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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: VITRAKVI as monotherapy is indicated for the treatment of adult and paediatric patients with solid tumours that display a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, - who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and - who…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with VITRAKVI should be initiated by physicians experienced in the administration of anticancer therapies. The presence of an NTRK gene fusion in a tumour specimen should be confirmed by a validated test prior to initiation of treatment with VITRAKVI.
3 Posology Adults The recommended dose in adults is 100 mg larotrectinib twice daily, until disease progression or until unacceptable toxicity occurs. Paediatric population Dosing in paediatric patients is based on body surface area (BSA).
The recommended dose in paediatric patients is 100 mg/m2 larotrectinib twice daily with a maximum of 100 mg per dose until disease progression or until unacceptable toxicity occurs. 2). Missed dose If a dose is missed, the patient should not take two doses at the same time to make up for a missed dose.
Patients should take the next dose at the next scheduled time. If the patient vomits after taking a dose, the patient should not take an additional dose to make up for vomiting. Dose modification For all grade 2 adverse reactions, continued dosing may be appropriate, though close monitoring to ensure no worsening of the toxicity is advised.
For all grade 3 or 4 adverse reactions not referring to liver function test abnormalities: - VITRAKVI should be withheld until the adverse reaction resolves or improves to baseline or grade 1. Resume at the next dose modification if resolution occurs within 4 weeks.
- VITRAKVI should be permanently discontinued if an adverse reaction does not resolve within 4 weeks. The recommended dose modifications for VITRAKVI for adverse reactions are provided in Table 1. 0 m2 Paediatric patients aged less than 3 months First 75 mg twice daily 75 mg/m2 twice daily 25 mg/m2 twice daily Second 50 mg twice daily 50 mg/m2 twice daily - Third 100 mg once daily 25 mg/m2 twice daily a - a Paediatric patients on third dose modification at 25 mg/m2 twice daily should remain on this dose (25 mg/m2 twice daily) even if body surface area increases during the treatment.
VITRAKVI should be permanently discontinued in patients who are unable to tolerate VITRAKVI after three dose modifications. 4 The recommended dose modifications in case of liver function tests abnormalities during treatment with VITRAKVI are provided in Table 2.
Table 2:
Summary of the safety profile The most common adverse drug reactions (≥ 20%) of VITRAKVI in order of decreasing frequency were increased ALT (36%), increased AST (33%), vomiting (30%), anaemia (28%), constipation (28%), diarrhoea (27%), nausea (24%), fatigue (23%), and dizziness (20%).
The majority of adverse reactions were grade 2 or 3. Grade 4 was the highest reported grade for adverse reactions neutrophil count decreased (2%), ALT increased (1%), AST increased, leukocyte count decreased, platelet count decreased, muscular weakness and blood alkaline phosphatase increased (each in < 1%).
The highest reported grade was grade 3 for adverse reactions anaemia (7%), weight increased (6%), diarrhoea (4%), gait disturbance and vomiting (each 1%), and fatigue, dizziness, paraesthesia, nausea, myalgia, and constipation (each in < 1%).
Permanent discontinuation of VITRAKVI for treatment emergent adverse reactions occurred in 2% of patients (2 cases each of neutrophil count decreased, ALT increased, and AST increased, 1 case each of gait disturbance, and muscular weakness).
The majority of adverse reactions leading to dose reduction occurred in the first three months of treatment. Tabulated list of adverse reactions The safety of VITRAKVI was evaluated in 361 patients with TRK fusion-positive cancer in one of three on-going clinical trials, Studies 1, 2 (“NAVIGATE”), and 3 (“SCOUT”) and post-marketing.
0 years (range: 0, 90) with 37% of patients being paediatric patients. 1). The adverse drug reactions reported in patients (n=361) treated with VITRAKVI are shown in Table 3 and Table 4. The adverse drug reactions are classified according to the System Organ Class.
Frequency groups are defined by the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), and not known (cannot be estimated from available data).
Efficacy across tumour types The benefit of VITRAKVI has been established in single arm trials encompassing a relatively small sample of patients whose tumours exhibit NTRK gene fusions. Favourable effects of VITRAKVI have been shown on the basis of overall response rate and response duration in a limited number of tumour types.
1). , no satisfactory treatment options). 8). For the majority of neurologic reactions, onset occurred within the first three months of treatment. 2). 8). The majority of ALT and AST increases occurred within 3 months of starting treatment.
Cases of hepatotoxicity with increases in ALT and/or AST of grade 2, 3 or 4 severity and increases in bilirubin ≥ 2x ULN have been reported. 2). Liver function including ALT, AST, ALP and bilirubin should be monitored before the first dose, then every 2 weeks during the first month of treatment, then monthly for the next 6 months of treatment, then periodically during treatment.
2). 5). 6). 6).
1.
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Recommended dose modifications and management for VITRAKVI for liver function test abnormalities Laboratory parameters Recommended measures Grade 2 ALT and/or AST (>3x ULN and ≤5x ULN) - Conduct serial laboratory evaluations frequently after the observation of grade 2 toxicity, until resolved, to establish whether a dose interruption or reduction is required.
Grade 3 ALT and/or AST (>5x ULN and ≤20x ULN) or Grade 4 ALT and/or AST (>20x ULN), with bilirubin <2x ULN - Withhold treatment until the adverse reaction resolves or improves to baseline. Monitor liver function frequently until resolution or return to baseline.
Permanently discontinue treatment if an adverse reaction does not resolve. - Resume at the next dose modification if adverse reactions resolve. Treatment should only be resumed in patients where the benefit outweighs the risk. - Permanently discontinue treatment if a grade 4 ALT and/or AST elevation occurs after resuming treatment.
ALT and/or AST ≥3x ULN with bilirubin ≥2x ULN - Withhold treatment and monitor liver function frequently until resolution or return to baseline. - Consider permanent treatment discontinuation. - Treatment should only be resumed in patients where the benefit outweighs the risk.
- If resumed, start at the next lower dose. Monitor liver function frequently upon restart. - Permanently discontinue treatment if adverse reaction recurs after resuming treatment. 2). Hepatic impairment The starting dose of VITRAKVI should be reduced by 50% in patients with moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment.
2). 2). Co-administration with strong CYP3A4 inhibitors If co-administration with a strong CYP3A4 inhibitor is necessary, the VITRAKVI dose should be reduced by 50%. 5). 5 Method of administration VITRAKVI is for oral use. VITRAKVI is available as a capsule or oral solution with equivalent oral bioavailability and may be used interchangeably.
The patient should be advised to swallow the capsule whole with a glass of water. Due to the bitter taste, the capsule should not be opened, chewed or crushed. The capsules can be taken with or without food but should not be taken with grapefruit or grapefruit juice.
Within each frequency group, undesirable effects are presented in order of decreasing seriousness. 9 Table 3: Adverse drug reactions reported in TRK fusion-positive cancer patients treated with VITRAKVI at recommended dose (overall safety population, n=361) and post-marketing System organ class Frequency All grades Grades 3 and 4 Blood and lymphatic system disorders Very common Anaemia Neutrophil count decreased (Neutropenia) Leukocyte count decreased (Leukopenia) Common Platelet count decreased (Thrombocytopenia) Anaemia Neutrophil count decreased (Neutropenia)a Leukocyte count decreased (Leukopenia)a Uncommon Platelet count decreased (Thrombocytopenia)a, b Nervous system disorders Very common Dizziness Common Gait disturbance Paraesthesia Gait disturbance Uncommon Dizziness Paraesthesia Gastrointestinal disorders Very common Nausea Constipation Vomiting Diarrhoea Common Dysgeusiac Diarrhoea Vomiting Uncommon Nausea Constipation Hepatobiliary disorders Not known Liver injuryd Musculoskeletal and connective tissue disorders Very common Myalgia Common Muscular weakness Uncommon Myalgia Muscular weaknessa, b General disorders and administration site conditions Very common Fatigue Uncommon Fatigue Investigations Very common Alanine aminotransferase (ALT) increased Aspartate aminotransferase (AST) increased Weight increased (Abnormal weight gain) Common Blood alkaline phosphatase increased Alanine aminotransferase (ALT) increaseda Aspartate aminotransferase (AST) increaseda Weight increased (Abnormal weight gain) Uncommon Blood alkaline phosphatase increaseda, b a grade 4 reactions were reported b each grade frequency was less than <1% c ADR dysgeusia includes the preferred terms “dysgeusia” and “taste disorder” d includes cases with ALT/AST ≥3x ULN and bilirubin ≥2x ULN 10 Table 4: Adverse drug reactions reported in TRK fusion-positive paediatric cancer patients treated with VITRAKVI at recommended dose (n=135); all grades System organ class Frequency Infants and toddlers (n=43)a Children (n=67)b Adolescents (n=25)c Paediatric patients (n=135) Blood and lymphatic system disorders Very common Anaemia Neutrophil count decreased (Neutropenia) Leukocyte count decreased (Leukopenia) Platelet count decreased (Thrombocytopenia) Anaemia Neutrophil count decreased (Neutropenia) Leukocyte count decreased (Leukopenia) Anaemia Neutrophil count decreased (Neutropenia) Leukocyte count decreased (Leukopenia) Anaemia Neutrophil count decreased (Neutropenia) Leukocyte count decreased (Leukopenia) Platelet count decreased (Thrombocytopenia) Common Platelet count decreased (Thrombocytopenia) Platelet count decreased (Thrombocytopenia) Nervous system disorders Very common Dizziness Common Dizziness Dizziness Paraesthesia Gait disturbance Paraesthesia Gait disturbance Dizziness Paraesthesia Gait disturbance Gastrointestinal disorders Very common Nausea Constipation Vomiting Diarrhoea Nausea Constipation Vomiting Diarrhoea Nausea Constipation Vomiting Diarrhoea Nausea Constipation Vomiting Diarrhoea Common Dysgeusia Dysgeusia Musculoskeletal and connective tissue disorders Very common Myalgia Myalgia Myalgia Common Muscular weakness Muscular weakness Muscular weakness Muscular weakness General disorders and administration site conditions Very common Fatigue Fatigue Fatigue Fatigue Investigations Very common Alanine aminotransferase (ALT) increased Aspartate aminotransferase (AST) increased Weight increased (Abnormal weight gain) Blood alkaline phosphatase increased Alanine aminotransferase (ALT) increased Aspartate aminotransferase (AST) increased Weight increased (Abnormal weight gain) Blood alkaline phosphatase increased Alanine aminotransferase (ALT) increased Aspartate aminotransferase (AST) increased Weight increased (Abnormal weight gain) Blood alkaline phosphatase increased Alanine aminotransferase (ALT) increased […]