Imiquimod cream treatment benefit and side effects, for skin health
March 6 2017 by
Ray Sahelian, M.D.


Imiquimod is used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

How should Imiquimod medicine be used?
Imiquimod comes as a topical cream in unit-of-use packages. It is important to wash your hands before and after applying imiquimod to your skin. One packet of imiquimod is used to apply a thin layer of cream to the wart area three times per week, just before going to sleep. A schedule of Monday, Wednesday, Friday or Tuesday, Thursday, Saturday is suggested. Rub the imiquimod cream into the skin until no more cream is visible. Do not put any covering on the area. Imiquimod should be left on the skin for 6 to 10 hours. Upon waking, wash the area with mild soap and water to remove excess cream. Use imiquimod as directed. Do not use more or less of it or use it more often than prescribed by your doctor.


Adverse effect, negative reaction
J Eur Acad Dermatol Venereol. 2014. Development of recalcitrant skin ulcers as a side-effect of treatment with topical 5% imiquimod cream: Report of two cases.


Imiquimod cream

Imiquimod cream is indicated for the topical treatment of external genital and perianal warts (condyloma acuminata) in adult patients. Imiquimod cream is available as a 5% cream in single use sachets. Imiquimod cream should be applied 3 times per week to the cleaned wart area, prior to sleeping and should remain on the skin for 6 to 10 hours. Imiquimod cream treatment should continue until there is clearance of visible genital or perianal warts or for a maximum of 16 weeks per episode of warts.


Imiquimod cream  may help accelerate the resolution of superficial hemangiomas in infants. These "strawberry" birthmarks are benign skin lesions consisting of dense, usually elevated masses of dilated blood vessels. Dr. Nhung T. C. Ho and colleagues at the University of Toronto reviewed the outcomes of 16 girls and 2 boys, median age 18 weeks, with a total of 22 hemangiomas, most of which were on the head. The immune response modifier imiquimod was initially used three times weekly in all patients but was increased to five times weekly in eight patients. Imiquimod cream was applied for periods ranging from 7 to 46 weeks. All 12 superficial hemangiomas showed improvement and complete clearance was achieved in 4. There was little improvement in the 3 mixed and 3 deep hemangiomas. There were no apparent internal imiquimod side effects, and irritation and crusting were the most common skin-related side effects. Journal of the American Academy of Dermatology, January 2007.


Skin Cancer

Imiquimod has been successfully used for treatment of various epithelial cutaneous neoplasms. Imiquimod 5% cream has been tested as treatment of Bowen's disease and invasive squamous cell carcinoma (SCC) in patients who were unsuitable candidates for surgery. Topical application of imiquimod 5% cream might represent an alternative topical treatment to surgery in selected cases of Bowen's disease and invasive SCC.


Imiquimod cream for basal cell skin cancer

5% imiquimod cream is a treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 80 % at an average of 4 year follow up. Sometimes complications can occur, see below.

Invasive squamous cell carcinoma after treatment of carcinoma in situ with 5% imiquimod cream.
Australas J Dermatol. 2006. Goh MS. Department of Dermatology, Austin Hospital, Heidelberg, Victoria, Australia.
Squamous cell carcinoma in situ has the potential to progress to invasive squamous cell carcinoma. This report presents two cases of punch biopsy-proven squamous cell carcinoma in situ, treated with once-daily application of 5% imiquimod cream for 6 weeks. Both patients developed moderate local inflammatory reactions during treatment. The first patient demonstrated clinical clearance of the scalp lesion after treatment. Two months later, he re-presented with a subcutaneous nodule at the same site. Histology was consistent with recurrent squamous cell carcinoma. Five months following excision of the recurrent tumour, he presented with metastatic squamous cell carcinoma to a cervical lymph node. The second patient had low-grade chronic lymphocytic leukaemia and presented with squamous cell carcinoma in situ of the leg that failed to clear clinically after treatment with imiquimod. He presented 4 months later with a focus of invasive squamous cell carcinoma within the lesion.


Two-year interim results from a 5-year study evaluating clinical recurrence of superficial basal cell carcinoma after treatment with imiquimod 5% cream daily for 6 weeks.
Australas J Dermatol. 2006. Fremantle, Western Australia, Australia.
Imiquimod 5% cream is approved in the USA, Europe and Australia to treat superficial basal cell carcinoma, using a regimen of once daily, 5 times per week for 6 weeks. Vehicle-controlled, phase III clinical trials show that imiquimod is safe and effective for treating superficial basal cell carcinoma with dosing 5 or 7 times per week for 6 weeks. This phase III, open-label study evaluates the long-term (5 years) clinical efficacy and safety of dosing once daily, for which this manuscript reports the 2-year time point in the follow-up period. For the 169 enrolled subjects, the tumour selected for treatment was assessed clinically to determine initial clearance at the 12-week post-treatment visit. If clinically clear of superficial basal cell carcinoma, subjects entered a 5-year, long-term follow-up period. Subjects were evaluated for recurrence at the 3-, 6-, 12- and 24-month follow-up visits. The initial clearance rate at 12 weeks post treatment was 94.1%. The proportion of subjects who were clinically clear at the 2-year follow-up visit was estimated to be 82.0%. Imiquimod was tolerated when applied daily, with erythema reported for all subjects participating in the study. The recurrence rate observed suggests that once daily dosing and 5x/week dosing yield similar clearance rates, but daily dosing increases local skin reactions.


Erythroplasia of Queyrat treated with imiquimod 5% cream.
J Am Acad Dermatology. 2006. Dermatology Clinic, University of Catania, Catania, Italy
Imiquimod is an immune response-modifying agent with potent antiviral and antitumor activity effective in the treatment of various skin disorders, including in situ carcinoma of the skin (Bowen's disease). The case of a 64-year-old man affected by an in situ carcinoma of the glans mucosa, namely erythroplasia of Queyrat, successfully treated with imiquimod 5% cream is described. Because the results of tests for human papillomavirus infection were negative in this case, we suggest that imiquimod may have acted through an antitumor effect mediated by cytokine activation. This compound may represent an alternative treatment in patients with erythroplasia of Queyrat, although the dosing schedule and treatment duration require further evaluation.

Imiquimod for Paget's Disease

Treatment of mammary and extramammary Paget's skin disease with topical imiquimod.
J Dermatolog Treatment. 2006.
Paget's disease is an uncommon epidermal cancer, affecting all skin regions wherever apocrine glands are present. It is divided into extramammary (EMPD) and mammary Paget's disease (MPD). It can be confined to the epithelium or may be associated with an underlying adenocarcinoma. The diagnosis is confirmed by skin biopsy and the treatment depends on characteristics of the underlying cancer. Surgery is the first-line treatment. Imiquimod, a topical immunomodulator, approved its efficiency in several skin neoplasms and has been shown as a safe treatment for EMPD. However, it has never been reported for the treatment of MPD. Observations: We report on two cases of EMPD and mammary Paget's disease successfully treated with imiquimod 5% cream. This non-surgical method may be considered as a primary treatment when Paget's disease is not associated with an underlying malignancy. The good prognosis with a long-term survival, the anatomic localization and the poor general condition of elderly people may favor imiquimod as an alternative treatment. On the other hand, it will reduce the extent of excision when it anticipates surgery.


Safety of imiquimod 5% cream in the treatment of molluscum contagiosum in children
Imiquimod cream 5%, a toll-like receptor 7 agonist, induces alpha-interferon upon topical application, prompting off-label usage to treat children with molluscum contagiosum. Systemic drug levels were low after single and multiple doses of imiquimod 5% cream in children. Imiquimod cream appears to be safe for use in children for brief periods.


How it works, mechanism of action
Imidazoquinolins are a new group of compounds that recently entered into clinical practice as anti-tumor and anti-viral immune modulators. They are low molecular weight synthetic guanosine-like molecules. Although imiquimod, the most widely used imidazoquinolin, is recommended for the treatment of several forms of skin cancer and papillomas, the molecular mechanisms of its action are not fully understood. In particular, imiquimod has been characterized as a specific agonist of Toll-like receptor 7 (TLR7) and is widely used in this capacity in a large number of experimental studies and clinical trials. There are also indications of a direct interaction of imiquimod with adenosine receptors and other molecules that regulate the synthesis of cyclic adenosine monophosphate.


Questions and emails
My father has been recently diagnosed with early stage EMPD Extramammary Paget's disease. He has been referred to a Radiologist to explore PDT photodynamic therapy possibilities. I’m wondering why Imiquimod cream 5% was not prescribed to begin immediate treatment before exploring PDT or surgical excision. Should he have been given a script for this alternative treatment to surgery and other treatments? He is a very healthy 64 year old prostate cancer survivor. No other malignancies were found following full evaluation / CT scan, etc. Was Imiquimod cream not prescribed due to radical prostectomy 2 years ago?
   This is not my area of expertise, hence I don't have an opinion.


I would suggest that you and your staff take a much closer look at marketed drugs containing the active ingredient imiquimod. In my opinion it is a very dangerous drug. It should definitely not be a “patient applied” drug. It is “uncontrollable chemotherapy” treatment. And finally, the FDA reports there has been dozens of deaths attributed to the use of this drug since the FDA approval date in 1997. This is a drug that has not been properly and honestly marketed by its manufacturers but has been and continues to be sold on completely false pretenses that it is safe and equal to solaraze, carac, and other 5-FU “direct cell destructive” creams.