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

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.