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 tablets are indicated:
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 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 recommendations.
Adults, adolescents, and children aged 6 years and older should be dosed according to Table 1.
Table 1. Dosing recommendations:
| Morning | Evening | |
|---|---|---|
| Ivacaftor as monotherapy | ||
| 6 years and older, ≥25 kg | One ivacaftor 150 mg tablet | One ivacaftor 150 mg tablet |
| Ivacaftor in combination with tezacaftor/ivacaftor | ||
| 6 years to <12 years, <30 kg | One tezacaftor 50 mg/ivacaftor 75 mg tablet | One ivacaftor 75 mg tablet |
| 6 years to <12 years, ≥30 kg | One tezacaftor 100 mg/ivacaftor 150 mg tablet | One ivacaftor 150 mg tablet |
| 12 years and older | One tezacaftor 100 mg/ivacaftor 150 mg tablet | One ivacaftor 150 mg tablet |
| Ivacaftor in combination with ivacaftor/tezacaftor/elexacaftor | ||
| 6 years to <12 years, <30 kg | Two ivacaftor 37.5 mg/tezacaftor 25 mg/ elexacaftor 50 mg tablets | One ivacaftor 75 mg tablet |
| 6 years to <12 years, ≥30 kg | Two ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg tablets | One ivacaftor 150 mg tablet |
| 12 years and older | Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg tablets | One ivacaftor 150 mg tablet |
The morning and evening dose should be taken approximately 12 hours apart with fat-containing food (see Method of administration).
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.
Patients receiving Kalydeco in a combination regimen should be advised not to take more than one dose of either medicinal product at the same time.
When co-administered with moderate or strong inhibitors of CYP3A, either as monotherapy or in a combination regimen with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor, the dose should be reduced (see Table 2 for the recommended dose). Dosing intervals should be modified according to clinical response and tolerability (see sections 4.4 and 4.5).
Table 2. Dosing recommendations for concomitant use with moderate or strong CYP3A inhibitors:
| Moderate CYP3A inhibitors | Strong CYP3A inhibitors | |
|---|---|---|
| Ivacaftor as monotherapy | ||
| 6 years and older, ≥25 kg | One morning tablet of ivacaftor 150 mg once daily. No evening dose. | One morning tablet of ivacaftor 150 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| Ivacaftor in a combination regimen with tezacaftor/ivacaftor | ||
| 6 years to <12 years, <30 kg | Alternate each morning: - one tablet of tezacaftor 50 mg/ivacaftor 75 mg on the first day - one tablet of ivacaftor 75 mg on the next day. Continue alternating tablets each day. No evening dose. | One morning tablet of tezacaftor 50 mg/ivacaftor 75 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| 6 years to <12 years, ≥30 kg | Alternate each morning: - one tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily on the first day - one tablet of ivacaftor 150 mg on the next day Continue alternating each day. No evening dose. | One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| 12 years and older | Alternate each morning: - one tablet of tezacaftor 100 mg/ivacaftor 150 mg on the first day - one tablet of ivacaftor 150 mg on the next day Continue alternating tablets each day. No evening dose. | One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| Ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor | ||
| 6 years to <12 years, <30 kg | Alternate each morning: - two tablets of ivacaftor 37.5 mg/tezacaftor 25 mg/ elexacaftor 50 mg on the first day - one tablet of ivacaftor 75 mg on the next day Continue alternating tablets each day. No evening dose. | Two morning tablets of ivacaftor 37.5 mg/tezacaftor 25 mg/ elexacaftor 50 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| 6 years to <12 years, ≥30 kg | Alternate each morning: - two tablets of ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg on the first day - one tablet of ivacaftor 150 mg on the next day Continue alternating tablets each day. No evening dose. | Two morning tablets of ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
| 12 years and older | Alternate each morning: - two tablets of ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg on the first day - one tablet of ivacaftor 150 mg on the next day Continue alternating tablets each day. No evening dose. | Two morning tablets of ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg twice a week, approximately 3 to 4 days apart. No evening dose. |
Very limited data are available for elderly patients treated with ivacaftor (administered as monotherapy or in a combination regimen). No dose adjustment specific to this patient population is required (see section 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 ivacaftor as monotherapy or in a combination regimen in patients with mild hepatic impairment (Child-Pugh Class A).
For patients with moderate hepatic impairment (Child-Pugh Class B) the dose of ivacaftor as monotherapy should be reduced to 150 mg once daily.
For patients with severe hepatic impairment (Child-Pugh Class C), the dose of ivacaftor as monotherapy should be reduced to 150 mg every other day or less frequently.
For use as an evening dose in a combination regimen with tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor see Table 3 for dosing regimen recommendations.
Table 3. Dosing recommendations for patients with moderate or severe hepatic impairment:
| Moderate (Child-Pugh Class B) | Severe (Child-Pugh Class C) | |
|---|---|---|
| Ivacaftor as monotherapy | ||
| 6 years and older, ≥25 kg | One morning tablet of ivacaftor 150 mg once daily. No evening dose. | Use is not recommended unless the benefits are expected to outweigh the risks. If used: one morning tablet of ivacaftor 150 mg every other day or less frequently. Dosing interval should be modified according to clinical response and tolerability. No evening dose. |
| Ivacaftor in a combination regimen with tezacaftor/ivacaftor | ||
| 6 years to <12 years, <30 kg | One morning tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily. No evening dose. | Use is not recommended unless the benefits are expected to outweigh the risks. If used: one morning tablet of tezacaftor 50 mg/ivacaftor 75 mg once daily or less frequently. Dosing interval should be modified according to clinical response and tolerability. No evening dose. |
| 6 years to <12 years, ≥30 kg | One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily. No evening dose. | Use is not recommended unless the benefits are expected to outweigh the risks. If used: one morning tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily or less frequently. Dosing interval should be modified according to clinical response and tolerability. No evening dose. |
| 12 years and older | One morning tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily. No evening dose. | Use is not recommended unless the benefits are expected to outweigh the risks. If used: one morning tablet of tezacaftor 100 mg/ivacaftor 150 mg once daily or less frequently. Dosing interval should be modified according to clinical response and tolerability. No evening dose. |
| Ivacaftor in a combination regimen with ivacaftor/tezacaftor/elexacaftor | ||
| 6 years to <12 years, <30 kg | Use not recommended. Use should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used: alternate each day between two ivacaftor 37.5 mg/tezacaftor 25 mg/ elexacaftor 50 mg tablets and one ivacaftor 37.5 mg/tezacaftor 25 mg/ elexacaftor 50 mg tablet. No evening dose. | Should not be used. |
| 6 years to <12 years, ≥30 kg | Use not recommended. Use should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used: alternate each day between two ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg tablets and one ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg tablet. No evening dose. | Should not be used. |
| 12 years and older | Use not recommended. Use should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks.* If used: alternate each day between two ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg tablets and one ivacaftor 75 mg/tezacaftor 50 mg/ elexacaftor 100 mg tablet. No evening dose. | Should not be used.* |
* See sections 4.4 and 4.8
The safety and efficacy of ivacaftor have not been established in children less than 4 months of age as monotherapy, neither in combination with tezacaftor/ivacaftor in children less than 6 years of age or in combination with ivacaftor/tezacaftor/elexacaftor in children less than 6 years of age. 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.
Patients should be instructed to swallow the tablets whole. The tablets should not be chewed, crushed, or broken before swallowing because there are no clinical data currently available to support other methods of administration.
Ivacaftor tablets should be taken with fat-containing food.
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.
This medicinal product does not require any special storage conditions.
Thermoform (PolyChloroTriFluoroEthylene [PCTFE]/foil) blister or a High-Density PolyEthylene (HDPE) bottle with a polypropylene child-resistant closure, foil-lined induction seal and molecular sieve desiccant.
Kalydeco 75 mg film-coated tablets:
The following pack sizes are available:
Kalydeco 150 mg film-coated tablets:
The following pack sizes are available:
Not all pack sizes may be marketed
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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