Ivacaftor

KALYDECO is indicated for the treatment of cystic fibrosis (CF) in patients aged 1 month and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data. If the patient's genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of a CFTR mutation followed by verification with bi-directional sequencing when recommended by the mutation test instructions for use. KALYDECO is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator indicated for the treatment of cystic fibrosis (CF) in patients aged 1 month and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor based on clinical and/or in vitro assay data.

Ivacaftor is a potentiator of the CFTR protein. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel open probability (or gating) of CFTR protein located at the cell surface. The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation. CFTR Chloride Transport Assay in Fischer Rat Thyroid (FRT) cells expressing mutant CFTR The chloride transport response of mutant CFTR protein to ivacaftor was determined in Ussing chamber electrophysiology studies using a panel of FRT cell lines transfected with individual CFTR mutations.

Age Weight Dosage Administration 1 month to less than 2 months 3 kg or greater One 5.8 mg packet every 12 hours Mixed with one teaspoon (5 mL) of soft food or liquid and administered orally with fat-containing food 2 months to less than 4 months 3 kg or greater One 13.4 mg packet every 12 hours 4 months to less than 6 months 5 kg or greater One 25 mg packet every 12 hours 6 months to less than 6 years 5 kg to less than 7 kg One 25 mg packet every 12 hours 7 kg to less than 14 kg One 50 mg packet every 12 hours 14 kg or greater One 75 mg packet every 12 hours 6 years and older - One 150 mg tablet every 12 hours Taken orally with fat-containing food See full prescribing information for the recommended dosage in patients aged 6 months and older with moderate or severe hepatic impairment. See full prescribing information for dosage modifications due to drug interactions with KALYDECO.

None. None

Elevated transaminases (ALT or AST): Transaminases (ALT and AST) should be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter. In patients with a history of transaminase elevations, more frequent monitoring of liver function tests should be considered. Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve. Interrupt dosing in patients with ALT or AST of greater than 5 times the upper limit of normal (ULN). Following resolution of transaminase elevations, consider the benefits and risks of resuming KALYDECO dosing. Hypersensitivity reactions: Anaphylaxis has been reported with KALYDECO in the postmarketing setting. Initiate appropriate therapy in the event of a hypersensitivity reaction.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Transaminase Elevations Hypersensitivity Reactions, Including Anaphylaxis Intracranial Hypertension Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors Cataracts The most common adverse drug reactions to KALYDECO (≥8% of patients with CF who have a G551D mutation in the CFTR gene) were headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, and dizziness.

Potential for other drugs to affect ivacaftor CYP3A inhibitors: Reduce KALYDECO dosage in patients aged 6 months and older when co-administered with strong CYP3A inhibitors (e.g., ketoconazole) or moderate CYP3A inhibitors (e.g., fluconazole). KALYDECO is not recommended in patients aged 1 month to less than 6 months when co-administered with strong or moderate CYP3A inhibitors. Avoid food or drink containing grapefruit.

Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30°C (59°F-86°F).