Pralsetinib is a targeted therapy drug primarily used for non-small cell lung cancer and thyroid cancer with specific gene mutations. The usage and dosage should be adjusted according to the patient's condition, and attention should be paid to drug resistance mechanisms and potential adverse reactions. The following will provide a detailed introduction to its usage, drug resistance, and precautions.

1. Usage and dosage

The commonly used dose of Pratinib is 400 milligrams once daily, and treatment is continued until disease progression or intolerable toxicity occurs. Children with thyroid cancer (aged 12 and above) receive the same dosage as adults.

(1) Dose adjustment

For adverse reactions, the dosage needs to be gradually reduced: first to 300 milligrams per day, second to 200 milligrams per day, and third to 100 milligrams per day. When unable to tolerate 100 milligrams, the medication should be discontinued.

(2) Combination therapy adjustment

When used in combination with potent CYP3A4 inhibitors, the dosage should be reduced to 200 milligrams or 100 milligrams per day; If used in combination with an inducer, the dosage needs to be doubled from the 7th day onwards.

2. Drug resistance mechanism

Pratinib works by inhibiting the RET fusion gene, and resistance may arise from secondary mutations (such as RETV804M), pathway activation, or phenotype transformation. At present, there is no standard solution to overcome it, and subsequent treatment needs to be guided through genetic testing.

3. Precautions

The use of Pratinib requires focused monitoring of interstitial lung disease, hypertension, liver toxicity, and bleeding events. Immediate intervention is required when relevant symptoms appear, and the dosage may be adjusted or discontinued if necessary.

(1) Interstitial lung disease

Suspend medication at level 1-2 and reduce dosage after recovery; Grade 3-4 or recurrence requires permanent discontinuation of medication. When patients experience coughing and difficulty breathing, they should be promptly screened.

(2) Hypertension

Grade 3 hypertension requires temporary suspension of treatment and lowering of blood pressure, followed by reduction and recovery after control; Level 4 requires permanent discontinuation of medication. Blood pressure should be monitored regularly during treatment.

(3) Hepatotoxicity

If the liver enzymes are elevated at levels 3-4, medication should be suspended and reduced after recovery. Monitor liver function every 2 weeks for the first 3 months of treatment.

(4) Special populations

Pregnant women are prohibited from taking medication, and breastfeeding should be avoided within one week of discontinuation. Patients with mild to moderate liver and kidney dysfunction do not need to adjust the dosage.