Niacin hepatotoxicity

Niacin 50 to 750 mg tabs or caps, i m med i ate- re I ease 250 to 750 mg sustained-release 1 -5 g/day in three or more divided doses 1-2 g/day (never exceed 2 g/day due to increased risk of hepatotoxicity) hyperuricemia. 

Several different niacin formulations are available niacin immediate-release (IR), niacin sustained-release (SR), and niacin extended-release (ER).28,29 These formulations differ in terms of dissolution and absorption rates, metabolism, efficacy, and side effects. Limitations of niacin IR and SR are flushing and hepatotoxicity, respectively. These differences appear related to the dissolution and absorption rates of niacin formulations and its subsequent metabolism. Niacin IR is available by prescription (Niacor ) as well as a dietary supplement which is not regulated by the FDA.28 Currently, there are no FDA-approved niacin SR products, thus, all SR products are available only as dietary supplements. 

Regimens intended to increase HDL levels should include either gemfibrozil or niacin, bearing in mind that statins combined with either of these drugs may result in a greater incidence of hepatotoxicity or myositis. 

The beneficial and adverse effects of nicotinic acid (niacin) have been reviewed (12). Standard nicotinic acid from an immediate-release formulation is metabolized primarily by conjugation, which results in a high frequency of flushing. Long-acting nicotinic acid is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Modified-release nicotinic acid, on the other hand, has a more balanced metabolism and causes fewer of both types of adverse effects. 

Coppola A, Brady PG, Nord HJ (1994) Niacin-induced hepatotoxicity unusual presentations. South Med J 87 30-32. 

Adverse effects of niacin are most commonly seen when this vitamin is used at pharmacological doses above I g/day in the treatment of dyslipidemia. Notable adverse effects include flushing due to vasodilatation dermatological effects including dry skin pruritus and hyperkeratosis gastrointestinal effects including peptic ulcer,. stomach pain, nausea. and diarrhea elevations in serum uric acid and glucose and hepatotoxicity. ... 

Chronic megadoses of niacin may be associated with hyperglycemia, hyperuricemia, cardiac arrhythmias, hepatotoxicity, cystoid maculopathy, myopathy, peptic ulcers, and hyperkeratotic pigmented skin lesions. These problems may occur with doses exceeding 3gday. ... 

Niacin-induced vasodilation is believed to be mediated by prostaglandins. The mechanism of hepatotoxicity associated with niacin use is unknown. 

Niacin TLDL and VLDL Synthesis 4-Triglyceride and cholesterol 4VLDL, 4LDL, fHDL Problems with patient acceptance good in combination with bile acid resins extended-release niacin causes less flushing and is less hepatotoxic than sustained-release niacin... 

Over-the-connter, snstained-release niacin preparations and Niaspan are effective up to a total daily dose of 2 g per day. All doses of sustained-release niacin, but particularly doses above 2 g per day, have been reported to cause hepatotoxicity, which may occur soon after beginning therapy or after several years of nse. The potential for severe liver damage shonld preclnde its nse in most patients, inclnding those who have taken an eqnivalent dose of crystalline niacin safely for many years and are considering switching to a sustained-release preparation. Niaspan may be less likely to cause hepatotoxicity. 

Niacin may cause hepatotoxicity with prolonged therapy. This is usually manifested as nausea and vomiting, with altered liver enzyme profile. 

The most common serious side effects are hepatotoxicity, manifested as elevated serum transaminases and hyperglycemia Both regular (crystalline) niacin and sustained-release niacin have been reported to cause severe liver toxicity, and sustained-release niacin can cause fulminant hepatic failure. An extended-release niacin (NIASPAN), appears to be less likely to cause severe hepatotoxicity, perhaps because it is administered only once daily. The incidence of flushing and pruritus with this preparation is not substantially different from that with regular niacin. Severe hepatotoxicity is more likely to occur when patients take >2 g of sustained-release, over-the-counter preparations. Affected patients experience flu-like fatigue and weakness. Usually, serum transaminases are elevated serum albumin levels decline, and total cholesterol and LDL-C levels decline substantially. 

The two primary adverse effects of the HMG-CoA reductase inhibitors are hepatotoxicity and myopathy. Patients taking these drugs should have liver function tests performed before starting therapy and then at regular intervals during therapy. Serum concentrations of alanine and aspartate aminotransferase are used as markers of hepatocellular toxicity. The answer is (B). The major recognized effect of niacin is reduction of VLDL secretion by the Uver (Figure 35-2). The answer is (C). 

Serious hepatic toxicity can occur with niacin, but it is almost entirely associated with use of SR formulations. In a randomized clinical trial, 12 out of 23 patients (52%) taking SR niacin developed hepatotoxicity while none of 23 patients taking IR niacin did (McKenney et al. 1994). Therefore, IR or ER... 

ER niacin has shown little hepatotoxicity in clinical trials (Guyton and Bays 2007). However, ER niacin has only been studied as a once-daily dose at bedtime and therefore the safety of twice daily ER niaein is unknown. 

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