Sonidegib

Indications

Sonidegib is used for: Indicated for adults with locally advanced, basal cell carcinoma (BCC)

Adult Dose

Basal Cell Carcinoma Indicated for adults with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy 200 mg PO qDay on empty stomach 1 hr before or 2 hr after meals Continue treatment until disease progression or unacceptable toxicity Hepatic impairment Hepatic impairment: Mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment: No dose adjustment required

Child Dose

Renal Dose

Renal impairment: No dose adjustment required

Administration

Swallow capsule on an empty stomach, at least 1 hr before or 2 hr after a meal

Contra Indications

Hypersensitivity

Precautions

Can cause embryo-fetal death or severe birth defects when administered to a pregnant woman (see Black Box Warnings and Pregnancy sections) Advise patients not to donate blood or blood products while taking sonidegib and for at least 20 months after the last dose because their blood or blood products might be given to a female of reproductive potential Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase elevations, occur with Hedgehog pathway inhibitors Avoid coadministration with moderate/strong CYP3A inhibitors or inducers

Pregnancy-Lactation

Pregnancy Based on sonidegib’s mechanism of action, can cause fetal harm when administered to a pregnant woman There are no available data on the use in pregnant women In animal reproduction studies, oral administration of sonidegib during organogenesis at doses below the recommended human dose of 200 mg resulted in embryotoxicity, fetotoxicity, and teratogenicity in rabbits (teratogenic effects observed included severe midline defects, missing digits, and other irreversible malformations) Verify pregnancy status of females of reproductive potential prior to initiating Advise females of reproductive potential to use effective contraception during treatment and for at least 20 months after the last dose Do not donate blood for at least 20 months after the last dose Males Unknown if sonidegib is present in semen Advise male patients to use condoms, even after a vasectomy, to avoid potential drug exposure to pregnant partners and female partners of reproductive potential during treatment and for at least 8 months after the last dose Do not donate semen for at least 8 month or blood for at least 20 months Lactation Unknown if distributed in human breast milk Because of the potential for serious adverse reactions in breastfed infants from sonidegib, advise a nursing woman not to breastfeed during treatment and for 20 months after the last dose

Interactions

Adverse Effects

Side effects of Sonidegib : >10% Muscle spasms (54%) Alopecia (53%) Dysgeusia (46%) Fatigue (41%) Nausea (39%) Diarrhea (32%) Musculoskeletal pain (32%) Decreased weight (30%) Decreased appetite (23%) Myalgia (19%) Abdominal pain (18%) Headache (15%) Pain (14%) Vomiting (11%) 1-10% Pruritus (10%)

Mechanism of Action

Hedgehog (Hh) pathway inhibitor; the Hh signaling pathway is important in embryogenesis, but in adults, it is mostly inactive; signaling is relayed by key proteins, including smoothened (SMO) Hh ligand-expressing cancerous epithelial cells that are activated by the Hh signaling pathway may cause growth promotion; sonidegib binds to and inhibits SMO, a transmembrane protein involved in Hedgehog signal transduction