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. |
| Molecular Weight | 412.42 |
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 | Avoid due to risk of fetal harm. Based on animal studies and mechanism of action, capmatinib may cause fetal toxicity. No adequate human data. |
| 2nd trimester | Avoid. Potential teratogenicity and fetal toxicity. No well-controlled studies in pregnant women. |
| 3rd trimester | Avoid. Risk of fetal harm, particularly during organogenesis. |
Clinical note
Comprehensive clinical and safety monograph for TABRECTA (TABRECTA).
| Placental transfer | Based on molecular weight (412.42 Da) and animal studies, capmatinib is expected to cross the placenta. No human data. |
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions, advise women not to breastfeed during treatment and for 1 week after last dose. |
■ FDA Black Box Warning
None
| Serious Effects |
None known based on drug labeling. However, caution in severe hepatic impairment.
| 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. |
| Food/Dietary | Take TABRECTA on an empty stomach, at least 1 hour before or 2 hours after a meal. Avoid grapefruit and grapefruit juice as they are moderate CYP3A4 inhibitors. Avoid St. John's wort, a strong CYP3A4 inducer, which may decrease capmatinib exposure. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | TABRECTA (capmatinib) is a MET inhibitor indicated for metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutation. Monitor for peripheral edema, which may require dose interruption or reduction. Assess liver function tests (ALT, AST) and bilirubin at baseline and periodically. Interstitial lung disease/pneumonitis may occur; discontinue if confirmed. Strong CYP3A4 inducers (e.g., rifampin) should be avoided; reduce dose with moderate CYP3A4 inhibitors. Administer on an empty stomach (no food for 1 hour before and 2 hours after). |
| Patient Advice | Take TABRECTA on an empty stomach, 1 hour before or 2 hours after a meal. · Do not crush or break tablets; swallow whole with water. · Tell your doctor about all medications, including over-the-counter drugs and supplements, as some may interact. · Watch for swelling in legs, ankles, or hands; report new or worsening symptoms. · Report signs of liver problems: jaundice, dark urine, or right upper quadrant pain. · Seek medical attention for new or worsening respiratory symptoms like cough or shortness of breath. · Avoid grapefruit and grapefruit juice during treatment. · Do not take St. John's wort as it may reduce drug effectiveness. |