ORKAMBI Granules Ref.[51441] Active ingredients: Ivacaftor Ivacaftor and Lumacaftor Lumacaftor

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.

Posology

Table 1. Dosing recommendations in patients aged 1 year and older:

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 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.

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, the dose should be reduced to one sachet every other day 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:

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 sachet every other day 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).

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 moderate or severe hepatic impairment (see Table 3).

Table 3. Dose adjustment recommendations for patients with moderate or severe hepatic impairment:

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

Paediatric population

The safety and efficacy of Orkambi in children aged less than 1 year have not yet been established. No data are available.

Method of administration

For oral use.

Each sachet is for single use only.

The entire content 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. Some examples of soft foods or liquids include puréed fruits or vegetables, flavoured yogurt, applesauce, water, milk, breast milk, infant formula or juice. Food or liquid should be at room temperature or below. Once mixed, the product has been shown to be stable for one hour, and therefore should be ingested during this period.

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.

3 years.

Once mixed, the mixture has been shown to be stable for one hour.

This medicinal product does not require any special storage conditions.

Orkambi granules are packaged in a foil laminate [biaxially-oriented polyethylene terephthalate/polyethylene/foil/polyethylene (BOPET/PE/Foil/PE)] sachet.

Pack size of 56 (4 wallets with 14 sachets per wallet) sachets.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.