Nuplazid (pimavanserin): Parkinson’s Drug Uses & Side Effects

What is Nuplazid (pimavanserin), and how is it used?

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

What are the side effects of Nuplazid (pimavanserin)?

WARNING

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.

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

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 the presence of congenital prolongation of the QT interval

Common Adverse Reactions:

What is the dosage of Nuplazid (pimavanserin)?

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

Nuplazid (pimavanserin) is available as 17 mg strength tablets. The white to off-white, round, coated tablets are debossed on one side with a “P” and “17” on the reverse side.

Nuplazid can be taken with or without food.

What drugs interact with Nuplazid (pimavanserin)?

Class 1A antiarrhythmics:

Class 3 antiarrhythmics:

Antipsychotics:

Antibiotics:

Strong CYP3A4 Inhibitors:

Strong CYP3A4 Inducers:

Is Nuplazid (pimavanserin) safe to use while pregnant or breastfeeding?

There are no data on Nuplazid use in pregnant women that would allow assessment of the drug-associated risk of major congenital malformations or miscarriage. In animal reproduction studies, no adverse developmental effects were seen when pimavanserin was administered orally to rats or rabbits during the period of organogenesis at doses up to 10- or 12-times the maximum recommended human dose (MRHD) of 34 mg/day, respectively. Administration of pimavanserin to pregnant rats during pregnancy and lactation resulted in maternal toxicity and lower pup survival and body weight at doses which are 2-times the MRHD of 34 mg/day.

There is no information regarding the presence of pimavanserin in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Nuplazid and any potential adverse effects on the breastfed infant from Nuplazid or from the underlying maternal condition.

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How does Nuplazid (pimavanserin) work?

The mechanism of action of pimavanserin in the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis is unknown. However, the effect of pimavanserin 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.

In vitro, pimavanserin acts as an inverse agonist and antagonist at serotonin 5-HT2A receptors with high binding affinity (Ki value 0.087 nM) and at serotonin 5-HT2C receptors with lower binding affinity (Ki value 0.44 nM). Pimavanserin shows low binding to sigma 1 receptors (Ki value 120 nM) and has no appreciable affinity (Ki value >300 nM), to serotonin 5-HT2B, dopaminergic (including D2), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.

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