FDA OKs Ivacaftor (Kalydeco) for Preschoolers With CF

Megan Brooks


March 18, 2015

The US Food and Drug Administration (FDA) has approved ivacaftor (Kalydeco, Vertex Pharmaceuticals) for children aged two to five years with cystic fibrosis (CF) who have one of 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

These mutations are: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, and R117H. Ivacaftor is already approved in the US for people aged 6 years or older with these mutations.

To meet the needs of young children who may not be able to swallow a pill, the company developed a weight-based oral granule formulation of ivacaftor that can be mixed in soft foods or liquids.

The expanded approval is based on results of an open-label, phase 3 study that evaluated the safety and pharmacokinetics of weight-based dosing of ivacaftor (50 mg or 75 mg twice daily) in two- to five-year-old children, Vertex notes in a news release.

CF is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. Ivacaftor is an oral CFTR potentiator designed to keep CFTR proteins at the cell surface open more often to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

"Children with cystic fibrosis can begin to experience meaningful lung function decline and struggle to gain weight at a very young age, underscoring the importance of starting treatment early in life," Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex said in the release.

"With today's approval, children as young as two years of age now have a medicine to treat the underlying cause of their CF, bringing us one step closer to our goal of helping the vast majority of people with this devastating disease."

Elevated transaminase levels have been reported in patients taking ivacaftor. It is recommended that alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels be assessed before starting ivacaftor, every three months during the first 12 months of treatment, and annually thereafter. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve, the company notes. Dosing should be interrupted in patients with ALT or AST levels greater than five times the upper limit of normal. After resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing, the company advises.

Coadministration of ivacaftor with drugs that are strong CYP3A inducers, such as the antibiotics rifampin and rifabutin, seizure medications (phenobarbital, carbamazepine, or phenytoin), and the herbal supplement St John's wort, substantially decreases exposure of ivacaftor and may diminish effectiveness, and is not recommended, the company says. "The dose of ivacaftor must be adjusted when used concomitantly with strong and moderate CYP3A inhibitors or when used in patients with moderate or severe hepatic disease," the company notes.

Cases of noncongenital lens opacities/cataracts have been reported in children aged up to 12 years treated with ivacaftor; baseline and follow-up eye examinations are recommended.

The most common adverse effects associated with ivacaftor include headache; upper respiratory tract infection (the common cold), including sore throat, nasal or sinus congestion, and runny nose; abdominal pain; diarrhea; rash; and dizziness. A complete list of the adverse reactions can be found in the product labeling for ivacaftor.


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