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Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing

      Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (>6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) ≥4 (primary end point) and the percentage of patients with a maximum GFSS of ≥4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of ≥4 (p <0.001) and the percentage of patients with a maximum GFSS of ≥4 (p <0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.
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      References

        • Knopp R.H.
        • Ginsberg J.
        • Albers J.J.
        • Hoff C.
        • Ogilvie J.T.
        • Warnick G.R.
        • Burrows E.
        • Retzlaff B.
        • Poole M.
        Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin.
        Metabolism. 1985; 34: 642-650
        • Birjmohun R.S.
        • Hutten B.A.
        • Kastelein J.J.
        • Stroes E.S.
        Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice.
        Neth J Med. 2004; 62: 229-234
        • Illingworth D.R.
        • Stein E.A.
        • Mitchel Y.B.
        • Dujovne C.A.
        • Frost P.H.
        • Knopp R.H.
        • Tun P.
        • Zupkis R.V.
        • Greguski R.A.
        Comparative effects of lovastatin and niacin in primary hypercholesterolemia: a prospective trial.
        Arch Intern Med. 1994; 154: 1586-1595
        • Mills E.
        • Prousky J.
        • Raskin G.
        • Gagnier J.
        • Rachlis B.
        • Montori V.M.
        • Juurlink D.
        The safety of over-the-counter niacin.
        BMC Clin Pharmacol. 2003; 3: 4-11
        • Cheng K.
        • Wu T.J.
        • Wu K.K.
        • Sturino C.
        • Metters K.
        • Gottesdiener K.
        • Wright S.D.
        • Wang Z.
        • Lai E.
        • Waters M.G.
        • Waters M.G.
        Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans.
        Proc Natl Acad Sci U S A. 2006; 103: 6682-6687
        • Sturino C.F.
        • O'Neill G.
        • Lachance N.
        • Boyd M.
        • Berthelette C.
        • Labelle M.
        • Li L.
        • Roy B.
        • Scheigetz J.
        • Tsou N.
        • Aubin Y.
        • Bateman K.P.
        • Chauret N.
        • Day S.H.
        • Levesque J.F.
        • Seto C.
        • Silva J.H.
        • Trimble L.A.
        • Carriere M.C.
        • Denis D.
        • Greig G.
        • Kargman S.
        • Lamontagne S.
        • Mathieu M.C.
        • Sawyer N.
        • Slipetz D.
        • Abraham W.M.
        • Jones T.
        • McAuliffe M.
        • Piechuta H.
        • Nicoll-Griffith D.A.
        • Wang Z.
        • Zamboni R.
        • Young R.N.
        • Metters K.M.
        Discovery of a potent and selective prostaglandin D(2) receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524).
        J Med Chem. 2007; 50: 794-806
        • Paolini J.F.
        • Mitchel Y.B.
        • Reyes R.
        • Kher U.
        • Lai E.
        • Watson D.J.
        • Norquist J.M.
        • Meehan A.G.
        • Bays H.E.
        • Davidson M.
        • Ballantyne C.M.
        Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia.
        Am J Cardiol. 2008; 101: 625-630
        • Maccubbin D.
        • Bays H.E.
        • Olsson A.G.
        • Elinoff V.
        • Elis A.
        • Mitchel Y.
        • Sirah W.
        • Betteridge A.
        • Reyes R.
        • Yu Q.
        • Kuznetsova O.
        • Sisk C.M.
        • Pasternak R.C.
        • Paolini J.F.
        Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.
        Int J Clin Pract. 2008; 62: 1959-1970
        • Norquist J.M.
        • Watson D.J.
        • Yu Q.
        • Paolini J.F.
        • McQuarrie K.
        • Santanello N.C.
        Validation of a questionnaire to assess niacin-induced cutaneous flushing.
        Curr Med Res Opin. 2007; 23: 1549-1560