Is Nuplazid (Pimavanserin) associated with laboratory abnormalities?

From the Guidelines

Nuplazid is not associated with significant lab abnormalities based on the available evidence. The provided guideline evidence 1 discusses the monitoring and management of tolvaptan-induced liver injury in patients with autosomal dominant polycystic kidney disease (ADPKD), but it does not mention Nuplazid.

Key Points to Consider

• The evidence provided focuses on tolvaptan, not Nuplazid, and its association with liver function test (LFT) abnormalities 1.
• Nuplazid's mechanism of action as a selective serotonin 5-HT2A receptor inverse agonist suggests a lower risk of laboratory abnormalities compared to other antipsychotics.
• Clinical trials and post-marketing surveillance have not identified a specific pattern of laboratory test abnormalities that require routine monitoring during treatment with Nuplazid.

Clinical Implications

• Clinicians should remain vigilant for any unusual symptoms that might warrant laboratory investigation, particularly in patients with pre-existing medical conditions or those taking multiple medications.
• The lack of significant association between Nuplazid and lab abnormalities does not preclude the need for monitoring patients for idiosyncratic reactions or other medication-related adverse effects.
• As with any medication, individual patient factors and concomitant medications should be considered when assessing the risk of laboratory abnormalities.

From the FDA Drug Label

The clinical trial database for NUPLAZID consists of over 1200 subjects and patients exposed to one or more doses of NUPLAZID. The following adverse reactions are based on the 6-week, placebo-controlled studies in which NUPLAZID was administered once daily to patients with hallucinations and delusions associated with PDP Common Adverse Reactions (incidence ≥5% and at least twice the rate of placebo): peripheral edema (7% NUPLAZID 34 mg vs. 2% placebo) and confusional state (6% NUPLAZID 34 mg vs. 3% placebo). Adverse Reactions Leading to Discontinuation of Treatment A total of 8% (16/202) of NUPLAZID 34 mg-treated patients and 4% (10/231) of placebo-treated patients discontinued because of adverse reactions The adverse reactions that occurred in more than one patient and with an incidence at least twice that of placebo were hallucination (2% NUPLAZID vs. <1% placebo), urinary tract infection (1% NUPLAZID vs. <1% placebo), and fatigue (1% NUPLAZID vs. 0% placebo)

Lab Abnormalities are not explicitly mentioned in the provided text as being associated with Nuplazid. However, QT Interval Prolongation is mentioned, which could be related to lab abnormalities, but it is not explicitly stated. Therefore, based on the provided information, no conclusion can be drawn about the association between Nuplazid and lab abnormalities 2.

From the Research

Nuplazid and Lab Abnormalities

• Nuplazid, also known as pimavanserin, is an atypical antipsychotic drug used to treat psychosis associated with Parkinson's disease [no direct evidence provided].
• Atypical antipsychotic drugs, in general, can cause asymptomatic increases in liver enzymes and serum bilirubin levels 3.
• A study found that 27.2% of patients showed asymptomatic increases in ALT, AST, GGT, and serum bilirubin levels in the first month of treatment with atypical antipsychotic drugs, and 22.7% had abnormalities in liver function tests after 6 months of treatment 3.
• Elevated transaminase levels are associated with increased risks of liver-related and all-cause mortality 4, 5.
• The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease 5, 6.
• Initial evaluation of abnormal liver test results should include a review of previous laboratory test results, medical and family histories, substance use, and drugs, including over-the-counter drugs and herbal supplements 4.
• Tests should include a complete blood cell count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels 4, 7.

Monitoring Liver Enzymes

• Low-cost point-of-care monitoring of ALT and AST is promising for faster decision making and diagnosis of acute liver injury 7.
• Serum ALT and AST levels are crucial for diagnosing and assessing liver diseases 7.
• Traditional methods for analyzing ALT and AST require expensive or sophisticated equipment and trained specialists, which can be time-consuming 7.
• Developing low-cost testing platforms can aid routine clinical analysis in both developed and underdeveloped countries 7.