(Bold for FDA approved)
• Histamine is a wake-promoting neurotransmitter released from the tuberomammillary nucleus in the hypothalamus
• Histamine 3 receptors are presynaptic autoreceptors; thus, when histamine binds to these receptors it shuts down further histamine release
• Antagonism/inverse agonism of histamine 3 receptors by pitolisant therefore disinhibits histamine release, boosting histamine levels in the brain and enhancing wakefulness
• Can take up to 8 weeks for some patients to achieve a clinical response
• Insomnia, anxiety, nausea, decreased appetite
• Increased heart rate, tachycardia
• Visual hallucinations, hypnagogic hallucinations
unusual
unusual
Wait
• Lower the dose
• If unacceptable side effects persist, discontinue use
• 17.8–35.6 mg once daily upon wakening
• Tablet 4.45 mg, 17.8 mg
• Has been evaluated and found safe and effective in trials up to 1 year
• The need for continued treatment should be reevaluated periodically
• No
• Pitolisant prolongs the QTc interval, so monitor patients with renal impairment for increased QTc
• Moderate to severe renal impairment: initial dose 8.9 mg once daily; titrate to a maximum dose of 17.8 mg once daily after 7 days
• Not recommended for use in end-stage renal disease
• Dose adjustment not necessary in patients with mild hepatic impairment
• Moderate hepatic impairment: initial dose 8.9 mg once daily; titrate to a maximum dose of 17.8 mg once daily after 14 days
• Pitolisant prolongs the QTc interval, so monitor patients with hepatic impairment for increased QTc
• Severe hepatic impairment: contraindicated
• Pitolisant prolongs the QTc interval, so its use should be avoided in patients with a history of cardiac arrhythmias, symptomatic bradycardia, hypokalemia, hypomagnesemia, or congenital prolongation of the QTc interval
• Limited experience in patients over 65
• Some patients may tolerate lower doses better
• Safety and efficacy have not been established
• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001
• Controlled studies have not been conducted in pregnant women
• Case reports have not determined a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• When administered to pregnant rats during organogenesis, the no observed adverse effect level (NOAEL) for embryofetal toxicity is 27 times the maximum recommended human dose (MRHD) based on mg/m2 body surface area
• When administered to pregnant rabbits during organogenesis, the NOAELs for maternal toxicity and embryofetal development are 2 and 4 times the MRHD based on mg/m2` body surface
• When administered to pregnant rats from gestation day 7 through lactation, maternal toxicity, including death, occurred at 22 times the MRHD based on mg/m2 body surface area; at the maternally toxic dose, fetal toxicity and major malformations occurred
• Unknown if pitolisant is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk
• Recommended either to discontinue drug or bottle feed
Based on data Published online by Cambridge University Press
Compiled by Dr. Jash Ajmera