In summary, it is likely that niacin will be prescribed more frequently in the future, since the National Cholesterol Education Program calls for aggressive treatment of high cholesterol levels. The cause of niacin-induced hepatitis is not known. However, the ease of access to SR preparations, which do not require a prescription, is cause for concern. Evidence exists that sustained-release niacin, with respect to both dosage and severity, is more hepatotoxic than crystalline niacin. Three patients who developed hepatitis during treatment with sustained-release niacin were rechallenged with equivalent or higher doses of crystalline niacin, with no evidence of recurring hepatocellular damage.
Hepatotoxic effects are an uncommon but well-documented complication of niacin therapy.
Cholestatic and hepatocellular reactions have been described clinically, with liver biopsy findings of parenchymal necrosis and centrilobular cholestasis in most patients. Although the mechanism by which niacin or one of its metabolites induces hepatic injury is unknown, evidence exists to suggest a dose-related, direct toxic effect rather than an idiosyncratic drug reaction. Although all forms of niacin have shown efficacy in modifying serum lipid levels, differences exist in their side effect profiles. Sustained-release niacins produce less cutaneous flushing, but a greater frequency and severity of hepatic and gastrointestinal side effects have been observed. Although most cases of hepatotoxic reactions are mild and reversible, fulminant hepatic failure has been reported, occurring within days of switching a patient from crystalline to SR niacin.