A histamine- 3H3 receptor antagonist/inverse agonist for treatment of excessive daytime sleepiness or cataplexy in adults with narcolepsy.
The first H3-receptor antagonist/inverse agonist available and the first non-controlled substance for this indication.
Brand name Wakix.
It enhances the activity of histaminergic neurons in the brain that function to improve a person’s wakefulness.
With narcolepsy, a deficiency of hypothalamic cells producing the neuropeptide orexin leads to reduced excitation of neurons that produce wakefulness promoting neurotransmitters such as histamine.
This agent binds selectively to H3 receptors and acts an antagonist/inverse agonist to increase histamine levels.
It significantly reduces cataplexy attacks.
Routes of administration-oral.
The Epworth sleepiness scale showed significant improvement with pitolisant compared to placebo, and non-inferiority to modafinil for narcolepsy.
Side effects include difficulty sleeping, nausea, headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disorders, tiredness, vomiting, vertigo and dyspepsia.
it’s most common adverse effects ate headache at 18%, insomnia 6%, nausea 6%.
it can prolong QT interval and should not be used in patients with QT interval prolongation, a history of cardiac arrhythmias, symptomatic bradycardia, hypokalemia, or hypomagnesemia.
Its use is contraindicated with severe hepatic impairment or end stage renal disease.
Its safety in pregnancy and breast-feeding is unknown.
Serious but rare side effects are abnormal loss of weight and spontaneous abortion.
It is metabolized primarily by CYP2D6 into a lesser extent by CYP3A4.
Recommended initial dosage is two 4.45 mg tablets taken once daily upon waking: it can be increased to a maximum dose of 17.8 mg if necessary.