Class

• Histamine 3 antagonist/inverse agonist

PITOLISANT commonly prescribed for

(Bold for FDA approved)

How PITOLISANT works

• 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

How long until PITOLISANT works

• Can take up to 8 weeks for some patients to achieve a clinical response

Notable Side Effects

• Insomnia, anxiety, nausea, decreased appetite

Life Threatening Side Effects

• Increased heart rate, tachycardia

• Visual hallucinations, hypnagogic hallucinations

weight gain

unusual

sedation

unusual

What to do about PITOLISANT side effects

Wait

• Lower the dose

• If unacceptable side effects persist, discontinue use

usual dosage range

• 17.8–35.6 mg once daily upon wakening

Dosage Forms

• Tablet 4.45 mg, 17.8 mg

long term use

• Has been evaluated and found safe and effective in trials up to 1 year

• The need for continued treatment should be reevaluated periodically

habit forming

• No

Renal Impairment

• 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

Hepatic Impairment

• 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

Cardiac Impairment

• 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

Elderly

• Limited experience in patients over 65

• Some patients may tolerate lower doses better

Children and Adolescents

• Safety and efficacy have not been established

Pregnancy

• 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

Breast Feeding

• 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