Dosage of Pralsetinib

This product should be administered under the guidance of a physician experienced in the treatment of the relevant indications. The dosage regimen shall be formulated based on the patient’s individual conditions (such as tumor type, RET gene mutation status, and treatment response). Please follow the dosage and administration guidelines below and read the subsequent detailed instructions carefully.

Recommended Dosage and Administration

Initial Dose: 400 mg, administered orally once daily.

Treatment Course: Continue treatment until disease progression or unacceptable toxicity occurs.

Missed Dose Management: If a missed dose is remembered on the same day, take it as soon as possible and resume the normal dosing schedule the next day. If vomiting occurs after administration, do not take an extra dose and proceed with the next scheduled dose.

Patient Selection: Patients must be confirmed to have RET gene fusion through testing (FDA-approved testing methods are available for non-small cell lung cancer [NSCLC]; none are currently available for thyroid cancer).

Dosage Adjustment Guidelines for Adverse Reactions

Interstitial Lung Disease (ILD)/Pneumonitis

Grade 1–2: Withhold GAVRETO until resolution, then resume treatment at a reduced dose (refer to Table 1 in the package insert). Permanently discontinue the drug if the adverse reaction recurs.

Grade 3–4: Permanently discontinue the drug.

Hypertension

Grade 3 (persistent): Withhold treatment until blood pressure is controlled, then resume at a reduced dose.

Grade 4: Permanently discontinue the drug.

Hepatotoxicity

Grade 3–4: Withhold treatment and monitor AST/ALT levels weekly until they return to ≤ Grade 1 or baseline, then resume at a reduced dose. Permanently discontinue the drug if a Grade ≥3 event recurs.

Hemorrhagic Events

Grade 3–4: Withhold treatment until recovery to baseline or Grade 0–1. Permanently discontinue the drug in case of severe or life-threatening hemorrhage.

Other Adverse Reactions

Grade 3–4: Withhold treatment until improvement to ≤ Grade 2, then resume at a reduced dose. Permanently discontinue the drug if a Grade 4 event recurs.

Dosage Adjustments for Drug Interactions

Concomitant Use with CYP3A/P-gp Inhibitors

Avoidance recommended: Co-administration with strong/moderate CYP3A inhibitors, P-gp inhibitors, and their combination inhibitors should be avoided.

If co-administration is unavoidable: Dose reduction is required.

Examples:

Original dose 400 mg → Reduce to 200 mg when co-administered with strong CYP3A inhibitors or combined strong inhibitors.

Original dose 300 mg → Reduce to 200 mg when co-administered with moderate CYP3A inhibitors or P-gp inhibitors.

Original dose 200 mg → Reduce to 100 mg when co-administered with the above-mentioned inhibitors.

After discontinuation of inhibitors: Resume the original dose after a waiting period of 3–5 half-lives.

Concomitant Use with CYP3A Inducers

Avoidance recommended: Co-administration with strong/moderate CYP3A inducers should be avoided.

If co-administration is unavoidable: Dose escalation is required.

Examples:

Original dose 400 mg → Increase to 800 mg when co-administered with strong inducers; increase to 600 mg when co-administered with moderate inducers.

Original dose 300 mg → Increase to 600 mg when co-administered with strong inducers; increase to 500 mg when co-administered with moderate inducers.

Original dose 200 mg → Increase to 400 mg when co-administered with strong inducers; increase to 300 mg when co-administered with moderate inducers.

After discontinuation of inducers: Resume the original dose after at least 14 days.

from FDA，2024.03