FDA

Pimavanserin

Approved 16 Jan 2024OralCapsule

The FDA lists this product in 3 strengths and forms.

Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.

Indications

Pimavanserin capsule is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis [see Clinical Studies (14) ]. Pimavanserin capsule is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. (1)

Contraindications

Pimavanserin 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) ] . Known hypersensitivity to pimavanserin or any of its components. (4)

Warnings and precautions

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)

5.1Increased 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. Pimavanserin 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] .

At a glance

Brand name: Pimavanserin
Active substance: pimavanserin tartrate
Route: Oral
Dosage form: Capsule
Applicant: MSN
Status: Discontinued
FDA approval: 16 Jan 2024
Application: ANDA214925-001

Indications

Contraindications

Warnings and precautions

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)

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Pregnancy and breastfeeding

8.1Pregnancy 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 [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. 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 up to 14-times the MRHD of 34 mg/day based on AUC. 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.

Adverse reactions

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 Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 pimavanserin consists of over 1200 subjects and patients exposed to one or more doses of pimavanserin. 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 pimavanserin 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).

The majority of patients receiving long-term treatment received 34 mg once-daily (N=459). Over 300 patients have been treated for more than 6 months; over 270 have been treated for at least 12 months; and over 150 have been treated for at least 24 months. The following adverse reactions are based on the 6-week, placebo-controlled studies in which pimavanserin was administered once daily to patients with hallucinations and delusions associated with PDP.

Common Adverse Reactions (incidence ≥5% and at least twice the rate of placebo): peripheral edema (7% pimavanserin 34 mg vs. 2% placebo) and confusional state (6% pimavanserin 34 mg vs. 3% placebo). Adverse Reactions Leading to Discontinuation of Treatment A total of 8% (16/202) of pimavanserin 34 mg-treated patients and 4% (10/231) of placebo-treated patients discontinued because of adverse reactions. The adverse reactions that occurred in more than one patient and with an incidence at least twice that of placebo were hallucination (2% pimavanserin vs. <1% placebo), urinary tract infection (1% pimavanserin vs. <1% placebo), and fatigue (1% pimavanserin vs. 0% placebo).

Adverse reactions that occurred in 6-week, placebo-controlled studies and that were reported at an incidence of ≥2% and >placebo are presented in Table 1 . Table 1 Adverse Reactions in Placebo-Controlled Studies of 6-Week Treatment Duration and Reported in ≥2% and >Placebo Percentage of Patients Reporting Adverse Reaction Pimavanserin 34 mg Placebo N=202 N=231 Gastrointestinal disorders Nausea 7% 4% Constipation 4% 3% General disorders Peripheral edema 7% 2% Gait disturbance 2% <1% Psychiatric disorders Hallucination 5% 3% Confusional state 6% 3% Adverse Reactions in Demographic Subgroups Examination of population subgroups in the 6-week, placebo-controlled studies did not reveal any differences in safety on the basis of age (≤75 vs. >75 years) or sex.

Because the study population was predominantly Caucasian (91%; consistent with reported demographics for PD/PDP), racial or ethnic differences in the safety profile of pimavanserin could not be assessed. In addition, in the 6-week, placebo-controlled studies, no clinically relevant differences in the incidence of adverse reactions were observed among those with a Mini-Mental State Examination (MMSE) score at entry of <25 versus those with scores ≥25.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of pimavanserin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include rash, urticaria, reactions consistent with angioedema (e.g., tongue swelling, circumoral edema, throat tightness, and dyspnea), somnolence, falls, agitation and aggression.

Pimavanserin

Indications

Contraindications

Warnings and precautions

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis

At a glance

Two medicines in one question?

Pimavanserin

Indications

Contraindications

Warnings and precautions

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis

At a glance

Two medicines in one question?

5.2QT Interval Prolongation

Interactions

7.2Drugs Having No Clinically Important Interactions with Pimavanserin Based

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information