cimetidine for warts?

i was going through piles of old medical articles, intent on throwing them out in this electronic age, but then found one from 2005 looking at the use of cimetidine for warts (see plantar warts cimetidine ampodmedj2005 in dropbox, or J Am Podiatr Med Assoc 95(3):229). i have had several very impressive cases where using cimetidine, an H2-blocker but also used in the past as an immunoenhancer for some chemotherapy regimes, really worked. the first case was a 5yo male i saw about 25 years ago with very extensive longstanding perianal warts (condyloma acuminata). the dermatologist was planning rather extensive surgery, but commented to me that there were often responses to cimetidine. the patient took the med and the warts completely vanished within 1-2 weeks. the second case was me, complaining of a rather painful plantar wart. i saw our podiatrist, who tried liquid nitrogen therapy (which exceeded my pain threshold, though i had thought that was very high). so, i tried imiquimod for 6 weeks, to no avail. given my experience with cimetidine with condyloma, i asked the podiatrist if cimetidine might help, and he produced this paper. so, several weeks after stopping the imiquimod, i began cimetidine 800mg bid and the wart was completely gone, literally within days!! i have recommended cimetidine to several people since then, with variable results (though a few also being quite dramatic. including a young woman with really bad genital warts, where the warts recurred after extensive cryotherapy, and the dermatologists were at a loss on what to do next. i suggested cimetidine and the warts resolved within days and did not recur). in this light, here is the study i found:

--8-year retrospective analysis of cimetidine as first-line therapy for pedal verruca (plantar warts). 216 patients treated, 169 (78%) completed questionnaires a minimum of 15 months post-therapy

--90 males, 126 females; 180 were <18 yo, 18 were >25 yo

--cimetidine dose: kids --25-40 mg/kg/d in divided doses, adults 800 bid

--results:

    --overall treatment success rate for all age groups: 84.3%

    ​--12 recurrences were after the completion of the study (7.2%): 7 in kids (5%) and 5 in adults (20%); in 2 of the recurrences, retreatment with cimetidine worked without further recurrences

    --mean duration of treatment was 6.1 weeks in kids and 7.9 weeks in adults

    --in looking at the specific patients involved, 27 patients had personal or family history of autoimmune diseases (treatment success in 81.5%), 13 patients had prior failed surgical excision/curettage (cimetidine worked in 84.6%), 9 patients had successful response despite stopping the cimetidine early because of adverse effects, 5 patients had had symptomatic warts for >100 weeks with 80% success on cimetidine

    ​--of the 47 patients who did not complete the questionnaires, 40 had documented outcomes by their clinician and 80% were treated successfully

    --adverse effects: 15.7% (7.4% were GI, rather interestingly for cimetidine).

so, a few points

--on review of what exists in the literature, there was another open-label study of 47 patients with multiple, nongenital warts treated with oral cimetidine for 3 months (at 30-40 mg/kg and a higher dose of 800mg tid for adults) finding improvement in 87% of children and 68% of adults, and complete clearance in 56% of kids and 44% of adults. followup data showed no recurrences in the 65% of patients they could reach who had complete clearance by the end of the study, though warts recurred if treatment stopped before all warts had cleared (see Clin Exper Dermalol 2000; 25: 183).

--there were 2 RCTs looking at cimetidine, but the only RCT I could find was of 54 patients with nongenital warts of at least 6 months duration, putting 36 patients on cimetidine 400mg tid vs placebo, finding positive responses in 37% on cimetidine and 25% on placebo,  a nonsignificant difference (ie, though the cimetidine group did better, this was too small a study to draw conclusions (see Arch Dermatol 1997: 133: 533)). of note, another report (Eur J Dermatol 2003; 13(5): 445) found that only high-dose cimetidine worked clinically (30-40 mg/kg/d vs <20 mg/kg/d), and that those who responded had increased levels of IL-2 and IFN-gamma mRNA levels (as produced by Th1 cells) and decreased IL-16 mRNA levels in tissues of effectively treated warts. and the inconclusive RCT used a lower dose.

--overall, cimetidine does seem to work somewhat better in kids (who do have higher likelihood of spontaneous resolution, though the success rate above is impressive). i could not find much data regarding condyloma acuminata, other than occasional anecdotal reports (J Urol 2000; 164:1074, which found 4 of 4 kids with extensive genital warts had resolution with 3 months of cimetidine; though there are also some small reports of failure)​. and bigger, better RCTs are pretty unlikely to happen, given this is a cheap generic drug, hence unlikely to get a drug company to sponsor.

--how should it be given??? unclear. i have used the higher doses above (adults: 800mg bid; kids 30-40 mg/kg) until the warts resolve. of note, in the above studies, most people got the drug for 2-3 months. and some not responding by that time did so by extending the course several months more.

--i should also add that in my experience, i have had better response to condyloma acuminata with cimetidine than with repeated cryotherapy, or use of caustics such as podophyllin. i have prescribed imiquimod cream with some success, though it is also irritating and very expensive (and only approved for those >12yo)

--so, it is with some trepidation that i present this study, since the RCTs were not so good, cimetidine is not even listed as an option by the CDC in their sexually-transmitted disease compendium, and Up-To-Date mentions it dismissively. but given the above anecdotes (one quite close to my heart), and given that this is such a benign treatment, it might be worth considering. 

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