Pitolisant is a potent, orally active histamine H3‑receptor antagonist/inverse agonist. It blocks histamine auto-receptors enhancing the activity of brain histaminergic neurons, a major arousal system with widespread projections to the whole brain. Pitolisant also modulates various neurotransmitter systems, increasing acetylcholine, noradrenaline and dopamine release in the brain (pitolisant summary of product characteristics [SPC]).
Pitolisant (Wakix: Lincoln Medical Limited) received a marketing authorisation from the European Medicines Agency (EMA) in March 2016 for the treatment of narcolepsy with or without cataplexy in adults. In April 2016, the EMA recommended that its status as an orphan medicinal product should also be maintained. Pitolisant was launched in the UK in September 2016.
Pitolisant is available as 4.5 mg tablets (which contain 5 mg of pitolisant hydrochloride equivalent to 4.5 mg of pitolisant) and 18 mg tablets (which contain 20 mg of pitolisant hydrochloride equivalent to 18 mg of pitolisant). Treatment should be initiated by a clinician experienced in the treatment of sleep disorders. Pitolisant should be used at the lowest effective dose, depending on individual response and tolerance, without exceeding 36 mg per day (pitolisant SPC).
It should be titrated as follows:
Week 1: initial dose of 9 mg (2×4.5 mg tablets) per day.
Week 2: the dose may be increased to 18 mg (1×18 mg tablet) per day or decreased to 4.5 mg (1×4.5 mg tablet) per day.
Week 3: the dose may be increased to 36 mg (2×18 mg tablets) per day.
At any time the dose can be decreased (down to 4.5 mg per day) or increased progressively (up to 36 mg per day) according to response. The total daily dose should be given as a single dose in the morning during breakfast.
The company estimate that approximately one third of people will be maintained on 18 mg per day and two thirds of people will require 36 mg per day (source: Lincoln Medical Ltd, October 2016).
The summary of product characteristics states that long-term efficacy data are limited and the continued efficacy of pitolisant should be regularly evaluated.
Limited data are available in older people, and dosing should be adjusted according to their renal and hepatic status. In people with renal impairment, the maximum daily dose is 18 mg. In people with mild hepatic impairment no dosage adjustment is required. In people with moderate hepatic impairment, 2 weeks after treatment is started, the daily dose can be increased but only to a maximum daily dose of 18 mg. Pitolisant is contraindicated in people with severe hepatic impairment.
The safety and efficacy of pitolisant in children up to 18 years of age has not been established.
Pitolisant 4.5 mg tablets and pitolisant 18 mg tablets cost £310.00 for 30 tablets excluding VAT (MIMS, February 2017).