dity, and
• have no satisfactory alternative treatments or that have progressed following treatment.
This indication is approved under accelerated approval based on overall response rate andduration of response [see Clinical Studies (14)]. Continued approval for this indication may becontingent upon verification and description of clinical benefit in confirmatory trials.
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion intumor specimens [see Clinical Studies (14)]. An FDA-approved test for the detection of NTRKgene fusion is not currently available.
2.2 Recommended Dosage
Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of at Least1.0 Meter-SquaredThe 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 MeterSquaredThe 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 inTable 1.
Table 1 Recommended Dosage Modifications for VITRAKVI for Adverse
Reactions
Dosage Modification
Adult and
Pediatric Patients with Body
Surface Area of at Least 1.0 m2
Pediatric Patients with Body
Surface Area Less Than 1.0 m2
First 75 mg orally twice daily 75 mg/m2 orally twice daily
Second 50 mg orally twice daily 50 mg/m2 orally twice daily
Third 100 mg orally once daily 25 mg/m2 orally twice dailyPermanently discontinue VITRAKVI in patients who are unable to tolerate VITRAKVI after
three dose modifications.
2.4 Dosage Modifications for Coadministration with Strong CYP3A4 InhibitorsAvoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration of a
strong CYP3A4 inhibitor cannot be avoided, reduce the VITRAKVI dose by 50%. After theinhibitor has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dosetaken prior to initiating the CYP3A4 inhibitor [see Drug Interactions (7.1), ClinicalPharmacology (12.3)].
2.5 Dosage Modifications for Coadministration with Strong CYP3A4 InducersAvoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration of astrong CYP3A4 inducer cannot be avoided, double the VITRAKVI dose. After the inducer hasbeen discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose taken prior toinitiating the CYP3A4 inducer [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
2.6 Dosage Modifications for Patients with Hepatic ImpairmentReduce the starting dose of VITRAKVI by 50% in patients with moderate (Child-Pugh B) tosevere (Child-Pugh C) hepatic impairment [see Use in Specific Populations (8.6), ClinicalPharmacology (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 |
