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Dosage of Larotrectinib

1.Patient Selection  

Select patients for treatment with Larotrectinib based on the presence of a NTRK gene fusion in  tumor specimens.

2.Recommended Dosage

Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of at Least  1.0 Meter-Squared.

The recommended dosage of Larotrectinib is 100 mg orally twice daily, with or without food,  until disease progression or until unacceptable toxicity.  

Recommended Dosage in Pediatric Patients with Body Surface Area Less Than 1.0 Meter-Squared.

The recommended dosage of Larotrectinib is 100 mg/m² orally twice daily, with or without food,  until disease progression or until unacceptable toxicity.

3.Dosage Modifications for Adverse Reactions

For Grade 3 or 4 adverse reactions:  

Withhold Larotrectinib until adverse reaction resolves or improves to baseline or Grade 1.  Resume at the next dosage modification if resolution occurs within 4 weeks.  

Permanently discontinue Larotrectinib if an adverse reaction does not resolve within 4 weeks.

The recommended dosage modifications for Larotrectinib for adverse reactions are provided in  Table 1.

Permanently discontinue Larotrectinib in patients who are unable to tolerate Larotrectinib after  three dose modifications.  

4.Dosage Modifications for Coadministration with Strong CYP3A4 Inhibitors

Avoid coadministration of strong CYP3A4 inhibitors with Larotrectinib. If coadministration of a  strong CYP3A4 inhibitor cannot be avoided, reduce the Larotrectinib dose by 50%. After the  inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the Larotrectinib dose  that was used prior to initiating the CYP3A4 inhibitor.  

5.Dosage Modifications for Coadministration with Strong or Moderate CYP3A4  Inducers 

Avoid coadministration of strong CYP3A4 inducers with Larotrectinib. If coadministration of a  strong CYP3A4 inducer cannot be avoided, double the Larotrectinib dose. Additionally, for  coadministration with a moderate CYP3A4 inducer, double the Larotrectinib dose. After the  inducer has been discontinued for 3 to 5 elimination half-lives, resume the Larotrectinib dose that  was used prior to initiating the CYP3A4 inducer.  

6.Dosage Modifications for Patients with Hepatic Impairment

Reduce the starting dose of Larotrectinib by 50% in patients with moderate (Child-Pugh B) to  severe (Child-Pugh C) hepatic impairment.

7.Administration

Larotrectinib capsule or oral solution may be used interchangeably.  Do not make up a missed dose within 6 hours of the next scheduled dose.  If vomiting occurs after taking a dose of Larotrectinib, take the next dose at the scheduled time.

Capsules:Swallow capsules whole with water. Do not chew or crush the capsules.

from FDA，2022.11