title: Role of nicotinic acid and nicotinamide in nicorandil-induced ulcerations: from hypothesis to demonstration.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University Hospital, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Trechot
authors.affiliation: Department of Toxicology, University Hospital, Nancy, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Jouzeau
authors.affiliation: Department of Dermatology, University Hospital, Nancy, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Brouillard
authors.affiliation: Department of Toxicology, University Hospital, Nancy, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Scala-Bertola
authors.affiliation: Center of Pharmacovigilance, University Hospital, Nancy, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petitpain
authors.affiliation: Department of Dermatology, University Hospital, Nancy, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cuny
authors.affiliation: Department of Pathology, University Hospital, Nancy, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gauchotte
authors.affiliation: Department of Dermatology, University Hospital, Nancy, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Schmutz
authors.affiliation: Department of Dermatology, University Hospital, Nancy, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Barbaud
mesh_terms: D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D009525:Niacin / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism*; D020108:Nicorandil / Q000009:adverse effects* / Q000378:metabolism; D012883:Skin Ulcer / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D014665:Vasodilator Agents / Q000009:adverse effects*
chemical_list: D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D009525:Niacin
keywords: dosage; nicorandil; nicotinamide; nicotinic acid; ulcer
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