Vismodegib is a hedgehog (Hh) pathway inhibitor, which is described chemically as 2-Chloro- N -(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide. The molecular formula is C 19 H 14 Cl 2 N 2 O 3 S. The molecular weight is 421.3 g/mol and the structural formula is: Vismodegib is a crystalline free base with a pKa (pyridinium cation) of 3.8, appearing as a white to tan powder. The solubility of vismodegib is pH dependent with 0.1 µg/mL at pH 7 and 0.99 mg/mL at pH 1. The partition coefficient (log P) is 2.7. ERIVEDGE (vismodegib) for oral administration is supplied in capsules containing 150 mg vismodegib and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, sodium lauryl sulfate, povidone, sodium starch glycolate, talc, and magnesium stearate (non-bovine). The capsule shell contains gelatin, titanium dioxide, red iron oxide, and black iron oxide. The black printing ink contains shellac and black iron oxide. Chemical Structure

ERIVEDGE is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery and who are not candidates for radiation. ERIVEDGE ® (vismodegib) is a hedgehog pathway inhibitor indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery and who are not candidates for radiation.

Capsules: 150 mg with "150 mg" printed on pink opaque body and "VISMO" printed on grey opaque cap in black ink. 150 mg capsules.

The recommended dosage is 150 mg orally once daily

Important Safety Information Verify pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE

Recommended Dosage The recommended dosage of ERIVEDGE is 150 mg taken orally once daily, with or without food, until disease progression or until unacceptable toxicity . Swallow capsules whole. Do not open or crush capsules . If a dose of ERIVEDGE is missed, resume dosing with the next scheduled dose

Dosage Modifications for Adverse Reactions Withhold ERIVEDGE for up to 8 weeks for intolerable adverse reactions until improvement or resolution. Treatment durations shorter than 8 weeks prior to interruptions have not been studied. Permanently discontinue ERIVEDGE if patients experience severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS) . Interrupt ERIVEDGE for severe or intolerable musculoskeletal adverse reactions. Permanently discontinue ERIVEDGE for recurrent, severe or intolerable musculoskeletal adverse reactions .

Embryo-Fetal Toxicity: Advise patients not to donate blood or blood products while receiving ERIVEDGE and for 24 months after the final dose of ERIVEDGE Advise males not to donate semen during and for 3 months after therapy Severe Cutaneous Adverse Reactions: Permanently discontinue ERIVEDGE in patients with these reactions Musculoskeletal Adverse Reactions: Temporary dose interruption or discontinuation may be required for these reactions Premature fusion of the epiphyses 5.1 Embryo-Fetal Toxicity Based on its mechanism of action, ERIVEDGE can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. In animal reproduction studies, vismodegib was embryotoxic, fetotoxic, and teratogenic at maternal exposures lower than the human exposures at the recommended dose of 150 mg once daily . Females of Reproductive Potential Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating ERIVEDGE. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during therapy with ERIVEDGE and for 24 months after the final dose . Males Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm. Advise males to use condoms, even after a vasectomy, to avoid potential drug exposure in pregnant partners and female partners of reproductive potential during therapy and for 3 months after the final dose of ERIVEDGE. Advise male patients not to donate semen during and for 3 months after the final dose of ERIVEDGE . Blood Donation Advise patients not to donate blood or blood products while receiving ERIVEDGE and for 24 months after the final dose of ERIVEDGE

Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with ERIVEDGE . Permanently discontinue ERIVEDGE in patients with these reactions

Musculoskeletal Adverse Reactions Musculoskeletal adverse reactions, which may be accompanied by serum creatine phosphokinase (CPK) elevations, have occurred with ERIVEDGE and other drugs which inhibit the hedgehog (Hh) pathway. In the pooled safety population in clinical trials of ERIVEDGE, musculoskeletal and connective tissue adverse reactions occurred in 78% of patients treated, with 7% (9/138) reported as Grade 3. The most frequent manifestations of musculoskeletal and connective tissue adverse reactions (all grades) reported were muscle spasms (72%) and arthralgias (16%). In a post-approval clinical trial of 1232 patients, Grade 3 or 4 elevations in serum CPK laboratory values occurred in 2.4% of the 453 patients who had any CPK measurement . Obtain baseline serum creatine phosphokinase (CPK) and creatinine levels and as clinically indicated (e.g., if muscle symptoms are reported). Depending on the severity of symptoms, temporary dose interruption or discontinuation may be required for musculoskeletal adverse reactions or serum CPK elevation

Premature Fusion of the Epiphyses Premature fusion of the epiphyses has been reported in pediatric patients exposed to ERIVEDGE. In some cases, fusion progressed after drug discontinuation . ERIVEDGE is not indicated for pediatric patients.