Genetic Implications:
Pronunciation:
pi-tol-i-sant
Trade Name(s)
Ther. Class.
central nervous system stimulants
Pharm. Class.
histamine H3 antagonist/agonist
Treatment of excessive daytime sleepiness or cataplexy in patients with narcolepsy.
Acts as a histamine-3 (H3) receptor antagonist/reverse agonist. Exact mechanism by which it minimizes excessive daytime sleepiness in narcolepsy unknown.
Therapeutic Effect(s):
Reduced perception of falling asleep during daily life activities.
Absorption: 90% absorbed following oral administration.
Distribution: Extensively distributed to tissues.
Protein Binding: 91–96%.
Metabolism and Excretion: Primarily metabolized by the liver by the CYP2D6 isoenzyme, and to a lesser extent by the CYP3A4 isoenzyme; the CYP2D6 enzyme system exhibits genetic polymorphism (~7% of population may be poor metabolizers and may have significantly ↑ pitolisant concentrations and an ↑ risk of adverse effects).Primarily excreted in urine (90%; <2% as unchanged drug), with only 2% excreted in feces.
Half-life: 20 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 2–5 hr | 24 hr |
Contraindicated in:
Use Cautiously in:
CNS: headache, anxiety, hallucinations, insomnia, irritability, sleep disturbances
CV: QT INTERVAL PROLONGATION, tachycardia
Derm: rash
GI: abdominal pain, dry mouth, nausea
Metabolic: cataplexy, ↓ appetite
MS: pain
Resp: upper respiratory tract infection
Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
PO (Adults): 8.9 mg once daily in the morning upon awakening for 1 wk, then ↑ to 17.8 mg once daily in the morning upon awakening for 1 wk; may then ↑ to 35.6 mg once daily in the morning upon awakening. Concurrent use of strong CYP2D6 inhibitors (initiation of therapy)– 8.9 mg once daily in the morning upon awakening for 1 wk, then ↑ to 17.8 mg once daily in the morning upon awakening (max dose = 17.8 mg/day). Concurrent use of strong CYP2D6 inhibitors (stabilized on therapy)– ↓ pitolisant dose by 50%. Concurrent use with strong CYP3A4 inducers– If stable on 8.9 mg once daily, ↑ to 17.8 mg once daily over 7 days; if stable on 17.8 mg once daily, ↑ to 35.6 mg once daily over 7 days. Poor CYP2D6 metabolizers– 8.9 mg once daily in the morning upon awakening for 1 wk, then ↑ to 17.8 mg once daily in the morning upon awakening (max dose = 17.8 mg/day).
Hepatic Impairment
PO (Adults): Moderate hepatic impairment (Child-Pugh B)– 8.9 mg once daily in the morning upon awakening for 2 wk, then ↑ to 17.8 mg once daily in the morning upon awakening (max dose = 17.8 mg/day).
Renal Impairment
PO (Adults): CCr 15–59 mL/min/1.73 m2 – 8.9 mg once daily in the morning upon awakening for 1 wk, then ↑ to 17.8 mg once daily in the morning upon awakening (max dose = 17.8 mg/day).
Tablets: 4.45 mg, 17.8 mg
Assess ECG before starting therapy to determine whether patient has a prolonged QT interval. Monitor patients with hepatic or renal impairment for increased QTc. May require dose modification.
Advise patient to notify health care professional if signs and symptoms on QTc interval prolongation (feel faint, lose consciousness, heart palpitations) occur.
Decrease in daytime sleepiness or cataplexy in adults with narcolepsy.