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LARO
All solid tumours
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
For the treatment of patients with locally advanced or metastatic NTRK fusion-positive solid tumours (without a known acquired resistance mutation), who have a good performance status and have no satisfactory treatment options (including surgery and/or radiation) available for their current tumour site.
larotrectinib
Exceptional Access Program
(larotrectinib - For the treatment of unresectable locally advanced, or metastatic solid tumours with neurotrophic tyrosine receptor kinase (NTRK) gene fusion, according to clinical criteria)
(EAP Website)
Larotrectinib capsule or oral solution have equivalent oral bioavailability.
| larotrectinib | 100 mg | PO | BID |
Low – No routine prophylaxis; PRN recommended
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Doses should be modified according to the protocol by which the patient is being treated.
Confirm the presence of NTRK gene fusion in a tumour specimen using a validated test prior to initiation.
Dosage with toxicity
| Dose Level | Larotrectinib Dose |
| 0 | 100 mg twice daily |
| -1 | 75 mg twice daily |
| -2 | 50 mg twice daily |
| -3 | 100 mg once daily |
| -4 | Discontinue |
| Toxicity | Severity | Action |
| Hepatic toxicity | Grade 2 ALT and/or AST (> 3 to 5 x ULN) |
Monitor liver function closely until resolved, to establish whether a dose interruption or reduction is required. |
|
Grade 3 ALT and/or AST |
Hold until ≤ Grade 1 or baseline; monitor liver function closely. Restart only if the benefit outweighs the risk at 1 dose level ↓. Discontinue if it does not resolve or if a Grade 4 ALT and/or AST elevation occurs after restarting treatment. |
|
| Grade 4 ALT and/or AST (> 20 x ULN), with bilirubin < 2 x ULN |
||
| ALT and/or AST ≥ 3 x ULN, with bilirubin ≥ 2 x ULN |
Hold until ≤ Grade 1 or baseline; monitor liver function closely. Consider discontinuation. Restart only if the benefit outweighs the risk at 1 dose level ↓ with close monitoring. Discontinue if recurs. |
|
| Other toxicities | Grade 3 or 4 |
Hold up to 4 weeks until ≤ Grade 1 or baseline; restart at 1 dose level ↓ Discontinue if it does not resolve after 4 weeks. |
Hepatic Impairment
| Hepatic Impairment | Starting Dose (% of usual dose) |
| Child-Pugh A | No dose adjustment |
| Child-Pugh B or Child-Pugh C | 50% |
Renal Impairment
No dose adjustment is required for patients with renal impairment.
Dosage in the Elderly
No dose adjustment is necessary in elderly patients. Age has no effect on the systemic exposure of larotrectinib. The safety profile in patients ≥ 65 years was generally consistent with younger patients. Adverse effects that were observed more frequently in elderly patients included fatigue, anemia, dizziness, fall, gait disturbance, hyponatremia, dyspnea, anorexia, muscular weakness and peripheral neuropathy.
Children
Refer to dosing information in the product monograph.
Refer to larotrectinib drug monograph(s) for additional details of adverse effects.
|
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), |
|
|
|
Refer to larotrectinib drug monograph(s) for additional details.
-
Avoid concomitant use with strong CYP3A4 inhibitors; if unavoidable, reduce larotrectinib dose by 50%. If the CYP3A inhibitor is discontinued, increase the larotrectinib dose (after 3-5 half-lives of the inhibitor) to the dose used before starting the inhibitor.
-
Monitor for toxicity when used concomitantly with moderate CYP3A4 inhibitors; reduce larotrectinib dose as clinically indicated.
-
CYP3A4 inducers:
- Avoid concomitant use with strong CYP3A4 inducers if possible.
- Double larotrectinib dose if used with moderate or strong CYP3A4 inducers.
- If the CYP3A4 inducer is discontinued, decrease the larotrectinib dose (after 3-5 half-lives of the inducer) to the dose used before starting the inducer.
-
Avoid concomitant use with CYP3A4 substrates with narrow therapeutic range; if unavoidable, monitor for toxicity and consider dose reduction of substrate.
Refer to larotrectinib drug monograph(s) for additional details.
Administration
- Administer larotrectinib with or without food.
- Capsules should be swallowed whole with a glass of water and not crushed, dissolved, or opened.
- Grapefruit, starfruit, Seville oranges, their juices or products should be avoided during larotrectinib treatment.
- If a dose is missed, the dose should be skipped and the next dose should be taken at the usual time. Patients should not take two doses at the same time to make up for a missed dose.
- If the patient vomits after taking a dose, an additional dose should not be taken.
- Store capsules at room temperature 15°C to 30°C.
- Store oral solution refrigerated at 2°C to 8°C. Do not freeze. Discard 30 days after first opening.
Contraindications
- Patients who are hypersensitive to this drug or any of its components
Other Warnings/Precautions
- Patients should use caution when driving, operating machinery or performing tasks that require alertness if they experience fatigue or neurologic adverse events while taking larotrectinib.
Pregnancy/Lactation
- This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Fertility Effects: Documented in studies with female animals
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
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Liver function tests; Baseline, every 2 weeks for the first month, then monthly for the next 6 months, and at each visit (more frequent in patients who develop transaminase elevations)
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CBC; Baseline and at each visit
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Renal function tests; Baseline and as clinically indicated
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Clinical toxicity assessment for infection, bleeding, fatigue, weight gain, GI, neurological and psychiatric effects; At each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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CADTH Reimbursement Recommendation: Larotrectinib (Vitrakvi), September 2021.
Hong DS, Shen L, van Tilburg CM, et al. Long-term efficacy and safety of larotrectinib in an integrated dataset of patients with TRK fusion cancer. J Clin Oncol 2021 39:15 suppl, 3108.
Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020 Apr;21(4):531-40.
Larotrectinib drug monograph. Ontario Health (Cancer Care Ontario).
September 2025 Expanded into full regimen monograph
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
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