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 6 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%) 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
Click here to access full Prescribing Information.
Reference:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020. 2. The Clinical and Functional Translation of CFTR (CFTR2); Available at http://cftr2.org. List of CFTR2 mutations. https://www.cftr2.org/mutations_history/CFTR2_11March2019.xlsx. Accessed December 1, 2020. 3. National Center for Biotechnology Information. ClinVar. Available at https://www.ncbi.nlm.nih.gov/clinvar/. Accessed December 1, 2020.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2019. 2. Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe508del. N Engl J Med. 2017;377(21):2013-2023. 3. Cystic Fibrosis Foundation. Patient Registry Annual Data Report 2015. Bethesda, MD. Cystic Fibrosis Foundation; 2016. 4. Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe508del. NEngl J Med. 2017;377(21)(suppl1-29):2013-2023. 5. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0258 (v2.0); 2019. 6. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0551 (v2.0); 2019. 7. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009;135(6):1610-1618.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; June 2019. 2. Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017;377(21):2024-2035. 3. Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017;377(21)(suppl1-25):2024-2035. 4. CFQ-R Cystic Fibrosis Questionnaire-REVISED. Cystic Fibrosis Foundation. Quittner, Modi, Watrous and Messer, 2000. Revised 2002. CFQ-R—Parent, English Version 2.0. 5. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire-Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest. 2009;135(6):1610-1618.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020. 2. Walker S, Flume P, McNamara J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 to 11 years with cystic fibrosis. J Cyst Fibros. 2019:1-6. doi: 10.1016/j.jcf.2019.06.009. 3. Walker S, Flume P, McNamara J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 to 11 years with cystic fibrosis. J Cyst Fibros. 2019:(suppl1-10). doi: 10.1016/j.jcf.2019.06.009. 4. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-2254; 2019. 5. CFQ-R Cystic Fibrosis Questionnaire- REVISED. Cystic Fibrosis Foundation. Quittner, Modi, Watrous and Messer, 2000. Revised 2002. CFQ-R—Parent, English Version 2.0.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-0004 (v2.0); 2019.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020. 2. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison’s Manual of Medicine. 17th ed. New York, NY: McGraw-Hill Medical; 2009.
References:
1. SYMDEKO [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; December 2020. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-3538; 2019. 3. FDA U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 1, 2020. 4. Kunze A, Huwyler J, Camenisch G, Poller B. Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014;42(9):1514-1521.