Posology : מינונים

4.2 Posology and method of administration

Narcolepsy with or without cataplexy
Treatment should be initiated by a physician experienced in the treatment of sleep disorders.

Posology

Wakix should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day: -      Week 1: initial dose of 9 mg (two 4.5 mg tablets) per day.
-      Week 2: the dose may be increased to 18 mg (one 18 mg tablet) per day or decreased to 4.5 mg (one 4.5 mg tablet) per day.
-      Week 3: the dose may be increased to 36 mg (two 18 mg tablets) per day.

At any time the dose can be decreased (down to 4.5 mg per day) or increased (up to 36 mg per day) according to the physician assessment and the patient’s response.

The total daily dose should be administered as a single dose in the morning during breakfast.

Maintenance of efficacy
As long-term efficacy data are limited (see section 5.1), the continued efficacy of treatment should be regularly evaluated by the physician.

Special populations

Elderly
Limited data are available in elderly. Therefore, dosing should be adjusted according to their renal and hepatic status.

Renal impairment
In patients with renal impairment, the maximum daily dose should be 18 mg.

Hepatic impairment
In patients with moderate hepatic impairment (Child-Pugh B) two weeks after initiation of treatment, the daily dose can be increased without exceeding a maximal dose of 18 mg (see section 5.2).
Pitolisant is contra-indicated in patients with severe hepatic impairment (Child-Pugh C) (see section 4.3). No dosage adjustment is required in patients with mild hepatic impairment.

Paediatric population
The safety and efficacy of pitolisant in children aged from 0 to 18 years old have not yet been established. Wakix is not indicated for paediatric population

Poor metabolizers
By comparison to CYP2D6 extensive metabolisers, higher systemic exposure (up to 3 fold) is observed in CYP2D6 poor metabolisers. In the up-titration scheme, dose increment should take into account this higher exposure.

Obstructive sleep apnoea (OSA)

Treatment should be initiated by a healthcare professional experienced in the treatment of OSA and cardiovascular risk. OSA disease should be annually reassessed.

Wakix is not a therapy for the underlying airway obstruction in patients with OSA. Primary OSA therapy should be maintained or periodically rechallenged in patients not tolerating primary OSA therapy.

Posology

Pitolisant should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 18 mg/day: - Week 1: initial dose of 4.5 mg (one 4.5 mg tablet) per day.
- Week 2: the dose may be increased to 9 mg (two 4.5 mg tablets) per day.
- Week 3: the dose may be increased to 18 mg (one 18 mg tablet) per day or decreased to 4.5 mg (one 4.5 mg tablet) per day.

At any time the dose can be decreased (down to 4.5 mg per day) or increased (up to 18 mg per day) according to the physician assessment and the patient’s response.

The total daily dose should be administered as a single dose in the morning during breakfast.

Maintenance of efficacy
As long-term efficacy data are limited (see section 5.1), the continued efficacy of treatment should be regularly evaluated by the physician.


Special populations
Elderly
Limited data are available in elderly. Therefore, dosing should be adjusted according to their individual response and tolerance.
Insomnia has been reported in higher rate in the elderly and dosing should be adjusted accordingly (see section 4.8).

Renal impairment
No dose adjustment is necessary.

Hepatic impairment
No dosage adjustment is required in patients with mild hepatic impairment.
In patients with moderate hepatic impairment (Child-Pugh B), the titration period should be two weeks up-titration steps instead of one after initiation of treatment, due to expected longer half-life and higher exposure, and a dosage adjustment in patients with moderate hepatic impairment could eventually be considered depending on individual response and tolerance (see section 5.2).
Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C) (see section 4.3).

Paediatric population
There is no relevant use of Wakix in the paediatric population in Obstructive Sleep Apnoea (OSA).

CYP2D6 metabolizers phenotype (If known)
By comparison to CYP2D6 extensive metabolizers, higher systemic exposure (up to 3 fold) is observed in CYP2D6 poor metabolizers and lower exposure (by 0.8-fold) is observed in CYP2D6 ultra-rapid metabolizers. No differences in systemic exposure is observed between CYP2D6 extensive and intermediate metabolizers.
In the up-titration scheme, dose increment should take into account the higher exposure in CYP2D6 poor metabolizers, and a dosage adjustment in patients with known poor CYP2D6 metabolizer genotype could be considered depending on individual response and tolerance (see section 5.2).
Furthermore, no dose recommendation can currently be given for CYP2D6 ultra-rapid metabolizers taking a CYP3A inducer, because the PK is currently unknown in this subpopulation.

Method of administration

For oral use.