Retsevmo®Selpercatinib Capsules

1. Indications and Usage
RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC): Treatment of adult patients with locally advanced or metastatic RET fusion-positive NSCLC.
RET Mutation-Positive Medullary Thyroid Cancer (MTC): Treatment of adult and pediatric patients (≥12 years) with advanced or metastatic RET mutation-positive MTC who require systemic therapy.
RET Fusion-Positive Thyroid Cancer (TC): Treatment of adult and pediatric patients (≥12 years) with advanced or metastatic RET fusion-positive TC who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is applicable).
2. Dosage and Administration
Administration: Oral administration. Swallow capsules whole. Do not chew, crush, or open the capsules.
Food Requirement: Can be taken with or without food.
Standard Dose:
Weight ≥50 kg: 160 mg twice daily (approximately every 12 hours).
Weight <50 kg: 120 mg twice daily (approximately every 12 hours).
Missed Dose or Vomiting: If a dose is missed or if vomiting occurs at any time after administration, take the next dose at the usual scheduled time. Do not make up for the missed dose.
Dose Reduction: Mandatory dose reduction (e.g., to 120 mg BID or 80 mg BID) for severe toxicities.
3. Mechanism of Action
Selpercatinib is a potent, selective, small-molecule inhibitor of RET wild-type and oncogenic RET fusions and mutations.
It inhibits RET kinase activity and downstream signaling pathways (e.g., MAPK, PI3K), leading to inhibition of tumor cell proliferation and induction of apoptosis.
4. Safety and Warnings
Hepatotoxicity: Elevations in ALT and AST are common. Monitor liver function tests before initiation and during treatment.
Hypertension: Monitor blood pressure regularly. Do not initiate treatment in patients with uncontrolled hypertension.
QTc Interval Prolongation: Monitor ECG and electrolytes periodically, especially in patients with cardiac history or those taking CYP3A inhibitors.
Bleeding Events: Serious bleeding can occur. Withhold prior to major surgery to reduce risk of impaired wound healing.
Embryo-Fetal Toxicity: May cause fetal harm. Contraception is required for females and males during treatment and for at least 1 week after the final dose.
5. Adverse Reactions
Common adverse reactions (incidence ≥25%) include:
Laboratory Abnormalities: Increased ALT, Increased AST, Hyperglycemia, Hypertension, Hypocalcemia, Hyponatremia.
Clinical Symptoms: Dry mouth, Diarrhea, Fatigue, Edema, Rash, Constipation, Dysgeusia.
6. Drug Interactions
CYP3A Inhibitors: Avoid co-administration with strong/moderate CYP3A inhibitors (e.g., ketoconazole) as they increase Selpercatinib exposure. If unavoidable, reduce dose.
CYP3A Inducers: Avoid co-administration with strong/moderate CYP3A inducers (e.g., rifampin) as they reduce efficacy.
Antacids: Avoid concomitant use with proton pump inhibitors (PPIs), H2 antagonists, or antacids as they may decrease drug exposure.
7. Pharmaceutical Information
Chemical Name: 6-(2-hydroxy-2-methylpropoxy)-4-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile.
Molecular Formula: C29H31N7O3.
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).