VITRAKVI Capsule / Oral solution (2019)

Βιβλιογραφική αναφορά

Συγγραφείς

Bayer HealthCare Pharmaceuticals Inc.

Λέξεις κλειδιά

50419-390 50419-391 50419-392

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1. Indications and Usage

VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance ...

2. Dosage and Administration

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 ...

3. Dosage Forms and Strengths

Capsules: 25 mg: white opaque hard gelatin capsule, size 2, with blue printing of BAYER cross and 25 mg on body of capsules. 25 mg larotrectinib is equivalent to 30.7 mg larotrectinib sulfate. ...

4. Contraindications

None.

5. Warnings and Precautions

5.1 Neurotoxicity Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and ...

6. Adverse Reactions

The following clinically significant adverse reactions are described elsewhere in the labeling: Neurotoxicity [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions ...

6.1. Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another ...

7. Drug Interactions

7.1 Effects of Other Drugs on VITRAKVI Strong CYP3A4 Inhibitors Coadministration of VITRAKVI with a strong CYP3A4 inhibitor may increase larotrectinib plasma concentrations, which may result in a higher ...

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 ...

8.2. Lactation

Risk Summary There are no data on the presence of larotrectinib or its metabolites in human milk and no data on its effects on the breastfed child or on milk production. Because of the potential for serious ...

8.3. Females and Males of Reproductive Potential

Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating VITRAKVI [see Use in Specific Populations (8.1)]. Contraception VITRAKVI can cause embryo-fetal ...

8.4. Pediatric Use

The safety and effectiveness of VITRAKVI in pediatric patients was established based upon data from three multicenter, open-label, single-arm clinical trials in adult or pediatric patients 28 days and ...

8.5. Geriatric Use

Of 176 patients in the overall safety population who received VITRAKVI, 22% of patients were ≥65 years of age and 5% of patients were ≥75 years of age. Clinical studies of VITRAKVI did not include sufficient ...

8.6. Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A). Larotrectinib clearance was reduced in subjects with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic ...

8.7. Renal Impairment

No dose adjustment is recommended for patients with renal impairment of any severity [see Clinical Pharmacology (12.3)].

11. Description

Larotrectinib is a kinase inhibitor. VITRAKVI (larotrectinib) capsules and oral solution are formulated using larotrectinib sulfate. The molecular formula for larotrectinib sulfate is C21H ...

12.1. Mechanism of Action

Larotrectinib is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In a broad panel of purified enzyme assays, larotrectinib inhibited TRKA, TRKB, and TRKC with IC50 ...

12.2. Pharmacodynamics

Cardiac Electrophysiology At a dose 9-fold higher than the recommended adult dose, VITRAKVI does not prolong QTc intervals to any clinically relevant extent.

12.3. Pharmacokinetics

The pharmacokinetics of larotrectinib were studied in healthy subjects and adult and pediatric patients with locally advanced or metastatic solid tumors. In healthy subjects who received a single dose ...

13.1. Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been conducted with larotrectinib. Larotrectinib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assays, with or without metabolic activation, or in ...

13.2. Animal Toxicology and/or Pharmacology

In general toxicology studies conducted in rats and monkeys and in reproductive toxicology studies conducted in rats and rabbits, administration of larotrectinib led to increased food consumption and increased ...

14. Clinical Studies

The efficacy of VITRAKVI was evaluated in pediatric and adult patients with unresectable or metastatic solid tumors with a NTRK gene fusion enrolled in one of three multicenter, open-label, single-arm ...

16.1. How Supplied

Capsules 25 mg: Hard gelatin opaque white capsule size #2 with blue printing of BAYER cross and 25 mg on the body of the capsule. 60 count bottle NDC# 50419-390-01 100 mg: Hard gelatin opaque ...

16.2. Storage and Handling

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 ...

17. Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Neurotoxicity Advise patients to notify their healthcare provider if they experience new or ...