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Imiquimod

Classification: A

Drug products: ALDARA, Bascellex, Zyclara

ATC code: D06BB10

Substances: imiquimod

Summary

One study has shown better effect in treatment of superficial basal cell carcinoma in women compared to men. Self-applied treatment with imikvimod in condyloma has shown better effect in women than in men.
 
Despite these findings our opinion is that the described differences do not motivate differentiated dosing or treatment in men and women.

Additional information

We found only one article on basal cell carcinoma, two on actinic keratosis and four on external genital warts although in Sweden, the prescription statistics indicate that imiquimod is mainly used in basal cell carcinoma and actinic keratosis.Topical imiquimod is an immunomodulatory agent stimulating the cytokine production in cells infected with HPV-virus which is a common cause of external genital warts [1].

Pharmacokinetics and dosing

A review of three double-blind placebo-controlled pharmacokinetic studies in healthy volunteers (one study in only women n=39, and two studies where the sex of the patients’ was not provided n=13) showed no systemic absorption of topically administered imiquimod. The study in 39 women showed that the high dose (250 mg) was associated with an increased immune response after 8 hours compared to baseline [1].

Effects

Basal cell carcinomaA subgroup analysis of a single-blind, multicenter randomized study (190 men, 195 women) comparing imiquimod and methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC) showed at 12-month follow-up that imiquimod had a better effect in women than in men (90% vs. 77%). According to the authors, the hormone estrogen has positive effects on the immune system similar to imiquimod [2].

Actinic keratosisA multicenter non-interventional cross-sectional study of patients with actinic keratosis (152 men, 160 women) showed that treatment with imiquimod was more likely in men than in women (OR 2.3). The group receiving photodynamic therapy had a higher ratio of women (OR 4.08) and more cases of severe actinic damage (OR 3.4) [3].According to the abstract of a multicenter observational study of treatment of actinic keratosis with imiquimod cream, topical diclofenac 3% in hyaluronic acid, cryotherapy, photodynamic or curettage showed that irrespective of treatment men, compared to women, had a more complete recovery, but also higher recurrence at 6 and 12 months and more new lesions 12 months after remission (OR 1.6 vs. 0.9, in the entire cohort) [4].

External genital wartsSeveral studies have shown a higher wart clearance rate in women than in men and one meta-analysis has shown a higher clearance in uncircumcised men than in circumcised men. A subgroup analysis of a double-blind, placebo-controlled randomized study (123 men, 86 women) of 5% cream in patients with external genital or perianal warts showed a higher wart clearance in women than in men (72% vs. 33%) [5]. Similarly, according to the SPC, the wart clearance rate was higher in women than in men (60 vs. 23%) and the time to complete clearance was shorter in women than in men (8 vs 12 weeks) [6]. A meta-analysis of subgroups in six randomized studies (444 circumcised men, 64 uncircumcised men, 466 women) showed a worse effect in circumcised men compared to uncircumcised men and women in clearance of condyloma acuminate [7]. In two of the included studies (115 men, 88 women)  the wart clearance  rate was 1.5-2 times higher in women than in men and the time to wart clearance with 5% cream was longer in men than in women (7 vs 3 months and 10 vs 8 weeks) [8,9]. According to the authors, the drug penetration is affected by the different degree of keratinization of the skin where the warts are located [7].

Adverse effects

A meta-analysis of subgroups in six randomized studies (444 circumcised men, 64 uncircumcised men, 466 women) showed that more women and uncircumcised men required a treatment rest period because of local cutaneous reactions in the once-daily than in the three times weekly dosing regimen. Among circumcised men there was no difference in cutaneous reactions between the two dosing regimens [7].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Updated: 2019-02-26

Date of litterature search: 2017-02-17

References

  1. Perry CM, Lamb HM. Topical imiquimod: a review of its use in genital warts. Drugs. 1999;58:375-90. PubMed
  2. Roozeboom MH, Nelemans PJ, Mosterd K, Steijlen PM, Arits AH, Kelleners-Smeets NW. Photodynamic therapy vs topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial. Br J Dermatol. 2015;172:739-45. PubMed
  3. Erlendsson AM, Egekvist H, Lorentzen HF, Philipsen PA, Stausbøl-Grøn B, Stender IM et al. Actinic keratosis: a cross-sectional study of disease characteristics and treatment patterns in Danish dermatology clinics. Int J Dermatol. 2016;55:309-16. PubMed
  4. Javor S, Chimenti S, Patrizi A, Stingeni L, Pellacani G, Cavicchini S et al. Relapsed actinic keratosis evaluation: an observational Italian multicenter prospective study Does gender have a role?. G Ital Dermatol Venereol. 2014;149:199-204. PubMed
  5. Sauder DN, Skinner RB, Fox TL, Owens ML. Topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations. Sex Transm Dis. 2003;30:124-8. PubMed
  6. ALDARA (imiquimod). Summary of Product Characteristics. European Medicines Agency (EMA); 2016
  7. Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR. Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. Sex Transm Dis. 2008;35:346-51. PubMed
  8. Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL et al. Self-administered topical 5% imiquimod cream for external anogenital warts HPV Study Group Human PapillomaVirus. Arch Dermatol. 1998;134:25-30. PubMed
  9. Beutner KR, Tyring SK, Trofatter KF, Douglas JM, Spruance S, Owens ML et al. Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts. Antimicrob Agents Chemother. 1998;42:789-94. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2017-03-02.] länk

Authors: Maria Enghag

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson