Nicorandil and ulcerations: the Trojan horse?

Tréchot, P.; Claeys, A.; Petitpain, Nadine; Javot, Lucie; Schmutz, J.‐L.; Barbaud, A.

doi:10.1111/j.1468-3083.2011.04172.x

Cited by 13 publications

(11 citation statements)

References 10 publications

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“…In 2012, we reinforced our hypothesis with the notion that in the case of 'external ulceration', the nicorandil ulcer is typically localised to the area where the trauma occurred (20).…”

Section: Hypothesessupporting

confidence: 82%

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

Tréchot¹,

Jouzeau

Brouillard

et al. 2013

International Wound Journal

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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.

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“…In 2012, we reinforced our hypothesis with the notion that in the case of 'external ulceration', the nicorandil ulcer is typically localised to the area where the trauma occurred (20).…”

Section: Hypothesessupporting

confidence: 82%

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

Tréchot¹,

Jouzeau

Brouillard

et al. 2013

International Wound Journal

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“…Although this is not in keeping with the hypothesis above [158][159][160][161], the accumulation of the allegedly ulcerogenic molecule would take place at the tissue level, likely without high serum concentrations observed in patients under niacin therapy.…”

Section: Discussionmentioning

confidence: 58%

“…Trechot et al [158][159][160][161] analysed an ulcerated skin biopsy from a patient exposed to nicorandil via mass spectrometry: they found high concentration of nicotinic acid (38g/mg of dried skin biopsy) and nicotinamide (11g/mg) in the cutaneous ulcer, as opposed to 21 and 4g/mg of nicotinic acid and nicotinamide from a random non-ulcerated skin sample from the same patient. Nicotinic acid and nicotinamide were estimated as <1g/mg of dried skin biopsy in a control, not exposed to nicorandil (one of the authors) [21].…”

Section: Discussionmentioning

confidence: 99%

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review

et al. 2016

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“…. Hence, aided by a POCOVE, nicotinic acid (pKa 4.9) that is abnormally distributed throughout the whole body could ulcerate the epithelial proliferation of the edge of the raw area, ultimately flooding the whole scar (22) (Figure 1).…”

Section: Nicorandil and Ulcers: Pathogeneses And Hypothesismentioning

confidence: 99%

Nicorandil: from ulcer to fistula into adjacent organs

Tréchot¹,

Petitpain²,

Guy³

et al. 2012

International Wound Journal

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Nicorandil is an original vasodilatator used to control angina by decreasing cardiac preload and afterload. Since 1997, many reports of single or multiple nicorandil-induced ulcerations have been published. To date, eight cases of nicorandil-induced fistula into adjacent organs have been described. The pathogeneses of nicorandil-induced ulceration and fistula into adjacent organs are not yet elucidated. The two main hepatic biotransformation pathways of nicorandil are denitration and reduction of the alkyl chain leading to nicotinamide and niconitic acid which merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate. This merging which is known as saturable, may contribute to a slow and abnormal distribution of nicotinamide and nicotinic acid out of the endogenous pool. Under these special conditions, providing these two molecules in situ, nicotinic acid associated with nicotinamide may ulcerate rather recent or maintained trauma. Ulcers and fistulae induced by nicorandil heal after withdrawal. Surgical intervention is unnecessary and inappropriate as it is ineffective and exacerbates morbidity. All practitioners should be correctly informed about these serious but preventable nicorandil side effects, which mostly occur in the elderly and fragile population. In the absence of corrective measures, withdrawal of this original and active drug should be considered.

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Nicorandil and ulcerations: the Trojan horse?

Cited by 13 publications

References 10 publications

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

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

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review

Nicorandil: from ulcer to fistula into adjacent organs

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