Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Vertex Pharmaceuticals (Ireland) Limited, Unit 49, Block F2, Northwood Court, Santry, Dublin 9, D09 T665, Ireland
Kalydeco granules are indicated for the treatment of infants aged at least 4 months, toddlers and children weighing 5 kg to less than 25 kg with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4.4 and 5.1).
Kalydeco should only be prescribed by physicians with experience in the treatment of cystic fibrosis. If the patient’s genotype is unknown, an accurate and validated genotyping method should be performed before starting treatment to confirm the presence of an indicated mutation in at least one allele of the CFTR gene (see section 4.1). The phase of the poly-T variant identified with the R117H mutation should be determined in accordance with local clinical recommendation.
Infants aged at least 4 months, toddlers, children, adolescents and adults should be dosed according to Table 1.
Table 1. Dosing recommendations for patients aged 4 months and older:
| Age | Weight | Dose | Total daily dose |
|---|---|---|---|
| 4 months to less than 6 months | ≥5 kg | 25 mg granules taken orally every 12 hours with fat-containing food | 50 mg |
| 6 months and older | ≥5 kg to <7 kg | 25 mg granules taken orally every 12 hours with fat-containing food | 50 mg |
| ≥7 kg to <14 kg | 50 mg granules taken orally every 12 hours with fat-containing food | 100 mg | |
| ≥14 kg to <25 kg | 75 mg granules taken orally every 12 hours with fat-containing food | 150 mg | |
| ≥25 kg | See Kalydeco tablets SmPC for further details. | ||
If 6 hours or less have passed since the missed morning or evening dose, the patient should be advised to take it as soon as possible and then take the next dose at the regularly scheduled time. If more than 6 hours have passed since the time the dose is usually taken, the patient should be advised to wait until the next scheduled dose.
When co-administered with strong inhibitors of CYP3A in patients aged 6 months and older, the ivacaftor dose should be reduced to one sachet (ivacaftor 25 mg for patients 5 kg to <7 kg; ivacaftor 50 mg for patients 7 kg to <14 kg; ivacaftor 75 mg for patients 14 kg to <25 kg) twice a week (see sections 4.4 and 4.5).
When co-administered with moderate inhibitors of CYP3A in patients aged 6 months and older, the ivacaftor dose is as above recommended but administered once daily (see sections 4.4 and 4.5).
Due to the variability in maturation of the cytochrome (CYP) enzymes involved in ivacaftor metabolism, treatment with ivacaftor is not recommended when co-administered with moderate or strong inhibitors of CYP3A in patients aged 4 months to less than 6 months, unless the benefits outweigh the risks. In such cases, the recommended dose is one packet of 25 mg granules twice weekly or less frequently (see sections 4.4 and 4.5). Dosing intervals should be modified according to clinical response and tolerability (see sections 4.4 and 5.2).
No dose adjustment is necessary for patients with mild to moderate renal impairment. Caution is recommended in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min) or end-stage renal disease (see sections 4.4 and 5.2).
No dose adjustment is necessary for patients aged 6 months and older with mild hepatic impairment (Child-Pugh Class A). For patients aged 6 months and older with moderate hepatic impairment (Child-Pugh Class B), a reduced dose of one sachet (ivacaftor 25 mg for patients 5 kg to <7 kg; ivacaftor 50 mg for patients 7 kg to <14 kg; ivacaftor 75 mg for patients 14 kg to <25 kg) once daily is recommended. There is no experience of the use of ivacaftor in patients aged 6 months and older with severe hepatic impairment (Child-Pugh Class C); therefore, its use is not recommended unless the benefits outweigh the risks. In such cases, the starting dose should be as above recommended, administered every other day. Dosing intervals should be modified according to clinical response and tolerability (see sections 4.4 and 5.2).
Due to variability in maturation of cytochrome (CYP) enzymes involved in ivacaftor metabolism, treatment with ivacaftor is not recommended in patients aged 4 months to less than 6 months with hepatic impairment, unless the benefits outweigh the risks. In such cases, the recommended dose is one sachet (ivacaftor 25 mg) once daily or less frequently. Dosing intervals should be modified according to clinical response and tolerability (see sections 4.4 and 5.2).
The safety and efficacy of ivacaftor in children aged less than 4 months have not been established. No data are available. Limited data are available in patients less than 6 years of age with an R117H mutation in the CFTR gene. Available data in patients aged 6 years and older are described in sections 4.8, 5.1 and 5.2.
For oral use.
Each sachet is for single use only.
Each sachet of granules should be mixed with 5 mL of age-appropriate soft food or liquid and completely and immediately consumed. Food or liquid should be at room temperature or below. If not immediately consumed, the mixture has been shown to be stable for one hour and therefore should be ingested during this period. A fat-containing meal or snack should be consumed just before or just after dosing.
Food or drink containing grapefruit should be avoided during treatment (see section 4.5).
No specific antidote is available for overdose with ivacaftor. Treatment of overdose consists of general supportive measures including monitoring of vital signs, liver function tests and observation of the clinical status of the patient.
4 years.
Once mixed, the mixture has been shown to be stable for one hour.
This medicinal product does not require any special storage conditions.
Biaxially Oriented Polyethylene Terephthalate/Polyethylene/Foil/Polyethylene (BOPET/PE/Foil/PE) sachet.
Kalydeco 25 mg granules in sachet, Kalydeco 50 mg granules in sachet, and Kalydeco 75 mg granules in sachet: Pack size of 56 sachets (contains 4 individual wallets with 14 sachets per wallet).
Kalydeco 75 mg granules in sachet: Pack size of 28 sachets (contains 4 individual wallets with 7 sachets per wallet).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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