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Selpercatinib is a highly selective and potent kinase inhibitor that works by targeting the mutation or fusion form of the RET (RearrangedDuringTransfection) gene.
1. Drug name: Selpercatinib
2. Trade name: Retevmo
3. Main ingredient: The active ingredient is Selpercatinib.
4. Specifications and properties: 40 mg capsule.
This product is a kinase inhibitor, used to treat:
1. Adult metastatic RET gene fusion-positive non-small cell lung cancer.
2. Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutated medullary thyroid cancer who require systemic therapy.
3. Adult and pediatric patients aged 12 years and above with advanced or metastatic RET gene fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine (if radioactive iodine is applicable).
Note: The latter two indications are approved based on the accelerated approval pathway, and continued approval may depend on verification of clinical benefit in confirmatory trials.
1. Patient selection: based on the presence of RET gene fusion or specific RET gene mutation in tumor tissue or plasma.
Recommended dosage (based on body weight):
2. Body weight < 50 kg: 120 mg, orally, twice daily.
Weight ≥ 50 kg: 160 mg orally twice daily.
Treatment should be continued until disease progression or unacceptable toxicity occurs.
3. How to take:
General requirements: Swallow the whole tablet, do not chew or crush. Twice a day, approximately 12 hours apart.
Taking with food: Usually it can be taken with or without food. However, if used in combination with a proton pump inhibitor (PPI), it must be taken with food.
Missed dose: If you miss a dose, you can take it again if it is more than 6 hours before the next dose; otherwise, you should skip the missed dose and take the next dose at the original planned time.
Vomiting: If you vomit after taking the medication, you should not take additional doses and wait until the next scheduled dose.
1. Dose reduction plan for adverse reactions:
First dose reduction: for patients <50 kg, reduce to 80 mg twice a day; for patients ≥50 kg, reduce to 120 mg twice a day.
The second reduction: for patients <50 kg, reduce to 40 mg twice a day; for patients ≥50 kg, reduce to 80 mg twice a day.
The third dose reduction: for patients <50 kg, reduce to 40 mg once a day; for patients ≥50 kg, reduce to 40 mg twice a day.
2. If you cannot tolerate three dose reductions, discontinue the drug permanently.
3. Adjustment principles for specific adverse reactions:
Hepatotoxicity (Grade 3/4): Suspend medication, then restart at two lower dose levels after recovery, and gradually adjust back.
Hypertension (Grade 3): Suspension of medication and resume at a reduced dose after control; (Grade 4): Permanent discontinuation of medication.
QT interval prolongation (Grade 3): suspend medication and reduce dose after recovery; (Grade 4): permanently discontinue medication.
Bleeding events (Grade 3/4): Suspend medication and evaluate after recovery; permanently discontinue medication if severe or life-threatening.
Hypersensitivity reactions (all grades): Withhold medication and use corticosteroids. After recovery, start with three lower dose levels, gradually dial back and taper steroids.
4. Dose adjustment due to drug interactions:
Avoid co-administration with strong/moderate CYP3A inhibitors. If it cannot be avoided, the dose needs to be reduced:
Original dose 120 mg bid → combined with moderate inhibitors: 80 mg bid; combined with strong inhibitors: 40 mg bid.
The original dose is 160 mg bid → combined with moderate inhibitors: 120 mg bid; combined with strong inhibitors: 80 mg bid.
5. Liver insufficiency:
Patients with severe liver damage need to reduce the dose: the original 120 mg bid is reduced to 80 mg bid; the original 160 mg bid is reduced to 80 mg bid.
1. Hepatotoxicity: common and potentially serious. Monitor ALT and AST before treatment, every 2 weeks for the first 3 months, and monthly thereafter. Withhold, reduce dose, or permanently discontinue medication based on severity.
2. High blood pressure: common and potentially serious. Optimize blood pressure before treatment and monitor blood pressure after 1 week of treatment and at least monthly thereafter. Withhold, reduce dose, or permanently discontinue medication based on severity.
3. QT interval prolongation: Concentration-dependent QTc prolongation may occur. Monitor electrocardiogram, electrolytes, and TSH at baseline and regularly during treatment. High-risk patients and those taking specific drugs together require enhanced monitoring. Withhold, reduce dose, or permanently discontinue medication based on severity.
4. Bleeding events: Serious or even fatal bleeding may occur. Severe or life-threatening bleeding should permanently discontinue the drug.
5. Hypersensitivity reaction: may occur, manifesting as fever, rash, joint pain/myalgia, etc. When this occurs, discontinue medication and use corticosteroids, and then reduce and gradually increase the dosage after recovery.
6. Risk of impaired wound healing: It may affect wound healing. The drug should be stopped for at least 7 days before elective surgery, and should be given at least 2 weeks after major surgery and until the wound has fully healed.
7. Embryo-fetal toxicity: May cause fetal harm. Women and men of childbearing potential should use effective contraceptive measures during treatment and for at least 1 week after the last dose. Avoid use by pregnant women.
1. Children: The safety and effectiveness have been established for patients 12 years old and above; it has not been established for patients under 12 years old.
2. Elderly patients (≥65 years old): No overall difference in safety or effectiveness was observed compared with younger patients.
3. Hepatic insufficiency: no dose adjustment is required for mild or moderate cases; dose reduction is required for severe cases.
4. Renal insufficiency: mild or moderate (CLcr ≥ 30 mL/min) no dose adjustment required; severe (CLcr < 30 mL/min) or in patients with end-stage renal disease. Recommended dosages have not been established.
5. Pregnancy: It may cause harm to the fetus. Inform pregnant women of the risk to the fetus.
6. Breastfeeding: Women are advised not to breastfeed during treatment and within 1 week after the last dose.
7. Fertility: May damage female and male fertility.
1. Common adverse reactions (≥25%):
Laboratory abnormalities: increased aspartate aminotransferase, increased alanine aminotransferase, increased blood sugar, decreased leukocytes, decreased albumin, decreased blood calcium, increased blood creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased blood sodium, and constipation.
Clinical symptoms: dry mouth and diarrhea.
2. Serious adverse reactions: including liver toxicity, severe hypertension, QT interval prolongation, severe bleeding, hypersensitivity reactions, etc.
There are currently no clear contraindications.
1. Drugs that should be avoided in combination:
Strong/moderate CYP3A inducers (such as rifampicin, bosentan): will significantly reduce the plasma concentration of serpatinib and weaken the efficacy.
Proton pump inhibitors (PPI), H2 receptor antagonists, and locally acting antacids: will reduce the plasma concentration of serpatinib. Concomitant use should be avoided.
2. Drugs that need to be combined with caution and whose dosage needs to be adjusted:
Strong/moderate CYP3A inhibitors (such as itraconazole, diltiazem): will significantly increase the plasma concentration of serpatinib and increase the risk of adverse reactions. If it cannot be avoided, the dose needs to be reduced and QT interval monitoring should be strengthened.
3. The impact of serpatinib on other drugs:
This product is a moderate CYP2C8 inhibitor and a weak CYP3A inhibitor. Concomitant use with drugs metabolized by CYP2C8 or CYP3A (such as repaglinide, midazolam) will increase the plasma concentrations of these drugs and may increase the risk of adverse reactions. Caution should be exercised during coadministration and consideration should be given to reducing the dose of the coadministered drugs.
QT interval prolonging drugs: Concomitant use with drugs known to prolong the QT interval may increase the risk and requires enhanced ECG monitoring.
4. Usage in combination with acid-suppressing drugs (if unavoidable):
Combined use with PPI: RETEVMO needs to be taken with food.
Combined use with H2 receptor antagonists: RETEVMO should be taken 2 hours before or 10 hours after taking H2 receptor antagonists.
Combined use with antacids: RETEVMO should be taken 2 hours before or 2 hours after taking antacids.
1. Store at room temperature between 20°C and 25°C (68°F and 77°F); short-distance transportation between 15°C and 30°C (59°F and 86°F) is allowed.
2. Please keep it out of the reach of children.