Larotrectinib side effects: what 874 FDA adverse event reports show

Larotrectinib · Vitrakvi · 17 reaction terms · 162 drug–reaction co-reports · data 2026-09-14

Drug class

Kinase Inhibitor

FDA label (Established Pharmacologic Class) · compare the class

Brand names

Vitrakvi

openFDA label

Who reports

874 reports · 74% serious · 161 with death outcome · 50% female

openFDA FAERS counts, all years, deduplication not applied

Used for

VITRAKVI is indicated for the treatment of adult and pediatric patients with solid tumors that: have a neurotrophic receptor tyrosine kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

FDA label, Indications and Usage

What it is

Larotrectinib is a kinase inhibitor. VITRAKVI (larotrectinib) capsules and oral solution are formulated using larotrectinib sulfate.

FDA label, Description section

Boxed warning

None in the current label

How to read this page. FAERS is a spontaneous-reporting system: counts are not incidence rates and a signal is not proof of causation. Each reaction below is run through an automated screen — is the term in the FDA label (known), in the indications (the disease being treated), an administrative/coding term, or none of these (unlabeled)? That screen is mechanical text matching, not a causality assessment. The 30 hand-written Bradford Hill assessments are on the causality assessment page. Not medical advice.

Causality screen of the 14 strongest signals

Labeled adverse reaction 2Labeled (related wording) 2Reporting / coding artifact 2Not in label — unassessed 8

What the badges mean

Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.

Strongest disproportionality signals

Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 3 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.

Show: hide coding/lab/outcome terms hide indication terms unlabeled only hide PRR-only

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Metastases to lung	13	27.0 15.8–46.4ROR 27.4 · χ² 300 / p 1e-67	26.1 EB05 16.1 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 21.1	no trial data cached
Metastases to central nervous system	12	22.5 12.8–39.5ROR 22.8 · χ² 225 / p 3e-51	21.6 EB05 12.8 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 17.6	no trial data cached
Drug resistance	20	18.7 12.1–28.8ROR 19.1 · χ² 318 / p 2e-71	18.3 EB05 12.3 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 13.9	no trial data cached
Liver function test increased	14	15.8 9.4–26.5ROR 16.0 · χ² 179 / p 4e-41	14.8 EB05 8.7 · IC025 +2.5 3/3 methods agree	Labeled (related wording) related wording	serious PRR 9.5	no trial data cached
Hepatic cytolysis	8	15.7 7.9–31.3ROR 15.9 · χ² 96 / p 6e-23	13.4 EB05 5.9 · IC025 +1.9 3/3 methods agree	Not in label — unassessed	serious PRR 12.2	no trial data cached
Metastases to liver	8	10.9 5.5–21.8ROR 11.0 · χ² 63 / p 1e-15	8.3 EB05 4.0 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 8.6	no trial data cached
Transaminases increased	10	10.8 5.8–20.0ROR 10.9 · χ² 79 / p 2e-19	8.7 EB05 4.6 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	no trial data cached
Thyroid cancer	5	9.9 4.1–23.7ROR 10.0 · χ² 32 / p 9e-9	6.3 EB05 2.7 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 7.7	no trial data cached
Hepatotoxicity (liver damage)	9	9.7 5.1–18.7ROR 9.8 · χ² 62 / p 2e-15	7.5 EB05 3.9 · IC025 +1.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.0	no trial data cached
Neurotoxicity	7	9.7 4.6–20.2ROR 9.7 · χ² 46 / p 6e-12	6.9 EB05 3.3 · IC025 +1.3 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.6	no trial data cached
Metastases to bone	6	8.8 4.0–19.5ROR 8.9 · χ² 34 / p 3e-9	6.0 EB05 2.8 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.9	no trial data cached
Pancreatic carcinoma	7	5.8 2.8–12.1ROR 5.8 · χ² 23 / p 8e-7	4.4 EB05 2.3 · IC025 +0.8 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	no trial data cached
Malignant neoplasm progression	23	5.4 3.6–8.1ROR 5.5 · χ² 79 / p 3e-19	4.9 EB05 3.5 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	serious PRR 3.9 · 96% clinician	no trial data cached
Withdrawal syndrome	9	5.1 2.7–9.8ROR 5.2 · χ² 26 / p 2e-7	4.2 EB05 2.4 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 2.5	no trial data cached

Trial evidence (ClinicalTrials.gov)

Trial cross-check not yet run for this drug (ClinicalTrials.gov pull covers the 800 most-reported drugs first).

Most frequently reported reactions

By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.

Reaction	Reports	PRR 95% CI · ROR · χ²/p	EBGM EB05 · IC025	Label screen	Serious-only & strata	Trial cross-check
Malignant neoplasm progression	23	5.4 3.6–8.1ROR 5.5 · χ² 79 / p 3e-19	4.9 EB05 3.5 · IC025 +1.6 3/3 methods agree	Reporting / coding artifact	serious PRR 3.9 · 96% clinician	no trial data cached
Drug resistance	20	18.7 12.1–28.8ROR 19.1 · χ² 318 / p 2e-71	18.3 EB05 12.3 · IC025 +3.0 3/3 methods agree	Reporting / coding artifact	serious PRR 13.9	no trial data cached
Liver function test increased	14	15.8 9.4–26.5ROR 16.0 · χ² 179 / p 4e-41	14.8 EB05 8.7 · IC025 +2.5 3/3 methods agree	Labeled (related wording) related wording	serious PRR 9.5	no trial data cached
Metastases to lung	13	27.0 15.8–46.4ROR 27.4 · χ² 300 / p 1e-67	26.1 EB05 16.1 · IC025 +2.8 3/3 methods agree	Not in label — unassessed	serious PRR 21.1	no trial data cached
Metastases to central nervous system	12	22.5 12.8–39.5ROR 22.8 · χ² 225 / p 3e-51	21.6 EB05 12.8 · IC025 +2.6 3/3 methods agree	Labeled (related wording) related wording	serious PRR 17.6	no trial data cached
Transaminases increased	10	10.8 5.8–20.0ROR 10.9 · χ² 79 / p 2e-19	8.7 EB05 4.6 · IC025 +1.8 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	no trial data cached
Withdrawal syndrome	9	5.1 2.7–9.8ROR 5.2 · χ² 26 / p 2e-7	4.2 EB05 2.4 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 2.5	no trial data cached
Hepatotoxicity (liver damage)	9	9.7 5.1–18.7ROR 9.8 · χ² 62 / p 2e-15	7.5 EB05 3.9 · IC025 +1.6 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 6.0	no trial data cached
Metastases to liver	8	10.9 5.5–21.8ROR 11.0 · χ² 63 / p 1e-15	8.3 EB05 4.0 · IC025 +1.6 3/3 methods agree	Not in label — unassessed	serious PRR 8.6	no trial data cached
Hepatic cytolysis	8	15.7 7.9–31.3ROR 15.9 · χ² 96 / p 6e-23	13.4 EB05 5.9 · IC025 +1.9 3/3 methods agree	Not in label — unassessed	serious PRR 12.2	no trial data cached
Pancreatic carcinoma	7	5.8 2.8–12.1ROR 5.8 · χ² 23 / p 8e-7	4.4 EB05 2.3 · IC025 +0.8 3/3 methods agree	Not in label — unassessed	serious PRR 4.5	no trial data cached
Neurotoxicity	7	9.7 4.6–20.2ROR 9.7 · χ² 46 / p 6e-12	6.9 EB05 3.3 · IC025 +1.3 3/3 methods agree	Labeled adverse reaction exact term	serious PRR 7.6	no trial data cached
Metastases to bone	6	8.8 4.0–19.5ROR 8.9 · χ² 34 / p 3e-9	6.0 EB05 2.8 · IC025 +1.0 3/3 methods agree	Not in label — unassessed	serious PRR 6.9	no trial data cached
Thyroid cancer	5	9.9 4.1–23.7ROR 10.0 · χ² 32 / p 9e-9	6.3 EB05 2.7 · IC025 +0.9 3/3 methods agree	Not in label — unassessed	serious PRR 7.7	no trial data cached
Myelosuppression	4	2.8 1.1–7.5ROR 2.8 · χ² 3 / p 0.040	2.4 EB05 1.1 · IC025 -0.5 PRR-only: not supported by EBGM or IC	Not in label — unassessed	serious PRR 1.6	no trial data cached

Unlabeled candidate signals

Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.

Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.

Common questions

What are the most reported side effects of Larotrectinib?

In FDA FAERS, the most frequently co-reported reaction terms for Larotrectinib are liver function test increased, metastases to lung, metastases to central nervous system, transaminases increased, withdrawal syndrome, hepatotoxicity. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.

Does Larotrectinib have an FDA boxed warning?

No. The FDA label retrieved for Larotrectinib has no boxed warning; see the label's Warnings and Precautions for the recognised risks.

Do FAERS signals prove that Larotrectinib causes these side effects?

No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.

Sources & methods

FDA label via openFDA (set ID 0c8ca614-58b2-4aa4-83d3-0387a8f782fd, effective 20260522; matched on openfda.generic_name.exact:"LAROTRECTINIB")
Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA count= aggregation, field patient.drug.openfda.generic_name.exact, 17 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction
Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
Seriousness and sex counts from openFDA count=serious, patient.patientsex, seriousnessdeath

Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.