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| {{DrugProjectFormSinglePage | | {| class="wikitable" |
| |authorTag=[[User: Martin Nino |Martin Nino, M.D.]] [mailto:martinnino@hotmail.com] | | ! colspan="4" |bbbbbb |
| |genericName=Pimavanserin
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| |aOrAn=an | | | colspan="2" | |
| |drugClass=[[atypical antipsychotic]] | | | |
| |indicationType=treatment | | | |
| |indication=patients with [[hallucinations]] and [[delusions]] associated with [[Parkinson's disease]] [[psychosis]] | | |- |
| |adverseReactions=[[peripheral edema]] and [[confusional state]] (≥5% and twice the rate of [[placebo]]). | | | colspan="2" | |
| |hasBlackBoxWarning=Yes | | | |
| |blackBoxWarningTitle=<span style="color:#FF0000;"> INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS</span> | | | |
| |blackBoxWarningBody=<i><span style="color:#FF0000;"> | | |- |
| 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.</span></i>
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| |fdaLIADAdult=======Indications====== | | | |
| Pimavanserin is indicated for the treatment of [[hallucinations]] and [[delusions]] associated with [[Parkinson's disease]] [[psychosis]].
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| ======Dosage======
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| :*'''General Dosing Information'''
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| The recommended dose of Pimavanserin is 34 mg, taken orally as two 17 mg strength tablets once daily, without [[titration]].
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| Pimavanserin can be taken with or without food.
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| :*'''Dosage Modifications for Concomitant Use with [[CYP3A4]] Inhibitors and Inducers'''
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| ::*Coadministration with Strong CYP3A4 Inhibitors
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| The recommended dose of Pimavanserin when coadministered with strong CYP3A4 inhibitors (e.g., [[ketoconazole]]) is 17 mg, taken orally as one tablet once daily.
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| ::*Coadministration with Strong CYP3A4 Inducers
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| Monitor patients for reduced efficacy if Pimavanserin is used concomitantly with strong CYP3A4 inducers; an increase in Pimavanserin dosage may be needed.
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| |offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in adult patients. | |
| |offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in adult patients. | |
| |fdaLIADPed=Safety and effectiveness have not been established in pediatric patients. | |
| |offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
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| |offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Pimavanserin in pediatric patients.
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| |contraindications=None
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| |warnings=======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.
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| 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 P[[arkinson's disease]] [[psychosis]].
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| ======[[QT Interval]] Prolongation======
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| 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.
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| |clinicalTrials=The following serious adverse reactions are discussed elsewhere in the labeling: | |
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| :*Increased Mortality in Elderly Patients with [[Dementia]]-Related [[Psychosis]]
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| :*[[QT Interval]] Prolongation
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| 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.
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| 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.
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| 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.
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| 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).
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| '''Adverse Reactions Leading to Discontinuation of Treatment'''
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| 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).
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| 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.
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| :*'''Table 1 Adverse Reactions in Placebo-Controlled Studies of 6-Week Treatment Duration and Reported in ≥2% and >Placebo'''
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| [[File:table1_pima.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
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| '''Adverse Reactions in Demographic Subgroups'''
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| 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.
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| |drugInteractions=======Drugs Having Clinically Important Interactions with Pimavanserin====== | |
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| :*'''Table 2 Clinically Important Drug Interactions with Pimavanserin'''
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| [[File:table2_pima.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
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