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PITOLISANT

ClassPITOLISANT commonly prescribed forHow PITOLISANT worksHow long until PITOLISANT worksNotable Side EffectsLife Threatening Side Effectsweight gainsedationWhat to do about PITOLISANT side effectsusual dosage rangeDosage Formslong term usehabit formingRenal ImpairmentHepatic ImpairmentCardiac ImpairmentElderlyChildren and AdolescentsPregnancyBreast Feeding

THERAPEUTICS

Class

  • Histamine 3 antagonist/inverse agonist

PITOLISANT commonly prescribed for

(Bold for FDA approved)

• Reducing excessive daytime sleepiness in patients with narcolepsy
• Cataplexy

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

SIDE EFFECTS

Notable Side Effects

• Insomnia, anxiety, nausea, decreased appetite

Life Threatening Side Effects

• Increased heart rate, tachycardia

• Visual hallucinations, hypnagogic hallucinations

weight gain

unusual

unusual

sedation

unusual

unusual

What to do about PITOLISANT side effects

Wait

• Lower the dose

• If unacceptable side effects persist, discontinue use

DOSING AND 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

SPECIAL POPULATIONS

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

Based on data Published online by Cambridge University Press

Compiled by Dr. Jash Ajmera