Cimetidine: A review of the recent developments and reports in cutaneous medicine
Noah Scheinfeld, MD
Dermatology Online Journal 9(2): 4

Department of Dermatology, St. Luke's-Roosevelt Hospital Center, New York.


Cimetidine, approved by the FDA for inhibition of gastric acid secretion, has been advocated for a number of dermatological diseases. The cutaneous uses and immunological effects of cimetidine have been actively studied over the past few years, and this review summarizes the literature accumulated since 1997.


Several reviews have assessed the use of cimetidine in dermatology in the last decade.[1] Since the last review was published in 2000,[2] over 500 articles have been published on cimetidine. In fact, cimetidine is a most actively researched medication, and more than 1,000 articles concerning it have been published in the last 5 years. To allow dermatologists to keep abreast of developments in the use of this medication, this review summarizes the literature since 1997 on the cutaneous benefits and side effects of cimetidine and its immunological effects.

Cimetidine-approved uses, side effects, and drug interactions

Cimetidine is approved by the FDA for the reduction of the secretion of gastric acid. It is used to alleviate the symptoms of peptic ulcer disease, erosive gastroesophageal reflux disease, and hypersecretory conditions including Zollinger-Ellison syndrome and multiple endocrine adenomas. It is available over the counter and by prescription. In dermatology it is most commonly used to treat warts, urticaria, and mastocytosis.

Cimetidine is generally taken without ill effect. Its side effects include dizziness and mild somnolence (at doses of 800–1600 mg/day), a reversible state of confusion (especially in the elderly with preexisting renal or hepatic disease), gastrointestinal upset, gynecomastia (may occur if treatment period is greater than 1 month), reversible dose-related increase in serum transaminases, and dose-related elevations in plasma creatinine.

Cimetidine can produce significant inhibition of cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4 P450 isoforms.[3] Of these isoforms, clinically significant inhibition is most important with CYP 3A4 and 1A2. It does not affect CYP 1A1 in rat models.[4] Clinically relevant interactions include theophylline, aminophylline, metoprolol, nifedipine and quinidine.[5] The interaction involving the beta-blockers, metoprolol and propranolol, results in significant sinus bradycardia and hypotension.[6] It does not interact with atenolol and nadolol. It can inhibit the metabolism of hydroxyzine and the conversion of dapsone to its toxic hydroxylamine, effects which are beneficial in dermatologic therapy.[7] Oral cimetidine prolongs clarithromycin absorption.[8] Cimetidine has been examined for its antimalarial properties in the presence or absence of chloroquine or pyrimethamine and was found to be synergistic with them.[9] It appears that cimetidine is safe in pregnancy.[10]


Cimetidine has immunomodulatory effects that include blocking suppressor T cells and facilitating cell-mediated immunity (CMI). The histamine-induced upregulation of IL-6 and IL-8 production, however, may be completely abrogated by a combination of pyrilamine and cimetidine.[11] In patients with allergic rhinitis, cimetidine decreases the number of CD4+ and increases the number of CD8+ lymphocytes.[12] Cimetidine and famotidine slightly reduce the O2- or H2O2 production of neutrophils in a dose-dependent manner, although ranitidine fails to do so.[13] Cimetidine inhibits nitric-oxide-associated nitrate production in a horse soft-tissue inflammation model.[14] It decreases interleukin 6 production by human keratinocytes.[15] It can block cell proliferation and c-fox gene transcription.[16] It also might have a role in suppressing delayed hypersensitivity reactions.[17] The exact role that these immunological effects play in the treatment of clinical disease has yet to be defined.

Common warts in adults

In the last 5 years, double-blind, placebo-controlled studies have finally been performed on cimetidine in the treatment of common warts. These studies have shown it to be ineffective; this ineffectiveness is shown most clearly in adults.[18] Some still advocate consideration of its use at a dose of 40 mg/kg/day,[19] but most reviewers do not.[20]

The role of cimetidine in children is a more open question.[21] In a 3-month open-label study of 47 patients with multiple, nongenital, viral warts who were treated with oral cimetidine, 56% of children cleared and 44% of adults cleared.[22] However, in a placebo-controlled study, its efficacy was not statistically superior to that of placebo, although a trend toward efficacy was suggested for younger subjects.[23] Moreover, a prospective, randomized, controlled trial of 40 patients (62% less than 15 years old) yielded negative results.[24] Thus, in cases where the use of topical medications is not possible, cimetidine might still have a role in the treatment of warts in children. Interestingly, however, a recently reported case described marked improvement in a 16 year old boy with epidermodysplasia after three months of oral cimetidine at 40mg/kg/day.[25] No relapse occurred over a six month follow up period.

One promising avenue for the use of cimetidine for treating warts is in conjunction with other therapies. Parsad et al. have reported that a combination regimen of cimetidine and levamisole is superior to cimetidine alone in treating warts in adults[26] and in children.[27] Levamisole is an immunomodulator that is approved by the FDA for use with 5-fluorouracil in the treatment of colon cancer. The original use of levamisole was as an antihelminthic.

Genital warts and papillomatosis

Cimetidine has been shown to be useful in the treatment of condylomata acuminata and papillomatosis. Four children treated with extensive condylomata acuminata of the genital and perigenital areas were treated with cimetidine 30–40 mg/kg; clearing of their condylomata was noted at 24 months following treatment.[28] Cimetidine was effective in the treatment of recurrent respiratory papillomatosis[29] and recalcitrant, diffuse conjunctival papillomatosis.[30]

Molluscum contagiosum

Molluscum contagiosum, a common illness in children, caused by a pox virus, has been treated with cimetidine. At a dose of 30–40 mg/kg/day, it has been used as a treatment for children[31] and adults.[32] In two patients, one with 60 lesions and the other with 200 lesions, cimetidine at 40 mg/kg/day in four divided doses for six weeks cleared all lesions.[33] However, other studies find it ineffective.[34] There is no evidence from double-blind, placebo-controlled studies that cimetidine clears molluscum contagiosum.

Urticaria and other mast-cell-mediated diseases

Cimetidine appears to have a role in the treatment of chronic idopathic urticaria and some other types of urticaria when used in combination with various H1 blockers.[35,36] For symptomatic dermatographism, the combination of an antihistamine and an H2 antagonist, such as chlorpheniramine and cimetidine, appears to be effective.[37] Cimetidine might also increase the latency time of heat-induced urticaria.[38] It appears that a combination regimen of H1 blockers, H2 blockers, and mast-cell stabilizers gives partial relief to the patients with mastocytosis.[39] Scombroid fish poisoning has been successfully treated with cimetidine.[40]


Because of its function as an immunomodulator, researchers have used cimetidine in research on melanoma. In horses, it has been used to treat melanoma, although no benefit has been found.[41] In immunodeficient mice with transplanted melanoma cell lines, administration of cimetidine combined with tamoxifen seems to decrease melanoma growth.[42] It should be noted that levamisole, mentioned above, has been extensively evaluated as an immunomodulator to ameliorate melanoma without significant effect.

Eosinophilic dermatoses

Several eosinophilic dermatoses have responded to cimeditine. It was successful when used for eosinophilic fascitis (however, after a 5-month course it was discontinued because of side effects).[43] It has been used to treat eosinophilic pustular folliculitis in children.[44] The beneficial effects might be a result of the interrelation of histamine, mast cells and eosinophils in allergy and allergic disease.

Cutaneous effects: pruritus and skin integrity

Cimetidine was useful in treating pruritus after a burn injury. In a study controlling for the effect of topical medications, a cetirizine-cimetidine combination demonstrated a dramatic improvement at 1 and 6 hours, and a moderate improvement at 12 hours after the initial administration of the medication when compared with a diphenhydramine-placebo combination.[45] Oral cimetidine accelerated the recovery of skin barrier function after disruption in a dry environment, but histamine and the histamine H2 receptor agonist, dimaprit, delayed barrier repair.[46]

Periodic fever, apthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome

Cimetidine has a valuable role in treating of PFAPA syndrome.[47] In one study, it was as an effective first-line therapy for PFAPA at 20 mg/kg/day, curing 49 of 83 patients.[48] Alternatively, other authorities state that glucocorticoids are the most highly effective in controlling symptoms. Tonsillectomy and cimetidine treatment were associated with remission in a small number of patients.[49] In another study of 8 children, cimetidine was effective with no side effects.[50]

Acute intermittent porphyria

Cimetidine has been suggested as a treatment for acute intermittent porphyria.[51] Its role seems to be as a second-line treatment to intravenous hemin, which is expensive but appears to be more effective than increased carbohydrate intake. At a dose of 800 mg/day, cimetidine may also have a role in the prophylaxis of acute episodes by maintaining a baseline suppression of ALA-synthase activity.[52]

Inhibition of Dapsone Toxicity

One of the most important uses of cimetidine in dermatological therapy is to reduce the dapsone induction of methemoglobinemia.[53] Cimetidine reduces the hepatic oxidation of dapsone to the hydroxylamine, thereby limiting methemoglobinemia formation. This strategy allows maintenance of higher daily dosages of dapsone, sometimes even in excess of 200 mg.[54] In one study, co-administration of cimetidine with dapsone kept methemoglobin levels at 30% below the control values for nearly three months. Eight patients with dermatitis herpetiformis, linear IgA disease, or folliculitis decalvans, who were on long term dapsone therapy (50-100 mg daily), added cimetidine, 1.6 g daily, for three months.[55] Their mean methemoglobin level fell from a baseline of 5.5 g/dl to 3.9 g/dl in the third week. The values remained low until week 12 when there was a return to baseline. There was no alteration in hemoglobin level from baseline (mean 12.7 g/dl) during the cimetidine therapy. However, there was a significant fall in the visual analogue score for headache. The patients also reported a significant decrease in lethargy. These improvements were not associated with any deterioration in the control of the various skin disorders. Similar findings were obtained in an earlier study in dermatitis herpetiformis patients.[56]

In rats, cimetidine has been shown to be more effective than ranitidine or famotidine in the reversible inhibition of the toxic metabolic pathway which produces dapsone's hydroxylamine metabolite.[57] Cimetidine also did not appear to inhibit the detoxification pathways of dapsone or cytosolic acetylation because of its greater affinity for cytochrome P-450.

Cutaneous side effects

Despite its common use, cimetidine has few cutaneous side effects. It can cause a delayed hypersensitivy reaction[58] and fixed drug eruption.[59] It has been reported to precipitate erythema multiforme and toxic epidermal necrolysis.[60] Cross-reaction with famotidine to induce erythema multiforme has been reported in cases where cimetidine-related erythema multiforme has already occurred.[61]


Cimetidine has yet to be proven to be an effective monotherapy for dermatological diseases. It seems that cimetidine is probably most effective when used in conjunction with other medications. In the same fashion that levamisole eventually was proven to be an effective secondary medication along with 5-fluorouracil in the treatment of cancer of the colon, cimetidine will probably be proven useful outside of its use as an antacid. Promising uses include treating urticaria in conjunction with other antihistamines, and treating warts in conjunction with levamisole. In addition, cimetidine's inhibitory effect on the metabolism of dapsone, chloroquine, and pyrimethamine can aid dermatological therapy by maintaining medication levels and decreasing toxicity. The multiple immunomodulating effects of cimetidine are significant but poorly understood. As its immunological effects are elucidated, new uses will emerge.


1. Aram H. Cimetidine in dermatology. Int J Dermatol 1987;26:161-6.

2. Paquette D, Rothe MJ.Unapproved dermatologic indications for H2 receptor antagonists, cromolyn sodium, and ketotifen. Clin Dermatol 2000;18:103-11.

3. Martinez C, Albet C, Agundez JA, Herrero E, Carrillo JA, Marquez M, Benitez J, Ortiz JA. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther 1999;65:369-76.

4. Levine M, Law EY, Bandiera SM, Chang TK, Bellward GD. In vivo cimetidine inhibits hepatic CYP2C6 and CYP2C11 but not CYP1A1 in adult male rats. J Pharmacol Exp Ther 1998;284:493-9.

5. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998;18:84-112.

6. Wolverton SE Hepatotoxicity of Drug Therapy p.780-797 in Comprehensive Dermatologic Drug Therapy SE Wolverton ed. W.B. Saunders Philadelphia 2001.

7. Bormann G, Gaber G, Fischer M, Marsch WC. Dapsone in rosacea fulminans. J Eur Acad Dermatol Venereol 2001;15:465-7.

8. Amsden GW, Cheng KL, Peloquin CA, Nafziger AN. Oral cimetidine prolongs clarithromycin absorption. Antimicrob Agents Chemother 1998;42:1578-80.

9. Paciorkowski A, Dai WW, Cerami A, Berger BJ. Synergism of cimetidine with anti-malarial agents.J Parasitol 1997;83:960-3.

10. Ruigomez A, Garcia Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L, Wallander MA, Johansson S. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 1999;150:476-81.

11. Kohda F, Koga T, Uchi H, Urabe K, Furue M. Histamine-induced IL-6 and IL-8 production are differentially modulated by IFN-gamma and IL-4 in human keratinocytes. J Dermatol Sci 2002;28:34-41.

12. Yang PC, Liu T, Zhang TY, Fan DS. The effect of the H2 antagonist cimetidine on the numbers of CD4+ and CD8+ cells in the nasal mucosa of patients with allergic rhinitis.Clin Otolaryngol 1997;22:93-5.

13. Mikawa K, Akamatsu H, Nishina K, Shiga M, Maekawa N, Obara H, Niwa Y. The effects of cimetidine, ranitidine, and famotidine on human neutrophil functions. Anesth Analg 1999;89:218-24.

14. Hunter RP, Short CR, McClure JR, Koch CE, Keowen ML, VanSteenhouse JL, Dees AA. Cimetidine inhibits nitric oxide associated nitrate production in a soft-tissue inflammation model in the horse. J Vet Pharmacol Ther 1999;22:136-47.

15. Shinoda S, Kameyoshi Y, Hide M, Morita E, Yamamoto S. Histamine enhances UVB-induced IL-6 production by human keratinocytes. Arch Dermatol Res 1998;290:429-34.

16. Wang LD, Hoeltzel M, Butler K, Hare B, Todisco A, Wang M, Del Valle J. Activation of the human histamine H2 receptor is linked to cell proliferation and c-fos gene transcription. Am J Physiol 1997 Dec;273:C2037-45.

17. Hewitt P, Armstrong N, Bowrey P, Cherian M, Morris D. Cimetidine prevents suppression of delayed hypersensitivity in an animal model of haemorrhagic shock. Injury 2002;33:673.

18. Bigby M. Snake oil for the 21st century. Arch Dermatol 1998; 134:1512-4.

19. Leman JA, Benton EC. Verrucas. Guidelines for management. Am J Clin Dermatol 2000;1:143-9.

20. Allen AL, Siegfried EC. What's new in human papillomavirus infection. Curr Opin Pediatr 2000;12:365-9.

21. Fischer G, Rogers M. Cimetidine therapy for warts in children. J Am Acad Dermatol 1997;37:289-90.

22. Gooptu C, Higgins CR, James MP. Treatment of viral warts with cimetidine: an open-label study. Clin Exp Dermatol 2000;25:183-5.

23. Rogers CJ, Gibney MD, Siegfried EC, Harrison BR, Glaser DA. Cimetidine therapy for recalcitrant warts in adults: is it any better than placebo? J Am Acad Dermatol 1999;41:123-7.

24. Karabulut AA, Sahin S, Eksioglu M. Is cimetidine effective for nongenital warts: a double-blind, placebo-controlled study. Arch Dermatol 1997;133:533-4. 25. Micali G, Nasca MR, Dall'Oglio F, Musumeci ML. Cimetidine therapy for epidermodysplasia verruciformis. J Am Acad Dermatol 2003;48:S9-10.

26. Parsad D, Saini R, Negi KS. Comparison of combination of cimetidine and levamisole with cimetidine alone in the treatment of recalcitrant warts. Australas J Dermatol 1999;40:93-5.

27. Parsad D, Pandhi R, Juneja A, Negi KS. Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children. Pediatr Dermatol 2001;18:349-52.

28. Franco I. Oral cimetidine for the management of genital and perigenital warts in children. J Urol 2000;164:1074-5.

29. Harcourt JP, Worley G, Leighton SE. Cimetidine treatment for recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol 1999;51:109-13.

30. Shields CL, Lally MR, Singh AD, Shields JA, Nowinski T.Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis. Am J Ophthalmol 1999;128:362-4.

31. Yashar SS, Shamiri B. Oral cimetidine treatment of molluscum contagiosum. Pediatr Dermatol 1999;16:493.

32. Husar K, Skerlev. M. Molluscum contagiosum from infancy to maturity. Clin Dermatol 2002;20:170-2.

33. Sharma AK. Cimetidine therapy for multiple molluscum contagiosum lesions. Dermatology 1998;197:194-5.

34. Cunningham BB, Paller AS, Garzon M. Inefficacy of oral cimetidine for nonatopic children with molluscum contagiosum. Pediatr Dermatol 1998;15:71-2.

35. Negro-Alvarez JM, Miralles-Lopez JC. Chronic idiopathic urticaria treatment. Allergol Immunopathol (Madr) 2001;29:129-32.

36. Sharma JK, Miller R, Murray S. Chronic urticaria: a Canadian perspective on patterns and practical management strategies. J Cutan Med Surg 2000:4:89-93.

37. Lee EE, Maibach HI. Treatment of urticaria. An evidence-based evaluation of antihistamines. Am J Clin Dermatol 2001;2:27-32.

37. Skrebova N, Takiwaki H, Miyaoka Y, Arase S. Localized heat urticaria: a clinical study using laser Doppler flowmetry. J Dermatol Sci 200;26:112-8.

39. Mardones P, Moyano C, Pena K, Quijada C. Systemic mastocytosis: clinical case. Rev Med Chil 1998;126:823-7.

40. Guss DA. Scombroid fish poisoning: successful treatment with cimetidine. Undersea Hyperb Med 1998;25:123-5.

41. MacGillivray KC, Sweeney RW, Del Piero F. Metastatic melanoma in horses. J Vet Intern Med 2002;16:452-6.

42. Szincsak N, Hegyesi H, Hunyadi J, Martin G, Lazar-Molnar E, Kovacs P, Rivera E, Falus A, Juhasz I. Cimetidine and a tamoxifen derivate reduce tumour formation in SCID mice xenotransplanted with a human melanoma cell line. Melanoma Res 2002;12:231-40.

43. Ristic B, Zecevic RD, Karadaglic DJ. Treatment of eosinophilic fasciitis with cimetidine. Vojnosanit Pregl 2001;58:437-40.

44. Rogers M. Successful treatment of eosinophilic pustulosis with oral cimetidine. Pediatr Dermatol 1999;16:335-6.

45. Baker RA, Zeller RA, Klein RL, Thornton RJ, Shuber JH, Marshall RE, Leibfarth AG, Latko JA. Burn wound itch control using H1 and H2 antagonists. J Burn Care Rehabil 2001;22(4):263-8.

46. Ashida Y, Denda M, Hirao T. Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment. J Invest Dermatol 2001;116:261-5.

47. Lee WI, Yang MH, Lee KF, Chen LC, Lin SJ, Yeh KW, Huang JL. PFAPA syndrome (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis).Clin Rheumatol 1999;18:207-13.

48. Pillet P, Ansoborlo S, Carrere A, Perel Y, Guillard JM. (P)FAPA syndrome: value of cimetidine. Arch Pediatr 2000 ;7:54-7.

49. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999;135:15-21.

50. Schibler A, Birrer P, Vella S. PFAPA syndrome: periodic fever, adenitis, pharyngitis and aphthous stomatitis. Schweiz Med Wochenschr 1997;127:1280-4.

51. Sasaki H. A new approach for the treatment of acute porphyria. Intern Med 1999;38:307-8.

52. Rogers PD. Cimetidine in the treatment of acute intermittent porphyria. Ann Pharmacother 1997;31:365-7.

53. Coleman MD. Dapsone toxicity: some current perspectives. Gen Pharmacol 1995;26(7):1461-7.

54. Coleman MD, Coleman NA. Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf 1996;14(6):394-405.

55. Rhodes LE, Tingle MD, Park BK, Chu P, Verbov JL, Friedmann PS. Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy. Br J Dermatol 1995;132(2):257-62.

56. Coleman MD, Rhodes LE, Scott AK, Verbov JL, Friedmann PS, Breckenridge AM, Park BK. The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in dermatitis herpetiformis patients. Br J Clin Pharmacol 1992;34(3):244-9.

57. Malfara WR, Pereira CP, Santos AC, Queiroz RH. Effects of H(2)-receptor antagonists on dapsone-induced methaemoglobinaemia in rats. Pharmacol Res 2002;45(4):269-73.

58. Evans RD, Yoho R, Eberly M, Donohoe S. Cimetidine and a delayed hypersensitivity reaction. Clin Podiatr Med Surg 2000;17:371-5.

59. Helmbold P, Hegemann B, Dickert C, Marsch WC. Symmetric psychotropic and nonpigmenting fixed drug eruption due to cimetidine (so-called baboon syndrome) Dermatology 1998;197:402-3.

60. Tidwell BH, Paterson TM, Burford B. Cimetidine-induced toxic epidermal necrolysis. Am J Health Syst Pharm 1998;55:163-4.

61. Horiuchi Y, Ikezawa K. Famotidine-induced erythema multiforme: cross-sensitivity with cimetidine. Ann Intern Med 1999;131:795.

© 2003 Dermatology Online Journal

Follow eScholarship on  
Document Info
Search Document
Table of Contents
Supporting Material
Document Metrics
Journal Info
Similar Items
peer reviewed Peer Reviewed


Cimetidine: A review of the recent developments and reports in cutaneous medicine

Journal Issue:

Dermatology Online Journal, 9(2)


Scheinfeld, Noah MD

Publication Date:


Publication Info:

Dermatology Online Journal, UC Davis


Privacy Policy
CDL logo   Powered by the California Digital Library
Items in eScholarship are protected by copyright, with all rights reserved, unless otherwise indicated.