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

Proposed MOA

The mechanism of action (MOA) in the treatment of hallucinations and delusions associated with Parkinson's disease psychosis is unclear.

Watch this video to learn more about the proposed mechanism of action of NUPLAZID.*

*The precise mechanism of action of NUPLAZID in the treatment of hallucinations and delusions associated with PD psychosis is unclear. However, the effect of NUPLAZID could be mediated through the combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors.1

In vitro, NUPLAZID is a serotonergic agent* with no appreciable affinity for dopaminergic, histaminergic, muscarinic, or adrenergic receptors.1

Isolated key for chart graph of proposed NUPLAZID® MOA
Isolated chart graph shows proposed NUPLAZID® MOA

*The precise mechanism of action of NUPLAZID in the treatment of hallucinations and delusions associated with PD psychosis is unclear. However, the effect of NUPLAZID could be mediated through the combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors.1 Lower Ki numbers indicate a greater binding affinity and thus a smaller amount of the drug is needed to block activity.2

See the effect of NUPLAZID versus placebo.

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IMPORTANT SAFETY INFORMATION and INDICATION

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.
  • NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.
  • Contraindication: 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.
  • Warnings and Precautions: QT Interval Prolongation

    • NUPLAZID prolongs the QT interval. The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics or Class 3 antiarrhythmics, certain antipsychotic medications, and certain antibiotics.

    • NUPLAZID 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 presence of congenital prolongation of the QT interval.

  • Adverse Reactions: The common adverse reactions (≥2% for NUPLAZID and greater than placebo) were peripheral edema (7% vs 2%), nausea (7% vs 4%), confusional state (6% vs 3%), hallucination (5% vs 3%), constipation (4% vs 3%), and gait disturbance (2% vs <1%).

  • Drug Interactions:

    • Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole) increases NUPLAZID exposure. Reduce NUPLAZID dose to 10 mg taken orally as one tablet once daily.

    • Coadministration with strong or moderate CYP3A4 inducers reduces NUPLAZID exposure. Avoid concomitant use of strong or moderate CYP3A4 inducers with NUPLAZID.

Indication NUPLAZID is indicated for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.

Dosage and Administration Recommended dose: 34 mg capsule taken orally once daily, without titration.

NUPLAZID is available as 34 mg capsules and 10 mg tablets.

Please read the full Prescribing Information, including Boxed WARNING.

References:
  1. Acadia Pharmaceuticals Inc. NUPLAZID® [package insert]. San Diego, CA; 2020.
  2. Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific basis and practical applications. 4th ed. New York, NY: Cambridge University Press; 2013.