Pimavanserin

The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with PDP is unclear. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT 2A receptors and to a lesser extent at serotonin 5-HT 2C receptors.

• NUPLAZID ® is indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis [ see Clinical Studies (14) ] . NUPLAZID is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.ICD-10: G20

• NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported [see Adverse Reactions (6.2) ] .contraindicated

Recommended dose is 34 mg taken orally once daily, without titration. ( 2.1 ) Can be taken with or without food. ( 2.2 ) Capsules may be swallowed whole or opened and entire contents sprinkled over a tablespoon of certain types of soft food. ( 2.2 ) 2.1 Recommended Dosage The recommended dose of NUPLAZID is 34 mg taken orally once daily, without titration. 2.2 Administration Information NUPLAZID can be taken with or without food [see Clinical Pharmacology (12.3) ] . NUPLAZID capsules can be taken whole, or opened and the entire contents sprinkled over a tablespoon (15 mL) of applesauce, yogurt, pudding, or a liquid nutritional supplement. Consume the drug/food mixture immediately without chewing; do not store for future use. 2.3 Dosage Modifications for Concomitant Use with CYP3A4 Inhibitors and Inducers Coadministration with Strong CYP3A4 Inhibitors The recommended dose of NUPLAZID when coadministered with strong CYP3A4 inhibitors is 10 mg, taken orally as one tablet once daily [see Drug Interactions (7.1) ]. Coadministration with Strong or Moderate CYP3A4 Inducers Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID [see Drug Interactions (7.1) ] .

QT Interval Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. ( 5.2 ) 5.1 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. 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. NUPLAZID is not approved for the treatment of patients with dementia who experience psychosis unless their hallucinations and delusions are related to Parkinson's disease [see Boxed Warning ]. 5.2 QT Interval Prolongation NUPLAZID prolongs the QT interval.

The following serious adverse reactions are discussed elsewhere in the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] QT Interval Prolongation [see Warnings and Precautions (5.2) ] Most common adverse reactions (≥5% and twice the rate of placebo): peripheral edema and confusional state. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acadia Pharmaceuticals Inc. at 1-844-422-2342 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trial database for NUPLAZID consists of over 1200 subjects and patients exposed to one or more doses of NUPLAZID. Of these, 616 were patients with hallucinations and delusions associated with Parkinson's disease psychosis (PDP). In the placebo-controlled setting, the majority of experience in patients comes from studies evaluating once-daily NUPLAZID doses of 34 mg (N=202) compared to placebo (N=231) for up to 6 weeks. In the controlled trial setting, the study population was approximately 64% male and 91% Caucasian, and the mean age was about 71 years at study entry. Additional clinical trial experience in patients with hallucinations and delusions associated with PDP comes from two open-label, safety extension studies (total N=497).

8.1 Pregnancy Risk Summary There are no data on NUPLAZID 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 [see Data ] . 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. Data 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 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.

Metabolism

Pimavanserin demonstrates dose-proportional pharmacokinetics after single oral doses from 17 to 255 mg (0.5- to 7.5-times the recommended dosage). The pharmacokinetics of pimavanserin are similar in both the study population and healthy subjects.

10.1 Human Experience The pre-marketing clinical trials involving NUPLAZID in approximately 1200 subjects and patients do not provide information regarding symptoms with overdose. In healthy subject studies, dose-limiting nausea and vomiting were observed. 10.2 Management of Overdose There are no known specific antidotes for NUPLAZID. In managing overdose, cardiovascular monitoring should commence immediately and should include continuous ECG monitoring to detect possible arrhythmias [see Warnings and Precautions (5.2) ] . If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine should not be used, as they have the potential for QT-prolonging effects that might be additive to those of NUPLAZID [see Drug Interactions (7.1) ]. Consider the long plasma half-life of pimavanserin (about 57 hours) and the possibility of multiple drug involvement. Consult a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice.

• Apr 29, 2016NDANDA207318Acadia Pharms Inc
• Jun 28, 2018NDANDA210793Acadia Pharms Inc
• Jan 16, 2024ANDAANDA214925Msn

1. 1Hallucination12,12223%
2. 2Death10,42620%
3. 3Drug Ineffective6,09212%
4. 4Product Dose Omission Issue4,1958.0%
5. 5Confusional State4,1197.9%
6. 6Fall3,8337.3%
7. 7Delusion2,6455.0%
8. 8Condition Aggravated2,2514.3%
9. 9Hallucination, Visual2,1874.2%
10. 10Parkinson^s Disease2,1844.2%
11. 11Gait Disturbance2,1094.0%
12. 12Urinary Tract Infection1,7203.3%
13. 13Somnolence1,6733.2%
14. 14Peripheral Swelling1,5953.0%
15. 15Adverse Drug Reaction1,5853.0%

The 10 most recently updated of 47 ClinicalTrials.gov registrations naming Pimavanserin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Psilocybin Efficacy With or Without Pimavanserin Pretreatment
  Not yet recruiting · Phase 1 · Phase 2 · Interventional · 20 enrolled · Johns Hopkins University
  NCT07610135updated 2026-06-08
• Psilocybin Therapy for Depression in Parkinson's Disease
  Recruiting · Phase 2 · Interventional · 60 enrolled · Joshua Woolley, MD, PhD
  NCT06455293updated 2026-06-02
• Pimavanserin for Insomnia in Veterans With PTSD
  Recruiting · Phase 2 · Interventional · 60 enrolled · VA Office of Research and Development
  NCT05441280updated 2026-05-04
• Investigating the Neuropsychological Effects of 5-HT2a Antagonism
  Recruiting · Interventional · 80 enrolled · University of Oxford
  NCT07022366updated 2026-04-29
• Pimavanserin for Rigid-compulsive Symptoms in Autism Spectrum Disorder
  Recruiting · Phase 2 · Interventional · 30 enrolled · New York State Psychiatric Institute
  NCT05999240updated 2026-04-01
• Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.
  Completed · Phase 2 · Interventional · 117 enrolled · University Hospital, Strasbourg, France
  NCT03947216updated 2026-03-16
• A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis
  Completed · Phase 3 · Interventional · 248 enrolled · Tasly Pharmaceutical Group Co., Ltd
  NCT06068465updated 2026-02-27
• Extension Study of Pimavanserin in Irritability Associated With Autism Spectrum Disorder
  Terminated · Phase 2 · Phase 3 · Interventional · 209 enrolled · ACADIA Pharmaceuticals Inc.
  NCT05555615updated 2025-12-03
• Comparing Antipsychotic Medications in LBD Over Time
  Recruiting · Phase 4 · Interventional · 94 enrolled · The University of Texas Health Science Center at San Antonio
  NCT05590637updated 2025-09-09
• Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis
  Recruiting · Phase 4 · Interventional · 358 enrolled · VA Office of Research and Development
  NCT04373317updated 2025-08-28

Frequently asked questions

How does Pimavanserin work?

The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with PDP is unclear. However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT 2A receptors and to a lesser extent at serotonin 5-HT 2C receptors.

What is Pimavanserin used for?

According to FDA labeling, Pimavanserin carries indications including: NUPLAZID ® is indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis [ see Clinical Studies (14) ] . NUPLAZID is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pimavanserin?

Pimavanserin is classified as Other antipsychotics, Atypical Antipsychotic, Serotonin Receptor Interactions.

What are the brand names for Pimavanserin?

Pimavanserin is marketed under brand names including Nuplazid.

What are the contraindications for Pimavanserin?

Pimavanserin labeling lists contraindications including: NUPLAZID is contraindicated in patients with a history of a hypersensitivity reaction to pimavanserin or any of its components. Rash, urticaria, and reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea) have been reported [see Adverse Reactions (6.2) ] .. Always consult the full prescribing information and a clinician.