TABRECTA

TABRECTA- capmatinib tablet, film coated
Novartis Pharmaceuticals Corporation

1 INDICATIONS AND USAGE

TABRECTA is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients for treatment with TABRECTA based on the presence of a mutation that leads to MET exon 14 skipping in tumor specimens [see Clinical Studies (14)]. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage

The recommended dosage of TABRECTA is 400 mg orally twice daily with or without food.

Swallow TABRECTA tablets whole. Do not break, crush or chew the tablets.

If a patient misses or vomits a dose, instruct the patient not to make up the dose, but to take the next dose at its scheduled time.

2.3 Dosage Modifications for Adverse Reactions

The recommended dose reductions for the management of adverse reactions are listed in Table 1.

Table 1: Recommended TABRECTA Dose Reductions for Adverse Reactions
Dose Reduction Dose and Schedule
First 300 mg orally twice daily
Second 200 mg orally twice daily

Permanently discontinue TABRECTA in patients who are unable to tolerate 200 mg orally twice daily.

The recommended dosage modifications of TABRECTA for adverse reactions are provided in Table 2.

Table 2: Recommended TABRECTA Dosage Modifications for Adverse Reactions
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ILD, interstitial lung disease; ULN, upper limit of normal.Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events).
Adverse Reaction Severity Dosage Modification
Interstitial Lung Disease (ILD)/Pneumonitis[see Warnings and Precautions (5.1)] Any grade Permanently discontinue TABRECTA.
Increased ALT and/or AST without increased total bilirubin[see Warnings and Precautions (5.2)] Grade 3 Withhold TABRECTA until recovery to baseline ALT/AST.If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume TABRECTA at a reduced dose.
Grade 4 Permanently discontinue TABRECTA.
Increased ALT and/or AST with increased total bilirubin in the absence of cholestasis or hemolysis[see Warnings and Precautions (5.2)] ALT and/or AST greater than 3 times ULN with total bilirubin greater than 2 times ULN Permanently discontinue TABRECTA.
Increased total bilirubin without concurrent increased ALT and/or AST[see Warnings and Precautions (5.2)] Grade 2 Withhold TABRECTA until recovery to baseline bilirubin.If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume TABRECTA at a reduced dose.
Grade 3 Withhold TABRECTA until recovery to baseline bilirubin.If recovered to baseline within 7 days, then resume TABRECTA at a reduced dose; otherwise permanently discontinue TABRECTA.
Grade 4 Permanently discontinue TABRECTA.
Other Adverse Reactions[see Adverse Reactions (6.1)] Grade 2 Maintain dose level. If intolerable, consider withholding TABRECTA until resolved, then resume TABRECTA at a reduced dose.
Grade 3 Withhold TABRECTA until resolved, then resume TABRECTA at a reduced dose.
Grade 4 Permanently discontinue TABRECTA.

3 DOSAGE FORMS AND STRENGTHS

Tablets:

  • 150 mg: pale orange brown, ovaloid, curved film-coated with beveled edges, unscored, debossed with ‘DU’ on one side and ‘NVR’ on the other side
  • 200 mg: yellow, ovaloid, curved film-coated with beveled edges, unscored, debossed with ‘LO’ on one side and ‘NVR’ on the other side

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

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 4.5% of patients treated with TABRECTA in GEOMETRY mono-1, with 1.8% of patients experiencing Grade 3 ILD/pneumonitis and one patient experiencing death (0.3%). Eight patients (2.4%) discontinued TABRECTA due to ILD/pneumonitis. The median time-to-onset of Grade 3 or higher ILD/pneumonitis was 1.4 months (range: 0.2 months to 1.2 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 13% of patients treated with TABRECTA in GEOMETRY mono-1. Grade 3 or 4 increased ALT/AST occurred in 6% of patients. Three patients (0.9%) discontinued TABRECTA due to increased ALT/AST. The median time-to-onset of Grade 3 or higher increased ALT/AST was 1.4 months (range: 0.5 to 4.1 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 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.

5.4 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)].

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