mk-0524 and Exanthema

Niacin commonly causes cutaneous flushing, which is partially alleviated by laropiprant, a selective antagonist of prostaglandin D2 at the DP1 receptor. Here we report an unusually high incidence of exanthematous eruption associated with the use of the extended-release (ER) niacin/laropiprant combination treatment in Hong Kong Chinese patients.. Among 201 patients treated with ER niacin/laropiprant 1000/20 mg over 7 days to assess flushing symptoms and 166 of the patients who continued the treatment for 12 weeks (doubling the dose after 4 weeks), 28 patients (14%) developed a highly pruritic cutaneous eruption at a mean of 5 days after starting the treatment or 4 days after increasing the dose. This resolved over several days after drug withdrawal with symptomatic treatment. Compared with the subjects who completed 12-weeks treatment uneventfully, those who developed cutaneous eruption were older, had significantly lower body weight, were taking background lipid-lowering treatment more frequently and had greater flushing responses in the first few days of treatment.. The relationship of the exanthematous eruption with lower body weight and the increase in dosage suggests a pharmacokinetic effect that may be related to increased exposure to niacin or its metabolites and provoked by inhibition of the DP1 receptor with laropiprant, as we have not seen this rash with niacin used alone. This may suggest that the southern Chinese population may have some genetic predisposition; as such, a high frequency of exanthematous reactions has not been reported in other populations.

Topics: Adult; Aged; Anti-Inflammatory Agents; Biopsy; Body Weight; Drug Combinations; Drug Eruptions; Exanthema; Female; Histamine Antagonists; Hong Kong; Humans; Indoles; Male; Middle Aged; Niacin; Pruritus; Skin; Vitamins