Metabolic, pharmacokinetic, and toxicological issues surrounding dapsone

ABSTRACT

Introduction: In their 70-year history, dapsone and other sulfones have been used as both antibacterial and anti-inflammatory agents. Dapsone has been the main active principle in the multidrug regimen recommended by the World Health Organization for the treatment of leprosy. In addition, dapsone has been successfully used to treat a wide range of dermatological and systemic disorders, mostly characterized by neutrophilic and eosinophilic accumulation and infiltration.

Areas covered: The PubMed database was searched using combinations of the following keywords: dapsone, sulfones, pharmacodynamics, pharmacology, adverse events, pharmacokinetics, drug interaction, dermatologic uses, and antimicrobial uses. This article reviews and updates the chemistry, pharmacokinetics, mechanism of action, adverse effects, drug interactions, and clinical application of sulfones.

Expert opinion: Dapsone exhibits clinical efficacy in several cutaneous and systemic conditions and is now generally accepted as the therapy of choice for leprosy and for rare dermatosis, as dermatitis herpetiformis. Careful patient selection and close monitoring during treatment are mandatory to provide safe and effective use of dapsone. Familiarity with sulfones and dapsone is crucial because of this agent retains its niche in the clinician’s therapeutic armamentarium.

KEYWORDS:

• Adverse events
• dapsone
• dermatitis herpetiformis
• dermatology
• drug interaction
• leprosy
• pharmacodynamics
• pharmacokinetics
• pharmacology
• toxicology

Article highlights

• Dapsone is highly effective in the treatment of a multitude of infectious diseases and dermatologic conditions. Concern over its side effect profile has limited its use in dermatology.

• Hematologic side effects and peripheral neuropathy are the most important adverse events manifesting dapsone therapy. Dapsone hypersensitivity syndrome is a life-threatening drug reaction. A prompt recognition of signs and symptoms associated with hypersensitivity syndrome is crucial to reduce mortality and irreversible sequelae.

• Adverse effects are, for the most part, dose-limiting, related to the duration of therapy, and reversible on discontinuation. Using the recommended monitoring protocols results in a significant decrease in the incidence of dapsone-related toxicities.

• Dapsone is a therapeutic valid alternative to conventional treatment in several dermatologic and non-dermatologic disorders. Familiarity with dapsone toxicology and drugs interaction is crucial to extend the use of this efficacious and low-cost drug.

• Large case series and randomized control trials are mandatory to better delineate efficacy and safety profile in adults, children, and special populations.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.