Larotrectinib
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From MedlinePlus, U.S. National Library of Medicine
Kinase Inhibitor
Dosing in kidney impairment
Renal Impairment No dose adjustment is recommended for patients with renal impairment of any severity [see Clinical Pharmacology ] .
Dosing in liver impairment
Dosage Modifications for Adverse Reactions For Grade 2 and higher liver function test abnormalities, refer to Section 2.4, Table 2, Dosage Modifications for Hepatotoxicity. For all other 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 reductions for VITRAKVI for adverse reactions are provided in Table 1. [See table below.] Permanently discontinue VITRAKVI in patients who are unable to tolerate VITRAKVI after three dose modifications.
Dosage Modifications for Hepatotoxicity The recommended dosage modifications for VITRAKVI liver function test abnormalities are provided in Table 2. For CTCAE Grade 2 ALT and/or AST elevation, monitor liver function frequently as clinically indicated, to establish whether a dose interruption or reduction is required [see Warnings and Precautions ] . [See table below.]
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 , Clinical Pharmacology ] .
Preparation and administration
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 that was used prior to initiating the CYP3A4 inhibitor [see Drug Interactions , Clinical Pharmacology ].
Dosage Modifications for Coadministration with Strong or Moderate CYP3A4 Inducers Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration of a strong CYP3A4 inducer cannot be avoided, double the VITRAKVI dose. Additionally, for coadministration with a moderate CYP3A4 inducer, double the VITRAKVI dose.
After the inducer has been discontinued for 3 to 5 elimination half-lives, resume the VITRAKVI dose that was used prior to initiating the CYP3A4 inducer [see Drug Interactions , Clinical Pharmacology ].
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 packaged in one bottle containing 100 mL 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. Oral Solution packaged in two bottles each containing 50 mL Store the glass bottles of VITRAKVI oral solution in the refrigerator.
Discard any unused VITRAKVI oral solution remaining after 31 days of first opening the bottle. Prior to preparing an oral dose for administration, refer to the Instructions for Use.
Drug interactions
Check larotrectinib against a medication listLabel text (6 paragraphs)
Strong CYP3A4 Inhibitors: Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. If coadministration cannot be avoided, reduce the VITRAKVI dose. ( 2.5 , 7.1 ) Moderate CYP3A4 Inhibitors: Monitor for adverse reactions more frequently in patients coadministered a moderate CYP3A4 inhibitor with VITRAKVI and reduce the VITRAKVI dosage based on severity of adverse reactions. ( 7.1 ) Strong CYP3A4 Inducers: Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. If coadministration cannot be avoided, increase the VITRAKVI dose. ( 2.6 , 7.1 ) Moderate CYP3A4 Inducers: Increase the VITRAKVI dose.
( 2.6 , 7.1 ) Sensitive CYP3A4 Substrates: Avoid coadministration of sensitive CYP3A4 substrates with VITRAKVI. ( 7.2 )
7.1 Effects of Other Drugs on VITRAKVI Strong and Moderate CYP3A4 Inhibitors Coadministration of VITRAKVI with a strong or moderate CYP3A4 inhibitor may increase larotrectinib plasma concentrations, which may result in a higher incidence of adverse reactions [see Clinical Pharmacology (12.3) ]. Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors, including grapefruit or grapefruit juice. If coadministration of strong CYP3A4 inhibitors cannot be avoided, modify VITRAKVI dose as recommended [see Dosage and Administration (2.5) ] .
In patients coadministered a moderate CYP3A4 inhibitor with VITRAKVI, monitor for adverse reactions more frequently and reduce the VITRAKVI dosage based on the severity of emergent adverse reactions [see Dosage and Administration (2.3) ] . Strong and Moderate CYP3A4 Inducers Coadministration of VITRAKVI with a strong or moderate CYP3A4 inducer may decrease larotrectinib plasma concentrations, which may decrease the efficacy of VITRAKVI [see Clinical Pharmacology (12.3) ]. Avoid coadministration of VITRAKVI with strong CYP3A4 inducers, including St. John's wort. If coadministration of strong CYP3A4 inducers cannot be avoided, modify VITRAKVI dose as recommended.
For coadministration with moderate CYP3A4 inducers, modify VITRAKVI dose as recommended [see Dosage and Administration (2.6) ].
7.2 Effects of VITRAKVI on Other Drugs Sensitive CYP3A4 Substrates Coadministration of VITRAKVI with sensitive CYP3A4 substrates may increase their plasma concentrations, which may increase the incidence or severity of adverse reactions [see Clinical Pharmacology (12.3) ] . Avoid coadministration of VITRAKVI with sensitive CYP3A4 substrates. If coadministration of these sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on literature reports in human subjects with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ] , VITRAKVI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on VITRAKVI use in pregnant women. Administration of larotrectinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily (see Data ) . Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis. Animal Data Larotrectinib crosses the placenta in animals.
Larotrectinib did not result in embryolethality at maternally toxic doses [up to 40 times the human exposure based on area under the curve (AUC) at the clinical dose of 100 mg twice daily] in embryo-fetal development studies in pregnant rats dosed during the period of organogenesis; however, larotrectinib was associated with fetal anasarca in rats from dams treated at twice-daily doses of 40 mg/kg [11 times the human exposure (AUC) at the clinical dose of 100 mg twice daily]. In pregnant rabbits, larotrectinib administration was associated with omphalocele at twice-daily doses of 15 mg/kg (0.7 times the human exposure at the clinical dose of 100 mg twice daily).
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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