Role of nicotinic acid and nicotinamide in nicorandil-induced ulcerations: from hypothesis to demonstration

Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil‐induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high‐dosage nicorandil or after an increased dosag...

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Published in:	International wound journal 2015-10, Vol.12 (5), p.527-530
Main Authors:	Trechot, Philippe, Jouzeau, Jean-Yves, Brouillard, Clotilde, Scala-Bertola, Julien, Petitpain, Nadine, Cuny, Jean-François, Gauchotte, Guillaume, Schmutz, Jean-Luc, Barbaud, Annick
Format:	Article
Language:	eng
Subjects:	Aged, 80 and over Biochemistry Biochemistry, Molecular Biology dosage Female Humans Life Sciences Molecular biology Niacin - metabolism Niacinamide - metabolism nicorandil Nicorandil - adverse effects Nicorandil - metabolism nicotinamide nicotinic acid Original Skin Ulcer - chemically induced Skin Ulcer - metabolism Skin Ulcer - pathology ulcer Vasodilator Agents - adverse effects
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Summary:	Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil‐induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high‐dosage nicorandil or after an increased dosage of nicorandil, nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot appropriately merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate, which leads to abnormal distribution of these metabolites in the body. In recent or maintained trauma, nicotinamide increases blood flow at the edge of the raw area, inducing epithelial proliferation, while nicotinic acid ulcerates this epithelial formation, ultimately flooding the entire scar. We demonstrate, by comparison to a control patient non‐exposed to nicorandil, an abnormal amount of nicotinic acid (×38) and nicotinamide (×11) in the ulcerated area in a patient with NIUs. All practitioners, especially geriatricians, dermatologists and surgeons, must be aware of these serious and insidious side effects of nicorandil. It is critical to rapidly reassess the risk–benefit ratio of this drug for any patient, and not only for those with diverticular diseases.
ISSN:	1742-4801 1742-481X