Generic Name: Pimavanserin
Class: Atypical Antipsychotics
Chemical Name: N - [(4 - Fluorophenyl)methyl] - N - (1 - methyl - 4 - piperidinyl) - N′ - [[4 - (2 - methylpropoxy)phenyl]methyl] - urea
Molecular Formula: C25H34FN3O2
CAS Number: 706779-91-1
Warning: Increased Mortality In Elderly Patients With Dementia-related Psychosis
See full prescribing information for complete boxed warning.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.1
Pimavanserin is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson's disease psychosis.1
Pimavanserin is an atypical antipsychotic agent.
Uses for Nuplazid
Pimavanserin has the following uses:
Pimavanserin is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.1
Nuplazid Dosage and Administration
Pimavanserin is available in the following dosage form(s) and strength(s):
Tablets: 17 mg.1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Recommended dose is 34 mg, taken orally as two 17 mg tablets once daily, without titration.1
Can be taken with or without food.1
Cautions for Nuplazid
Increased Mortality In Elderly Patients With Dementia-related Psychosis
Antipsychotic drugs increase the all-cause risk of death in elderly patients with dementia-related psychosis. Analyses of 17 dementia-related psychosis placebo-controlled trials (modal duration of 10 weeks and largely in patients taking atypical antipsychotic drugs) revealed a risk of death in the drug-treated patients of between 1.6- to 1.7-times that in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in placebo-treated patients. 1
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Pimavanserin is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson's disease psychosis.1
QT Interval Prolongation
Pimavanserin prolongs the QT interval. The use of pimavanserin should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain antibiotics (e.g., gatifloxacin, moxifloxacin). Pimavanserin should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsades de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval.1
Risk Summary: There are no data on pimavanserin use in pregnant women that would allow assessment of the drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, no adverse developmental effects were seen when pimavanserin was administered orally to rats or rabbits during the period of organogenesis at doses up to 10- or 12-times the maximum recommended human dose (MRHD) of 34 mg/day, respectively. Administration of pimavanserin to pregnant rats during pregnancy and lactation resulted in maternal toxicity and lower pup survival and body weight at doses which are 2-times the MRHD of 34 mg/day. 1
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 1
Animal Data: Pimavanserin was not teratogenic in pregnant rats when administered during the period of organogenesis at oral doses of 0.9, 8.5, and 51 mg/kg/day, which are 0.2- and 10-times the maximum recommended human dose (MRHD) of 34 mg/day based on AUC at mid and high doses, respectively. Maternal toxicity included reduction in body weight and food consumption at the highest dose.1
Administration of pimavanserin to pregnant rats during pregnancy and lactation at oral doses of 8.5, 26, and 51 mg/kg/day, which are 0.14- to 14-times the MRHD of 34 mg/day based on AUC, caused maternal toxicity, including mortality, clinical signs including dehydration, hunched posture, and rales, and decreases in body weight and/or food consumption at doses ≥26 mg/kg/day (2-times the MRHD based on AUC). At these maternally toxic doses there was a decrease in pup survival, reduced litter size, and reduced pup weights and food consumption. Pimavanserin had no effect on sexual maturation, neurobehavioral function including learning and memory, or reproductive function in the first generation pups at doses up to 14-times the MRHD of 34 mg/day based on AUC.1
Pimavanserin was not teratogenic in pregnant rabbits during the period of organogenesis at oral doses of 4.3, 43, and 85 mg/kg/day, which are 0.2- to 12-times the MRHD of 34 mg/day based on AUC. Maternal toxicity, including mortality, clinical signs of dyspnea and rales, decreases in body weight and/or food consumption, and abortions, occurred at doses 12-times the MRHD of 34 mg/day based on AUC.1
There is no information regarding the presence of pimavanserin in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for pimavanserin and any potential adverse effects on the breastfed infant from pimavanserin or from the underlying maternal condition.1
Safety and effectiveness of pimavanserin have not been established in pediatric patients. 1
No dose adjustment is required for elderly patients.1
Parkinson's disease is a disorder occurring primarily in individuals over 55 years of age. The mean age of patients enrolled in the 6-week clinical studies with pimavanserin was 71 years, with 49% 65-75 years old and 31% >75 years old. In the pooled population of patients enrolled in 6-week, placebo-controlled studies (N=614), 27% had Mini-Mental State Examination (MMSE) scores from 21 to 24 compared to 73% with scores ≥25. No clinically meaningful differences in safety or effectiveness were noted between these two groups. 1
No dosage adjustment for pimavanserin is needed in patients with mild to moderate (CrCL ≥30 mL/min, Cockcroft-Gault) renal impairment.1
Use of pimavanserin is not recommended in patients with severe renal impairment (CrCL <30 mL/min, Cockcroft-Gault). Pimavanserin has not been evaluated in this patient population.1
Use of pimavanserin is not recommended in patients with hepatic impairment. Pimavanserin has not been evaluated in this patient population.1
Other Specific Populations
No dosage adjustment is required based on patient's age, sex, ethnicity, or weight. These factors do not affect the pharmacokinetics of pimavanserin.1
Common Adverse Effects
Most common adverse reactions (≥5% and twice the rate of placebo): peripheral edema and confusional state.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Strong CYP3A4 inhibitors (e.g., ketoconazole): Reduce pimavanserin dose by one-half.1
Strong CYP3A4 inducers: Monitor for reduced efficacy. Increase in pimavanserin dosage may be needed.1
The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with Parkinson's disease psychosis is unknown. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors. 1
Advice to Patients
Advise patients to inform their healthcare providers if there are any changes to their current prescription or over-the-counter medications, since there is a potential for drug interactions.1
AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
ACADIA Pharmaceuticals Inc
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Date published: September 09, 2016
Last reviewed: September 09, 2016
Date modified: October 12, 2016
1. ACADIA Pharmaceuticals Inc. NUPLAZID (pimavanserin tartrate) ORAL prescribing information. 2016 Apr.