DailyMed Label: VITRAKVI

DailyMed Label: VITRAKVI

2023

DailyMed Prescription

VITRAKVI

LAROTRECTINIB

Bayer HealthCare Pharmaceuticals Inc.

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-390

NDC: 50419-391

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-393

NDC: 50419-393

NDC: 50419-390

NDC: 50419-391

NDC: 50419-392

NDC: 50419-392

NDC: 50419-392

NDC: 50419-392

NDC: 50419-390

NDC: 50419-391

NDC: 50419-390

NDC: 50419-391

NDC: 50419-390

NDC: 50419-391

NDC: 50419-390

NDC: 50419-390

NDC: 50419-391

NDC: 50419-391

NDC: 50419-392

NDC: 50419-392

NDC: 50419-393

NDC: 50419-393

Larotrectinib is a kinase inhibitor. VITRAKVI (larotrectinib) capsules and oral solution are formulated using larotrectinib sulfate. The molecular formula for larotrectinib sulfate is C 21 H 24 F 2 N 6 O 6 S and the molecular weight is 526.51 g/mol for the sulfate salt and 428.44 g/mol for the free base. The chemical name is (3 S )- N -{5-[(2 R )-2-(2,5-difluorophenyl)-1-pyrrolidinyl]pyrazolo[1,5-a]pyrimidin-3-yl}-3-hydroxy-1-pyrrolidinecarboxamide sulfate. Larotrectinib sulfate has the following chemical structure: Larotrectinib sulfate is an off-white to pinkish yellow solid that is not hygroscopic. The aqueous solubility of larotrectinib at 37ᴼC is pH dependent (very soluble at pH 1.0 and freely soluble at pH 6.8, according to USP descriptive terms of solubility). VITRAKVI (larotrectinib) capsules and oral solution are for oral use. Each capsule contains 25 mg or 100 mg larotrectinib (30.7 mg and 123 mg larotrectinib sulfate, respectively) in a hard gelatin capsule. The capsule is composed of gelatin, titanium dioxide, and edible ink. The oral solution packaged in one bottle containing 100 mL contains 20 mg/mL larotrectinib (24.6 mg/mL larotrectinib sulfate) and the following inactive ingredients: purified water, hydroxypropyl betadex, sucrose, glycerin, sorbitol, citric acid, sodium phosphate, sodium citrate dihydrate, propylene glycol and flavoring. Preserved with methylparaben and potassium sorbate. The oral solution packaged in two bottles each containing 50 mL contains 20 mg/mL larotrectinib (24.6 mg/mL larotrectinib sulfate) and the following inactive ingredients: purified water, hydroxypropyl betadex, sucralose, sodium citrate, strawberry flavor, and citric acid. Preserved with sodium benzoate. image of the chemical structure of VITRAKVI

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 mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment. Select patients for therapy based on an FDA-approved test [see Dosage and Administration ( 2.1 )]. This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. VITRAKVI is a kinase inhibitor 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 mutation, • are metastatic or where surgical resection is likely to result in severe morbidity, and • have no satisfactory alternative treatments or that have progressed following treatment.   Select patients for therapy based on an FDA-approved test. ( 1 , 2.1 ) This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials ( 1 , 14 ).

• Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion ( 2.1 , 14 ). • Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of 1 Meter-Squared or greater: 100 mg orally twice daily ( 2.2 ) • Recommended Dosage in Pediatric Patients with Body Surface Area of Less Than 1 Meter-Squared: 100 mg/m 2 orally twice daily ( 2.2 ) Select patients for treatment with VITRAKVI based on the presence of a NTRK gene fusion in tumor specimens [see Clinical Studies ( 14 )] . Information on FDA-approved tests is available at http://www.fda.gov/companiondiagnostics. Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of at Least 1 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 Meter-Squared The recommended dosage of VITRAKVI is 100 mg/m 2 orally twice daily, with or without food, until disease progression or until unacceptable toxicity. 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 . Table 1 Recommended Dosage Reductions for VITRAKVI for Adverse Reactions Dosage Reduction Adult and Pediatric Patients with Body Surface Area of 1 m 2 or Greater Pediatric Patients with Body Surface Area Less Than 1 m 2 First 75 mg orally twice daily 75 mg/m 2 orally twice daily Second 50 mg orally twice daily 50 mg/m 2 orally twice daily Third 100 mg orally once daily 25 mg/m 2 orally twice daily a a Pediatric patients on 25 mg/m 2 orally twice daily should remain on this dosage even if body surface area becomes greater than 1 m 2 during the treatment. Maximum dose should be 25 mg/m 2 orally twice daily at the third dosage modification. Permanently discontinue VITRAKVI in patients who are unable to tolerate VITRAKVI after three dose modifications. 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 ( 5.3 )]. Table 2 Recommended Dosage Modifications for VITRAKVI for Hepatotoxicity Severitya Dosage Modification AST or ALT ≥ 5 x ULN with bilirubin ≤ 2 x ULN [see Warnings and Precautions (5.3)] • Withhold VITRAKVI until recovery to ≤ Grade 1 or return to baseline. • Resume VITRAKVI at the next lower dose level. • Permanently discontinue if a Grade 4 AST and/or ALT elevation occurs after resuming VITRAKVI. AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes • Permanently discontinue VITRAKVI. ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal aGrading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 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 ( 7.1 ), Clinical Pharmacology ( 12.3 )]. 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 ( 7.1 ), Clinical Pharmacology ( 12.3 )]. 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 )] . 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.

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. • 100 mg: white opaque hard gelatin capsule, size 0, with blue printing of "BAYER" cross and "100 mg" on body of capsule. 100 mg larotrectinib is equivalent to 123 mg larotrectinib sulfate. Oral Solution packaged in one bottle containing 100 mL • 20 mg/mL: clear yellow to orange solution. 20 mg/mL larotrectinib is equivalent to 24.6 mg/mL larotrectinib sulfate. Oral Solution packaged in two bottles each containing 50 mL • 20 mg/mL: colorless to yellow or orange or red or brownish solution. 20 mg/mL larotrectinib is equivalent to 24.6 mg/mL larotrectinib sulfate. • Capsules: 25 mg, 100 mg ( 3 ) • Oral Solution: 20 mg/mL ( 3 )

None. None. ( 4 )

• Central Nervous System (CNS) Effects: Advise patients and caretakers of the risk of CNS adverse reactions including dizziness, cognitive impairment, mood disorders, and sleep disturbances. Advise patients not to drive or operate hazardous machinery if experiencing neurotoxicity. Withhold and modify dosage, or permanently discontinue VITRAKVI based on severity. ( 2.3 , 5.1 ) • Skeletal Fractures: Promptly evaluate patients with signs or symptoms of fractures. ( 5.2 ) • Hepatotoxicity: Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and every 2 weeks during the first 2 months of treatment, then monthly thereafter or as clinically indicated. Temporarily withhold, reduce dose, or permanently discontinue VITRAKVI based on severity. ( 2.4 , 5.3 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females with reproductive potential of potential risk to the fetus and to use effective contraception. ( 5.4 , 8.3 ) Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances. In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients. Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification, and 20% required dose interruption. Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥ 1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients. Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification, and 5% required dose interruption. Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption. Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed [see Dosage and Administration ( 2.3 )] . Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients. Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures. Hepatotoxicity including drug-induced liver injury (DILI) has been reported in patients taking VITRAKVI. In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively [see Adverse Reactions (6.1)]. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) of patients. There have been reports in adult patients from clinical studies and postmarketing cases of Grade ≥ 2 increases in ALT and/or AST with increases in bilirubin ≥ 2 x ULN. Obtain liver function tests (ALT, AST, ALP and bilirubin) before initiation of VITRAKVI and monitor every 2 weeks during the first 2 months of treatment, then monthly thereafter, or more frequently following the occurrence of Grade 2 or greater AST or ALT elevation. Temporarily withhold, reduce the dose, or permanently discontinue VITRAKVI based on severity [see Dosage and Administration ( 2.4 )]. 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, VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the last dose of VITRAKVI [see Use in Specific Populations ( 8.1 , 8.3 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling:

• 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 ) 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 )]. 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.

• Lactation: Advise not to breastfeed. ( 8.2 ) • Hepatic Impairment: Reduce the starting dose of VITRAKVI in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment. ( 2.7 , 8.7 ) 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). 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 adverse reactions in breastfed children, advise women not to breastfeed during treatment with larotrectinib and for 1 week after the last dose. 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 harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Females Advise female patients of reproductive potential to use effective contraception during treatment with VITRAKVI and for 1 week after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with VITRAKVI and for 1 week after the last dose. Infertility Females Based on histopathological findings in the reproductive tracts of female rats in a 1-month repeated-dose study, VITRAKVI may reduce fertility [See Nonclinical Toxicology ( 13.1 )] . 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 older [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14 )]. The efficacy of VITRAKVI was evaluated in 12 pediatric patients and is described in the Clinical Studies section [see Clinical Studies ( 14 )] . The safety of VITRAKVI was evaluated in 92 pediatric patients who received VITRAKVI. Of these 92 patients, 36% were <1 month to < 2 years (n = 33), 41% were 2 years to < 12 years (n = 38), and 23% were 12 years to < 18 years (n = 21); 29% had metastatic disease, 42% had locally advanced disease, and 27% had primary CNS; and 86% had received prior treatment for their cancer, including surgery, radiotherapy, or systemic therapy. The most common cancers were infantile fibrosarcoma (37%), primary CNS tumors (27%), soft tissue sarcoma (24%), and thyroid cancer (7%). The median duration of exposure was 7.4 months (range: 0.4 months to 39 months). Due to the small number of pediatric and adult patients, the single arm design of clinical studies of VITRAKVI, and confounding factors such as differences in susceptibility to infections between pediatric and adult patients, it is not possible to determine whether differences in the incidence of adverse reactions to VITRAKVI are related to patient age or other factors. Adverse reactions occurring more frequently (at least a 10% increase in per-patient incidence) in pediatric patients compared to adult patients were pyrexia (45% versus 13%), vomiting (42% versus 17% in adults), diarrhea (35% versus 23% in adults), rash (28% versus 15% in adults), upper respiratory tract infection (23% versus 8% in adults), nasopharyngitis (16% versus 6% in adults), and otitis media and rhinitis (each 14% versus 0.5% in adults). Laboratory abnormalities occurring more frequently (at least a 10% increase in per-patient incidence) in pediatric patients compared to adult patients were AST increased (63% versus 49% in adults), neutrophil count decrease (60% versus 16% in adults), leukocyte count decrease (39% versus 27% in adults), hyperkalemia (36% versus 15%), and lymphocyte increase (24% versus 0.5%). Two of the 92 pediatric patients discontinued VITRAKVI due to an adverse reaction (Grade 3 increased ALT and Grade 3 decreased neutrophil count). The pharmacokinetics of VITRAKVI in the pediatric population were similar to those seen in adults [see Clinical Pharmacology ( 12.3 )]. Juvenile Animal Toxicity Data Larotrectinib was administered in a juvenile toxicity study in rats at twice daily doses of 0.2, 2 and 7.5 mg/kg from postnatal day (PND) 7 to 27 and at twice daily doses of 0.6, 6 and 22.5mg/kg between PND 28 and 70. The dosing period was equivalent to human pediatric populations from newborn to adulthood. The doses of 2/6 mg/kg twice daily [approximately 0.7 times the human exposure (AUC) at the clinical dose of 100 mg twice daily] and 7.5/22.5 mg/kg twice daily (approximately 4 times the human exposure at the clinical dose of 100 mg twice daily) resulted in mortality between PND 9 to 99; a definitive cause of death was not identified in the majority of cases. The main findings were transient central nervous system-related signs including head flick, tremor, and circling in both sexes. An increase in the number of errors in a maze swim test occurred in females at exposures of approximately 4 times the human exposure (AUC) at the clinical dose of 100 mg twice daily. Decreased growth and delays in sexual development occurred in the mid- and high-dose groups. Mating was normal in treated animals, but a reduction in pregnancy rate occurred at the high-dose of 7.5/22.5 mg/kg twice daily (approximately 4 times the human exposure at the clinical dose of 100 mg twice daily). Of 279 patients in the overall safety population who received VITRAKVI, 19% of patients were ≥ 65 years of age and 5% of patients were ≥ 75 years of age. Clinical studies of VITRAKVI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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 impairment [see Clinical Pharmacology ( 12.3 )] . Reduce VITRAKVI dose as recommended [see Dosage and Administration ( 2.7 )] . No dose adjustment is recommended for patients with renal impairment of any severity [see Clinical Pharmacology ( 12.3 )] .

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 white capsule size #0 with blue printing of "BAYER" cross and "100 mg" on the body of the capsule. • 60 count bottle       NDC# 50419-391-01 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 Packaged in One Bottle Containing 100 mL 20 mg/mL: Clear yellow to orange solution. • One bottle containing 100 mL       NDC# 50419-392-01 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F). Do not freeze. Oral Solution Packaged in Two Bottles Each Containing 50 mL 20 mg/mL: Colorless to yellow or orange or red or brownish solution. • Two bottles each containing 50 mL NDC# 50419-393-03 Refrigerate oral solution at 2°C to 8°C (36°F to 46°F). Do not freeze.

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 IC 50 values between 5-11 nM. One other kinase TNK2 was inhibited at approximately 100-fold higher concentration. TRKA, B, and C are encoded by the genes NTRK1, NTRK2, and NTRK3 . Chromosomal rearrangements involving in-frame fusions of these genes with various partners can result in constitutively-activated chimeric TRK fusion proteins that can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression. Larotrectinib had minimal activity in cell lines with point mutations in the TRKA kinase domain, including the clinically identified acquired resistance mutation, G595R. Point mutations in the TRKC kinase domain with clinically identified acquired resistance to larotrectinib include G623R, G696A, and F617L. Cardiac Electrophysiology At a dose 9-fold higher than the recommended adult dose, VITRAKVI does not prolong QTc intervals to any clinically relevant extent. 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 of VITRAKVI capsules, systemic exposure (C max and AUC) of larotrectinib was dose proportional over the dose range of 100 mg to 400 mg (1 to 4 times the recommended adult dose) and slightly greater than proportional at doses of 600 mg to 900 mg (6 to 9 times the recommended adult dose). In adult patients who received VITRAKVI capsules 100 mg twice daily in Study LOXO-TRK-14001, peak plasma levels (C max ) of larotrectinib were achieved at approximately 1 hour after dosing and steady-state was reached within 3 days. Mean steady-state larotrectinib [coefficient of variation (CV%)] for C max was 788 (81%) ng/mL and AUC 0-24hr was 4351 (97%) ng*h/mL. Absorption The mean absolute bioavailability of VITRAKVI capsules was 34% (range: 32% to 37%). In healthy subjects, the AUC of VITRAKVI oral solution was similar to that of the capsules and the C max was 36% higher with the oral solution. Effect of Food The AUC of larotrectinib was similar and the C max was reduced by 35% after oral administration of a single 100 mg capsule of VITRAKVI to healthy subjects taken with a high-fat meal (approximately 900 calories, 58 grams carbohydrate, 56 grams fat and 43 grams protein) compared to the C max and AUC in the fasted state. Distribution The mean (CV%) volume of distribution (V ss ) of larotrectinib is 48 (38%) L following intravenous administration of larotrectinib in healthy subjects. Larotrectinib is 70% bound to human plasma proteins in vitro and binding is independent of drug concentrations. The blood-to-plasma concentration ratio is 0.9. Elimination The mean (CV%) clearance (CL/F) of larotrectinib is 98 (44%) L/h and the half-life is 2.9 hours following oral administration of VITRAKVI in healthy subjects. Metabolism Larotrectinib is metabolized predominantly by CYP3A4. Following oral administration of a single [ 14 C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, unchanged larotrectinib constituted 19% and an O-linked glucuronide constituted 26% of the major circulating radioactive drug components in plasma. Excretion Following oral administration of a single [ 14 C] radiolabeled 100 mg dose of larotrectinib to healthy subjects, 58% (5% unchanged) of the administered radioactivity was recovered in feces and 39% (20% unchanged) was recovered in urine. Specific Populations Age (range: 28 days to 82 years), sex, and body weight (range: 3.8 kg to 179 kg) had no clinically meaningful effect on the pharmacokinetics of larotrectinib. Pediatric Patients In pediatric patients, the larotrectinib geometric mean (%CV) AUC 0-24hr by age subgroup was: 3348 (66%) ng*h/mL in patients 1 month to < 2 years (n = 9), 4135 (36%) ng*h/mL in patients 2 to < 12 years (n = 15), and 3108 (69%) ng*h/mL and in patients 12 to < 18 years (n = 9). Patients with Renal Impairment Following oral administration of a single 100 mg dose of VITRAKVI capsules in subjects with end-stage renal disease (e.g., subjects who required dialysis), the AUC 0-INF of larotrectinib increased 1.5-fold and C max increased 1.3-fold as compared to that in subjects with normal renal function (creatinine clearance ≥ 90 mL/min as estimated by Cockcroft-Gault). The pharmacokinetics of VITRAKVI in patients with moderate to severe renal impairment (creatinine clearance ≤ 60 mL/min) have not been studied. Patients with Hepatic Impairment Following oral administration of a single 100 mg dose of VITRAKVI capsules, the AUC 0-INF of larotrectinib increased 1.3-fold in subjects with mild hepatic impairment (Child-Pugh A), 2-fold in subjects with moderate hepatic impairment (Child-Pugh B) and 3.2-fold in subjects with severe hepatic impairment (Child-Pugh C) as compared to that in subjects with normal hepatic function. The C max was similar in subjects with mild and moderate hepatic impairment and the C max of larotrectinib increased 1.5-fold in subjects with severe hepatic impairment as compared to that in subjects with normal hepatic function [see Dosage and Administration ( 2.7 ), Use in Specific Populations ( 8.6 )] . Drug Interaction Studies Clinical Studies Effect of CYP3A Inhibitors: Coadministration of a single 100 mg dose of VITRAKVI capsules with itraconazole (strong CYP3A inhibitor) increased the AUC0-INF of larotrectinib by 4.3-fold and the Cmax by 2.8-fold as compared to VITRAKVI administered alone [see Dosage and Administration ( 2.5 ), Drug Interactions ( 7.1 )]. Coadministration of VITRAKVI with fluconazole (moderate CYP3A4 inhibitor) is predicted to increase VITRAKVI steady state AUC by 2.7-fold and Cmax by 1.9-fold. Effect of CYP3A Inducers: Coadministration of a single 100 mg dose of VITRAKVI capsules with rifampin (strong CYP3A inducer) decreased the AUC0-INF of larotrectinib by 81% and the Cmax by 71% as compared to VITRAKVI administered alone [see Dosage and Administration ( 2.6 ), Drug Interactions ( 7.1 )]. Coadministration of VITRAKVI with efavirenz (moderate CYP3A4 inducer) is predicted to decrease steady state AUC of VITRAKVI by approximately 72% and Cmax by 60% compared to VITRAKVI administered alone [see Dosage and Administration ( 2.6 ), Drug Interactions ( 7.1 )]. Effect of Strong P-glycoprotein (P-gp) Inhibitors: Coadministration of a single 100 mg dose of VITRAKVI capsules with a P-gp inhibitor (rifampin) increased the AUC 0-INF of larotrectinib by 1.7-fold and the C max by 1.8-fold as compared to VITRAKVI administered alone. Effect of Larotrectinib on CYP3A4 Substrates: Coadministration of VITRAKVI capsules 100 mg twice daily with a sensitive CYP3A4 substrate (midazolam) increased both the AUC 0-INF and C max of midazolam by 1.7-fold as compared to midazolam administered alone. The AUC 0-INF and C max of 1-hydroxymidazolam, the main metabolite of midazolam, were both increased 1.4-fold as compared to when midazolam was administered alone [see Drug Interactions ( 7.2 )] . In Vitro Studies Effect of Transporter on Larotrectinib: Larotrectinib is a substrate for P-gp and BCRP. Larotrectinib is not a substrate of OAT1, OAT3, OCT1, OCT2, OATP1B1, or OATP1B3. Effect of Larotrectinib on Transporters: Larotrectinib is not an inhibitor of BCRP, P-gp, OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, BSEP, MATE1 and MATE2-K at clinically relevant concentrations. Effect of Larotrectinib on CYP Substrates: Larotrectinib is not an inhibitor or inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations.

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 the in vitro mammalian mutagenesis assays, with or without metabolic activation. In vivo, larotrectinib was negative in the mouse micronucleus test. Fertility studies with larotrectinib have not been conducted. In a 3-month repeat-dose toxicity study in the rat, larotrectinib had no effects on spermatogenesis at 75 mg/kg/day (approximately 7 times the human exposure at the 100 mg twice daily dose). Additionally, larotrectinib had no histological effects on the male reproductive tract in rats or monkeys at doses resulting in exposures up to 10 times the human exposure (AUC 0-24hr ) at the 100 mg twice daily clinical dose. In a 1-month repeat-dose study in the rat, decreased uterine weight and uterine atrophy were seen at 200 mg/kg/day [approximately 45 times the human exposure (AUC) at the 100 mg twice daily dose]. Fewer corpora lutea and increased incidence of anestrus were also noted at doses ≥ 60 mg/kg/day (approximately 10 times the human exposure at the 100 mg twice daily dose). Decreased fertility occurred in a juvenile animal study [see Use in Specific Populations ( 8.4 )] . There were no findings in female reproductive organs in repeat-dose studies in monkeys at exposures up to 22 times the human exposure at the 100 mg twice daily dose. 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 body weight at doses resulting in exposures 0.6 times the human exposure at the 100 mg twice daily clinical dose. Obesity has also been one phenotypic outcome of some human syndromes resulting from congenital mutations in NTRK2 resulting in altered TRK signaling.

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 clinical trials: Study LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431). All patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease. Adult patients received VITRAKVI 100 mg orally twice daily and pediatric patients (18 years or younger) received VITRAKVI 100 mg/m 2 up to a maximum dose of 100 mg orally twice daily until unacceptable toxicity or disease progression. Identification of positive NTRK gene fusion status was prospectively determined in local laboratories using next generation sequencing (NGS) or fluorescence in situ hybridization (FISH). NTRK gene fusions were inferred in three patients with infantile fibrosarcoma who had a documented ETV6 translocation identified by FISH. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by a blinded independent review committee (BIRC) according to RECIST v1.1. The assessment of efficacy was based on the first 55 patients with solid tumors with an NTRK gene fusion enrolled across the three clinical trials. Baseline characteristics were: median age 45 years (range 4 months to 76 years); 22% <18 years of age, and 78% ≥18 years of age; 53% male; 67% White; 7% Hispanic/Latino, 4% Asian, 4% Black; and ECOG performance status (PS) 0-1 (93%) or 2 (7%). Eighty-two percent of patients had metastatic disease, including patients with brain metastases, and 18% had locally advanced, unresectable disease. Ninety-eight percent of patients had received prior treatment for their cancer, including surgery, radiotherapy, or systemic therapy. Of these, 82% (n = 45) received prior systemic therapy with a median of two prior systemic regimens and 35% (n = 19) received three or more prior systemic regimens. The most common cancers were salivary gland tumors (22%), soft tissue sarcoma (20%), infantile fibrosarcoma (13%), and thyroid cancer (9%). A total of 50 patients had NTRK gene fusions detected by NGS and 5 patients had NTRK gene fusions detected by FISH. Efficacy results are summarized in Tables 5, 6, and 7. Table 5 Efficacy Results for Patients with Solid Tumors Harboring NTRK Gene Fusions Efficacy Parameter VITRAKVI N = 55 Overall response rate (95% CI) 75% (61%, 85%)   Complete response rate 25% *   Partial response rate 49% Duration of response (DOR) N = 41   Median DOR 32.9 ** (14.8, NE *** )   Range (months) 1.6+, 50.6+   % with Observed DOR > 12 months 63%   % with Observed DOR > 24 months 49% + Denotes ongoing response. * 5% were pathological complete response. Patients undergoing a surgical resection whose post-operative pathologic assessment showed no viable tumor cells and negative margins were pathological complete responders provided that no other sites of disease were present. ** Kaplan-Meier estimates *** NE: Not evaluable Table 6 Efficacy Results by Tumor Type Tumor Type Patients (N=55) ORR DOR % 95% CI Range (months) Salivary gland 12 83% (52%, 98%) 7.7, 44.7+ Soft tissue sarcoma 11 91% (59%, 100%) 3.6+, 50.6+ Infantile fibrosarcoma 7 100% (59%, 100%) 1.6+, 28.6+ Thyroid 5 100% (48%, 100%) 3.7, 32.9 Lung 4 75% (19%, 99%) 8.2, 36.8+ Melanoma 4 50% NA 1.9+, 23.2+ * Colon 4 25% NA 5.6 * Gastrointestinal stromal tumor 3 100% (29%, 100%) 9.5, 31.1+ Cholangiocarcinoma 2 SD, NE NA NA Appendix 1 SD NA NA Breast 1 PD NA NA Pancreas 1 SD NA NA NA = not applicable due to small numbers or lack of response; CR = complete response; PR = partial response; NE = not evaluable; SD = stable disease; PD = progressive disease; NR = not reached. + Denotes ongoing response. * Observed values at data cutoff, not a range. Table 7 Efficacy Results by NTRK Fusion Partner NTRK Partner*   Patients (N=55) ORR DOR % 95% CI Range (months) ETV6-NTRK3 25 84% (64%, 96%) 3.7, 44.7+ TPM3-NTRK1 9 56% (21%, 86%) 3.7, 27.5+ LMNA-NTRK1 5 40% (5%, 85%) 5.6, 50.6+ Inferred ETV6-NTRK3 3 100% (29%, 100%) 1.6+, 28.6+ ** IRF2BP2-NTRK1 2 CR, PR NA 3.7, 36.8+ SQSTM1-NTRK1 2 pCR, PR NA 9.9, 12.9+ PDE4DIP-NTRK1 1 PR NA 3.6+ *** PPL-NTRK1 1 CR NA 28.2+ *** STRN-NTRK2 1 PR NA 5.6 *** TPM4-NTRK3 1 pCR NA 25.6+ *** TPR-NTRK1 1 PR NA 8.2 *** TRIM63-NTRK1 1 PR NA 1.9+ *** CTRC-NTRK1 1 SD NA NA GON4L-NTRK1 1 NE NA NA PLEKHA6-NTRK1 1 SD NA NA CR = complete response; PR = partial response; pCR = pathological complete response; NE = not evaluable; SD = stable disease; NA = not applicable; NR = Not reached. + Denotes ongoing response. * Fusion partners identified in the primary analysis set (N=55) may not represent all potential fusion partners.   ** Duration of response censored at the time of surgery for one pediatric patient with unresectable infantile fibrosarcoma who underwent resection following partial response and who remained disease-free at data cutoff. *** Observed values at data cutoff, not a range.

PATIENT INFORMATION VITRAKVI (vi trak vee) (larotrectinib) capsules VITRAKVI (vi trak vee) (larotrectinib) oral solution What is VITRAKVI? VITRAKVI is a prescription medicine that is used to treat adults and children with solid tumors (cancer) that: • are caused by certain abnormal NTRK genes and • have spread or if surgery to remove their cancer is likely to cause severe complications, and • there is no acceptable treatment option or the cancer grew or spread on other treatment. Your healthcare provider will perform a test to make sure that VITRAKVI is right for you. It is not known if VITRAKVI is safe and effective in children younger than 28 days of age. Before taking VITRAKVI, tell your healthcare provider about all of your medical conditions, including if you: • have liver problems • have nervous system (neurological) problems • are pregnant or plan to become pregnant. VITRAKVI can harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with VITRAKVI or think you may be pregnant. • If you are able to become pregnant, your healthcare provider may do a pregnancy test before you start treatment with VITRAKVI. • Females who are able to become pregnant should use effective birth control (contraception) during treatment and for 1 week after the last dose of VITRAKVI. Talk to your healthcare provider about birth control methods that may be right for you. • Males with female partners who are able to become pregnant should use effective birth control during treatment with VITRAKVI and for 1 week after the last dose of VITRAKVI. • are breastfeeding or plan to breastfeed. It is not known if VITRAKVI passes into your breast milk. Do not breastfeed during treatment and for 1 week after the last dose of VITRAKVI. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how VITRAKVI works and VITRAKVI may affect how other medicines work. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take VITRAKVI? • Take VITRAKVI exactly as your healthcare provider tells you. • Do not change your dose or stop taking VITRAKVI unless your healthcare provider tells you. • VITRAKVI comes in capsules and as an oral solution. • If your healthcare provider prescribes VITRAKVI oral solution: • Your healthcare provider will provide you with the VITRAKVI oral solution, oral syringes and bottle adaptors or send you to a pharmacy that can provide you with VITRAKVI oral solution, oral syringes and bottle adaptors. • Your healthcare provider should show you how to correctly measure and give a dose of VITRAKVI oral solution. • See the detailed Instructions for Use that comes with VITRAKVI oral solution for information about the correct way to measure and give a dose of VITRAKVI oral solution. If you have any questions, talk to your healthcare provider or pharmacist. • VITRAKVI is usually taken by mouth 2 times a day. • Swallow VITRAKVI capsules whole with water. Do not chew or crush the capsules. • Take VITRAKVI with or without food. • If you vomit after taking a dose of VITRAKVI, wait and take the next dose at your scheduled time. • If you miss a dose of VITRAKVI, take it as soon as you remember. If your next scheduled dose is due within 6 hours, skip the missed dose and take your next dose at your regular time. • If you take too much VITRAKVI, call your healthcare provider or go to the nearest hospital emergency room right away. What should I avoid while taking VITRAKVI? • VITRAKVI can make you feel dizzy. Do not drive or operate machinery until you know how VITRAKVI affects you. • Avoid taking St. John’s wort, eating grapefruit, or drinking grapefruit juice during treatment with VITRAKVI. What are the possible side effects of VITRAKVI? VITRAKVI may cause serious side effects, including:   • Central nervous system (CNS) problems . VITRAKVI may cause dizziness, confusion, problems with concentration, attention, and memory, changes in your mood, and sleep problems. Tell your healthcare provider if you develop any of these symptoms or they get worse.   • Bone fractures . Bone fractures can happen with VITRAKVI. Tell your healthcare provider if you develop pain, changes in your ability to move around, or bone abnormalities.   • Liver problems . Abnormal liver blood tests may occur with VITRAKVI and can sometimes become serious. Your healthcare provider will do blood tests to check your liver function before starting and during treatment with VITRAKVI as needed. Tell your healthcare provider right away if you develop new or worsening symptoms of liver problems including: • yellowing of your skin or the white part of your eyes (jaundice) • dark or brown urine • pain in the upper right side of your stomach area (abdomen) • bruising or bleeding more easily than normal • tiredness • nausea or vomiting • loss of appetite Your healthcare provider may decrease your dose, temporarily stop or permanently stop your treatment with VITRAKVI if you develop serious side effects. The most common side effects of VITRAKVI include: • low red blood cell and white blood cell counts • muscle and bone pain • tiredness • low levels of protein called albumin in the blood • increased levels of enzyme called alkaline phosphatase in the blood (test for liver or bone problems) • increase in certain liver blood tests • cough • constipation • diarrhea • dizziness • low levels of calcium in the blood • nausea • vomiting • fever • stomach (abdomen) pain VITRAKVI may affect fertility in females and may affect your ability to become pregnant. Talk to your healthcare provider if this is a concern for you. These are not all the possible side effects with VITRAKVI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store VITRAKVI? • Store VITRAKVI capsules at room temperature between 68°F to 77°F (20°C to 25°C). • Store VITRAKVI oral solution in the refrigerator between 36° F to 46° F (2° C to 8° C). Do not freeze. • Throw away (dispose of) any unused VITRAKVI oral solution: ▪ Bottle of 100 mL: remaining 90 days after first opening the bottle ▪ Bottle of 50 mL: remaining 31 days after first opening the bottle Keep VITRAKVI and all medicines out of the reach of children. General information about the safe and effective use of VITRAKVI. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use VITRAKVI for a condition for which it was not prescribed. Do not give VITRAKVI to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about VITRAKVI that is written for health professionals. What are the ingredients in VITRAKVI? Active ingredient: larotrectinib Inactive ingredients: Capsule: gelatin, titanium dioxide and edible ink Oral Solution Packaged in One Bottle Containing 100 mL: purified water, hydroxypropyl betadex, sucrose, glycerin, sorbitol, citric acid, sodium phosphate, sodium citrate dihydrate, propylene glycol and flavoring. Preserved with methylparaben and potassium sorbate. Oral Solution Packaged in Two Bottles Each Containing 50 mL: purified water, hydroxypropyl betadex, sucralose, sodium citrate, strawberry flavor, and citric acid. Preserved with sodium benzoate.   Manufactured for Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ 07981 For more information, go to www.VITRAKVI.com or call 1-888-842-2937 This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 11/2023

Package Label - 25 mg - 60 Capsules PRINCIPAL DISPLAY PANEL NDC 71777- 390 -01 VITRAKVI® (larotrectinib) capsules 25 mg Usual Dosage: See prescribing information. Rx only. 60 capsules. Keep out of reach of children. Store at 20°C to 25°C (68°F to 77°F). Excursions permitted from 15°C to 30°C (59° to 86°F). Manufactured for Loxo Omcology, Inc. Stamford, CT 06901      86579626 (01)10371777390012 Bayer LOXO Each capsule contains 25 mg larotrectinib (equivalent to 30.7 mg larotrectinib sulfate). image of 25 mg label principal panel - 60 capsules