Laropiprant

Source: Wikipedia, the free encyclopedia.
Niacin/laropiprant
Combination of
Hypolipidemic agent
LaropiprantProstaglandin receptor antagonist
Clinical data
Trade namesCordaptive, Tredaptive
AHFS/Drugs.comUK Drug Information
License data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • Withdrawn
Identifiers
ECHA InfoCard
100.207.712 Edit this at Wikidata
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Laropiprant
Clinical data
Other namesMK-0524A
AHFS/Drugs.comInternational Drug Names
ATC code
  • none
Legal status
Legal status
  • Withdrawn
Identifiers
  • (−)-[(3R)-4-(4-chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
JSmol)
  • O=S(=O)(c1cc(F)cc2c1n(c3c2CC[C@@H]3CC(=O)O)Cc4ccc(Cl)cc4)C
  • 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
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Laropiprant (

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.[1]

Mechanism of action

Niacin in cholesterol lowering doses (500–2000 mg per day) causes facial flushes by stimulating biosynthesis of

dilates the blood vessels via activation of the prostaglandin D2 receptor subtype DP1, increasing blood flow and thus leading to flushes.[1][2] Laropiprant acts as a selective DP1 receptor antagonist to inhibit the vasodilation of prostaglandin D2-induced activation of DP1.[1]

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,[3] but this medication also increases the risk of gastrointestinal bleeding,[4] though the increased risk is less than 1 percent.[5]

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.[6]

On April 28, 2008, the

U.S. Food and Drug Administration (FDA) issued a "not approved" letter for Cordaptive.[7] Tredaptive was approved by the European Medicines Agency (EMA) on July 3, 2008.[8]

On January 11, 2013, Merck & Co Inc. announced they were withdrawing the drug worldwide as a result of European regulators recommendations.[9]

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.[10]

References

  1. ^ a b c "Tredaptive Prescribing Information" (PDF). Merck & Co. Retrieved 2009-11-14.
  2. S2CID 32102745
    .
  3. ^ Kunin RA (1976). "The Action of Aspirin in Preventing the Niacin Flush and its Relevance to the Antischizophrenic Action of Megadose Niacin" (PDF). Orthomolecular Psychiatry. 5 (2): 89–100. Retrieved 2009-11-14.
  4. S2CID 33742424
    .
  5. ^ Paddock C (31 August 2009). "For Healthy People Daily Aspirin May Do More Harm Than Good". Medical News Today.
  6. S2CID 2126240
    .
  7. BusinessWeek. Archived from the original
    on May 2, 2008. Retrieved 2009-11-13.
  8. ^ "Tredaptive European Public Assessment Report" (PDF). European Medicines Agency. Retrieved November 13, 2009.
  9. ^ "Merck withdraws cholesterol drug Tredaptive globally". Reuters. January 11, 2013. Retrieved 11 January 2013.[dead link]
  10. S2CID 23548060
    .
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