Ivacaftor

Ivacaftor is a small molecule drug used to treat cystic fibrosis in people who have at least one CFTR gene mutation known to respond to ivacaftor. It is marketed under the brand name Kalydeco and was developed by Vertex Pharmaceuticals. Ivacaftor is a CFTR potentiator, meaning it increases the probability that the CFTR chloride channel remains open at the cell surface, thereby improving chloride transport and hydration of secretions.

Indications for ivacaftor include cystic fibrosis patients with gating mutations, such as G551D, and later expanded to additional gating mutations and to younger age groups for eligible mutations. The precise mutations and age ranges approved for ivacaftor vary by regulatory region, and not all CFTR mutations respond to this therapy. Genetic testing or mutation-specific guidance is used to identify eligible patients.

Administration and dosing: Ivacaftor is taken by mouth as an oral tablet every 12 hours, ideally with a fat-containing meal to enhance absorption. Dosing is age- and mutation-specific, and a liquid formulation is available for younger children. Prescribing information provides exact dose adjustments based on age, weight, and genotype.

Pharmacokinetics and interactions: The drug is metabolized primarily by hepatic cytochrome P450 3A (CYP3A). Strong CYP3A inhibitors or inducers can markedly affect ivacaftor exposure, requiring dose adjustments or avoidance of certain combinations. Ivacaftor may be used in combination with other CFTR modulators in some regimens, and such combinations have their own interaction profiles.

Safety: Common adverse effects include headache, nasal congestion, upper respiratory tract infections, and abdominal discomfort. Ivacaftor can elevate liver enzymes, so baseline and periodic liver function tests are recommended, with therapy re-evaluated if liver injury is suspected or detected.