Generic
Selpercatinib
1 brands available in the market
At a glance
Selpercatinib is a RET kinase inhibitor used for the treatment of metastatic RET fusion-positive non-small cell lung cancer, RET-mutant medullary thyroid cancer, and RET fusion-positive thyroid cancer.
Description
Selpercatinib is a kinase inhibitor that inhibits wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3. It also inhibits FGFR 1, 2, and 3 at higher concentrations. In cellular assays, selpercatinib inhibits RET at approximately 60-fold lower concentrations than FGFR1 and 2, providing selective antitumor activity in RET-dependent tumors.
Indications
- Metastatic RET fusion-positive non-small cell lung cancer (NSCLC)
- Advanced or metastatic RET-mutant medullary thyroid cancer (MTC) (≥12 years)
- Advanced or metastatic RET fusion-positive thyroid cancer (≥12 years, radioactive iodine-refractory)
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
RET Kinase Inhibitor
Pharmacology
Selpercatinib inhibits wild-type RET and mutant RET isoforms and VEGFR1/3 with IC50 values of 0.92-67.8 nM. It also inhibits FGFR 1, 2, and 3 at higher concentrations. In cellular assays, selpercatinib inhibits RET at approximately 60-fold lower concentrations than FGFR1/2 and 8-fold lower than VEGFR3, providing selective antitumor activity in RET-dependent tumors.
Mechanism of action
Inhibits RET kinase to prevent RET-dependent tumor cell proliferation.
Dosage
Adult and Pediatric (≥12 years) Dose (Oral):
- Weight <50 kg: 120 mg twice daily (approximately every 12 hours)
- Weight ≥50 kg: 160 mg twice daily
Dose Modifications with Acid-Reducing Agents:
- With PPI: Take selpercatinib with food
- With H2 receptor antagonist: 2 hours before or 10 hours after
- With locally-acting antacid: 2 hours before or 2 hours after
Administration
- Swallow capsules whole; do not crush or chew
- Take approximately every 12 hours daily
- If vomiting occurs, do not take an additional dose; continue at the next scheduled time
Missed dose
- Missed dose: Take if more than 6 hours until next dose; if less than 6 hours, skip
- If vomiting occurs, do not take an additional dose
Side effects
Common Side Effects:
- Elevated liver enzymes
- Elevated blood glucose
- Decreased white blood cell count
- Decreased albumin
- Decreased calcium
- Dry mouth, diarrhea
- Elevated creatinine
- Hypertension
- Fatigue, peripheral edema
- Decreased platelets
- Elevated cholesterol, decreased sodium, constipation
Precautions & warnings
- Hepatotoxicity: Monitor ALT/AST at baseline, every 2 weeks for first 3 months, then monthly
- Hypertension: Do not initiate if uncontrolled; monitor weekly then monthly
- QT prolongation: Monitor at-risk patients; correct electrolytes
- Hemorrhagic events: Permanently discontinue for severe or life-threatening hemorrhage
- Hypersensitivity: Withhold if fever, rash, arthralgia/myalgia occur; start corticosteroids
- Tumor lysis syndrome: Monitor at-risk patients and provide hydration
Contraindications
- Severe hypersensitivity reactions
Drug interactions
- Acid-reducing agents (PPI, H2RA, antacids): Decrease selpercatinib plasma concentrations; avoid; modify administration timing if unavoidable
- Strong and moderate CYP3A inhibitors: Increase selpercatinib plasma concentrations; avoid; reduce dose and monitor QT if unavoidable
- Strong and moderate CYP3A inducers: Decrease selpercatinib plasma concentrations; avoid
Food interactions
Caution is advised when consuming alcohol with Selpercatinib; consult your doctor.
Use in pregnancy
Use in Pregnancy: Animal studies show adverse effects; advise pregnant women of potential fetal risk; use only if clearly needed; consult your doctor.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: No data on presence in human milk; do not breastfeed during treatment and for 1 week after the last dose; consult your doctor.
Pediatric use
Indicated for pediatric patients 12 years and older for MTC and RET fusion-positive thyroid cancer; safety not established in patients <12 years
Geriatric use
No overall differences observed between elderly (>65 years) and younger patients
Renal / hepatic impairment
Renal Impairment: Mild-severe (eGFR >15-89): no dose adjustment; ESRD dose not established; consult your doctor.
Hepatic Impairment: Severe (bilirubin >3-10×ULN): reduce dose; mild-moderate: no dose adjustment; consult your doctor.
Overdose effects
Limited overdose experience; provide supportive care and monitor vital signs in overdose.
Storage conditions
Store below 30°C in a cool and dry place, protected from light; keep out of reach of children.
Chemical structure
Selpercatinib