Imiquimod

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 Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).