title: [Pharmacokinetic drug interaction between miconazole mucoadhesive tablet and tacrolimus: About 3 case-reports in transplant patients].
abstract: Loramyc®is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval. No recommendation currently exists in case of co-prescription of Loramyc®and immunosuppressive agents which are counter-indicated as a matter of principle. Herein, we present 3 cases of transplanted patients, requiring miconazole mucoadhesive tablet, who presented a tacrolimus overdose. These cases illustrate that of therapeutic drug monitoring is feasible in order to prevent the occurrence of overdoses and adverse reactions related.
authors.affiliation: Centre régional de pharmacovigilance, CHU de Grenoble-Alpes, avenue Maquis du Grésivaudan, Pavillon E, CS 10217, 38043 Grenoble cedex 09, France. Electronic address: mlepelley@chu-grenoble.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Lepelley
authors.affiliation: Centre régional de pharmacovigilance, CHU de Grenoble-Alpes, avenue Maquis du Grésivaudan, Pavillon E, CS 10217, 38043 Grenoble cedex 09, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Logerot
authors.affiliation: Service de pharmacologie-toxicologie, CHU de Grenoble-Alpes, 38043 Grenoble, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fonrose
authors.affiliation: Centre régional de pharmacovigilance, CHU de Grenoble-Alpes, avenue Maquis du Grésivaudan, Pavillon E, CS 10217, 38043 Grenoble cedex 09, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Villier
mesh_terms: D000328:Adult; D000368:Aged; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008825:Miconazole / Q000009:adverse effects* / Q000493:pharmacokinetics; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects* / Q000493:pharmacokinetics; D066027:Transplant Recipients
chemical_list: D065688:Cytochrome P-450 CYP2C9 Inhibitors; D007166:Immunosuppressive Agents; D008825:Miconazole; D016559:Tacrolimus
keywords: Comprimé mucoadhésif; Cytochrome P450; Interaction pharmacocinétique; Miconazole; Mucoadhesive tablet; Pharmacokinetic drug interaction; Tacrolimus