanthoma subtype) have been reported in patients treated with vemurafenib (see section 4.8).

It is recommended that all patients receive a dermatologic eva luation prior to initiation of therapy and be monitored routinely while on therapy. Any suspicious skin lesions should be excised, sent for dermatopathologic eva luation and treated as per local standard of care. The prescriber should examine the patient monthly during and up to six months after treatment for cuSCC. In patients who develop cuSCC, it is recommended to continue the treatment without dose adjustment. Monitoring should continue for 6 months following discontinuation of vemurafenib or until initiation of another anti-neoplastic therapy. Patients should be instructed to inform their physicians upon the occurrence of any skin changes.

Non-Cutaneous Squamous Cell Carcinoma (non-cuSCC)

Cases of non-cuSCC have been reported in clinical trials where patients received vemurafenib. Patients should undergo a head and neck examination, consisting of at least a visual inspection of oral mucosa and lymph node palpation prior to initiation of treatment and every 3 months during treatment.

In addition, patients should undergo a chest Computerised Tomography (CT) scan, prior to treatment and every 6 months during treatment.

Anal examinations and pelvic examinations (for women) are recommended before and at the end of treatment or when considered clinically indicated.

Following discontinuation of vemurafenib, monitoring for non-cuSCC should continue for up to 6 months or until initiation of another anti-neoplastic therapy. Abnormal findings should be managed according to clinical practices.

New primary melanoma

New primary melanomas have been reported in clinical trials. Cases were managed with excision and patients continued treatment without dose adjustment. Monitoring for skin lesions should occur as outlined above for cutaneous squamous cell carcinoma.

Other Malignancies

Based on mechanism of action, vemurafenib may cause progression of cancers associated with RAS mutations (see section 4.8). Carefully consider benefits and risks before administering vemurafenib to patients with a prior or concurrent cancer associated with RAS mutation.

Liver injury

Liver laboratory abnormalities may occur with vemurafenib (see section 4.8). Liver enzymes (transaminases and alkaline phosphatase) and bilirubin should be monitored before initiation of treatment and monthly during treatment, or as clinically indicated. Laboratory abnormalities should be managed with dose reduction, treatment interruption or with treatment discontinuation (see sections 4.2 and 4.4).

Hepatic impairment

No adjustment to the starting dose is needed for patients with hepatic impairment. Patients with mild hepatic impairment due to liver metastases without hyperbilirubinaemia may be monitored according t