VITRAKVI Capsule / Oral solution Ref.[10108] Active ingredients: Larotrectinib

2.1 Patient Selection

Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion in tumor specimens [see Clinical Studies (14)]. An FDA-approved test for the detection of NTRK gene fusion is not currently available.

2.2 Recommended Dosage

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

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

2.3 Dosage Modifications for Adverse Reactions

For Grade 3 or 4 adverse reactions:

• Withhold VITRAKVI 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 VITRAKVI if an adverse reaction does not resolve within 4 weeks.

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

Table 1. Recommended Dosage Modifications for VITRAKVI for Adverse Reactions:

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

2.4 Dosage Modifications for Coadministration with Strong CYP3A4 Inhibitors

Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration of a strong CYP3A4 inhibitor cannot be avoided, reduce the VITRAKVI dose by 50%. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose taken prior to initiating the CYP3A4 inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for Coadministration with Strong CYP3A4 Inducers

Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration of a strong CYP3A4 inducer cannot be avoided, double the VITRAKVI dose. After the inducer has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose taken prior to initiating the CYP3A4 inducer [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

2.6 Dosage Modifications for Patients with Hepatic Impairment

Reduce the starting dose of VITRAKVI by 50% in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.7 Administration

VITRAKVI 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 VITRAKVI, take the next dose at the scheduled time.

Capsules:

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

Oral Solution:

• Store the glass bottle of VITRAKVI oral solution in the refrigerator. Discard any unused VITRAKVI oral solution remaining after 90 days of first opening the bottle.
• Prior to preparing an oral dose for administration, refer to the Instructions for Use.

Capsules

Store capsules at room temperature 20°C to 25°C (68°F to 77°F); temperature excursions between 15°C and 30°C (59°F to 86°F) are permitted [see USP Controlled Room Temperature].

Oral Solution

Refrigerate oral solution at 2°C to 8°C (36°F to 46°F). Do not freeze.