Dosing and Administration for KALYDECO® (ivacaftor)1

Dosing Information
 

Dosage Forms1
oral

Oral Granules

Not actual size.

Recommended Dose

For patients age 6 months to <6 years, the recommended dose is weight-based

  • 5 kg to <7 kg: One 25-mg packet every 12 hours
  • 7 kg to <14 kg: One 50-mg packet every 12 hours
  • >14 kg: One 75-mg packet every 12 hours
Dosage Forms1
kalydeco

 

Tablets

Not actual size.

Recommended Dose

For patients age 6 years and older

  • One 150-mg tablet every 12 hours
KALYDECO oral granules and tablets should be taken with fat-containing food. Food containing grapefruit or Seville oranges should also be avoided.
dosing containers

Patients should continue taking all of their prescribed CF therapies with KALYDECO1

  • A safe and efficacious dose of KALYDECO for pediatric patients less than 6 months of age has not been established. The use of KALYDECO (oral granules) in children under the age of 6 months is not recommended1

Dosage Adjustments1

KALYDECO DOSAGE ADJUSTMENTS1
DOSE AND ADMINISTRATION FREQUENCY
HEPATIC IMPAIRMENT
Severe impairment (Child‑Pugh Class C)b One dose once daily, or lessc
Moderate impairment (Child‑Pugh Class B) One dose once dailyc
Mild impairment (Child‑Pugh Class A) No dose adjustment required
CYP3A
Co-administration with strong CYP3A inhibitorsd One dose twice a weekc
Co-administration with moderate CYP3A inhibitorse One dose once dailyc

bUse with caution after weighing the risks and benefits of treatment.1 

cOne dose=one tablet or one packet of oral granules.1

dUse of KALYDECO with a strong CYP3A inhibitor significantly increased ivacaftor exposure. Examples include ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin.1

eUse of KALYDECO with a moderate CYP3A inhibitor increased ivacaftor exposure. Examples include fluconazole and erythromycin. Food containing grapefruit or Seville oranges should also be avoided.1

Use of KALYDECO with strong CYP3A inducers significantly decreases the exposure of ivacaftor. Co-administration of KALYDECO with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John’s wort is not recommended.


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

Pregnancy1

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).

Lactation1

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.

Pediatric use1

KALYDECO is indicated for the treatment of CF in pediatric patients 6 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 efficacy 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 efficacy of KALYDECO in patients aged 2 to less than 6 years 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 2 to less than 6 years of age. Safety of KALYDECO in this population 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 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 efficacy of KALYDECO in patients aged 6 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 6 months to less than 24 months of age. Safety of KALYDECO in this population was derived from 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 efficacy of KALYDECO in patients with CF younger than 6 months have not been established. The use of KALYDECO in children under the age of 6 months is not recommended.

Geriatric use1

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.

Hepatic impairment1

No dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh Class A). Reductions in dose are recommended for patients with moderate (Child-Pugh Class B) and severe hepatic impairment (Child-Pugh Class C).

Please see dose adjustments for moderate and severe hepatic impairment above

Renal impairment1

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

1. PREPARATION

  • Caregiver should hold the packet with the perforation on top, shake the packet gently to settle the granules, and tear or cut the packet open along the perforation
  • Caregiver should mix all granules into 1 teaspoon (5 mL) of age-appropriate soft food or liquid
  • Food or liquid should be at or below room temperature

preperation


EXAMPLES OF SOFT FOODS OR LIQUIDS INCLUDE:

  • Puréed fruits or vegetables, yogurt or applesauce
  • Water, milk, or juice
  • Prepared breastmilk or infant formula

2. ADMINISTRATION1

  • After mixing, caregiver should give within 1 hour
  • Caregiver should make sure the child finishes the dose completely

3. GIVE WITH FAT-CONTAINING FOOD1

  • Food that contains fat must be taken just before or after the oral granules dose

EXAMPLES OF FAT-CONTAINING FOODS INCLUDE:

  • Cheese pizza
  • Peanut butter    
  • Butter
  • Eggs
  • Whole-milk dairy products (e.g., whole milk, cheese, and yogurt)

soft foods

Food containing grapefruit or Seville oranges may increase exposure of ivacaftor, and should be avoided during treatment with KALYDECO1

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