Laropiprant

Niacin/laropiprant

Combination of
Niacin	Hypolipidemic agent
Laropiprant	Prostaglandin receptor antagonist
Clinical data
Trade names	Cordaptive, Tredaptive
AHFS/Drugs.com	UK Drug Information
Licence data	EMA:Link
Legal status	Withdrawn
Routes of administration	Oral
Identifiers
ATC code	C10AD52 (WHO)
PubChem	CID: 11948701
NY (what is this?)  (verify)

Laropiprant

Systematic (IUPAC) name
(−)-[(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status	Withdrawn
Identifiers
CAS Number	571170-77-9 Y
ATC code	none
PubChem	CID: 9867642
IUPHAR/BPS	3356
ChemSpider	8043333
UNII	G7N11T8O78 N
KEGG	D08940 Y
ChEMBL	CHEMBL426559 N
Synonyms	MK-0524A
Chemical data
Formula	C21H19ClFNO4S
Molecular mass	435.90 g/mol
SMILES O=S(=O)(c1cc(F)cc2c1n(c3c2CC[C@@H]3CC(=O)O)Cc4ccc(Cl)cc4)C
InChI InChI=1S/C21H19ClFNO4S/c1-29(27,28)18-10-15(23)9-17-16-7-4-13(8-19(25)26)20(16)24(21(17)18)11-12-2-5-14(22)6-3-12/h2-3,5-6,9-10,13H,4,7-8,11H2,1H3,(H,25,26)/t13-/m1/s1 Key:NXFFJDQHYLNEJK-CYBMUJFWSA-N
NY (what is this?)  (verify)

Laropiprant (INN) was a drug used in combination with niacin to reduce blood cholesterol (LDL and VLDL) 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 prostaglandin D₂ receptors (DP₁), increasing blood flow and thus leading to flushes. Laropiprant acts as a selective DP₁ antagonist, reducing the vasodilation.

Taking 325 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, but this medication also increases the risk of gastrointestinal bleeding, 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 (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 treatment and had an increase in adverse effects.