Drug updated on 4/17/2024
| Dosage Form | Tablet (oral; tezacaftor/ivacaftor and ivacaftor: 50 mg/75 mg and 75 mg); Tablet (oral; tezacaftor/ivacaftor and ivacaftor: 100 mg/150 mg and 150 mg) |
| Drug Class | CFTR potentiators and correctors |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- For the treatment of patients with cystic fibrosis (CF) 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.
Summary
- Tezacaftor and ivacaftor (Symdeko) is indicated for the treatment of patients with cystic fibrosis aged 6 years and older who are homozygous for the F508del mutation or have at least one mutation in the cystic fibrosis transmembrane conductance regulator gene that responds to tezacaftor/ivacaftor.
- Two systematic reviews/meta-analyses were reviewed, providing real-world evidence on adverse events associated with Symdeko as well as its efficacy compared to other CFTR modulators such as lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor.
- The first review found that while generally well-tolerated, discontinuation rates and adverse event frequency may be higher than observed in clinical trials; respiratory-related adverse events were more frequent with lumicafter-ivafter combination therapy compared to tezafter-ivafter (Symdeko).
- A signal was identified for mental health and neurocognitive adverse events across all four CFTR modulators studied including Symdeko; pharmacists play a key role in monitoring these potential side effects especially in real-world settings.
- The second review evaluated single correctors monotherapy along with dual therapies like lumicafter-ivaafter or tezaafter-ivaafter (Symdeko), concluding that additional data reduced evidence supporting efficacy of dual therapy but still showed small improvements in quality of life, respiratory function, lower pulmonary exacerbation rates when compared to placebo.
- Triple therapy demonstrated improvements over both mono-and-dual therapies including FEV1 and QoL outcomes without significant difference in adverse events rate among people having one or two F508del variants aged 12 years or older; further randomized controlled trials are needed particularly among children under 12 years old and those suffering from severe lung disease.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Symdeko (tezacaftor and ivacaftor) Prescribing Information. | 2023 | Vertex Pharmaceuticals Inc., Boston, MA |
Systematic Reviews / Meta-Analyses
| Document Title | Year | Source |
|---|---|---|
| Real-world safety of CFTR modulators in the treatment of cystic fibrosis: a systematic review. | 2021 | Journal of Clinical Medicine |
| Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). | 2020 | Cochrane Database of Systematic Reviews |
| Modulator treatments for cystic fibrosis: effectiveness and value final evidence report and meeting summary. | 2020 | ICER |