Larotrectinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of larotrectinib.
Drugs List
Therapeutic Indications
Uses
Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion +ve solid tumours
Treatment of adult and paediatric patients with solid tumours with Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indications should be consulted.
Adults
100mg twice daily.
Children
100mg per metre squared twice daily. Maximum of 100mg twice daily.
Patients with Hepatic Impairment
Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment: Reduce starting dose by 50%.
Additional Dosage Information
Co-administration with strong CYP3A4 inhibitor should be avoided, however if co-administration is necessary, reduce dose by 50%. After the strong CYP3A4 inhibitor has been discontinued for 3 to 5 elimination half-lives, larotrectinib should be resumed at the dose taken prior to initiation of the CYP3A4 inhibitor.
Dose modification
Missed dose
If a dose was missed or the patient vomited after administration, next dose should be taken at the next scheduled time.
Adult and paediatric patients with body surface area of at least 1 metre squared First dose modification: 75mg twice daily. Second dose modification: 50mg twice daily. Third dose modification: 100mg once daily.
Paediatric patients with body surface area less than 1 metre squared First dose modification: 75mg/metre squared twice daily. Second dose modification: 50mg/metre squared twice daily. Third dose modification: 25mg/metre squared twice daily.
Paediatric patients on 25mg/metre squared twice daily should remain on this dose even if BSA becomes greater than 1 metre squared. The maximum dose should be 25mg/metre squared twice daily at the third dose modification.
For all grade 2 adverse reactions
Continue the dose and follow the laboratory elevations for 1 to 2 weeks until resolved to establish whether a dose interruption or reduction is required.
For grade 3 or 4 adverse reactions Withhold treatment until resolves or improves to baseline or grade 1, then resume treatment at next dose modification. If adverse reaction does not resolve within 4 weeks, permanently discontinue. Treatment should be permanently discontinued if patient is unable to tolerate after three dose modifications.
Contraindications
Breastfeeding
Pregnancy
Precautions and Warnings
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
Moderate hepatic impairment
Reduce dose in patients with moderate hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm positive NTRK gene fusion status of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain propylene glycol
Some formulations contain sucrose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor hepatic function before, monthly for 3 months, then periodically
Monitor for signs of neurological toxicity
Interrupt treatment and/or reduce dose for any grade 3 toxicity
Advise patient not to take St John's wort concurrently
Advise patient to avoid grapefruit products
Female: Contraception required during and for 1 month after treatment
Male & female: Two methods of contraception required (including barrier)
Male: Use barrier contraception during and for 1 month after treatment
Breastfeeding: Do not breastfeed during and for 3 days after treatment
Pregnancy and Lactation
Pregnancy
Larotrectinib is contraindicated during pregnancy.
The manufacturer recommends that larotrectinib is avoided during pregnancy. There is no data of use of larotrectinib in pregnant women. Animal studies did not show direct or indirect reproductive toxicity.
Lactation
Larotrectinib is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during larotrectinib treatment, and for 3 days following the last dose. It is not known whether larotrectinib is excreted in human milk and therefore a risk to the breastfeeding infant cannot be excluded.
Side Effects
Alanine aminotransferase increased
Anaemia
Aspartate aminotransferase increased
Constipation
Dizziness
Dysgeusia
Fatigue
Gait abnormality
Increase in alkaline phosphatase
Leukopenia
Muscle weakness
Myalgia
Nausea
Neutropenia
Paraesthesia
Vomiting
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: April 2021
Reference Sources
Summary of Product Characteristics: Vitrakvi 20mg/ml oral solution. Bayer plc. Revised August 2020.
Summary of Product Characteristics: Vitrakvi 20mg/ml oral solution (Strawberry flavour). Bayer plc. Revised September 2021.
Summary of Product Characteristics: Vitrakvi 25mg hard capsules. Bayer plc. Revised August 2020.
Summary of Product Characteristics: Vitrakvi 100mg hard capsules. Bayer plc. Revised August 2020.
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