For: Cystic Fibrosis
Symdeko (ivacaftor/tezacaftor tablets and ivacaftor tablets) is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator and CFTR corrector combination for the treatment of cystic fibrosis in patients aged 6 years and older who are homozygous for the F508del mutation or who have at least one mutation in the CFTR) gene that is responsive to Symdeko. SYMDEKO is co-packaged as a tezacaftor/ivacaftor fixed-dose combination tablet and an ivacaftor tablet.
The tezacaftor 50 mg/ivacaftor 75 mg fixed-dose combination tablets are supplied as white, capsule-shaped tablets containing 50 mg of tezacaftor and 75 mg of ivacaftor. Each tablet is debossed with "V50" on one side and plain on the other. Ivacaftor 75 mg tablets are supplied as light blue, film-coated, capsule-shaped tablets containing 75 mg of ivacaftor. Each tablet is printed with the characters "V 75" on one side and plain on the other. SYMDEKO is supplied as:
56-count tablet carton containing a 4-week supply (4 weekly wallets, each with 14 tablets) NDC 51167-113-01
The tezacaftor 100 mg/ivacaftor 150 mg fixed-dose combination tablets are supplied as yellow, capsule-shaped tablets containing 100 mg of tezacaftor and 150 mg of ivacaftor. Each tablet is debossed with "V100" on one side and plain on the other. Ivacaftor 150 mg tablets are supplied as light blue, film-coated, capsule-shaped tablets containing 150 mg of ivacaftor. Each tablet is printed with the characters "V 150" on one side and plain on the other. SYMDEKO is supplied as:
56-count tablet carton containing a 4-week supply (4 weekly wallets, each with 14 tablets) NDC 51167-661-01
Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature].
These highlights do not include all the information needed to use SYMDEKO safely and effectively. See full prescribing information for SYMDEKO.
SYMDEKO� (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use
Initial U.S. Approval: 2018
INDICATIONS AND USAGE
SYMDEKO is a combination of tezacaftor and ivacaftor, indicated for the treatment of patients with cystic fibrosis (CF) aged 12 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. (12.1, 14)
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.
DOSAGE AND ADMINISTRATION
Adults and pediatric patients ages 12 years and older: one tablet (containing tezacaftor 100 mg/ivacaftor 150 mg) in the morning and one tablet (containing ivacaftor 150 mg) in the evening, approximately 12 hours apart. SYMDEKO should be taken with fat-containing food. (2.1, 12.3)
Reduce dose in patients with moderate and severe hepatic impairment. (2.2, 8.6, 12.3)
Reduce dose when co-administered with drugs that are moderate or strong CYP3A inhibitors. (2.3, 7.2, 12.3)
DOSAGE FORMS AND STRENGTHS
SYMDEKO is co-packaged as tezacaftor 100 mg/ivacaftor 150 mg fixed dose combination tablets and ivacaftor 150 mg tablets. (3)
WARNINGS AND PRECAUTIONS
Elevated transaminases (ALT or AST): Transaminases (ALT and AST) should be assessed prior to initiating SYMDEKO, every 3 months during the first year of treatment, and annually thereafter. In 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., patients with ALT or AST >5 � upper limit of normal (ULN), or ALT or AST >3 � ULN with bilirubin >2 � ULN. Following resolution of transaminase elevations, consider the benefits and risks of resuming treatment. (5.1, 6)
Use with CYP3A inducers: Concomitant use with strong CYP3A inducers (e.g., rifampin, St. John's wort) substantially decrease exposure of ivacaftor and may decrease the exposure of tezacaftor, which may reduce therapeutic effectiveness. Therefore, co-administration is not recommended. (5.2, 7.1, 12.3)
Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients treated with SYMDEKO. Baseline and follow-up examinations are recommended in pediatric patients initiating SYMDEKO treatment. (5.3, 8.4)
The most common adverse drug reactions to SYMDEKO (occurring in ?3% of patients) were headache, nausea, sinus congestion, and dizziness. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Vertex Pharmaceuticals Incorporated at 1-877-634-8789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
CYP3A inhibitors: Reduce SYMDEKO dose when co-administered with strong (e.g., ketoconazole) or moderate (e.g., fluconazole) CYP3A inhibitors. Avoid food containing grapefruit or Seville oranges. (2.3, 7.2, 12.3)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.