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Pimavanserin

Medically reviewed by Drugs.com. Last updated on Jul 29, 2020.

Pronunciation

(pim a VAN ser in)

Index Terms

  • ACP-103
  • Pimavanserin Tartrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as tartrate:

Nuplazid: 34 mg [contains brilliant blue fcf (fd&c blue #1)]

Tablet, Oral, as tartrate:

Nuplazid: 10 mg

Nuplazid: 17 mg [DSC] [contains saccharin sodium]

Brand Names: U.S.

  • Nuplazid

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic

Pharmacology

Pimavanserin acts as an inverse agonist and antagonist with high affinity for 5-HT2A receptors and low affinity for 5-HT2C and sigma 1 receptors; no affinity for 5-HT2B, dopaminergic (including D2), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.

Distribution

Vd: 2173 L

Metabolism

Primarily via CYP3A4 and CYP3A5; forms active N-desmethylated metabolite (AC-279)

Excretion

Feces (<1.5% as unchanged drug); urine (<1% as unchanged drug; <1% as metabolites)

Time to Peak

6 hours (median: 4 to 24 hours)

Half-Life Elimination

Pimavanserin: ~57 hours; N-desmethylated metabolite: ~200 hours

Protein Binding

~95%

Use: Labeled Indications

Parkinson disease psychosis: Treatment of hallucinations and delusions associated with Parkinson disease psychosis

Contraindications

Hypersensitivity (eg, rash, urticaria, tongue swelling, circumoral edema, throat tightness, dyspnea) to pimavanserin or any component of the formulation.

Dosing: Adult

Parkinson disease psychosis: Oral: 34 mg once daily

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Discontinuation of therapy: The American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA [Addington 2005]; WFSBP [Hasan 2012]). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months, and the APA guidelines recommend reducing the dose by 10% each month (APA [Lehman 2004]; CPA [Addington 2005]). When switching antipsychotics, 3 strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited, and results are conflicting (Cerovecki 2013; Remington 2005).

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: May be administered without regard to food.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Pimavanserin. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Pimavanserin. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Pimavanserin. Management: Decrease the pimavanserin dose to 10 mg daily when combined with strong CYP3A4 inhibitors. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

St John's Wort: May decrease the serum concentration of Pimavanserin. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Peripheral edema (7%)

Central nervous system: Confusion (6%), hallucination (5%), abnormal gait (2%)

Gastrointestinal: Nausea (7%), constipation (4%)

Frequency not defined: Cardiovascular: Prolonged QT interval on ECG

<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, angioedema, drowsiness, falling, skin rash, urticaria

ALERT: U.S. Boxed Warning

Increased mortality in elderly patients with dementia-related psychosis:

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 disease psychosis.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving) (Hermanowicz 2016).

• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risks increase with age. Use with caution in patients at risk for aspiration pneumonia (ie, Alzheimer disease), particularly in patients >75 years of age (Herzig 2017; Maddalena 2004).

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability (Landi 2005; Seppala 2018).

• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia) (Hermanowicz 2016).

• QT prolongation: Use is associated with QTc prolongation. Avoid use in patients with a history of cardiac arrhythmias, history of QT prolongation, concomitant use of medications that prolong the QT interval, and other circumstances that may increase the risk of torsades de pointes and/or sudden death (including symptomatic bradycardia, hypokalemia, and/or hypomagnesemia, and congenital long QT syndrome).

Disease-related concerns:

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in dementia with Lewy bodies; antipsychotics may worsen dementia symptoms, and patients with dementia with Lewy bodies are more sensitive to the extrapyramidal side effects (APA [Reus 2016]). Pimavanserin is not approved for the treatment of dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson disease psychosis.

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). When assessing for risk of withdrawal, consider duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); renal and liver function (annually and as clinically indicated); ECG (as clinically indicated) (Lehman 2004; Marder 2004); fall risk (baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk) (Landi 2005; Seppala 2018).

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat hallucinations (seeing or hearing things that are not there) and strange thoughts that happen with Parkinson disease.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Fast heartbeat

• Abnormal heartbeat

• Swelling in the arms or legs

• Sensing things that seem real but are not

• Confusion

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.