larotrectinib sulfate: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
larotrectinib sulfate: clinical details
Prescribing considerations
- Confirm an NTRK gene fusion in tumour tissue using a validated assay before initiation.
- Treatment should be initiated by a clinician experienced in anticancer therapy.
- Evidence comes mainly from single-arm studies across relatively small tumour-specific groups; use is restricted to patients without satisfactory treatment options.
- Review hepatic impairment and all CYP3A, P-gp and BCRP interactions before treatment.
- Neurological toxicity and hepatotoxicity may require interruption, adjustment or discontinuation according to severity.
Contraindications and cautions
- Hypersensitivity to larotrectinib or any formulation excipient.
Monitoring
- Check ALT, AST, alkaline phosphatase and bilirubin before treatment and regularly thereafter, with more frequent testing if abnormalities develop.
- Assess for dizziness, paraesthesia, gait disturbance and other neurological changes.
- Perform pregnancy testing before treatment where relevant and review contraception.
Clinical pharmacology
Larotrectinib is an ATP-competitive selective inhibitor of TRKA, TRKB and TRKC. It is principally metabolised by CYP3A4/5 and is a substrate of CYP3A, P-gp and BCRP; it also weakly inhibits CYP3A.
Formulation and product differences
- Capsules and oral solution have equivalent oral bioavailability and may be interchanged under specialist direction.
- Capsules must be swallowed whole.
- The strawberry-flavoured oral solution is suitable for oral-syringe administration and may be given through a nasogastric tube; it contains sodium benzoate and requires refrigerated storage after opening.
larotrectinib sulfate preparations and strengths
Capsule
Route: Oral
Strengths: 25 mg, 100 mg
Oral solution
Route: Oral
Strengths: 20 mg/mL
larotrectinib sulfate interactions
A full medication review is needed before and during treatment, including prescribed, non-prescribed and herbal products.
Strong or moderate CYP3A, P-gp or BCRP inhibitors, including clarithromycin, itraconazole, ritonavir and voriconazole
These can increase larotrectinib exposure and the risk of adverse effects, requiring specialist review.
CYP3A or P-gp inducers, including carbamazepine, phenytoin, rifampicin and St John’s wort
These can substantially reduce larotrectinib exposure and should generally be avoided.
Narrow-therapeutic-range CYP3A substrates, including ciclosporin, fentanyl, sirolimus and tacrolimus
Larotrectinib may increase their exposure and toxicity, so closer review may be required.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.