Laropiprant

Laropiprant

Laropiprant (INN) is used in combination with niacin to reduce blood cholesterol (LDL and VLDL). Merck & Co. planned to market this combination under the trade names Cordaptive in the US and Tredaptive in Europe. Both brands contain 1000 mg of niacin and 20 mg of laropiprant in each tablet.[1] Laropiprant itself has no cholesterol lowering effect, but it reduces facial flushes induced by niacin. In a trial with 1613 patients, 10.2% patients stopped taking the medication in the combination drug group versus 22.2% under niacin monotherapy.[2]

History

On April 28, 2008, the U.S. Food and Drug Administration (FDA) issued a "not approved" letter for Cordaptive.[3] Tredaptive was approved by the European Medicines Agency (EMA) on July 3, 2008.[4]

In December of 2012 results of the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that the combination of niacin and laropiprant did not have any beneficial effects when compared with statin treatment and had an increase in adverse effects.[5]

On January 11, 2013, Merck & Co Inc. announced they are withdrawing the drug worldwide as a result of European regulators recommendations.[6]

Mechanism of action

Niacin in cholesterol lowering doses (500–2000 mg per day) causes facial flushes by stimulating biosynthesis of prostaglandin D2 (PGD2), especially in the skin. PGD2 acts as a vasodilator via prostaglandin D2 receptors (DP1), increasing blood flow and thus leading to flushes.[1][7] Laropiprant acts as a DP1 antagonist, reducing the vasodilation.[1]

Taking 650 mg of aspirin 20–30 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis,[8] but this medication also increases the risk of gastrointestinal bleeding,[9] though the increased risk is less than 1 percent.[10]

References