Safety of extended-release niacin/laropiprant in patients with dyslipidemia

J Clin Lipidol. 2010 Mar-Apr;4(2):105-112.e1. doi: 10.1016/j.jacl.2010.02.002. Epub 2010 Feb 12.

Abstract

Objective: To evaluate the safety profile of extended-release niacin/laropiprant (ERN/LRPT), pooling data from studies in the clinical development program.

Methods: Data were pooled from three active- or placebo-controlled phase 3 studies and three 1-year extensions of phase 2 studies that ranged from 12 to 52 weeks (N = 4747): ERN/LRPT = 2548; ERN or Niaspan® (ERN-NSP = 1268); or simvastatin or placebo (SIMVA-PBO = 931).

Results: The safety and tolerability profile for ERN/LRPT was similar to that of ERN-NSP, except for fewer flushing-related adverse experiences and discontinuations with ERN/LRPT than ERN-NSP. The incidence of consecutive ≥3× the upper limit of normal increases in alanine aminotransferase and/or aspartate aminotransferase was numerically (but not statistically) greater with ERN/LRPT (1.0%) than ERN-NSP (0.5%) and similar to SIMVA-PBO (0.9%). Elevations were reversible with therapy discontinuation and not associated with clinical hepatotoxicity. There was no evidence that ERN/LRPT administered alone or concurrently with a statin had adverse effects on muscle. ERN/LRPT and ERN-NSP produced small median increases in fasting blood glucose levels (∼4 mg/dL) after 24 weeks of treatment, consistent with known effects of niacin.

Conclusion: The favorable safety and tolerability profile of ERN/LRPT for up to 1 year supports the use of LRPT to achieve improved therapeutic dosing of niacin, an agent with comprehensive lipid-modifying efficacy and shown to reduce cardiovascular risk.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Delayed-Action Preparations
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy
  • Female
  • Flushing / chemically induced
  • Humans
  • Hypolipidemic Agents / administration & dosage*
  • Hypolipidemic Agents / adverse effects*
  • Indoles / administration & dosage*
  • Indoles / adverse effects*
  • Liver / drug effects
  • Male
  • Middle Aged
  • Muscles / drug effects
  • Niacin / administration & dosage*
  • Niacin / adverse effects*
  • Patient Compliance
  • Receptors, Prostaglandin / antagonists & inhibitors

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Hypolipidemic Agents
  • Indoles
  • MK-0524
  • Receptors, Prostaglandin
  • prostanoid D receptor 1, human
  • Niacin