Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

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. The effect may be quantitatively different depending on tumour type, as well as on concomitant genetic alterations (see section 5.1). For these reasons, VITRAKVI should only be used if there are no treatment options for which clinical benefit has been established, or where such treatment options have been exhausted (i.e., no satisfactory treatment options).

Neurologic reactions

Neurologic reactions including dizziness, gait disturbance and paraesthesia were reported in patients receiving larotrectinib (see section 4.8). For the majority of neurologic reactions, onset occurred within the first three months of treatment. Withholding, reducing, or discontinuing VITRAKVI dosing should be considered, depending on the severity and persistence of these symptoms (see section 4.2).

Hepatotoxicity

Abnormalities of liver function tests including increased ALT, AST, alkaline phosphatase (ALP) and bilirubin have been observed in patients receiving larotrectinib (see section 4.8). 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 in adult patients.
In patients with hepatic transaminase elevations, withhold, modify dose or permanently discontinue VITRAKVI based on the severity (see section 4.2).

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. In patients who develop transaminase elevations, more frequent testing is needed (see section 4.2).


Co-administration with CYP3A4/P-gp inducers
Avoid co-administration of strong or moderate CYP3A4/P-gp inducers with VITRAKVI due to a risk of decreased exposure (see section 4.5).

Contraception in female and male

Women of childbearing potential must use highly effective contraception while taking VITRAKVI and for at least one month after stopping treatment (see sections 4.5 and 4.6).
Males of reproductive potential with a non-pregnant woman partner of child bearing potential should be advised to use highly effective contraception during treatment with VITRAKVI and for at least one month after the final dose (see section 4.6).

Important information about some of the ingredients
Sodium benzoate: this medicinal product contains 2 mg per 1 mL.
Sodium: this medicinal product contains less than 1 mmol sodium (23 mg) per 5 mL, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

VITRAKVI has a moderate influence on the ability to drive and use machines. Dizziness and fatigue have been reported in patients receiving larotrectinib, mostly grade 1 and 2 during the first 3 months of treatment. This may influence the ability to drive and use machines during this time period. Patients should be advised not to drive and use machines, until they are reasonably certain VITRAKVI therapy does not affect them adversely (see section 4.4).