Selpercatinib instructions

1. Generic name: Serpatinib

Product name: Retsevmo

All names: Selpercatinib, Selpercatinib, Selpercatinib, LOXO-292

2. Indications:

1. RET fusion-positive non-small cell lung cancer (NSCLC): Selpercatinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer who have rearranged (RET) gene fusion during transfection.

2. RET-mutant medullary thyroid cancer (MTC): Selpatinib is indicated for the treatmentAdult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer and RET mutations detected by an FDA-approved test who require systemic therapy.

3. RET fusion-positive thyroid cancer: Serpatinib is indicated for the treatment ofAdult and pediatric patients 12 years of age and older with RET gene fusion-positive advanced or metastatic thyroid cancer who require systemic therapy as detected by an FDA-approved test and are refractory to radioactive iodine (if radioactive iodine is appropriate)

4. Other RET fusion-positive solid tumors: Serpatinib is indicated for the treatment of adult patients with locally advanced or metastatic solid tumors with RET gene fusion who have progressed on or after previous systemic therapy or who have no satisfactory alternative treatment options.

3. Usage and dosage:

1. Recommended dose: The recommended dose of selpatinib based on body weight is: 120 mg for patients less than 50 kg and 160 mg for patients 50 kg or more. Serpatinib should be taken orally twice a day (approximately every 12 hours) until disease progression or unacceptable toxicity occurs. Do not take a missed dose unless it is more than 6 hours before your next scheduled dose.

2. Dose adjustment: If the patient experiences adverse reactions after using serpatinib , the dose should be adjusted. If the dose is insufficientPatients 50 kg or more were reduced to 80 mg orally twice daily for the first time, 40 mg orally twice daily for the second time, and 40 mg orally once daily for the third time; patients 50 kg or above were reduced to 120 mg orally twice daily for the first time, 80 mg orally twice daily for the second time, and 40 mg orally twice daily for the third time. Patients who cannot tolerate three dose reductions should permanently discontinue serpatinib.

(1) Severe hepatic impairment: For patients with severe hepatic impairment who take 120mg or 160mg, the dose of selpatinib should be reduced to 80mg orally administered twice daily.

3. Combined medication:

(1) Avoid concurrent use of proton pump inhibitors, histamine 2 (H2) receptor antagonists, or locally acting antacids with serpatinib. If concomitant use cannot be avoided, when taken with a proton pump inhibitor, it should be taken with food; take serpatinib 2 hours before or 10 hours after taking an H2 receptor antagonist; take serpatinib 2 hours before or 2 hours after taking a locally acting antacid.

(2) Avoid coadministration of strong and moderate CYP3A inhibitors with serpatinib. If concurrent use of strong or moderate CYP3A inhibitors cannot be avoided, the dose of selpatinib should be reduced. For patients taking 120 mg, reduce to 80 mg or 40 mg, and for patients taking 160 mg, reduce to 120 mg or 80 mg. After discontinuing the inhibitor 3 to 5 elimination half-lives, continue serpatinib at the dose before starting the CYP3A inhibitor.

4. Adverse reactions:

The most common adverse reactions (≥25%) with serpatinib are edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. . The most common serious adverse reactions (≥2%) were pneumonia, pleural effusion, abdominal pain, bleeding, anaphylaxis, dyspnea, and hyponatremia. Fatal adverse reactions occurred in 3% of patients, including sepsis, respiratory failure, hemorrhage, pneumonia, cardiac arrest, sudden death and heart failure. The most common grade 3 or 4 laboratory abnormalities (≥5%) were lymphopenia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium.

5. Storage:

Serpatinib is usually formulated in capsules and is typically stored20°C to 25°C (68°F to 77°F); temperature fluctuations between 15°C and 30°C (59°F to 86°F) are allowed.

6. Mechanism of action:

Serpatinib is a kinase inhibitor that inhibits wild-type RET and multiple mutant RET isoforms as well as VEGFR1 and VEGFR3, with IC50 values ranging from 0.92nM to 67.8nM. In other enzyme assays, sepatinib also inhibited FGFR 1, 2, and 3 at higher clinically achievable concentrations. In cellular analyses, serpatinib inhibited RET at concentrations approximately 60-fold lower than FGFR1 and 2 and approximately 8-fold lower than VEGFR3.

Certain point mutations in RET or chromosomal rearrangements involving in-frame fusion of RET with various partners can lead to constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation in tumor cell lines. In in vitro and in vivo tumor models, serpatinib demonstrated antitumor activity in cells containing constitutively activated RET proteins resulting from gene fusions and mutations, including CCDC6-RET, KIF5B-RET, RET V804M, and RET M918T. In addition, serpatinib showed antitumor activity in mice intracranially implanted with patient-derived RET fusion-positive tumors.

The original drug Serpatinib has not yet been launched in China, so it is not covered by medical insurance. Domestic patients cannot yet purchase this drug. Serpatinib marketed overseas The original drug has a US version and a European version. The price of the US version is about 150,000 yuan per box of 80mg*60 pills. The price of the European version of 80mg*56 pills per box is about 21,000 yuan (the price may fluctuate due to the exchange rate), which is expensive. There are also serpatinibgeneric drugs produced abroad. The specification produced by a Bangladesh pharmaceutical factory is 40mg*30 pills per box and the price is about 4,300 yuan (the price may fluctuate due to the exchange rate). The ingredients of the generic drugs are basically the same as those of the original drug.