Rechallenge With Crystalline Niacin After Drug-Induced Hepatitis From Sustained-Release Niacin

Hepatic toxicity of unmodified and time-release preparations of niacin

“…This is also true of the 51-year-old man reported by Christensen et al [8], the 44-year-old man reported by Mullin et al [ll], and the 62-yearold man reported by Henkin et al [12]. The dosages reported to cause adverse effects in these patients, as well as in most other cases summarized in Table III, were well above the usual doses of 0.25 to 1.0 g/day of time-release niacin recommended in recent reference manuals [15,20].…”

Niacin‐Induced Anicteric Microvesicular Steatotic Acute Liver Failure

“…niaCin-inDuCeD HepatotoXiCity References Age Sex Form Dose (g/d) Duration ALP (U/L) TB (mg/dL) AST (U/L) ALT (U/L) PT (s)/INR Histology Winter and Boyer (4) /-Increase in portal fibrosis; mild proliferation of bile ductules; sparse portal inflammatory infiltrate consisting of chronic inflammatory cells; centrilobular parenchymal cell swelling with cytoplasmic vacuolization; no cell necrosis or lobular inflammation; few mitotic figures and canalicular bile plugs Patterson et al (6) /-Distorted architecture with massive and submassive lobular collapse and increased fibrosis in a few areas of collapse; marked cholestasis with canalicular bile plugging; many hepatocytes with swollen vacuolated cytoplasm; normal intralobular ducts Clementz and Holmes (/-Massive hepatic necrosis with collapse of the architecture; pigment-laden macrophages within areas of collapse; cholestasis within remaining, viable hepatic parenchyma; minimal fatty change in some remaining hepatocytesHenkin et al(14) lobular collapse with increased fibrosis in some areas of collapse; pronounced cholestasis with canalicular bile plugging; vacuolated cytoplasmEtchason et al(12) Abbreviations: F, female; M, male.…”

The bioavailability of sustained release nicotinic acid formulations.

“…Hepatotoxic reactions have occurred in many subjects who have used sustained-release preparations some of whom have tolerated conventional nicotinic acid preparations without any problem (Christensen et al, 1961;Henkin et al, 1990;Hodis, 1990). The first-pass metabolism of nicotinic acid seems to be more extensive when sustained release formulations are ingested.…”

“…Various sustained-release preparations of nicotinic acid have been developed in an attempt to prevent the sideeffects associated with the rapid drug absorption. Nevertheless serious hepatotoxic reactions have been reported in some patients receiving such preparations, despite having tolerated conventional dosage forms (Henkin et al, 1990;Hodis, 1990). The potential hepatotoxicity associated with the use of sustained release preparations, their poorly characterized bioavailability and the dosedependency of nicotinic acid kinetics (Mrochek et al, 1976) prompted us to compare the bioavailability of three formulations with different rates of nicotinic acid release in vitro.…”