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Niacin (nicotinic acid), one of the naturally occurring B-complex vitamins (vitamin B3), is a well established treatment for hyperlipidaemia. At therapeutic dosages, niacin produces beneficial effects on lipids, including decreases in plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels, increases in high-density lipoprotein (HDL) cholesterol (HDL-C) levels, decreases in triglyceride (TG) levels and decreases in lipoprotein(a) [Lp(a)] levels.[1,2] Niacin is the most effective drug available for elevating HDL-C levels[1] and was the first lipid-modifying drug to significantly decrease cardiovascular events in the Coronary Drug Project.[3] In the Guidelines from the US National Cholesterol Education Adult Treatment Panel III (NCEP ATP III)[4] updated in 2004,[5] the primary goal of therapy for patients with atherosclerotic disease due to dyslipidaemia is the lowering of LDL-C levels.
The beneficial effects of niacin on the lipid profile are dose related, with a dosage of 2000 mg/day producing markedly greater improvements in various lipid parameters than lower dosages of the drug.[6] However, dose-related niacin-associated adverse effects, such as flushing (or 'hot flashes') of the face and trunk, occur in more than 90% of patients receiving treatment with immediate-release formulations of niacin. Flushing is mainly the result of vasodilation, which is caused by niacin-mediated release of prostaglandin (PG)-D2, and is independent of its lipid-modifying effects.[6]
Studies have shown a reduced incidence and intensity of flushing in patients receiving treatment with an extended-release (ER) formulation of niacin (while retaining lipid-modifying efficacy) compared with the immediate-release formulation.[7,8] Nevertheless, flushing remains a problem for many patients and gradual upwards titration of the dose over weeks or months to an effective therapeutic dose may be required to reduce flushing. Moreover, flushing can remain a problem for many patients and discontinuation of niacin treatment is fairly common.[6] With the aim of improving the tolerability profile of niacin, potentially improving adherence to treatment, and allowing a simplified and accelerated dose-advancement regimen,[9,10] a fixed-dose combination tablet containing ER niacin and laropiprant, an anti-flushing agent, ER niacin/laropiprant (Tredaptive(TM)), has been developed and is now approved for use in the EU and some other countries, including Switzerland, Mexico, Norway, Iceland, Peru, Hong Kong, New Zealand, Macau, the Phillipines, Singapore, Croatia, Australia and South Korea.
This article provides an overview of the pharmacological properties of...