Target key serotonin receptors associated with PD psychosis

NUPLAZID targets 5-HT2A and 5-HT2C1,2*

  • NUPLAZID® (pimavanserin) binds to 5-HT2A receptors with a 5-fold higher selectivity over 5-HT2C receptors (K1 value 0.087 in nM vs K1 value 0.44 nM)1

*Binding affinity based on in vitro studies.

Lower K1 numbers indicate a greater binding affinity and thus a smaller amount of the drug is needed to block activity.

Proposed mechanism of action for NUPLAZID

Watch this video for the proposed mechanism of action for NUPLAZID. The precise mechanism of action of NUPLAZID in the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis is unknown. However, the effect of NUPLAZID could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors. Watch the full MOA video in RESOURCES.

Important Safety Information for NUPLAZID (pimavanserin) 17-mg Tablets

Important Safety Information for NUPLAZID (pimavanserin) 17-mg Tablets

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.

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 most 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: Strong CYP3A4 inhibitors (eg, ketoconazole) increase NUPLAZID concentrations. Reduce the NUPLAZID dose by one-half. Strong CYP3A4 inducers may reduce NUPLAZID exposure, monitor for reduced efficacy. Increase in NUPLAZID dosage may be needed.

Pregnancy: Use of NUPLAZID in pregnant women has not been evaluated and should therefore be used in pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Pediatric Use: Safety and efficacy have not been established in pediatric patients.

Dosage and Administration

Recommended dose: 34 mg per day, taken orally as two 17-mg tablets once daily, without titration.

Indication

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

To report SUSPECTED ADVERSE REACTIONS, contact ACADIA Pharmaceuticals Inc. at 1-844-4ACADIA (1-844-422-2342) or FDA at www.fda.gov/medwatch , or call 1-800-FDA-1088.

Please read the full Prescribing Information including Boxed WARNING.

This website is intended for use by US residents.

Important Safety Information for NUPLAZID (pimavanserin) 17-mg Tablets

Important Safety Information for NUPLAZID (pimavanserin) 17-mg Tablets

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.

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 most 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: Strong CYP3A4 inhibitors (eg, ketoconazole) increase NUPLAZID concentrations. Reduce the NUPLAZID dose by one-half. Strong CYP3A4 inducers may reduce NUPLAZID exposure, monitor for reduced efficacy. Increase in NUPLAZID dosage may be needed.

Pregnancy: Use of NUPLAZID in pregnant women has not been evaluated and should therefore be used in pregnancy only if the potential benefit justifies the potential risk to the mother and fetus.

Pediatric Use: Safety and efficacy have not been established in pediatric patients.

Dosage and Administration

Recommended dose: 34 mg per day, taken orally as two 17-mg tablets once daily, without titration.

Indication

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

To report SUSPECTED ADVERSE REACTIONS, contact ACADIA Pharmaceuticals Inc. at 1-844-4ACADIA (1-844-422-2342) or FDA at www.fda.gov/medwatch , or call 1-800-FDA-1088.

Please read the full Prescribing Information including Boxed WARNING.

This website is intended for use by US residents.

References:

  1. NUPLAZID® (pimavanserin) prescribing information, ACADIA.
  2. Data on file, ACADIA.