Common drug-drug interactions in antifungal treatments for superficial fungal infections

ABSTRACT

Introduction: Antifungal agents can be co-administered alongside several other medications for a variety of reasons such as the presence of comorbidities. Pharmacodynamic interactions such as synergistic and antagonistic interactions could be the result of co-administered medications. Pharmacokinetic interactions could also transpire through the inhibition of metabolizing enzymes and drug transport systems, altering the absorption, metabolism and excretion of co-administered medications. Both pharmacodynamic and pharmacokinetic interactions can result in hospitalization due to serious adverse effects associated with antifungal agents, lower therapeutic doses required to achieve desired antifungal activity, and prevent antifungal resistance.

Areas covered: The objective of this review is to summarize pharmacodynamic and pharmacokinetic interactions associated with common antifungal agents used to treat superficial fungal infections. Pharmacodynamic and pharmacokinetic interactions that impact the therapeutic effects of antifungal agents and drugs that are influenced by the presence of antifungal agents was the context to which these antifungal agents were addressed.

Expert opinion: The potential for drug-drug interactions is minimal for topical antifungals as opposed to oral antifungals as they have minimal exposure to other co-administered medications. Developing non-lipophilic antifungals that have unique metabolizing pathways and are topical applied are suggested properties that could help limit drug-drug interactions associated with future treatments.

KEYWORDS:

• Terbinafine
• itraconazole
• tavaborole
• efinaconazole
• antifungal agents
• drug interactions
• superficial infections

Article highlights

• Drug-drug interactions with antifungal agents can lead to life threatening adverse effects such as prolonged QT intervals, neuromuscular toxicity, torsade de pointes, rhabdomyolysis and even death.

• Antifungal agents are inhibitors of key metabolizing P450 enzymes (e.g., CYP 3A4) and membrane bound transport systems (e.g., P-glycoprotein), affecting the absorption, metabolism and excretion of co-administered drugs.

• Drug interactions such as synergy, antagonism and additive interactions have been reported to occur due to the presence of antifungal agents possibly altering the therapeutic dosages of co-administered drugs.

This box summarizes key points contained in the article.

Declaration of interest

AK Gupta is a clinical trials investigator and speaker for Valeant Canada as well as a consultant for Moberg and Sandoz. SG Versteeg is employed by Mediprobe Research Inc., a site where clinical trials are run under supervision of AK Gupta. NH Shear is a consultant for AbbVie, Amgen, Actelion, Biogen, Celgene, Centocor, Janssen, Lilly, Merck, Novartis, Pfizer, Takeda as well as a speaker for AbbVie, Janssen and Novartis. He also has sponsorship with Janssen and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed that they have received an IIR grant from Pfizer Inc, research support from Chiesi Pharmaceuticals and Merck Sharp & Dohme, lecture fees from Basilea Pharmaceutica Ltd. Chiesi and Merck Sharp & Dohme, and from Astellas, Austria, and is member of an advisory board of Merck Sharp & Dohme.

Additional information

Funding

This paper was not funded