What are the most common adverse effects of Pimavanserin (Nuplazid)?

Most Common Adverse Effects of Pimavanserin

The most common adverse effects of pimavanserin (Nuplazid) are peripheral edema (7%), confusional state (6%), nausea (7%), hallucinations (5%), and constipation (4%). 1

Primary Adverse Effects

Based on placebo-controlled clinical trials, the following adverse reactions occur most frequently with pimavanserin:

• Common adverse reactions (incidence ≥5% and at least twice the rate of placebo):

  • Peripheral edema (7% with pimavanserin vs. 2% with placebo) 1
  • Confusional state (6% with pimavanserin vs. 3% with placebo) 1
  • Nausea (7% with pimavanserin vs. 4% with placebo) 1

• Other significant adverse reactions (≥2% and greater than placebo):

  • Hallucinations (5% with pimavanserin vs. 3% with placebo) 1
  • Constipation (4% with pimavanserin vs. 3% with placebo) 1
  • Gait disturbance (2% with pimavanserin vs. <1% with placebo) 1

Adverse Reactions Leading to Discontinuation

Approximately 8% of patients treated with pimavanserin discontinued treatment due to adverse reactions, compared to 4% with placebo. The most common reasons for discontinuation included:

• Hallucination (2% vs. <1% with placebo) 1
• Urinary tract infection (1% vs. <1% with placebo) 1
• Fatigue (1% vs. 0% with placebo) 1

Serious Adverse Effects and Warnings

Pimavanserin carries several important warnings that clinicians should be aware of:

• QT interval prolongation: Pimavanserin prolongs the QT interval and should be avoided in patients with:

  • Known QT prolongation 1
  • Concurrent use of other QT-prolonging medications (Class 1A or Class 3 antiarrhythmics, certain antipsychotics, certain antibiotics) 1
  • History of cardiac arrhythmias 1
  • Symptomatic bradycardia, hypokalemia, or hypomagnesemia 1

• Increased mortality in elderly patients with dementia-related psychosis: Pimavanserin carries a boxed warning regarding increased mortality risk in elderly patients with dementia-related psychosis 1

Post-Marketing Adverse Effects

Post-marketing surveillance has identified additional adverse reactions that were not observed in clinical trials:

• Rash and urticaria 1
• Reactions consistent with angioedema (tongue swelling, circumoral edema, throat tightness, dyspnea) 1
• Somnolence 1
• Falls 1
• Agitation and aggression 1
• Fecal incontinence 1

Recent pharmacovigilance studies have shown an upward trend in adverse event reporting for pimavanserin, with psychiatric disorders being the most significant category of adverse events 2.

Special Populations

• Demographic differences: No significant differences in adverse effect profiles were observed based on age (≤75 vs. >75 years) or sex 1
• Cognitive status: No clinically relevant differences in adverse reactions were observed among patients with different cognitive status (MMSE <25 vs. ≥25) 1

Drug Interactions

• Strong CYP3A4 inhibitors: Increase pimavanserin exposure, requiring dose reduction to 10 mg once daily 1
• Strong or moderate CYP3A4 inducers: Reduce pimavanserin exposure; concomitant use should be avoided 1

Monitoring Recommendations

When initiating pimavanserin therapy, clinicians should:

• Monitor for signs of QT prolongation, especially in patients with risk factors 1
• Be vigilant for psychiatric symptoms including confusion, hallucinations, and agitation 1
• Watch for peripheral edema, particularly in patients with cardiovascular comorbidities 1
• Monitor for gastrointestinal symptoms such as nausea and constipation 1