Gavreto®Pralsetinib Capsules

1. Indications and Usage
RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC): Treatment of adult patients with metastatic or locally advanced RET fusion-positive NSCLC .
RET Mutation-Positive Medullary Thyroid Cancer (MTC): Treatment of adult and pediatric patients (12 years and older) 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 and older) 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. Capsules must be swallowed whole with water. Do not chew, open, or crush the capsules .
Food Requirement: Must be taken on an empty stomach. Take at least 2 hours before or 1 hour after a meal .
Standard Dose:
Recommended Dose: 400 mg once daily .
Missed Dose: If a dose is missed, skip it and resume at the usual time for the next scheduled dose. Do not make up for the missed dose .
Dose Reduction: Mandatory dose reduction (to 300 mg, then 200 mg, then 100 mg) for severe toxicities .
3. Mechanism of Action
Pralsetinib is a potent, selective, oral 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
Interstitial Lung Disease (ILD)/Pneumonitis: Can cause severe and fatal ILD/pneumonitis. Monitor for respiratory symptoms (dyspnea, cough). Interrupt or permanently discontinue based on severity .
Hypertension: Monitor blood pressure regularly. Do not initiate treatment in patients with uncontrolled hypertension .
Hepatotoxicity: Monitor liver function tests (ALT, AST) regularly .
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:
Constipation, Hypertension.
Fatigue, Asthenia.
Musculoskeletal pain (e.g., arthralgia, myalgia).
Diarrhea, Dysgeusia (taste disturbance).
Laboratory Abnormalities: Lymphopenia, Neutropenia, Leukopenia, Anemia, Elevated ALT/AST .
6. Drug Interactions
CYP3A Substrate:
Inhibitors: Avoid co-administration with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin). If unavoidable, reduce dose .
Inducers: Avoid co-administration with strong CYP3A inducers (e.g., rifampin) as they reduce efficacy .
P-gp Substrate: P-gp inhibitors may increase Pralsetinib exposure .
7. Pharmaceutical Information
Chemical Name: (cis)-N-((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4-methyl-6-((5-methyl-1H-pyrazol-3-yl)amino)pyrimidin-2-yl)benzenesulfonamide .
Molecular Formula: C26H26FN7O3S .
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) .