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INDICATIONS AND USAGE

SYMDEKO is 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.

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.

INDICATED MUTATIONS IN PATIENTS 12 YEARS AND OLDER

CFTR Mutations That Produce CFTR Protein Responsive to SYMDEKO1-3*

F508del/F508del*
c.1521_1523delCTT
E56K
c.166G>A
R347H
c.1040G>A
A1067T
c.3199G>A
E831X
c.2491G>T
R352Q
c.1055G>A
A455E
c.1364C>A
F1052V
c.3154T>G
R74W
c.220C>T
D110E
c.330C>A
F1074L
c.3222T>A
S945L
c.2834C>T
D110H
c.328G>C
K1060T
c.3179A>C
S977F
c.2930C>T
D1152H
c.3454G>C
L206W
c.617T>G
2789+5G→A
c.2657+5G>A
D1270N
c.3808G>A
P67L
c.200C>T
3272-26A→G
c.3140-26A>G
D579G
c.1736A>G
R1070W
c.3208C>T
3849+10kbC→T
c.3718-2477C>T
E193K
c.577G>A
R117C
c.349C>T
711+3A→G
c.579+3A>G
F508del/F508del*
c.1521_1523delCTT
L206W
c.617T>G
A1067T
c.3199G>A
P67L
c.200C>T
A455E
c.1364C>A
R1070W
c.3208C>T
D110E
c.330C>A
R117C
c.349C>T
D110H
c.328G>C
R347H
c.1040G>A
D1152H
c.3454G>C
R352Q
c.1055G>A
D1270N
c.3808G>A
R74W
c.220C>T
D579G
c.1736A>G
S945L
c.2834C>T
E193K
c.577G>A
S977F
c.2930C>T
E56K
c.166G>A
2789+5G→A
c.2657+5G>A
E831X
c.2491G>T
3272-26A→G
c.3140-26A>G
F1052V
c.3154T>G
3849+10kbC→T
c.3718-2477C>T
F1074L
c.3222T>A
711+3A→G
c.579+3A>G
K1060T
c.3179A>C
  • A patient must have 2 copies of the F508del mutation or at least one copy of another responsive mutation listed above in this table to be indicated.

Professional Resources

Learn more about SYMDEKO™ (tezacaftor/ivacaftor and ivacaftor)—the materials below provide clinical information that may help support your practice.

SYMDEKO CLINICAL RESULTS BROCHURE
Review SYMDEKO efficacy, safety, DDIs, and dosing
INITIATION GUIDE
Review considerations for initiating SYMDEKO
FULL PRESCRIBING INFORMATION
Download the full Prescribing Information

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IMPORTANT SAFETY INFORMATION

Transaminase (ALT or AST) Elevations
  • Elevated transaminases have been observed in patients with CF treated with 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 of liver function tests should be considered
  • Dosing should be interrupted in the event of significant elevations and laboratory tests should be closely followed until abnormalities resolve. Following resolution of transaminase elevations, consider the benefits and risks of resuming SYMDEKO dosing

INDICATIONS AND USAGE

SYMDEKO™ (tezacaftor/ivacaftor and ivacaftor) is 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.

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.

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
Pediatric Use
  • The safety and efficacy of SYMDEKO in patients with CF younger than 12 years of age have not been studied
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%] SYMDEKO-treated patients vs 0 for placebo). There were no deaths in the placebo controlled trials, and one death in the open label extension study due to respiratory failure and influenza infection in a patient who had discontinued SYMDEKO 7 weeks prior
Most Common Adverse Reactions
  • The most common adverse reactions in Trials 1 and 3 occurring in ≥3% patients treated with SYMDEKO (N=334) and at a higher rate than for placebo (N=343) were headache, nausea, sinus congestion, and dizziness

Click here to access the full Prescribing Information.

References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; February 2018.
2. The Clinical and Functional TRanslation of CFTR (CFTR2); available at http://cftr2.org. List of CFTR2 mutations. https://www.cftr2.org/sites/default/files/CFTR2_8December2017.xlsx. Accessed January 22, 2018.
3. National Center for Biotechnology Information. ClinVar. Available at https://www.ncbi.nlm.nih.gov. Accessed January 22, 2018.

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