PIMAVANSERIN

brands

Class

• Atypical antipsychotic; serotonin 2A/2C antagonist/inverse agonist

PIMAVANSERIN commonly prescribed for

(Bold for FDA approved)

How PIMAVANSERIN works

• Antagonism/inverse agonism at serotonin 2A receptors

• Pimavanserin is also an antagonist/inverse agonist at serotonin 2C receptors (activity is very low compared to that at serotonin 2A receptors)

How long until PIMAVANSERIN works

• In a clinical trial, psychotic symptom improvement reached significance within 1 month

Notable Side Effects

• Peripheral edema

• Confusional state

• Nausea

Life Threatening Side Effects

• QTc prolongation

• Increased risk of death and cerebrovascular events in elderly patients with dementia- related psychosis has occurred with antipsychotic use

weight gain

unusual

sedation

unusual

What to do about PIMAVANSERIN side effects

• Wait

• Wait

• Wait

• Discontinue if side effects are intolerable

usual dosage range

• 34 mg once daily

Dosage Forms

• Tablet 10 mg

• Capsule 34 mg

long term use

• Not studied, but long-term maintenance treatment is often necessary for Parkinson’s disease psychosis

habit forming

• No

Renal Impairment

• Dose adjustment not necessary

• Use with caution in patients with severe impairment or end-stage renal disease

Hepatic Impairment

• Dose adjustment not necessary

Cardiac Impairment

• Pimavanserin can cause QTc prolongation and should be avoided in patients with known QTc prolongation or in combination with drugs that are known to prolong QTc interval

• Pimavanserin should be avoided in patients with a history of cardiac arrhythmias, symptomatic bradycardia, hypokalemia, or hypomagnesemia, or presence of congenital prolongation of the QTc interval

Elderly

• Dose adjustment not necessary

• Pimavanserin is not approved for the treatment of dementia-related psychosis UNRELATED to the hallucinations and delusions associated with Parkinson’s disease psychosis, such as the behavioral symptoms of comorbid Alzheimer dementia

• However, pimavanserin is not contraindicated for patients with dementia RELATED to Parkinson’s disease who have hallucinations and delusions of Parkinson’s disease psychosis

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

• In rat and rabbit studies, pimavanserin did not demonstrate teratogenicity at doses up to 10 or 12 times the maximum recommended human dose (MRHD)

• In rat studies, doses 2 times the MRHD in humans based on the AUC resulted in maternal toxicity, including mortality and reduced body weight and food consumption, with corresponding decreases in pup survival, reduced litter size, and reduced pup body weight

Breast Feeding

• Unknown if pimavanserin is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended to either discontinue drug or bottle feed unless the potential benefit to the mother justifies the potential risk to the child

• Infants of women who choose to breast feed while on pimavanserin should be monitored for possible adverse effects