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
Orkambi tablets are indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (see sections 4.2, 4.4, and 5.1).
Orkambi should only be prescribed by physicians 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 the F508del mutation on both alleles of the CFTR gene.
Table 1. Dosing recommendations in patients aged 6 years and older:
| Age | Strength | Dose (every 12 hours) | |
|---|---|---|---|
| Morning | Evening | ||
| 6 to <12 years | lumacaftor 100 mg/ivacaftor 125 mg | 2 tablets | 2 tablets |
| 12 years and older | lumacaftor 200 mg/ivacaftor 125 mg | 2 tablets | 2 tablets |
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).
If less than 6 hours have passed since the missed dose, the scheduled dose should be taken with fatcontaining 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.
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, the dose should be reduced to one tablet daily 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 (see Table 2).
Table 2. Treatment initiation in patients taking strong CYP3A inhibitors:
| Age | Strength | Week 1 of treatment | Week 2 onwards |
|---|---|---|---|
| 6 to <12 years | lumacaftor 100 mg/ivacaftor 125 mg | 1 tablet per day | From day 8 and thereafter dosing should be at the recommended daily dose |
| 12 years and older | lumacaftor 200 mg/ivacaftor 125 mg |
If treatment is interrupted for more than one week and then re-initiated while taking strong CYP3A inhibitors, the dose should be reduced to one tablet daily for the first week of treatment re-initiation (see Table 2). Following this period, the recommended daily dose should be continued (see section 4.5).
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 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 moderate or severe hepatic impairment, (see Table 3).
Table 3. Dose adjustment recommendations for patients with moderate or severe hepatic impairment:
| Age | Strength | Total Daily Dose | |||
|---|---|---|---|---|---|
| Moderate (Child-Pugh Class B) | Severe (Child-Pugh Class C) | ||||
| Morning | Evening | Morning | Evening | ||
| 6 to <12 years | lumacaftor 100 mg/ ivacaftor 125 mg | 2 tablets | 1 tablet | 1 tablet or less frequently* | 1 tablet or less frequently* |
| 12 years and older | lumacaftor 200 mg/ ivacaftor 125 mg | ||||
* Dosing interval should be modified according to clinical response and tolerability; the frequency may be reduced for both the morning dose and the evening dose.
The safety and efficacy of Orkambi in children aged less than 1 year have not yet been established. No data are available.
For oral use.
Patients should be instructed to swallow the tablets whole. Patients should not chew, break, or dissolve the tablets.
No specific antidote is available for overdose with lumacaftor/ivacaftor. Treatment of overdose consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
Adverse reactions that occurred at an increased incidence of ≥5% in the supratherapeutic dose period compared with the therapeutic dose period were headache, generalised rash, and increased transaminase.
Orkambi 100 mg/125 mg film-coated tablets: 3 years.
Orkambi 200 mg/125 mg film-coated tablets: 4 years.
This medicinal product does not require any special storage conditions.
Blister consisting of PolyChloroTriFluoroEthylene (PCTFE)/PolyVinyl Chloride (PVC) with a paper-backed aluminium foil lidding.
Orkambi 100 mg/125 mg film-coated tablets: Pack containing 112 (4 packs of 28) film-coated tablets.
Orkambi 200 mg/125 mg film-coated tablets: Multipacks containing 112 (4 packs of 28) film-coated tablets.
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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