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VITRAKVI is a brand name for Larotrectinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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 mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and…
Verbatim from this product's FDA label. Tap a section to expand.
1 , 14 ). 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) ] . In patients with secretory breast cancer, mammary analogue secretory cancer (MASC), congenital mesoblastic nephroma (CMN), or infantile fibrosarcoma, consider treatment without confirmation of NTRK rearrangements in tumor specimens.
gov/companiondiagnostics. 2 Recommended Dosage Recommended Dosage in Adult and Pediatric Patients with Body Surface Area of 1 Meter-Squared or greater 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.
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 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. 4 Dosage Modifications for Hepatotoxicity The recommended dosage modifications for VITRAKVI liver function test abnormalities are provided in Table 2.
3) ] The most common (≥ 20%) adverse reactions, including laboratory abnormalities, with VITRAKVI were increased AST, increased ALT, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. gov/medwatch . 1 Clinical Trial 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 drug and may not reflect the rates observed in practice.
Unless noted, data in WARNINGS AND PRECAUTIONS and below reflects exposure to VITRAKVI in 444 patients, including 62% patients exposed for greater than 6 months, 44% patients exposed for greater than 1 year, and 30% patients exposed for greater than 2 years.
VITRAKVI was studied in one adult dose-finding trial [LOXO-TRK-14001 (n = 75)], one pediatric dose-finding trial [SCOUT (n = 154)], and one single arm trial [NAVIGATE (n = 215)]. All patients had an unresectable or metastatic solid tumor and no satisfactory alternative treatment options or disease progression following treatment.
Across these 444 patients, the median age was 44 years (range: 18 days to 90 years); 35% were younger than 18 years; 53% were female; 59% were White, 24% were Asian and, 4% were Black; and 7% were Hispanic/Latino. Most adults (91%) received VITRAKVI 100 mg orally twice daily and 91% of pediatrics (< 18 years) received VITRAKVI 100 mg/m 2 twice daily up to a maximum dose of 100 mg twice daily.
4) ] . The most common serious adverse reactions (≥ 2%) were pneumonia, pyrexia, and dyspnea. Grade 3 or 4 adverse reactions occurred in 60% of patients; adverse reactions leading to dose interruption or modification occurred in 45% and 11% of patients, respectively, and 12% permanently discontinued VITRAKVI for adverse reactions.
5 WARNINGS AND PRECAUTIONS 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. 1 ) Skeletal Fractures: Promptly evaluate patients with signs or symptoms of fractures. 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. 3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females with reproductive potential of potential risk to the fetus and to use effective contraception.
1 Central Nervous System Effects Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances. 8% of patients. Cognitive impairment occurred in 11% of patients.
The median time to onset of cognitive impairment was 6 months (range: 2 days to 56 months). 1%). 2% of patients. Among the 49 patients with cognitive impairment, 6% required a dose modification, and 18% required dose interruption. Mood disorders occurred in 14% of patients.
3 months (range: 1 day to 65 months). 1%). 9% of patients. 6% required dose interruption. 9% of patients. Among the 96 patients who experienced dizziness, 6% of patients required a dose modification, and 5% required dose interruption. Sleep disturbances occurred in 12% of patients.
5%). 2% of patients. 7% required 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.
4 CONTRAINDICATIONS None. None. ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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3) ] . 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.
5 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%.
3) ]. 6 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. 3) ]. 3) ] . 8 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.
The most common adverse reactions (1% each) that resulted in permanent discontinuation of VITRAKVI were increased ALT and increased AST. 2%). Most (64%) adverse reactions leading to dose interruption occurred during the first three months of exposure.
The most common adverse reactions (≥ 20%), including laboratory abnormalities, in order of decreasing frequency were increased AST, increased ALT, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash.
Adverse reactions of VITRAKVI occurring in ≥ 10% of patients and laboratory abnormalities worsening from baseline in ≥ 20% of patients are summarized in Table 3 and Table 4, respectively. 03. (%) Grade 3-4 Grade 4 adverse reaction: 1 of cognitive impairment, 1 of pyrexia.
8 Nasopharyngitis 11 0 Clinically relevant adverse reactions occurring in ≤ 10% of patients include fractures (7%). 03 All Grades (%) Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available which ranged from 416 to 442 patients.
8 Lymphopenia 35 11 Neutropenia 34 11
3) ] . 2 Skeletal Fractures Skeletal fractures can occur in patients taking VITRAKVI. Among 444 patients who received VITRAKVI across clinical trials, fractures occurred in 7% of patients; 6% of 290 adult patients and 10% of 154 pediatric patients.
Median time to first fracture was 13 months (range 27 days to 73 months) in patients followed per fracture. 7% each). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement.
4% patients. , pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures. 3 Hepatotoxicity Hepatotoxicity including drug-induced liver injury (DILI) has occurred in patients taking VITRAKVI.
In patients who received VITRAKVI (n=444), increased AST of any grade occurred in 62% of patients and increased ALT of any grade occurred in 61%. 1) ] . 8 years). 9 years). 2% of patients, respectively. 9%) patients. There have been reports from clinical studies and postmarketing cases of Grade ≥ 2 increases in ALT and/or AST with increases in bilirubin ≥ 2 × 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.
4) ] . 4 Embryo-Fetal Toxicity 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.
7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. 3) ] .