warnings and cautions
5 WARNINGS AND PRECAUTIONS Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Permanently discontinue TABRECTA in patients with ILD/pneumonitis. ( 2.3 , 5.1 ) Hepatotoxicity : Monitor liver function tests. Withhold, dose reduce, or permanently discontinue TABRECTA based on severity. ( 2.3 , 5.2 ) Pancreatic Toxicity : Monitor amylase and lipase levels. Withhold, dose reduce, or permanently discontinue TABRECTA based on severity. ( 2.3 , 5.3 ) Hypersensitivity Reactions : Withhold or permanently discontinue TABRECTA based on severity. ( 2.3 , 5.4 ) Risk of Photosensitivity : May cause photosensitivity reactions. Advise patients to limit direct ultraviolet exposure. ( 5.5 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Interstitial Lung Disease (ILD)/Pneumonitis ILD/pneumonitis, which can be fatal, occurred in patients treated with TABRECTA [see Adverse Reactions (6.1)] . ILD/pneumonitis occurred in 4.8% of patients treated with TABRECTA in GEOMETRY mono-1, with 1.9% of patients experiencing Grade 3 ILD/pneumonitis and one patient experiencing death (0.3%). Nine patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis. The median time-to-onset of Grade 3 or higher ILD/pneumonitis was 1.8 months (range: 0.2 months to 1.7 years). Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold TABRECTA in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.3)] . 5.2 Hepatotoxicity Hepatotoxicity occurred in patients treated with TABRECTA [see Adverse Reactions (6.1)] . Increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) occurred in 15% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 7% of patients. Three patients (0.8%) discontinued TABRECTA due to increased ALT/AST. The median time-to-onset of Grade 3 or higher increased ALT/AST was 1.8 months (range: 0.5 to 46.4 months). Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TABRECTA, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TABRECTA [see Dosage and Administration (2.3)] . 5.3 Pancreatic Toxicity Elevations in amylase and lipase levels occurred in patients treated with TABRECTA [see Adverse Reactions (6.1)] . Increased amylase/lipase occurred in 14% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 and 4 increased amylase/lipase occurred in 7% and 1.9% of patients, respectively. Three patients (0.8%) discontinued TABRECTA due to increased amylase/lipase. The median time-to-onset of Grade 3 or higher increased amylase/lipase was 2 months (range: 0.03 to 31.1 months). Pancreatitis (Grade 3) occurred in one patient (0.3%); TABRECTA was permanently discontinued for this event. Monitor amylase and lipase at baseline and regularly during treatment with TABRECTA. Based on the severity of the adverse reaction, temporarily withhold, dose reduce, or permanently discontinue TABRECTA [see Dosage and Administration (2.3)] . 5.4 Hypersensitivity Reactions Serious hypersensitivity reactions occurred in patients treated with TABRECTA in clinical trials other than GEOMETRY mono-1 [see Adverse Reactions (6.1)] . Signs and symptoms of hypersensitivity included pyrexia, chills, pruritus, rash, decreased blood pressure, nausea and vomiting. Based on the severity of the adverse reaction, temporarily withhold or permanently discontinue TABRECTA [see Dosage and Administration (2.3)] . 5.5 Risk of Photosensitivity Based on findings from animal studies, there is a potential risk of photosensitivity reactions with TABRECTA [see Nonclinical Toxicology (13.2)] . In GEOMETRY mono-1, it was recommended that patients use precautionary measures against ultraviolet exposure such as use of sunscreen or protective clothing during treatment with TABRECTA. Advise patients to limit direct ultraviolet exposure during treatment with TABRECTA. 5.6 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, TABRECTA can cause fetal harm when administered to a pregnant woman. Oral administration of capmatinib to pregnant rats and rabbits during the period of organogenesis resulted in malformations at exposures less than the human exposure based on area under the curve (AUC) at the 400 mg twice daily clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with TABRECTA and for 1 week after the last dose [see Use in Specific Populations (8.1, 8.3)] .