Pimavanserin

Pimavanserin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino, M.D. [2]

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Black Box 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. 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.

Overview

Pimavanserin is an atypical antipsychotic that is FDA approved for the treatment of patients with hallucinations and delusions associated with Parkinson's disease psychosis. There is a Black Box Warning for this drug as shown here. Common adverse reactions include peripheral edema and confusional state (≥5% and twice the rate of placebo)..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

Pimavanserin is indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

Dosage

• General Dosing Information

The recommended dose of Pimavanserin is 34 mg, taken orally as two 17 mg strength tablets once daily, without titration.

Pimavanserin can be taken with or without food.

• Dosage Modifications for Concomitant Use with CYP3A4 Inhibitors and Inducers

• Coadministration with Strong CYP3A4 Inhibitors

The recommended dose of Pimavanserin when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) is 17 mg, taken orally as one tablet once daily.

• Coadministration with Strong CYP3A4 Inducers

Monitor patients for reduced efficacy if Pimavanserin is used concomitantly with strong CYP3A4 inducers; an increase in Pimavanserin dosage may be needed.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in pediatric patients.

Contraindications

None

Warnings

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. 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.

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. 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.

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 torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval.

Adverse Reactions

Clinical Trials Experience

The following serious adverse reactions are discussed elsewhere in the labeling:

• Increased Mortality in Elderly Patients with Dementia-Related Psychosis
• QT Interval Prolongation

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

This image is provided by the National Library of Medicine.

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.

Postmarketing Experience

There is limited information regarding Pimavanserin Postmarketing Experience in the drug label.

Drug Interactions

Drugs Having Clinically Important Interactions with Pimavanserin

• Table 2 Clinically Important Drug Interactions with Pimavanserin

This image is provided by the National Library of Medicine.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Pimavanserin in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pimavanserin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Pimavanserin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Pimavanserin in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Pimavanserin in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Pimavanserin in geriatric settings.

Gender

There is no FDA guidance on the use of Pimavanserin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Pimavanserin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Pimavanserin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Pimavanserin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Pimavanserin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Pimavanserin in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Pimavanserin Administration in the drug label.

Monitoring

There is limited information regarding Pimavanserin Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Pimavanserin and IV administrations.

Overdosage

There is limited information regarding Pimavanserin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Pimavanserin Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Pimavanserin Mechanism of Action in the drug label.

Structure

There is limited information regarding Pimavanserin Structure in the drug label.

Pharmacodynamics

There is limited information regarding Pimavanserin Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Pimavanserin Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Pimavanserin Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Pimavanserin Clinical Studies in the drug label.

How Supplied

There is limited information regarding Pimavanserin How Supplied in the drug label.

Storage

There is limited information regarding Pimavanserin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Pimavanserin Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Pimavanserin interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Pimavanserin Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Pimavanserin Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.