[Pharmacokinetic drug interaction between miconazole mucoadhesive tablet and tacrolimus: About 3 case-reports in transplant patients]

Therapie. 2017 Sep;72(4):475-482. doi: 10.1016/j.therap.2016.10.006. Epub 2017 Jan 12.
[Article in French]

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.

Keywords: Comprimé mucoadhésif; Cytochrome P450; Interaction pharmacocinétique; Miconazole; Mucoadhesive tablet; Pharmacokinetic drug interaction; Tacrolimus.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Cytochrome P-450 CYP2C9 Inhibitors / adverse effects*
  • Cytochrome P-450 CYP2C9 Inhibitors / pharmacokinetics
  • Drug Interactions*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics
  • Male
  • Miconazole / adverse effects*
  • Miconazole / pharmacokinetics
  • Middle Aged
  • Tacrolimus / adverse effects*
  • Tacrolimus / pharmacokinetics
  • Transplant Recipients*

Substances

  • Cytochrome P-450 CYP2C9 Inhibitors
  • Immunosuppressive Agents
  • Miconazole
  • Tacrolimus