Laropiprant (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

) was a drug used in combination with

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

to reduce blood cholesterol (

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

and

VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipo ...

) that is no longer sold, due to increases in side-effects with no cardiovascular benefit. Laropiprant itself has no cholesterol lowering effect, but it reduces facial flushes induced by niacin. Merck & Co. planned to market this combination under the trade names Cordaptive in the US and Tredaptive in Europe. Both brands contained 1000 mg of niacin and 20 mg of laropiprant in each tablet.

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 dilates the blood vessels via activation of the prostaglandin D₂ receptor subtype DP₁, increasing blood flow and thus leading to flushes. Laropiprant acts as a selective DP₁ receptor antagonist to inhibit the vasodilation of prostaglandin D₂-induced activation of DP₁. Taking 325 mg of

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

20–30 minutes prior to taking niacin has also been proven to prevent flushing in 90% of patients, presumably by suppressing prostaglandin synthesis, but this medication also increases the risk of

gastrointestinal bleeding Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include ...

, though the increased risk is less than 1 percent.

History

In the mid-2000s, in a trial with 1613 patients, 10.2% patients stopped taking the medication in the combination drug group versus 22.2% under niacin monotherapy. On April 28, 2008, the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) issued a "not approved" letter for Cordaptive. Tredaptive was approved by the European Medicines Agency (EMA) on July 3, 2008. On January 11, 2013, Merck & Co Inc. announced they were withdrawing the drug worldwide as a result of European regulators recommendations. The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) involved more than 25,000 adults. The treatment group received 2 g of extended-release niacin and 40 mg of laropiprant daily. Study results, reported in July 2014, showed that the combination of niacin and laropiprant did not have any beneficial effects when compared with a

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

treatment and had an increase in adverse effects.

References

{{Prostanoidergics Combination lipid-lowering drugs Drugs developed by Merck & Co. Indoles Chloroarenes Fluoroarenes Benzosulfones