What safety concerns are associated with wart medications containing 5-Fluorouracil (5-FU) and cantharidin?

From the Guidelines

Wart medications containing 5-Fluorouracil (5-FU) and cantharidin pose significant safety concerns, including severe local skin reactions, systemic absorption, and potential scarring, which require careful consideration and application by healthcare professionals in controlled settings. The safety concerns associated with these medications are multifaceted, including:

• Severe local skin reactions, such as pain, burning, inflammation, and tissue damage, which may lead to scarring 1
• Systemic absorption, particularly when used on large areas or with occlusive dressings, potentially causing serious side effects like bone marrow suppression, gastrointestinal disturbances, and neurotoxicity 1
• Contraindication during pregnancy due to potential teratogenic effects 1
• Risks of severe pain, extensive blistering beyond the application site, and potential scarring if not properly applied, associated with cantharidin 1
• Cantharidin should never be used on facial warts, genital warts, or on individuals with diabetes or circulation problems due to healing concerns 1
• Both medications should only be applied by healthcare professionals in controlled settings, not for home use, and patients should be thoroughly informed about potential adverse effects, proper wound care, and when to seek medical attention for complications 1

The British Association of Dermatologists' guidelines for the management of cutaneous warts 2014 provide recommendations for the use of 5-FU and cantharidin, including:

• 5-FU cream applied daily with occlusion for 4-12 weeks 1
• Cantharidin 0.7% solution applied every 3 weeks up to four times 1 However, these guidelines also emphasize the importance of careful consideration and caution when using these medications, due to their potential safety concerns.

In terms of specific safety concerns, the guidelines note that:

• Cryotherapy, which may be used in combination with 5-FU, is painful and may cause blistering, and caution must be used when applying it near cutaneous nerves, tendons, and the nail apparatus, and also in patients with impaired arterial or venous circulation 1
• Hypopigmentation or hyperpigmentation may occur, particularly in patients with darker skin types 1
• Hypertrophic scarring was reported in a patient using pyruvic acid 98% with 5-FU 2% for warts on the chest and arms 1

Overall, the safety concerns associated with wart medications containing 5-FU and cantharidin require careful consideration and application by healthcare professionals in controlled settings, with thorough patient education and monitoring for potential adverse effects.

From the FDA Drug Label

WARNINGS Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration. PRECAUTIONS General There is a possibility of increased absorption through ulcerated or inflamed skin.

The safety concerns associated with wart medications containing 5-Fluorouracil (5-FU) and cantharidin include:

• Local inflammation and ulceration if applied to mucous membranes
• Increased absorption through ulcerated or inflamed skin
• Systemic toxicity in patients with DPD enzyme deficiency, which can be life-threatening 2
• Irritation if applied on the eyelids or directly into the eyes, nose, or mouth Compounders or providers should exercise caution when handling these medications to avoid exposure and prevent adverse reactions. Patients should be instructed to avoid exposure to ultraviolet rays during and immediately following treatment with fluorouracil because the intensity of the reaction may be increased 2.

From the Research

Safety Concerns with Wart Medications Containing 5-FU and Cantharidin

• The combination of 5-Fluorouracil (5-FU) and cantharidin in wart medications may pose certain safety concerns, including:
  • Local skin reactions, such as pain, blistering, and hyper-/hypopigmentation, which are commonly reported with cantharidin treatment 3, 4
  • Potential for systemic toxicity with 5-FU, although this is rare and usually occurs with high doses or prolonged use 5
  • Risk of scarring, although this is not commonly reported with proper use of cantharidin by a physician 6
• Adverse effects are generally mild but common, and should be monitored, particularly in the pediatric population 3
• The safety and efficacy of combining 5-FU and cantharidin have not been extensively studied, and more research is needed to fully understand the potential risks and benefits of this combination 3, 4

Specific Safety Concerns with 5-FU

• 5-FU can cause local skin reactions, such as irritation, redness, and itching 5
• Systemic toxicity is rare, but can occur with high doses or prolonged use, and may include symptoms such as nausea, vomiting, and diarrhea 5
• 5-FU is generally well-tolerated in pediatric patients, but monitoring for adverse effects is still necessary 5

Specific Safety Concerns with Cantharidin

• Cantharidin can cause local skin reactions, such as pain, blistering, and hyper-/hypopigmentation 3, 4
• Risk of scarring is low, but can occur with improper use or in sensitive individuals 6
• Cantharidin is generally well-tolerated, but monitoring for adverse effects is still necessary, particularly in the pediatric population 3, 4