SIDE EFFECTS

The following adverse reactions are discussed in greater detail in another section of the label:

• Cutaneous Squamous Cell Carcinoma [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Dermatologic Reactions [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS]
• Liver Laboratory Abnormalities [see WARNINGS AND PRECAUTIONS]
• Photosensitivity [see WARNINGS AND PRECAUTIONS]
• Ophthalmologic Reactions [see WARNINGS AND PRECAUTIONS]
• New Primary Malignant Melanoma [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.

The adverse drug reactions (ADRs) described in this section were identified from Trial 1 and Trial 2 [see Clinical Studies]. In Trial 1, treatment naive patients with unresectable or metastatic melanoma (n=675) were allocated to ZELBORAF 960 mg orally twice daily or to dacarbazine 1000 mg/m² intravenously every 3 weeks. In Trial 2, (n=132) patients with metastatic melanoma and failure of at least one prior systemic therapy received treatment with ZELBORAF 960 mg orally twice daily. Adverse reactions reported in at least 10% of patients treated with ZELBORAF are presented in Table 2. The most common adverse reactions of any grade ( ≥ 30% in either study) reported in ZELBORAF-treated patients were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus and skin papilloma. The most common ( ≥ 5%) Grade 3 adverse reactions were cuSCC and rash. The incidence of Grade 4 adverse reactions was ≤ 4% in both studies.

The incidence of adverse events resulting in permanent discontinuation of study medication in Trial 1 was 7% for the ZELBORAF arm and 4% for the dacarbazine arm. In Trial 2, the incidence of adverse events resulting in permanent discontinuation of study medication was 3% in ZELBORAF-treated patients. The median duration of study treatment was 4.2 months for ZELBORAF and 0.8 months for dacarbazine in Trial 1, and 5.7 months for ZELBORAF in Trial 2.

Table 2: Adverse Reactions Reported in ≥ 10% of Patients Treated with ZELBORAF*

Clinically relevant adverse events reported in < 10% of patients treated with ZELBORAF in the Phase 2 and Phase 3 studies include:

Skin and subcutaneous tissue disorders: palmar-plantar erythrodysaesthesia syndrome, keratosis pilaris, erythema nodosum, Stevens-Johnson syndrome

Musculoskeletal and connective tissue disorders: arthritis

Nervous system disorders: dizziness, neuropathy peripheral, VIIth nerve paralysis

Neoplasms benign, malignant and unspecified (includes cysts and polyps): basal cell carcinoma

Infections and infestations: folliculitis

Investigations: weight decreased

Eye disorders: retinal vein occlusion, uveitis

Vascular disorders: vasculitis

Cardiac disorders: atrial fibrillation

Table 3 shows the incidence of worsening liver laboratory abnormalities in Trial 1 summarized as the proportion of patients who experienced a shift from baseline to Grade 3 or 4.

Table 3 Change From Baseline to Grade 3/4 Liver Laboratory Abnormalities*

Read the entire FDA prescribing information for Zelboraf (Vemurafenib Tablet) »