Tepmetko Tepotinib Hydrochloride Tablets

1. Indications and Usage
Non-Small Cell Lung Cancer (NSCLC):
Indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mesenchymal-epithelial transition (MET) exon 14 skipping mutation, as detected by an FDA-approved test.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: 450 mg once daily (2 tablets of 225 mg or 2 tablets of 250 mg depending on formulation).
Schedule: Continuous daily dosing.
Administration Instructions:
Take with food (must be taken with a meal).
Swallow tablets whole; do not crush, chew, or split.
If a dose is missed and cannot be taken within 8 hours of the scheduled time, skip the dose and resume at the next scheduled time.
If vomiting occurs, do not take an additional dose; resume at the next scheduled time.
3. Mechanism of Action
MET Kinase Inhibition:
Tepotinib is a potent, selective, small-molecule kinase inhibitor of MET.
Action:
It binds to the ATP-binding pocket of the MET kinase domain, inhibiting MET phosphorylation and downstream signaling pathways (such as PI3K/AKT and RAS/MAPK) that drive tumor cell proliferation and survival.
4. Safety and Warnings
Interstitial Lung Disease (ILD)/Pneumonitis:
Can cause fatal ILD/pneumonitis. Monitor for pulmonary symptoms (e.g., dyspnea, cough, fever). Discontinue permanently for diagnosed ILD/pneumonitis.
Hepatotoxicity:
Can cause severe elevations in ALT/AST. Monitor liver function tests (LFTs) before initiation, every 2 weeks for the first 3 months, and then monthly.
Embryo-Fetal Toxicity:
Can cause fetal harm. Effective contraception is required during treatment and for at least 1 week after the final dose.
Renal Impairment:
Can cause transient increases in serum creatinine (due to inhibition of renal tubular secretion) and rare cases of acute renal impairment.
5. Adverse Reactions
Most Common (Incidence ≥20%):
General: Peripheral edema (72.5%), Fatigue.
Gastrointestinal: Nausea (31.0%), Diarrhea (28.8%).
Metabolic: Hypoalbuminemia (32.9%), Increased Creatinine (29.1%).
Dermatologic: Rash, Alopecia.
6. Drug Interactions
Metabolic Pathway:
Primarily metabolized by CYP3A4 and CYP2C8.
Strong CYP3A4 Inhibitors/Inducers: Caution is advised; dose reduction may be required for strong inhibitors.
P-gp Inhibitors: Concomitant use may increase tepotinib exposure (e.g., with clarithromycin).
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Tepotinib Hydrochloride.
Appearance: White to off-white, film-coated tablets (225 mg or 250 mg).
Storage: Store at 20°C–25°C (68°F–77°F); excursions permitted to 15°C–30°C (59°F–86°F).