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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advicor (lovastatin and extended-release niacin) is the first cholesterol-lowering combination product to become available for the management of hyperlipidemia. Lovastatin significantly lowers low-density lipoprotein cholesterol, whereas niacin significantly lowers triglycerides and lipoprotein (a) and markedly increases high-density lipoprotein cholesterol. These effects are ideal for managing a variety of lipid disorders, including metabolic syndrome. Lovastatin and niacin reduce coronary heart disease mortality in primary and secondary prevention patients, respectively. The extended-release niacin component uses a unique technology to minimize adverse effects (e.g., flushing and hepatotoxicity) while retaining the same lipid-altering effects as immediate-release niacin. The combination product appears to be well tolerated, with discontinuation due to adverse effects other than flushing occurring in a similar percent of patients as for lovastatin in clinical trials. Approximately 9% of patients discontinued the combination product due to flush. No confined cases of myopathy or hepatotoxicity have been reported with this product. Once-daily dosing provides ease of administration that should improve compliance and result in a greater proportion of patients meeting their low-density lipoprotein cholesterol goals. The nomenclature surrounding niacin products used to treat dyslipidemias is confusing. While only two types of niacin formulations exist (immediate-release formulations and formulations which dissolve more slowly than immediate-release formulations), government regulations allow for slowly dissolved niacin formulations to be divided into two types of niacin products; those that are available over-the-counter (OTC) and those that are available by prescription only. Over-the-counter slowly dissolved niacin preparations are not classified as OTC per se, but are considered "nutritional supplements". For this reason, they fall under the jurisdiction of the Federal Trade Commission and do not fall under the umbrella of the FDA branch that controls dyslipidemic products (Endocrine and Metabolic Division of the Center for Drug Evaluation and Research). The slowly dissolved niacin nutritional supplements have not been reviewed by the FDA for safety nor efficacy in the treatment of dyslipidemia nor are they required to meet generic drug rules (even though various brands are available). These brands are described on their labels as "sustained-release", "timed-release", and "slow-release" for example. Only two slowly absorbed niacin products have been approved by the FDA for the treatment of dyslipidemia; they are Niaspan (Kos Pharmaceuticals, Inc., Miami, FL) and Advicor (Kos Pharmaceuticals, Inc., Miami, FL). The term "extended-release" has been given to these two products to simplify the terminology and differentiate the products from immediate-release niacin. In this review, we will use "extended-release" to refer to the FDA approved slowly dissolving niacin preparation and "sustained-release" to refer to the nutritional supplements (not FDA approved).
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PMID:Lovastatin and extended-release niacin combination product: the first drug combination for the management of hyperlipidemia. 1197 44

Niacin (nicotinic acid) favourably modifies all aspects of the lipoprotein profile; it raises high-density lipoprotein cholesterol (HDL-C) levels, lowers triglyceride, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) levels and reduces atherogenic small, dense LDL particles. One large monotherapy trial and multiple trials of niacin in combination with other lipid-modifying drugs show remarkable consistency in the ability of niacin to improve angiographic and clinical outcomes. In practice, however, the use of regular, immediate-release niacin (niacin IR) has been limited by the side effect of flushing. Sustained-release (SR) formulations, developed in order to reduce flushing, were found to cause serious hepatotoxicity at varying frequencies. Extended-release niacin (niacin ER; Niaspan), Kos Pharmaceuticals, Inc.) is a prescription formulation of niacin, administered once-daily at bedtime. Niacin ER is as effective in modifying lipoprotein levels as an equal daily dose of niacin IR and it causes less flushing. In addition, niacin ER administered once-daily is not associated with the increased hepatotoxicity reported with SR formulations. Niacin ER has been studied extensively in combination therapy with statins, including lovastatin in a recently introduced combination tablet. Myopathy has not been a substantial problem in statin/niacin ER combination therapy. Finally, a study of niacin ER given to diabetic patients showed only mild trends towards increased glycosylated haemoglobin concentrations and a need for additional antidiabetic medication. Thus, niacin ER represents an effective and safe option in the management of low levels of HDL-C and other lipoprotein abnormalities in a variety of settings.
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PMID:Extended-release niacin for modifying the lipoprotein profile. 1516 82

Prolonged-release (PR) nicotinic acid (niacin) [Niaspan] is an oral, once-daily formulation of the lipid-modifying drug designed to produce less vasodilatory flushing than crystalline immediate-release (IR) nicotinic acid and less hepatotoxicity than previous sustained-release formulations of nicotinic acid.PR nicotinic acid appears to retain the same level of efficacy as crystalline IR nicotinic acid and be better tolerated than older nicotinic acid formulations. Nicotinic acid has beneficial effects on all traditional blood lipid and lipoprotein fractions and is the most effective agent for increasing high-density lipoprotein (HDL)-cholesterol (HDL-C) and reducing lipoprotein(a). The effects of PR nicotinic acid are often additive when used in combination with HMG-CoA reductase inhibitors (statins), making it a useful addition when lipid goals are not achieved with the usual statin monotherapy or when additional correction of a specific lipid abnormality is required. PR nicotinic acid also slows atherosclerotic progression and even appears to produce regression of atherosclerosis in patients on stable statin therapy. PR nicotinic acid is a logical drug choice for treating atherogenic dyslipidaemia commonly associated with type 2 diabetes mellitus and the metabolic syndrome, and has been shown to be effective in patients with diabetes without adversely affecting glycaemic control in the majority of patients. The incidence of vasodilatory flushing with PR nicotinic acid is lower than with IR nicotinic acid and it decreases substantially over time as tolerance develops. To date, there has been no clinically significant hepatotoxicity observed with PR nicotinic acid. Therefore, once-daily PR nicotinic acid appears to maximise the potential benefits of nicotinic acid, while minimising any historical tolerability or safety concerns.
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PMID:Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. 1639 85

Familial combined hyperlipidemia (FCH) is a frequent familial lipid disorder associated with insulin resistance, low HDL cholesterol, high triglycerides and cholesterol levels with variable phenotypes within the same family. FCH is linked to a high risk for cardiovascular diseases. Treatment goals for lipid abnormalities are changing in recent years. Lowering elevated levels of LDL e Non HDL-cholesterol levels are primary targets of therapy. Lower LDL-C than 70 mg/dL seems to be useful to lower cardiovascular risk in patients with very high risk. Many statins are available, with different potencies and drug interactions. Combination therapy of statins and bile acid sequestrants or ezitimibe may be necessary to further decrease LDL cholesterol levels in order to meet guideline goals. High triglycerides and low HDL cholesterol are also important goals in the treatment of these patients, and frequently statins alone are insufficient to normalize the lipid profile. Combination therapy with fibrates will further lower triglycerides and increase HDL cholesterol levels; this combination is also associated with higher incidence of myopathy and liver toxicity; appropriate evaluation of patients' risk and benefits is necessary. Association of statin/niacin seems be very useful in patients with FCH, especially as niacin is the best drug to increase HDL cholesterol; this association is not linked to a higher frequency of myopathy. Niacin causes flushing, that can in part be managed with use of aspirin and extended release forms (Niaspan); niacin also may increase plasma glucose and uric acid levels. Evaluation of risks and benefits for each patient is needed.
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PMID:[Treatment of dyslipidemia: how and when to combine lipid lowering drugs]. 1676 1

Low HDL-cholesterol (<1.02 mmol/L [40 mg/dL] in men or <1.29 mmol/L [50 mg/dL] in women) occurs in about one-third of European patients with dyslipidemia and is an independent cardiovascular risk factor. Simultaneous correction of low HDL-cholesterol and high total-cholesterol and LDL-cholesterol may provide reductions in cardiovascular morbidity and mortality beyond those possible with statins alone. Nicotinic acid (niacin in the US) is the most effective means of increasing HDL-cholesterol available and has been shown to reduce cardiovascular event rates significantly. Niaspan (prolonged-release nicotinic acid) provides a convenient, once-daily means of administering nicotinic acid. Clinical studies with Niaspan have demonstrated marked, long-term increases in HDL-cholesterol with additional useful benefits on triglycerides, LDL-cholesterol, and lipid sub-profiles. The NAUTILUS study demonstrated the beneficial efficacy and tolerability profiles of Niaspan in a usual-care setting. The most common side-effect of Niaspan is flushing, which infrequently causes treatment discontinuation and which usually subsides over continued treatment. The ARBITER 2 and ARBITER 3 studies showed 1-2 years of treatment with Niaspan plus a statin induced regression of atherosclerosis in patients with coronary artery disease. The effect of Niaspan-statin treatment, relative to a statin alone, on clinical cardiovascular outcomes is currently under evaluation. Niaspan represents a practical means of correcting low HDL-cholesterol, an independent risk factor for adverse cardiovascular outcomes.
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PMID:Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study. 1796 77

Niacin (nicotinic acid) is not optimally used mainly because of flushing, a process mediated primarily by prostaglandin D(2), which leads to poor patient compliance and suboptimal dosing. This phase II dose-ranging study was designed to assess whether the prostaglandin D(2) receptor 1 antagonist laropiprant (LRPT; MK-0524) would (1) reduce extended-release niacin (ERN)-induced flushing in dyslipidemic patients and (2) support a novel accelerated ERN dosing paradigm: initiating ERN at 1 g and advancing rapidly to 2 g. In part A of the study, 154 dyslipidemic patients were randomized to LRPT 150 mg/day or placebo in a 9-week, 2-period crossover study. Patients who completed part A (n = 122) entered part B (after a 2-week washout), together with additional patients who entered part B directly (n = 290). Part B patients were randomized to placebo, ERN 1 g (Niaspan, no previous titration), or ERN 1 g coadministered with LRPT 18.75, 37.5, 75, or 150 mg for 4 weeks, with doubling of the respective doses for the remaining 4 weeks. Patients treated with LRPT plus ERN experienced significantly less ERN-induced flushing than those treated with ERN alone during the initiation of treatment (ERN 1 g, week 1) and the maintenance treatment (ERN 1 to 2 g, weeks 2 to 8). All doses of LRPT were maximally effective in inhibiting niacin-induced flushing. LRPT did not alter the beneficial lipid effects of ERN. LRPT plus ERN was well tolerated. In conclusion, the significant reduction in ERN-induced flushing provided by LRPT plus ERN supports an accelerated ERN dose-advancement paradigm to achieve rapidly a 2-g dose in dyslipidemic patients.
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PMID:Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. 1830 10

Niacin has long been used in the treatment of dyslipidemia and cardiovascular disease. Recent research on niacin has been focused on understanding the mechanism of action of niacin and preparation of safer niacin formulations. New findings indicate that niacin does the following: 1) it inhibits hepatic diacylglycerol acyltransferase 2, resulting in inhibition of triglyceride synthesis and decreased apolipoprotein B-containing lipoproteins; 2) it decreases the surface expression of hepatic adenosine triphosphate synthase beta-chain, leading to decreased holoparticle high-density lipoprotein catabolism and increased high-density lipoprotein levels; and 3) it increases redox potential in arterial endothelial cells, resulting in inhibition of redox-sensitive genes. Flushing, an adverse effect of niacin, results from niacin receptor GPR109A-mediated production of prostaglandin D2 and E2 via DP1 and EP2/4 receptors. DP1 receptor antagonist (laropiprant) attenuates the niacin flush. A reformulated preparation of extended-release niacin (Niaspan; Abbott, Abbott Park, IL) lowers flushing compared with an older Niaspan formulation. These advancements in niacin research have rejuvenated its use for the treatment of dyslipidemia and cardiovascular disease.
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PMID:Niacin: an old drug rejuvenated. 1908 Jul 27

Niacin is a water-soluble B vitamin (B3) known to have favorable effects on multiple lipid parameters, including raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglycerides (TGs), lipoprotein(a), and low-density lipoprotein cholesterol (LDL-C). Although LDL-C remains the primary target of lipid-altering therapy, current guidelines emphasize HDL-C and other modifiable lipid factors as key secondary targets. Thus, niacin is considered an important therapeutic option to help reduce the risk of cardiovascular disease in patients with mixed dyslipidemia who, in addition to high LDL-C, have elevated TGs and low HDL-C. Although available prescription niacin products, including immediate-release niacin (IR; Niacor) and an extended-release niacin formulation (Niaspan), have demonstrated safety and efficacy in randomized clinical trials, confusion remains among health care providers and their patients regarding the various commercially available nonprescription dietary supplement niacin products. These dietary supplements, which include IR, sustained-release (SR), and "no-flush" or "flush-free" niacin products, are not subject to the same stringent US Food and Drug Administration regulations as prescription drugs. In fact, both the American Heart Association and the American Pharmacists Association recommend against the use of dietary supplement niacin as a substitute for prescription niacin. Although some dietary supplement IR and SR niacin products have demonstrated a lipid response in clinical trials, products labeled as "no-flush" or "flush-free" that are intended to avoid the common niacin-associated adverse effect of flushing generally contain minimal or no free, pharmacologically active niacin and therefore lack beneficial lipid-modifying effects. To clarify important differences between available prescription and dietary supplement niacin products, this article contrasts current regulatory standards for dietary supplements and prescription drugs and provides an overview of available clinical data from key trials of niacin.
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PMID:Important considerations for treatment with dietary supplement versus prescription niacin products. 2147 95


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