Posology : מינונים

4.2 Posology and method of administration
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 a mutation in the CFTR gene (see section 4.1).


KALY_50_75_150-SPC-0424-V1                          Page 1 of 22
Posology
Adults, adolescents and children aged 2 years and older should be dosed according to Table 1.
Table 1: Dosing recommendations

Age/Weight           Dose                                 Total daily dose 
2 to 5 years         50 mg granules (one sachet) taken    100 mg (two old,                 orally every 12 hours with fat       sachets) containing food
<14 kg

2 to 5 years         75 mg granules (one sachet) taken    150 mg (two old,                 orally every 12 hours with fat-      sachets) containing food
≥14 kg to
<25 kg
6 years and          One 150 mg tablet taken orally       300 mg (two older,               every 12 hours with                  tablets) fat-containing food
≥25 kg


The morning and evening dose should be taken approximately 12 hours apart with fat-containing food (see Method of administration).

Missed dose
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.

Concomitant use of CYP3A inhibitors
When co-administered with moderate or strong inhibitors of CYP3A 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 mild, moderate or strong CYP3A inhibitors
Age/           Mild CYP3A inhibitors         Moderate CYP3A inhibitors         Strong CYP3A inhibitors Weight

2 to 5       No dose adjustment             One sachet of ivacaftor 50 mg   One sachet of ivacaftor 50 mg years old,                                  granules once daily             granules twice a week, approximately 3 to 4 days apart
<14 kg

2 to 5       No dose adjustment             One sachet of ivacaftor 75 mg   One sachet of ivacaftor 75 mg years old,                                  granules once daily             granules twice a week, approximately 3 to 4 days apart
≥14 kg to
<25 kg


KALY_50_75_150-SPC-0424-V1                      Page 2 of 22
Age/           Mild CYP3A inhibitors        Moderate CYP3A inhibitors              Strong CYP3A inhibitors Weight

6 years      No dose adjustment            One morning tablet of ivacaftor      One morning tablet of ivacaftor and older,                                 150 mg once daily                    150 mg twice a week, approximately 3 to 4 days apart
≥25 kg



Special populations
Elderly
Very limited data are available for elderly patients treated with ivacaftor. No dose adjustment specific to this patient population is required (see section 5.2).

Renal impairment
No dose adjustment is necessary for patients with mild to moderate renal impairment. 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 (see sections 4.4 and 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild hepatic impairment (Child-Pugh Class A). For patients with moderate hepatic impairment (Child-Pugh Class B), a reduced dose of one tablet or one sachet once daily is recommended. There is no experience of the use of Kalydeco in patients with severe hepatic impairment; therefore, its use is not recommended unless the benefits outweigh the risks. In such cases, the starting dose should be one tablet or one sachet every other day or less frequently (see Table 3).
Dosing intervals should be modified according to clinical response and tolerability (see sections 4.4 and 5.2).

Table 3: Dosing recommendations for patients with hepatic impairment
Age/          Mild (Child-Pugh             Moderate (Child-Pugh              Severe (Child-Pugh Weight        Class A)                     Class B)                          Class C) 
2 to 5 years No dose adjustment            One sachet of ivacaftor           Use is not recommended old,                                       50 mg once daily                  unless the benefits are expected to outweigh the
<14 kg                                                                       risks.

If used: one sachet of ivacaftor
50 mg every other day

Dosing interval should be modified according to clinical response and tolerability.


2 to 5 years No dose adjustment            One sachet of ivacaftor           Use is not recommended old,                                       75 mg once daily                  unless the benefits are expected to outweigh the
≥14 kg to                                                                    risks.
<25 kg
If used: one sachet of ivacaftor


KALY_50_75_150-SPC-0424-V1                     Page 3 of 22
75 mg every other day
Dosing interval should be modified according to clinical response and tolerability.

6 years and    No dose adjustment           One morning tablet of         Use is not recommended older,                                      ivacaftor 150 mg once daily   unless the benefits are ≥25 kg                                                                    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.

Paediatric population
Kalydeco is not indicated for children less than 2 years old.

Method of administration
For oral use.
Kalydeco should be taken with fat-containing food.

Food or drink containing grapefruit should be avoided during treatment (see section 4.5).

Film-coated tablets
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.

Granule in sachet
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.