Instructions for tucatinib

1. Generic name: Tucatinib

Product name:TUKYSA

All names: Tucatinib, Tucatinib, Tucatinib, Tukysa

2. Indications:

1. Metastatic breast cancer: tucatinib is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the setting of metastasis.

2. Unresectable or metastatic colorectal cancer: Tucatinib is suitable for combination therapy with trastuzumab Adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer who have progressed after receiving chemotherapy based on fluoropyrimidine, oxaliplatin, and irinotecan.

3. Usage and dosage:

1. Recommended dosage:

The recommended dose of tucatinib is300 mg orally twice daily and may be used in combination with other drugs (such as trastuzumab, capecitabine) until disease progression or unacceptable toxicity occurs. If the patient vomits or misses a dose of tucatinib, take the next dose at the usually scheduled time.

2. Dosage adjustment:

For adverse reactions (such as diarrhea, liver toxicity, etc.) after using tucatinib, reduce the dose to 250 mg orally twice a day for the first time, 200 mg orally twice a day for the second time, and reduce the dose to 150 mg orally twice a day for the third time. Patients who cannot tolerate 150 mg orally twice a day should permanently discontinue tucatinib. Patients with severe hepatic impairment may have the recommended dose reduced to 200 mg orally twice daily.

3. Combined medication:

Avoid the concomitant use of strong CYP2C8 inhibitors with tucatinib. If this cannot be avoided, reduce the recommended dose to 100 mg orally twice daily. After 3 elimination half-lives of discontinuing the strong CYP2C8 inhibitor, resume the tucatinib dose taken before starting the inhibitor.

4. Adverse reactions:

In clinical studies ofHER2-positive metastatic breast cancer, the most common adverse reactions of tucatinib were diarrhea, palmoplantar red blood cell paresthesias, nausea, hepatotoxicity, vomiting, stomatitis, decreased appetite, anemia, and rash. In clinical studies of RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer, the most common adverse reactions were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions and fever, and the most common laboratory abnormalities were increased creatinine, increased glucose, increased ALT, decreased hemoglobin, increased AST, increased bilirubin, increased alkaline phosphatase, lymphopenia, decreased albumin, leukopenia and sodium decrease.

5. Storage:

Tucatinib is usually stored at controlled room temperature, 20°C to 25°C (68°F to 77°F), with an allowed excursion range of 15°C to 30°C (59°F to 86°F), protected from moisture, and once opened, use within 3 months. TucatinibOpen bottleThrow away any unused tablets after 3 months.

6. Special groups:

1. Women: Based on findings in animals and its mechanism of action, tucatinib can cause fetal damage when administered to pregnant women. It is recommended that women and women of reproductive potential not breastfeed during treatment with tucatinib and for 1 week after the last dose.

2. Males: Male patients with female partners of reproductive potential should use effective contraceptive measures during treatment with tucatinib and within 1 week after the last dose.

3. Renal impairment: For patients with mild or moderate renal impairment, it is not recommended to adjust the dosage of tucatinib. Since capecitabine is contraindicated in patients with severe renal impairment, the combined use of tucatinib with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (creatinine clearance less than 30 mL/min).

4. Hepatic impairment: For patients with severe hepatic impairment, dose reduction is recommended.

7. Mechanism of action:

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, Tucatinib inhibits the phosphorylation of HER2 and HER3, thereby inhibiting downstream MAPK and AKT signaling and cell proliferation, and exhibits anti-tumor activity in HER2-expressing tumor cells. In vivo, tucatinib inhibits the growth of HER2-expressing tumors. Compared to medications alone,The combination of tucatinib and trastuzumab showed enhanced antitumor activity in vitro and in vivo.

It is understood that the original drug Tucatinib has not yet been launched in China, so it has not entered the scope of domestic medical insurance. Patients in need cannot yet purchase this drug in pharmacies or hospitals. The price of the European version of tucatinib original drug sold overseas is around RMB 72,000 (the price may fluctuate due to exchange rates), which is expensive. There are also generic drugs of tucatinib produced in other countries. The price of Tucatinib produced by a Lao pharmaceutical factory is around 6,400 yuan (the price may fluctuate due to the exchange rate). The price is much cheaper than the original drug, and the ingredients of foreign generic drugs are basically the same as the original drug.