Metastatic RET Fusion-Positive NSCLC: Used for adult patients with metastatic non-small cell lung cancer (NSCLC) that has RET gene fusion. This approval is based on tumor response and duration, and may require further confirmation in clinical trials.

RET-Mutant Medullary Thyroid Cancer (MTC): Indicated for adults and children aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who need systemic treatment.

RET Fusion-Positive Thyroid Cancer: Used for adults and children (12 years and above) with advanced or metastatic RET fusion-positive thyroid cancer that does not respond to radioactive iodine therapy (if applicable).

Selpercatinib is a kinase inhibitor that targets RET proteins and their mutated forms. It blocks RET signaling pathways, which play a key role in cancer cell growth. It also shows activity against VEGFR1, VEGFR3, and FGFR1-3 at higher concentrations. By inhibiting these pathways, Selpercatinib helps stop tumor growth and spread.

The recommended dosage of Selpercatinib based on body weight is:

• Less than 50 kg: 120 mg
• 50 kg or greater: 160 mg

Take Selpercatinib orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Swallow the capsules whole. Do not crush or chew the capsules. Do not take a missed dose unless it is more than 6 hours until next scheduled dose. If vomiting occurs after Selpercatinib administration, do not take an additional dose and continue to the next scheduled time for the next dose.

Dosage Modifications for Concomitant Use of Acid-Reducing Agents Avoid concomitant use of a PPI, a histamine-2 (H2) receptor antagonist, or a locally-acting antacid with Selpercatinib. If concomitant use cannot be avoided:

• Take Selpercatinib with food when co-administered with a PPI.
• Take Selpercatinib 2 hours before or 10 hours after administration of an H2 receptor antagonist.
• Take Selpercatinib 2 hours before or 2 hours after administration of a locally-acting antacid.

Acid-Reducing Agents: Concomitant use of Selpercatinib with acid-reducing agents decreases Selpercatinib plasma concentrations, which may reduce Selpercatinib anti-tumor activity. Avoid concomitant use of PPIs, H₂ receptor antagonists, and locally-acting antacids with Selpercatinib. If co-administration cannot be avoided, take Selpercatinib with food (with a PPI) or modify its administration time (with an H₂ receptor antagonist or a locally-acting antacid).

Strong and Moderate CYP3A Inhibitors: Concomitant use of Selpercatinib with a strong or moderate CYP3A inhibitor increases Selpercatinib plasma concentrations, which may increase the risk of Selpercatinib adverse reactions, including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Selpercatinib. If concomitant use of strong and moderate CYP3A inhibitors cannot be avoided, reduce the Selpercatinib dosage and monitor the QT interval with ECGs more frequently.

Strong and Moderate CYP3A Inducers: Concomitant use of Selpercatinib with a strong or moderate CYP3A inducer decreases Selpercatinib plasma concentrations, which may reduce Selpercatinib anti-tumor activity. Avoid co-administration of strong or moderate CYP3A inducers with Selpercatinib.

Common side effects of Selpercatinib include:

• Increased liver enzymes
• High blood sugar
• Low white blood cells and platelets
• Low calcium and sodium levels
• Dry mouth
• Diarrhea or constipation
• High blood pressure
• Fatigue
• Swelling in hands, legs, and feet
• Skin rash
• Increased creatinine and cholesterol levels

Pregnancy: Based on findings from animal studies, and its mechanism of action, SELPERCATINIB can cause fetal harm when administered to a pregnant woman. There are no available data on SELPERCATINIB use in pregnant women to inform drug-associated risk. Administration of Selpercatinib to pregnant rats during the period of organogenesis resulted in embryolethality and malformations at maternal exposures that were approximately equal to the human exposure at the clinical dose of 160 mg twice daily. Advise pregnant women of the potential risk to a fetus.

Lactation: There are no data on the presence of Selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with SELPERCATINIB and for 1 week after the final dose.

Hepatotoxicity: Selpercatinib may cause serious liver-related side effects. Liver enzymes (ALT, AST) should be checked before starting treatment, every 2 weeks during the first 3 months, and then regularly afterward. Depending on severity, treatment may need to be paused, dose reduced, or permanently stopped.

Hypertension: High blood pressure is common during treatment. Blood pressure should be controlled before starting therapy and monitored regularly. Anti-hypertensive medications may be required. Dose adjustment or discontinuation may be necessary in severe cases.

QT Interval Prolongation: Selpercatinib can affect heart rhythm by prolonging the QT interval. Patients at risk (e.g., with heart disease or electrolyte imbalance) should be closely monitored. Regular ECG and electrolyte checks are recommended. Dose changes or discontinuation may be needed.

Hemorrhagic Events: Serious and sometimes fatal bleeding can occur. If severe bleeding develops, Selpercatinib should be permanently discontinued.

Hypersensitivity: Allergic reactions such as fever, rash, joint pain, or muscle pain may occur. If this happens, treatment should be paused and corticosteroids started. After recovery, the drug may be restarted at a lower dose if tolerated.

Tumor Lysis Syndrome (TLS): TLS may occur, especially in patients with large or rapidly growing tumors. Preventive measures such as proper hydration and close monitoring are important.

Pediatric Use: Selpercatinib is approved for use in children aged 12 years and older for certain thyroid cancers, including medullary thyroid cancer and RET fusion-positive thyroid cancer requiring systemic therapy. Its use in pediatric patients is supported by adult clinical data along with additional safety and pharmacokinetic information in adolescents. However, its safety and effectiveness have not been established in children under 12 years of age or for other indications. In growing adolescents, monitoring of bone growth plates is recommended, and treatment may need to be paused or stopped if abnormalities occur.

Geriatric Use: Clinical studies have shown no significant difference in safety or effectiveness between older patients (above 65 years) and younger patients. However, careful monitoring is still advised.

Renal Impairment: No dose adjustment is required for patients with mild to severe kidney impairment. However, dosing recommendations are not established for patients with end-stage renal disease (ESRD).

Hepatic Impairment: Dose reduction is required in patients with severe liver impairment. No adjustment is needed for mild to moderate liver impairment, but patients should be monitored closely for side effects.

Cytotoxic Chemotherapy

Store below 30°C in a cool, dry place, protected from light. Keep out of reach of children.