Odomzo®Sonidegib Phosphate Capsules

1. Indications and Usage
Locally Advanced Basal Cell Carcinoma (laBCC): Treatment of adult patients with laBCC who have relapsed after surgery or radiation therapy, or who are not candidates for surgery or radiation therapy。
2. Dosage and Administration
Administration: Oral administration. Swallow capsules whole with water. Do not cut, crush, or chew the capsules。
Food Requirement: Must be taken on an empty stomach. Take at least 1 hour before or 2 hours after a meal. Food significantly increases drug exposure and toxicity risk。
Standard Dose:
Recommended Dose: 200 mg once daily until disease progression or unacceptable toxicity。
Missed Dose or Vomiting: If a dose is missed or vomiting occurs, skip the missed dose and resume the next dose at the scheduled time the following day. Do not double dose。
Dose Reduction: Dose reduction (e.g., to 100 mg or 200 mg every other day) or interruption is required for severe toxicities, particularly muscle injury or CK elevation。
3. Mechanism of Action
Sonidegib is a selective inhibitor of the Hedgehog (Hh) signaling pathway.
It binds to and inhibits the transmembrane protein Smoothened (SMO), a key component of the Hh pathway.
By blocking SMO, sonidegib prevents the activation of Gli transcription factors, thereby inhibiting tumor cell proliferation and growth in Hh pathway-driven cancers。
4. Safety and Warnings
Embryo-Fetal Toxicity: May cause severe birth defects or fetal death. Pregnancy testing is required before initiation. Females must use contraception during treatment and for 20 months after the final dose; males must use contraception during treatment and for 8 months after the final dose。
Muscle Injury: Can cause severe muscle injury (rhabdomyolysis). Monitor Creatine Kinase (CK) levels periodically. Withhold or discontinue for CK elevation or muscle symptoms。
Hepatotoxicity: Monitor liver function tests (ALT, AST) regularly。
Blood/Sperm Donation: Patients should not donate blood for 20 months and sperm for 8 months after the last dose。
5. Adverse Reactions
Common adverse reactions (incidence ≥10%) include:
Musculoskeletal: Muscle spasms, musculoskeletal pain, myalgia。
General: Fatigue, pyrexia。
Dermatologic: Alopecia (hair loss), pruritus。
Gastrointestinal: Nausea, diarrhea, dyspepsia, abdominal pain, vomiting。
Neurologic: Dysgeusia (taste disturbance), headache。
Laboratory Abnormalities: Increased CK, increased creatinine, anemia。
6. Drug Interactions
CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors (e.g., ketoconazole). Avoid moderate CYP3A inhibitors unless use is <14 days with close monitoring。
CYP3A Inducers: Avoid co-administration with strong or moderate CYP3A inducers (e.g., rifampin, carbamazepine) as they reduce efficacy。
Dietary Interactions: Avoid grapefruit or grapefruit juice。
7. Pharmaceutical Information
Chemical Name: N-[6-(cis-2,6-Dimethylmorpholin-4-yl)pyridine-3-yl]-2-methyl-4′-(trifluoromethoxy)[1,1′-biphenyl]-3 carboxamide diphosphate。
Molecular Formula: C25H25F3N3O3 · 2H3PO4。
Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)。