Products
Ivacaftor was approved by the FDA and EMA in 2012 and by Swissmedic in 2014 in film-coated tablet form (Kalydeco). Also available is a fixed combination with lumacaftor (Orkambi). In 2016, a granule was also approved. In 2018, the combination with tezacaftor was approved in the US and EU (Symdeko, Symkevi). In 2020, a fixed-dose combination with tezacaftor and elexacaftor was added (Trikafta).
Structure and properties
Ivacaftor (C24H28N2O3, Mr = 392.49 g/mol) is an oxoquinoline carboxamide. It exists as a white powder that is practically insoluble in water.
Effects
Ivacaftor (ATC R07AX02) is an enhancer of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This chloride channel is localized on the surface of numerous epithelial cells in various organs. Mutations in the CFTR gene are responsible for the development of cystic fibrosis. Ivacaftor increases chloride transport by affecting gating, thereby increasing the likelihood that chloride ions will flow through the channel.
Indications
For the treatment of patients with cystic fibrosis with certain mutations in the CFTR gene. The mutation must be confirmed with a diagnostic test before treatment.
Dosage
According to the SmPC. The drug is taken twice daily 12 hours apart with a meal containing fat (e.g., eggs, butter, peanut butter, pizza). This improves absorption by a factor of 2 to 4.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Ivacaftor is a substrate of CYP3A4/5, and concomitant administration of CYP inhibitors or inducers results in relevant drug-drug interactions. Ivacaftor is an inhibitor of CYP3A4 and P-glycoprotein and thus may affect the pharmacokinetics of other drugs.
Adverse effects
The most common possible adverse effects include headache, upper respiratory tract infection, nasal congestion, nausea, rash, rhinitis, dizziness, joint pain, and bacteria in sputum.
