Zepingping Gecacitinib Hydrochloride Tablets

1. Indications and Usage
Primary Myelofibrosis (PMF): Treatment of adult patients with intermediate or high-risk PMF.
PV-FIB: Treatment of adult patients with PV-FIB.
2. Dosage and Administration
Route of Administration: Oral administration ONLY.
Recommended Dosage: Starting dose is 100 mg twice daily.
Titration: Based on individual safety and tolerability, the dose may be increased to 150 mg twice daily.
Critical Administration Instructions:
Intake: Tablets must be swallowed whole; do not crush, chew, or break.
Missed Dose: If a dose is missed, take it as soon as remembered on the same day. If missed on the next day, take the regular dose at the usual time; do not double the dose.
Vomiting: If vomiting occurs after taking a dose, do not take an extra dose; take the next dose at the regular scheduled time.
Dose Modifications: Reduce to 50 mg twice daily or 100 mg once daily for adverse reactions. If unable to tolerate 50 mg twice daily, permanently discontinue the drug.
3. Mechanism of Action
JAK2 Inhibition: Gecacitinib is a potent and selective inhibitor of Janus kinase 2 (JAK2).
Pathway Blockade: It inhibits JAK2-mediated phosphorylation of STAT proteins, blocking downstream signaling pathways.
Clinical Effect: This reduces the proliferation and inflammatory cytokine production of neoplastic cells, leading to significant improvements in splenomegaly and myelofibrosis-related symptoms.
4. Safety and Warnings
Hepatotoxicity: Elevations in ALT, AST, and bilirubin occur. Monitor liver function tests before initiation, every 2 weeks for the first 3 months, and monthly thereafter.
Myelosuppression: Neutropenia, thrombocytopenia, and anemia are common. Monitor complete blood counts before initiation and regularly during treatment.
Infection Risk: Increased risk of serious bacterial, fungal, and viral infections (including herpes virus reactivation). Screen for HBV and TB prior to treatment.
Malignancy: An increased risk of malignancy (excluding NMSC) has been observed in JAK inhibitor trials; monitor patients appropriately.
Embryo-Fetal Toxicity: May cause fetal harm. Effective contraception is required for females and males with female partners during treatment and for at least 1 week after the final dose.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions (≥20%): Neutropenia, thrombocytopenia, anemia, increased ALT/AST, nausea, vomiting, pyrexia, and fatigue.
Common Grade 3-4 Adverse Reactions: Neutropenia, thrombocytopenia, anemia, and ALT/AST elevation.
Clinical Research Highlights: The GECACITIN-003 trial demonstrated that 100 mg twice daily significantly improved spleen volume and myelofibrosis symptoms with a manageable safety profile.
6. Drug Interactions
CYP3A Modulators: Gecacitinib is a substrate of CYP3A. Strong CYP3A inhibitors may increase exposure, and strong and moderate CYP3A inducers may decrease exposure; dose adjustments or avoidance is required.
CYP2C9 Substrates: Gecacitinib is an inhibitor. Concomitant use with sensitive CYP2C9 substrates may increase their exposure.
7. Pharmaceutical Information
Chemical Composition: Active Ingredient: Gecacitinib Hydrochloride.
Appearance: Film-coated tablets.
Packaging: Blister packaging (e.g., 50 mg or 100 mg per tablet).
Storage: Store at controlled room temperature; protect from moisture.