cholesterol, and triglycerides. ii. nicotinic acid is also indicated as adjunctive therapy for the treatment of adult patients with very high serum triglyceride levels (types iv and v hyperlipidemia) † who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them. such patients typically have serum triglyceride levels over 2000 mg/dl and have elevations of vldl cholesterol as well as fasting chylomicrons (type v hyperlipidemia) † . subjects who consistently have total serum or plasma triglycerides below 1000 mg/dl are unlikely to develop pancreatitis. therapy with nicotinic acid may be considered for those subjects with triglyceride elevations between 1,000 and 2,000 mg/dl who have a history of pancreatitis or of recurrent abdominal pain typical of pancreatitis. some type iv patients with triglycerides under 1,000 mg/dl may, through dietary or alcoholic indiscretion, convert to a type v pattern with massive triglyceride elevations accompanying fasting chylomicronemia, but the influence of nicotinic acid therapy on the risk of pancreatitis in such situations has not been adequately studied. drug therapy is not indicated for patients with type i hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of vldl. inspection of plasma refrigerated for 14 hours is helpful in distinguishing types i, iv, and v hyperlipoproteinemia 7 . † classification of hyperlipoproteinemias lipoproteins lipid elevations type elevated major minor c = cholesterol, tg = triglycerides ldl = low-density lipoprotein vldl = very low-density lipoprotein idl = intermediate-density lipoprotein i (rare) chylomicrons tg ↑→ c iia ldl c ..... iib ldl, vldl c tg iii (rare) idl c/tg ..... iv vldl tg ↑→ c v (rare) chylomicrons, vldl tg ↑→ c

sidered if elevations persist beyond discontinuation of the drug. nicotinic acid should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. active liver diseases or unexplained transaminase elevations are contraindications to the use of nicotinic acid. skeletal muscle rare cases of rhabdomyolysis have been associated with concomitant administration of lipid-altering doses (≥1 g/day) of nicotinic acid and hmg-coa reductase inhibitors. physicians contemplating combined therapy with hmg-coa reductase inhibitors and nicotinic acid should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. periodic serum creatine phosphokinase (cpk) and potassium determinations should be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.

eceiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents. elevated uric acid levels have occurred with nicotinic acid therapy, therefore use with caution in patients predisposed to gout.

er the course of several weeks. flushing, pruritus, and gastrointestinal distress are also greatly reduced by slowly increasing the dose of nicotinic acid and avoiding administration on an empty stomach. sustained-release (modified-release, timed-release) nicotinic acid preparations should not be substituted for equivalent doses of immediate-release (crystalline) nicotinic acid.

nicotinic acid versus 25.4% with placebo; p =n.s.), in a fifteen year cumulative follow-up there were 11% (69) fewer deaths in the nicotinic acid group compared to the placebo cohort (52.0% versus 58.2%; p=0.0004) 2 . the cholesterol-lowering atherosclerosis study (clas) was a randomized, placebo-controlled, angiographic trial testing combined colestipol and nicotinic acid therapy in 162 non-smoking males with previous coronary bypass surgery 3 . the primary, per subject cardiac endpoint was global coronary artery change score. after two years, 61% of patients in the placebo cohort showed disease progression by global change score (n=82), compared with only 38.8% of drug-treated subjects (n=80), when both native arteries and grafts were considered (p<0.005). in a follow-up to this trial in a subgroup of 103 patients treated for four years, again, significantly fewer patients in the drug-treated group demonstrated progression than in the placebo cohort (48% versus 85%, respectively; p< 0.0001) 4 . the familial atherosclerosis treatment study (fats) in 146 men ages 62 and younger with apolipoprotein b levels ≥125 mg/dl, established coronary artery disease, and family histories of vascular disease, assessed change in severity of disease in the proximal coronary arteries by quantitative arteriography 5 . patients were given dietary counseling and randomized to treatment with either conventional therapy with double placebo (or placebo plus colestipol if the ldl cholesterol was elevated); lovastatin plus colestipol; or nicotinic acid plus colestipol. in the conventional therapy group, 46% of patients had disease progression (and no regression) in at least one of nine proximal coronary segments. in contrast, progression (as the only change) was seen in only 25% in the nicotinic acid plus colestipol group. though not an original endpoint of the trial, clinical events (death, myocardial infarction, or revascularization for worsening angina) occurred in 10 of 52 patients who received conventional therapy, compared with 2 of 48 who received nicotinic acid plus colestipol. nicotinic acid (but not nicotinamide) in gram doses produces an average 10% to 20% reduction in total and ldl cholesterol, a 30% to 70% reduction in triglycerides, and an average 20% to 35% increase in hdl cholesterol. the magnitude of individual lipid and lipoprotein responses may be influenced by the severity and type of underlying lipid abnormality. the increase in total hdl is associated with a shift in the distribution of hdl sub-fractions (as defined by ultra-centrifugation) with an increase in the hdl 2 :hdl 3 ratio and an increase in apolipoprotein a-i content. the mechanism by which nicotinic acid exerts these effects is not entirely understood, but may involve several actions, including a decrease in esterification of hepatic triglycerides. nicotinic acid treatment also decreases the serum levels of apolipoprotein b-100 (apo b), the major protein component of the very low-density lipoprotein (vldl) and ldl fractions, and of lipoprotein a [lp(a)], a variant form of ldl independently associated with coronary risk. the effect of nicotinic acid-induced changes in lipids/lipoproteins on cardiovascular morbidity or mortality in individuals without pre-existing coronary disease has not been established. pharmacokinetics following an oral dose, the pharmacokinetic profile of nicotinic acid is characterized by rapid absorption from the gastrointestinal tract and a short plasma elimination half-life. at a 1 gram dose, peak plasma concentrations of 15 to 30 µg/ml are reached within 30 to 60 minutes. approximately 88% of an oral pharmacologic dose is eliminated by the kidneys as unchanged drug and nicotinuric acid, its primary metabolite. the plasma elimination half-life of nicotinic acid ranges from 20 to 45 minutes.