- The safety and efficacy of KALYDECO for patients <4 months have not been established. The use of KALYDECO (oral granules) in children <4 months is not recommended1
|KALYDECO DOSAGE ADJUSTMENTS1
|DOSAGE ADJUSTMENTS FOR PATIENTS AGE 4 TO <6 MONTHS
||DOSE AND ADMINISTRATION FREQUENCY
||Use is not recommended
|Co-administration with strong or moderate CYP3A inhibitorsa,b
||Concomitant use not recommended
|DOSAGE ADJUSTMENTS FOR PATIENTS AGE ≥6 MONTHS
|Severe impairment (Child-Pugh Class C)c
||One dose once daily, or less frequentlyd
|Moderate impairment (Child-Pugh Class B)
||One dose once dailyd
|Mild impairment (Child-Pugh Class A)
||No dose adjustment required
|Co-administration with strong CYP3A inhibitorsa
||One dose twice a weekd
|Co-administration with moderate CYP3A inhibitorsb
||One dose once dailyd
Missed dose of oral granules or tablets1
- If ≤6 hours have passed: Advise patient to take the dose with fat-containing food
- If >6 hours have passed: Advise patient to skip that dose, and resume the normal schedule for the following dose. A double dose should not be taken to make up for the forgotten dose
Use in Specific Populations
There are limited and incomplete human data from clinical trials and post marketing reports on use of KALYDECO in pregnant women. Placental transfer of ivacaftor was observed in pregnant rats and rabbits. In animal reproduction studies, oral administration of ivacaftor to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse effects on fetal development at doses that produced maternal exposures up to approximately 5 (rats) and 11 (rabbits) times the exposure at the maximum recommended human dose (MRHD).
There is no information regarding the presence of ivacaftor in human milk, the effects on the breastfed infant, or the effects on milk production. Ivacaftor is excreted into the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for KALYDECO, and any potential effects on the breastfed child from KALYDECO or from the underlying maternal condition.
For more information on pregnancy and lactation, please see full Prescribing Information.
KALYDECO is indicated for the treatment of CF in pediatric patients 4 months to 17 years of age who have 1 mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or in vitro assay data.
Placebo-controlled clinical trials included the following CF patients:
- 6 to 17 years of age with a G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H mutation in the CFTR gene
- 12 to 17 years of age who are heterozygous for the F508del mutation and a second mutation predicted to be responsive to ivacaftor
The effectiveness of KALYDECO in children aged 2 to less than 6 years was extrapolated from efficacy in patients 6 years of age and older with support from population pharmacokinetic analyses showing similar drug exposure levels in adults and children 2 to less than 6 years of age. The safety of KALYDECO in children 2 years to less than 6 years of age was derived from a 24-week, open-label, clinical trial in 34 patients ages 2 to less than 6 years (mean age 3 years) administered either 50 mg or 75 mg of ivacaftor oral granules twice daily (Trial 6). The type and frequency of adverse reactions in this trial were similar to those in patients 6 years and older. Transaminase elevations were more common in patients who had abnormal transaminases at baseline.
The effectiveness of KALYDECO in patients aged 4 months to less than 24 months was extrapolated from patients 6 years of age and older with support from population pharmacokinetic analyses showing similar drug exposure levels in adults and children 4 months to less than 24 months of age. Safety of KALYDECO in this population was derived from a cohort of 6 patients aged 4 months to less than 6 months (mean age 4.5 months at baseline), a cohort of 11 patients aged 6 months to less than 12 months (mean age 9.0 months at baseline), and a cohort of 19 patients aged 12 months to less than 24 months (mean age 15.2 months at baseline) in a 24-week, open-label clinical study, administered either 25 mg, 50 mg or 75 mg of ivacaftor granules twice daily (Trial 8). The safety profile of patients in this trial is similar to that observed in patients 2 years and older.
The safety and effectiveness of KALYDECO in patients with CF younger than 4 months have not been established. The use of KALYDECO in children under the age of 4 months is not recommended.
CF is largely a disease of children and young adults. Clinical trials of KALYDECO did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.
No dose adjustment is necessary for patients aged 6 months or older with mild hepatic impairment (Child-Pugh Class A).
A reduced dose is recommended in patients aged 6 months or older patients with moderate (Child-Pugh Class B).
Studies have not been conducted in patients with severe hepatic impairment (Child‑Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment. Therefore, use with caution at a reduced dose, in patients aged 6 months or older with severe hepatic impairment after weighing the risks and benefits of treatment.
Due to variability in maturation of cytochrome (CYP) enzymes involved in ivacaftor metabolism, treatment with KALYDECO is not recommended in patients aged 4 months to less than 6 months with hepatic impairment, unless the benefits outweigh the risks.
Please see dose adjustments for moderate and severe hepatic impairment above
KALYDECO has not been studied in patients with mild, moderate, or severe renal impairment or in patients with end‑stage renal disease. No dose adjustment is necessary for patients with mild to moderate renal impairment; however, caution is recommended while using KALYDECO in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min) or end‑stage renal disease.
How to administer KALYDECO oral granules: 3 steps1