Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Vertex Pharmaceuticals (Ireland) Limited, Unit 49, Block F2, Northwood Court, Santry, Dublin 9, D09 T665, Ireland
Kaftrio tablets are indicated in a combination regimen with ivacaftor for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (see section 5.1).
Kaftrio should only be prescribed by healthcare professionals with experience in the treatment of CF. If the patient’s genotype is unknown, an accurate and validated genotyping method should be performed to confirm the presence of at least one F508del mutation using a genotyping assay (see section 5.1).
Adults and paediatric patients aged 6 years and older should be dosed according to Table 1.
Table 1. Dosing recommendations for patients aged 6 years and older:
| Age | Weight | Morning dose | Evening dose |
|---|---|---|---|
| 6 to <12 years | <30 kg | Two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg tablets | One ivacaftor 75 mg tablet |
| 6 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 take the missed dose as soon as possible and continue on the original schedule.
If more than 6 hours have passed since:
Morning and evening doses should not be taken at the same time.
When co-administered with moderate CYP3A inhibitors (e.g., fluconazole, erythromycin, verapamil) or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin), the dose should be reduced as in Table 2 (see sections 4.4 and 4.5).
Table 2. Dosing schedule for concomitant use with moderate and strong CYP3A inhibitors:
| Age | Weight | Moderate CYP3A Inhibitors | Strong CYP3A Inhibitors |
|---|---|---|---|
| 6 to <12 years | <30 kg | Alternate each day: • Two ivacaftor 37.5 mg/tezacaftor 25 mg/elexacaftor 50 mg (IVA/TEZ/ELX) tablets on the first day • One ivacaftor 75 mg (IVA) tablet on the next day No evening IVA tablet dose. | Two IVA 37.5 mg/TEZ 25 mg/ELX 50 mg tablets twice a week, approximately 3 to 4 days apart. No evening IVA tablet dose. |
| 6 to <12 years | ≥30 kg | Alternate each day: • Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg (IVA/TEZ/ELX) tablets on the first day • One ivacaftor 150 mg (IVA) tablet on the next day. No evening IVA tablet dose. | Two IVA 75 mg/TEZ 50 mg/ELX 100 mg tablets twice a week, approximately 3 to 4 days apart. No evening IVA tablet dose. |
| 12 years and older | - | Alternate each day: • Two ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg (IVA/TEZ/ELX) tablets on the first day • One ivacaftor 150 mg (IVA) tablet on the next day No evening IVA tablet dose. | Two IVA 75 mg/TEZ 50 mg/ELX 100 mg tablets twice a week, approximately 3 to 4 days apart. No evening IVA tablet dose. |
No dose adjustment is recommended for the elderly patient population (see sections 4.4 and 5.2).
Treatment of patients with moderate hepatic impairment (Child-Pugh Class B) is not recommended. For patients with moderate hepatic impairment, the use of Kaftrio should only be considered when there is a clear medical need, and the benefits are expected to outweigh the risks. If used, it should be used with caution at a reduced dose (see Table 3).
Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C), but the exposure is expected to be higher than in patients with moderate hepatic impairment. Patients with severe hepatic impairment should not be treated with Kaftrio.
No dose adjustment is recommended for patients with mild (Child-Pugh Class A) hepatic impairment (see Table 3) (see sections 4.4, 4.8, and 5.2).
Table 3. Recommendation for use in patients aged 6 years and older with hepatic impairment:
| Age | Weight | Mild (Child-Pugh Class A) | Moderate (Child-Pugh Class B) | Severe (Child-Pugh Class C) |
|---|---|---|---|---|
| 6 to <12 years | <30 kg | No dose adjustment | Use not recommended. Treatment of patients with moderate hepatic impairment should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used, Kaftrio should be used with caution at a reduced dose, as follows: • Day 1: two IVA 37.5 mg/TEZ 25 mg/ELX 50 mg tablets in the morning • Day 2: one IVA 37.5 mg/TEZ 25 mg/ELX 50 mg tablet in the morning Continue alternating Day 1 and Day 2 dosing thereafter. The evening dose of the IVA tablet should not be taken. | Should not be used |
| 6 to <12 years | ≥30 kg | No dose adjustment | Use not recommended. Treatment of patients with moderate hepatic impairment should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used, Kaftrio should be used with caution at a reduced dose, as follows: • Day 1: two IVA 75 mg/TEZ 50 mg/ELX 100 mg tablets in the morning • Day 2: one IVA 75 mg/TEZ 50 mg/ELX 100 mg tablet in the morning Continue alternating Day 1 and Day 2 dosing thereafter. The evening dose of the IVA tablet should not be taken | Should not be used |
| 12 years and older | - | No dose adjustment | Use not recommended. Treatment of patients with moderate hepatic impairment should only be considered when there is a clear medical need and the benefits are expected to outweigh the risks. If used, Kaftrio should be used with caution at a reduced dose, as follows: • Day 1: two IVA 75 mg/TEZ 50 mg/ELX 100 mg tablets in the morning • Day 2: one IVA 75 mg/TEZ 50 mg/ELX 100 mg tablet in the morning Continue alternating Day 1 and Day 2 dosing thereafter. The evening dose of the IVA tablet should not be taken. | Should not be used |
No dose adjustment is recommended for patients with mild and moderate renal impairment. There is no experience in patients with severe renal impairment or end-stage renal disease (see sections 4.4 and 5.2).
The safety and efficacy of Kaftrio in combination with ivacaftor in children aged less than 2 years have not yet been established. No data are available.
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; chewing or crushing the tablet is not recommended.
Kaftrio should be taken with fat-containing food. Examples of meals or snacks that contain fat are those prepared with butter or oils or those containing eggs, cheeses, nuts, whole milk, or meats (see section 5.2).
Food or drink containing grapefruit should be avoided during treatment with Kaftrio (see section 4.5).
No specific antidote is available for overdose with IVA/TEZ/ELX. Treatment of overdose consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
Kaftrio 37.5 mg/25 mg/50 mg film-coated tablets: 3 years.
Kaftrio 75 mg/50 mg/100 mg film-coated tablets: 4 years.
This medicinal product does not require any special storage conditions.
Blister consisting of PCTFE (polychlorotrifluoroethylene) film laminated to PVC (polyvinyl chloride) film and sealed with blister foil lidding.
Pack size of 56 tablets (4 blister cards, each with 14 tablets).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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