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 unusedVITRAKVI 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.
3 DOSAGE FORMS AND STRENGTHS
Capsules
• 25 mg: white opaque hard gelatin capsule, size 2, with blue printing of “LOXO” and “LARO25 mg” on body of capsules. 25 mg larotrectinib is equivalent to 30.7 mg larotrectinibsulfate.
• 100 mg: white opaque hard gelatin capsule, size 0, with blue printing of “LOXO” and“LARO 100 mg” on body of capsule. 100 mg larotrectinib is equivalent to 123 mg
larotrectinib sulfate.
Oral Solution
• 20 mg/mL: clear yellow to orange solution. 20 mg/mL larotrectinib is equivalent to24.6 mg/mL larotrectinib sulfate.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Neurotoxicity
Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any gradeoccurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6%and 0.6% of patients, respectively [see Adverse Reactions (6.1)]. The majority (65%) ofneurologic adverse reactions occurred within the first three months of treatment (range: 1 day to2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%),dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%)occurred in a single patient. Neurologic adverse reactions leading to dose modification includeddizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor(1%).
Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive oroperate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold orpermanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVIdosage when resumed [see Dosage and Administration(2.3)].
5.2 Hepatotoxicity
Among the 176 patients who received VITRAKVI, increased transaminases of any gradeoccurred in 45%, including Grade 3 increased AST or ALT in 6% of patients [see AdverseReactions (6.1)]. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset ofincreased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading todose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT ledto permanent discontinuation in 2% of patients.
Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment,then monthly thereafter, and as clinically indicated. Withhold or permanently discontinueVITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed[see Dosage and Administration (2.3)].
5.3 Embryo-Fetal Toxicity
Based on literature reports in human subjects with congenital mutations leading to changes inTRK signaling, findings from animal studies, and its mechanism of action, VITRAKVI cancause fetal harm when administered to a pregnant woman. Larotrectinib resulted inmalformations in rats and rabbits at maternal exposures that were approximate |
