Clinical Inquiries

Are oral agents effective for the treatment of verruca vulgaris?

Sontheimer D, Brown ML, Paulson C. J Fam Pract 2006 Apr;55(4)353-4.

Evidence-based Answer

Of the available oral therapies for common warts, none has sufficient evidence to recommend it as an effective therapy (strength of recommendation [SOR]: B). To date, no oral agent has been shown to be effective in a randomized, placebo-controlled, double-blinded trial. Very limited evidence is emerging that zinc may be effective (SOR: C).

Evidence-based Summary

Oral therapies for common warts suffer from a lack rigorous clinical data regarding their efficacy. A detailed literature search found multiple trials evaluating various oral agents. However, only 6 trials met the selection criteria of randomized, controlled trials published in English.

Cimetidine (Tagamet) has been compared with placebo in 3 trials1-3 and was not found superior to placebo. Levamisole (Ergamisol), used in combination with cimetidine, has been compared with cimetidine alone in 2 trials,4,5 and was found to be effective at speeding regression of warts, with patients in the combination arm showing a mean regression time of 7.8 weeks compared with 11 weeks in the cimetidine alone group. These small studies involved 48 and 44 patients, respectively. In addition, 1 nonrandomized controlled trial6 found levamisole at 5 mg/kg for 3 days every 2 weeks to be superior to placebo in achieving complete cure of warts in a group of 40 patients.

Zinc is the only agent to demonstrate efficacy in a completely randomized and placebo-controlled study.7 However, this trial was unblinded, had only 40 subjects assigned to each agent, had a dropout rate of 46%, and did not follow intention-to-treat analysis.

Clinical Commentary

Persistent treatment with topical/intralesional therapy should continue to be the mainstay

Verruca vulgaris (the common wart) is frequently encountered by the family physician, often after unsuccessful topical treatment. Unfortunately, evidence is insufficient to warrant routine use of oral agents such as cimetidine, zinc, or levamisole in the treatment of refractory lesions. The added cost and potential side effects of proposed oral treatments isn’t justified until more rigorous studies show clear clinical efficacy. Persistent treatment with proven topical and intralesional therapy for refractory lesions should continue to be the mainstay of therapy for verruca vulgaris.

Recommendations from Others

Clinical Evidence lists cimetidine and levamisole as therapies of unknown effectiveness.8 The commentary on both agents notes that the size of each randomized controlled trial cited may have been too small to detect clinically important differences.

References

  1. Rogers CJ, Gibney MD, Siegfried EC, Harrsion BR, Glaser DAnull Cimetidine therapy for recalcitrant warts in adults: is it any better than placebo? J Am Acad Dermatol. 1999. Volume 41. Page(s): 123-127
  2. Karabulut AA, Sahin S, Eksioglu Mnull Is cimetidine effective for nongenital warts: a double-blind, placebo-controlled study. Arch Dermatol. 1997. Volume 133. Page(s): 533-534.
  3. Yilmaz E, Alpsoy E, Basaran Enull Cimetidine therapy for warts: a placebo-controlled, double-blind study. J Am Acad Dermatol. 1996. Volume 34. Page(s): 1005-1007.
  4. Parsad D, Pandhi R, Juneja A, Negi KSnull Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children. Pediatr Dermatol. 2001. Volume 18. Page(s): 349-352.
  5. Parsad D, Saini R, Negi KSnull Comparison of combination of cimetidine and levamisole with cimetidine alone in the treatment of recalcitrant warts. Australas J Dermatol. 1999. Volume 40. Page(s): 93-95.
  6. Amer M, Tosson Z, Soliman A, Selim AG, Salem A, al-Gendy AAnull Verrucae treated by levamisole. Int J Dermatol. 1991. Volume 30. Page(s): 738-740.
  7. Al-Gurairi FT, Al-Waiz M, Sharqui KEnull Oral zinc sulphate in the treatment of recalcitrant viral warts: randomized, placebo-controlled trial. Br J Dermatol. 2002. Volume 146. Page(s): 423-431.
  8. Bigby M, Gibbs Snull [monograph online], No. 13. London: BMJ Publishing Group, 2003. Updated June 2005. Available at: clinicalevidence.com. Accessed on October 14, 2005..