Posology : מינונים

4.2    Posology and method of administration

Orkambi should only be prescribed by physicians with experience in the treatment of CF.
Posology

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Table 1: Dosing recommendations in patients aged 6 years and older

Age                                Dose                              Total daily dose 6 to 11 years               2 tablets of lumacaftor                     lumacaftor 400 mg/ 100 mg/ivacaftor 125 mg every               ivacaftor 500 mg
12 hours
12 years and older          2 tablets of lumacaftor                     lumacaftor 800 mg/ 200 mg/ivacaftor 125 mg every               ivacaftor 500 mg
12 hours

Patients may start treatment on any day of the week.
This medicinal product should be taken with fat-containing food. A fat-containing meal or snack should be consumed just before or just after dosing (see section 5.2).

Missed dose
If less than 6 hours have passed since the missed dose, the scheduled dose should be taken with fat- containing food. If more than 6 hours have passed, the patient should be instructed to wait until the next scheduled dose. A double dose should not be taken to make up for the forgotten dose.

Concomitant use of CYP3A inhibitors
No dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking Orkambi. However, when initiating treatment in patients taking strong CYP3A inhibitors, reduce the dose to one tablet daily (lumacaftor 100 mg/ivacaftor 125 mg for patients aged 6 to 11 years; lumacaftor 200 mg/ivacaftor 125 mg for patients aged 12 years and older) for the first week of treatment to allow for the steady state induction effect of lumacaftor. Following this period, the recommended daily dose should be continued.

If treatment is interrupted for more than one week and then re-initiated while taking strong CYP3A inhibitors, reduce the dose to one tablet daily (lumacaftor 100 mg/ivacaftor 125 mg for patients aged 6 to 11 years; lumacaftor 200 mg/ivacaftor 125 mg for patients aged 12 years and older) for the first week of treatment re-initiation. Following this period, the recommended daily dose should be continued (see section 4.5).

Special populations

Renal impairment
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).

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 dose reduction is recommended.

There is no experience of the use of the medicinal product in patients with severe hepatic impairment (Child-Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment. Therefore, after weighing the risks and benefits of treatment, Orkambi should be used with caution in patients with severe hepatic impairment, at a reduced dose (see sections 4.4, 4.8 and 5.2).

For dose adjustments for patients with hepatic impairment see Table 2.
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Table 2: Dose adjustment recommendations for patients with hepatic impairment Hepatic impairment        Dose adjustment                         Total daily dose For patients aged 6 to 11 years
400 mg lumacaftor + 500 mg
Mild hepatic                                                      ivacaftor impairment                No dose adjustment
(Child-Pugh Class A)                                          For patients aged 12 years and older 800 mg lumacaftor +
500 mg ivacaftor
For patients aged 6 to11 years      For patients aged 6 to 11 years
2 tablets of 100 mg/125 mg in the   300 mg lumacaftor + morning + 1 tablet of 100 mg/125 mg 375 mg ivacaftor in the evening (12 hours later)
Moderate hepatic impairment
For patients aged 12 years and older    For patients aged 12 years and older (Child-Pugh Class B)
2 tablets of 200 mg/125 mg in the       600 mg lumacaftor + morning +                               375 mg ivacaftor
1 tablet of 200 mg/125 mg in the evening (12 hours later)
For patients aged 6 to 11 years         For patients aged 6 to 11 years 1 tablet of 100 mg/125 mg in the        200 mg lumacaftor + morning +                               250 mg ivacaftor
1 tablet of 100 mg/125 mg in the        or evening (12 hours later)                a reduced daily dose or
Severe hepatic            a reduced daily dose impairment
(Child-Pugh Class C)      For patients aged 12 years and older    For patients aged 12 years and older 1 tablet of 200 mg/125 mg in the        400 mg lumacaftor + morning +                               250 mg ivacaftor
1 tablet of 200 mg/125 mg in the        or evening (12 hours later)                a reduced daily dose or a reduced daily dose

Elderly people
The safety and efficacy of Orkambi in patients aged 65 years or older have not been evaluated.
Paediatric population
The safety and efficacy of Orkambi in children aged less than 6 years have not yet been established. No data are available (see section 5.1).

Method of administration

For oral use.
Patients should be instructed to swallow the tablets whole. Patients should not chew, break, or dissolve the tablets.


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