TABRECTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TABRECTA (TABRECTA).
Capmatinib is a potent and selective inhibitor of the MET receptor tyrosine kinase, including the mutant variant resulting from exon 14 skipping. It blocks MET phosphorylation and downstream signaling pathways, leading to reduced tumor cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4 and aldehyde oxidase (AO), with minor contributions from CYP2C8 and CYP1A2. |
| Excretion | Primarily hepatic metabolism; 70% of dose excreted in feces (22% unchanged); 30% in urine (12% unchanged). |
| Half-life | Terminal half-life approximately 13.7 hours (range 8.5–20.8 hours); supports twice-daily dosing. |
| Protein binding | 97% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Vd/F approximately 1000 L (≈14 L/kg for a 70 kg adult); indicates extensive extravascular distribution. |
| Bioavailability | Oral bioavailability 60% (range 40–80%); no intravenous formulation available. |
| Onset of Action | Oral: time to maximum concentration (Tmax) 1.8–2.4 hours; clinical effect observed within 2 weeks of continuous dosing. |
| Duration of Action | Sustained MET exon 14 skipping inhibition for >24 hours; continuous twice-daily dosing required for clinical effect. |
600 mg orally twice daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Insufficient data for severe renal impairment (eGFR <30 mL/min); use with caution. |
| Liver impairment | Child-Pugh A: 600 mg twice daily. Child-Pugh B: 400 mg twice daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; no FDA-approved pediatric dosing. |
| Geriatric use | No specific dose adjustment; elderly patients may have increased risk of adverse events; monitor renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TABRECTA (TABRECTA).
| Breastfeeding | No data available on the presence of capmatinib in human milk, its effects on the breastfed infant, or on milk production. Due to the potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least 1 week after the last dose. |
| Teratogenic Risk | Based on its mechanism of action as an MET inhibitor and animal studies showing embryofetal lethality and teratogenicity, Tabrecta (capmatinib) is contraindicated in pregnancy. There is a high risk of fetal harm; first trimester exposure may cause structural abnormalities, while second and third trimester exposure may impair fetal growth and development. |
■ FDA Black Box Warning
None
| Serious Effects |
None
| Precautions | ["Interstitial lung disease (ILD)/pneumonitis: Monitor for new or worsening respiratory symptoms; permanently discontinue if ILD is confirmed.","Hepatotoxicity: Monitor liver function tests; withhold, dose reduce, or permanently discontinue based on severity.","Photosensitivity: Advise patients to limit sun exposure and use protective measures.","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential of the risk."] |
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| Fetal Monitoring | Monitor for peripheral edema, nausea, vomiting, increased liver enzymes, and interstitial lung disease/pneumonitis. Obtain pregnancy test prior to initiation in females of reproductive potential. Advise effective contraception during treatment and for 1 week after the last dose. |
| Fertility Effects | Based on animal studies, capmatinib may impair fertility in males and females of reproductive potential. Reversibility unknown. |