Imiquimod is a toll-like receptor-7 agonist enhancing both the innate and acquired immune response. It activates the production of numerous compounds, including IFN-α, IL-1, -6, -8, -10, -12, and TNF-α, stimulates natural killer cells and the proliferation of B-cells. It also activates Langerhans cells and promotes their migration to the regional lymph nodes. Imiquimod stimulates TH-1 cells to produce IFN-g, which in turn can activate cytotoxic T lymphocytes. These cells provide long-term immune memory, which can offer future protection against the previously encountered virus or tumor.

Imiquimod cream is indicated for the topical treatment of-

• External genital and perianal warts in adults.
• Small superficial basal cell carcinomas in adults.
• Clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adult patients when size or number of lesions limit the efficacy and/or acceptability of cryotherapy and other topical treatment options are contraindicated or less appropriate.

External genital warts in adults: Imiquimod cream should be applied 3 times per week (example: Monday, Wednesday, and Friday; or Tuesday, Thursday, and Saturday) prior to normal sleeping hours, and should remain on the skin for 6 to 10 hours. Imiquimod cream treatment should continue until the clearance of visible genital or perianal warts or for a maximum of 16 weeks per episode of warts.

Imiquimod cream should be applied in a thin layer and rubbed on the clean wart area until the cream vanishes. Only apply to affected areas and avoid any application on internal surfaces. Imiquimod cream should be applied prior to normal sleeping hours. During the 6 to 10 hour treatment period, showering or bathing should be avoided. After this period it is essential that Imiquimod cream is removed with mild soap and water. Application of an excess of cream or prolonged contact with the skin may result in a severe application site reaction. A single use sachet is sufficient to cover a wart area of 20 cm2 (approx. 3 inches2). Sachets should not be re-used once opened. Hands should be washed carefully before and after application of cream. Uncircumcised males treating warts under the foreskin should retract the foreskin and wash the area daily.

Superficial basal cell carcinoma in adults: Apply Imiquimod cream for 6 weeks, 5 times per week (example: Monday to Friday) prior to normal sleeping hours, and leave on the skin for approximately 8 hours. Before applying Imiquimod cream, patients should wash the treatment area with mild soap and water and dry thoroughly. Sufficient cream should be applied to cover the treatment area, including one centimetre of skin surrounding the tumour. The cream should be rubbed into the treatment area until the cream vanishes. The cream should be applied prior to normal sleeping hours and remain on the skin for approximately 8 hours. During this period, showering and bathing should be avoided. After this period it is essential that Imiquimod cream is removed with mild soap and water. Sachets should not be re-used once opened. Hands should be washed carefully before and after application of cream. Response of the treated tumour to Imiquimod cream should be assessed 12 weeks after the end of treatment. If the treated tumour shows an incomplete response, a different therapy should be used. A rest period of several days may be taken if the local skin reaction to Imiquimod cream causes excessive discomfort to the patient, or if infection is observed at the treatment site. In this latter case, appropriate other measures should be taken.

Actinic keratosis in adults: Treatment should be initiated and monitored by a physician. Imiquimod cream should be applied 3 times per week (example: Monday, Wednesday and Friday) for four weeks prior to normal sleeping hours, and left on the skin for approximately 8 hours. Sufficient cream should be applied to cover the treatment area. After a 4-week treatment-free period, clearance of Actinic Keratosis should be assessed. If any lesions persist, treatment should be repeated for another four weeks. An interruption of dosing should be considered if intense local inflammatory reactions occur or if infection is observed at the treatment site. In this latter case, appropriate other measures should be taken. Each treatment period should not be extended beyond 4 weeks due to missed doses or rest periods. If the treated area does not show complete clearance at a follow-up examination about 8 weeks after the last 4-weeks course of treatment, an additional 4-weeks course of Imiquimod treatment may be considered. A different therapy is recommended if the treated lesion(s) shows insufficient response to Imiquimod. Actinic keratosis lesions that have cleared after one or two courses of treatment and subsequently recur can be re-treated with one or two further courses of Imiquimod cream following an at least 12 weeks treatment pause. Before applying Imiquimod cream, patients should wash the treatment area with mild soap and water and dry thoroughly. Sufficient cream should be applied to cover the treatment area, including one centimetre of skin surrounding the tumour. The cream should be rubbed into the treatment area until the cream vanishes. The cream should be applied prior to normal sleeping hours and remain on the skin for approximately 8 hours. During this period, showering and bathing should be avoided. After this period it is essential that Imiquimod cream is removed with mild soap and water. Sachets should not be re-used once opened. Hands should be washed carefully before and after application of cream.

Information applicable to all indications: If a dose is missed, the patient should apply the cream as soon as he/she remember and then he/she should continue with the regular schedule. However the cream should not be applied more than once a day.

Imiquimod cream is contraindicated in patients with hypersensitivity to imiquimod or cream excipients.

Reported side effects are pustules, genital candidiasis, vaginitis, bacterial infection, fungal infection, upper respiratory tract infection, vulvitis, rhinitis, influenza, lymphadenopathy, anorexia, insomnia, depression, irritability, headache, paraesthesia, dizziness, migraine, somnolence, conjunctival irritation, eyelid oedema, tinnitus, flushing, pharyngitis, nasal congestion, pharyngo laryngeal pain, nausea, abdominal pain, diarrhoea, vomitting, rectal disorder, rectal tenesmus, dry mouth, pruritus, folliculitis, rash erythematous, eczema, rash, increased sweating, urticaria, erythema, face oedema, skin ulcer, myalgia, arthralgia, back pain, pain in extremity, dysuria, genital pain in male, penile disorder, dyspareunia, erectile dysfunction, uterovaginal prolapse, vaginal pain, vaginitis atrophic, vulval disorder, and general disorders and administration site disorders such as pruritus, pain, burning, irritation, erythema, reaction, bleeding, papules, rash, inflammation asthenia, malaise, rigors, lethargy, discomfort, fatigue, discharge, oedema, scar, ulcer, vesicle, warmth, pyrexia etc. Reports have been received of localised hypopigmentation and hyperpigmentation following Imiquimod cream use. Clinical studies investigating the use of Imiquimod for the treatment of actinic keratosis have detected a 0.4% frequency of alopecia at the treatment site or surrounding area. Reductions in haemoglobin, white blood cell count, absolute neutrophils and platelets have been observed in clinical trials.

Overdose Effects

When applied topically, systemic overdosage with Imiquimod cream is unlikely due to minimal percutaneous absorption. Persistent dermal overdosing of Imiquimod cream could result in severe local skin reactions. Following accidental ingestion, nausea, emesis, headache, myalgia and fever could occur after a single dose of 200 mg Imiquimod which corresponds to the content of approximately 16 sachets. The most clinically serious adverse event reported following multiple oral doses of ≥ 200 mg was hypotension which resolved following oral or intravenous fluid administration.

Hypersensitivity to the active substance or to any of the excipients.

Use in Special Populations

Use in Children: Imiquimod cream is not recommended below the age of 12 years.

Use in Elderly: Imiquimod cream is recommended in elderly patient.

Effect on ability to drive and use machineries: Imiquimod cream is unlikely to produce any effect.

Pregnancy & Lactation

Use in Pregnancy B1. No human study is available. Imiquimod cream should only be used during pregnancy, if the potential benefit justifies the potential risk of fetus. No human study is available. Imiquimod cream should only be used during lactation if the potential benefit justifies the potential risk to the new-born baby.