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 granules are indicated in a combination regimen with ivacaftor for the treatment of cystic fibrosis (CF) in paediatric patients aged 2 to less than 6 years 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).
Paediatric patients aged 2 to less than 6 years should be dosed according to Table 1.
Table 1. Dosing recommendations for patients aged 2 to less than 6 years:
| Age | Weight | Morning dose | Evening dose |
|---|---|---|---|
| 2 to less than 6 years | 10 kg to <14 kg | One sachet of ivacaftor 60 mg/tezacaftor 40 mg/elexacaftor 80 mg granules | One sachet of ivacaftor 59.5 mg granules |
| ≥14 kg | One sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg granules | One sachet of ivacaftor 75 mg granules |
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:
OR
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 |
|---|---|---|---|
| 2 years to less than 6 years | 10 kg to <14 kg | Alternate each day: • One sachet of ivacaftor 60 mg/tezacaftor 40 mg/elexacaftor 80 mg(IVA/TEZ/ELX) granules on the first day • One sachet of ivacaftor 59.5 mg (IVA) granules on the next day No evening sachet of IVA granules. | One sachet of IVA 60 mg/TEZ 40 mg/ELX 80 mg granules twice a week, approximately 3 to 4 days apart. No evening sachet of IVA granules. |
| 2 years to less than 6 years | ≥14 kg | Alternate each day: • One sachet of ivacaftor 75 mg/tezacaftor 50 mg/elexacaftor 100 mg (IVA/TEZ/ELX) granules on the first day • One sachet of ivacaftor 75 mg (IVA) granules on the next day No evening sachet of IVA granules. | One sachet of IVA 75 mg/TEZ 50 mg/ELX 100 mg granules twice a week, approximately 3 to 4 days apart. No evening sachet of IVA granules. |
Treatment of patients aged 2 to less than 6 years with moderate hepatic impairment (Child-Pugh Class B) is not recommended. For patients aged 2 to less than 6 years 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 2 to less than 6 years with hepatic impairment:
| Age | Weight | Mild (Child-Pugh Class A) | Moderate (Child-Pugh Class B) | Severe (Child-Pugh Class C) |
|---|---|---|---|---|
| 2 years to less than 6 years | 10 kg to <14 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: • Days 1-3: one sachet of IVA 60 mg/TEZ 40 mg/ELX 80 mg granules each day • Day 4: no dose • Days 5-6: one sachet of IVA 60 mg/TEZ 40 mg/ELX 80 mg granules each day • Day 7: no dose Repeat above dosing schedule each week. The evening dose of the IVA granules should not be taken. | Should not be used. |
| 2 years to less than 6 years | ≥14 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: • Days 1-3: one sachet of IVA 75 mg/TEZ 50 mg/ELX 100 mg granules each day • Day 4: no dose • Days 5-6: one sachet of IVA75 mg/TEZ 50 mg/ELX 100 mg granules each day • Day 7: no dose Repeat above dosing schedule each week. The evening dose of the IVA granules 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. The entire contents of each sachet of granules should be mixed with one teaspoon (5 mL) of age-appropriate soft food or liquid and the mixture completely consumed. Food or liquid should be at room temperature or below. Each sachet is for single use only. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period. Some examples of soft food or liquids include pureed fruits or vegetables, yogurt, water, milk, or juice. A fatcontaining meal or snack should be consumed just before or after dosing.
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.
2 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) printed foil laminate sachet.
Pack size of 28 sachets (4 weekly wallets, each with 7 sachets).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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