INDICATIONS AND USAGE

SYMDEKO is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Transaminase (ALT or AST) Elevations

• Elevated transaminases have been observed in patients with CF receiving SYMDEKO, as well as with ivacaftor monotherapy. Assessments of transaminases (ALT and AST) are recommended prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring should be considered
• Dosing should be interrupted in patients with significant elevations of transaminases (e.g., ALT or AST >5x upper limit of normal [ULN], or ALT or AST >3x ULN with bilirubin >2x ULN) and laboratory tests should be closely followed until abnormalities resolve. Following resolution of transaminase elevations, consider the benefits and risks of resuming treatment

Hypersensitivity Reactions, Including Anaphylaxis

• Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the postmarketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue SYMDEKO and institute appropriate therapy. Consider the benefits and risks for the individual patient to determine whether to resume treatment with SYMDEKO

Concomitant Use With CYP3A Inducers

• Exposure to ivacaftor is significantly decreased and exposure to tezacaftor may be reduced by concomitant use of CYP3A inducers, which may reduce the therapeutic effectiveness of SYMDEKO. Co-administration of SYMDEKO with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort, is not recommended

Cataracts

• Cases of non-congenital lens opacities have been reported in pediatric patients treated with SYMDEKO, as well as with ivacaftor monotherapy. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with SYMDEKO

ADVERSE REACTIONS

Serious Adverse Reactions

• Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with SYMDEKO compared to placebo included distal intestinal obstruction syndrome, 3 (0.6%) patients treated with SYMDEKO vs. 0 placebo patients

Most Common Adverse Reactions

• The most common adverse reactions in Trials 1 and 3 occurring in ≥3% of patients treated with SYMDEKO (N=334) and at a higher rate than for placebo (N=343) were headache, nausea, sinus congestion, and dizziness
• The safety profile in patients age 6 to less than 12 years from an open-label Phase 3 trial (N=70) was similar to that observed in Trials 1 and 3

USE IN SPECIFIC POPULATIONS

Pediatric Use

• The safety and effectiveness of SYMDEKO in patients with CF younger than 6 years of age have not been studied

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