External genital warts, superficial basal cell carcinoma and actinic keratosis:Avoid contact with the eyes, lips and nostrils.Imiquimod has the potential to exacerbate inflammatory conditions of the skin.Imiquimod cream should be used with caution in patients with autoimmune conditions (refer to section 4.5). Consideration should be given to balancing the benefit of imiquimod treatment for these patients with the risk associated with a possible worsening of their autoimmune condition.Imiquimod cream should be used with caution in organ transplant patients (refer to section 4.5). Consideration should be given to balancing the benefit of imiquimod treatment for these patients with the risk associated with the possibility of organ rejection or graft-versus-host disease.Imiquimod cream therapy is not recommended until the skin has healed after any previous drug or surgical treatment. Application to broken skin could result in increased systemic absorption of imiquimod leadling to a greater risk of adverse events (refer to section 4.8 and 4.9)The use of an occlusive dressing is not recommended with imiquimod cream therapy.The excipients methylhydroxybenzoate (E218), propylhydroxybenzoate (E216), cetyl alcohol and stearyl alcohol may cause allergic reactions.Rarely, intense local inflammatory reactions including skin weeping or erosion can occur after only a few applications of imiquimod cream. Local inflammatory reactions may be accompanied, or even preceded, by flu-like systemic signs and symptoms including malaise, pyrexia, nausea, myalgias and rigors. An interruption of dosing should be considered.Imiquimod should be used with caution in patients with reduced haematologic reserve (refer to section 4.8d).
External genital warts:There is limited experience in the use of imiquimod cream in the treatment of men with foreskin-associated warts. The safety database in uncircumcised men treated with imiquimod cream three times weekly and carrying out a daily foreskin hygiene routine is less than 100 patients. In other studies, in which a daily foreskin hygiene routine was not followed, there were two cases of severe phimosis and one case of stricture leading to circumcision. Treatment in this patient population is therefore recommended only in men who are able or willing to follow the daily foreskin hygiene routine. Early signs of stricture may include local skin reactions (e.g. erosion, ulceration, oedema, induration), or increasing difficulty in retracting the foreskin. If these symptoms occur, the treatment should be stopped immediately. Based on current knowledge, treating urethral, intra-vaginal, cervical, rectal or intra-anal warts is not recommended. Imiquimod cream therapy should not be initiated in tissues where open sores or wounds exist until after the area has healed. Local skin reactions such as erythema, erosion, excoriation, flaking and oedema are common. Other local reactions such as induration, ulceration, scabbing, and vesicles have also been reported. Should an intolerable skin reaction occur, the cream should be removed by washing the area with mild soap and water. Treatment with imiquimod cream can be resumed after the skin reaction has moderated.The risk of severe local skin reactions may be increased when imiquimod is used at higher than recommended doses (see section 4.2). However, in rare cases severe local reactions that have required treatment and/or caused temporary incapacitation have been observed in patients who have used imiquimod according to the instructions. Where such reactions have occurred at the urethral meatus, some women have experienced difficulty in urinating, sometimes requiring emergency catheterisation and treatment of the affected area.No clinical experience exists with imiquimod cream immediately following treatment with other cutaneously applied drugs for treatment of external genital or perianal warts. Imiquimod cream should be washed from the skin before sexual activity. Imiquimod cream may weaken condoms and diaphragms, therefore concurrent use with imiquimod cream is not recommended. Alternative forms of contraception should be considered.In immunocompromised patients, repeat treatment with imiquimod cream is not recommended.While limited data have shown an increased rate of wart reduction in HIV positive patients, imiquimod cream has not been shown to be as effective in terms of wart clearance in this patient group.
Superficial basal cell carcinoma:Imiquimod has not been evaluated for the treatment of basal cell carcinoma within 1 cm of the eyelids, nose, lips or hairline.During therapy and until healed, affected skin is likely to appear noticeably different from normal skin. Local skin reactions are common but these reactions generally decrease in intensity during therapy or resolve after cessation of imiquimod cream therapy. There is an association between the complete clearance rate and the intensity of local skin reactions (e.g. erythema). These local skin reactions may be related to the stimulation of local immune response. If required by the patient's discomfort or the severity of the local skin reaction, a rest period of several days may be taken. Treatment with imiquimod cream can be resumed after the skin reaction has moderated.The clinical outcome of therapy can be determined after regeneration of the treated skin, approximately 12 weeks after the end of treatment.No clinical experience exists with the use of imiquimod cream in immunocompromised patients.No clinical experience exists in patients with recurrent and previously treated BCCs, therefore use for previously treated tumours is not recommended.Data from an open label clinical trial suggest that large tumours (>7.25 cm2) are less likely to respond to imiquimod therapy.The skin surface area treated should be protected from solar exposure.
Actinic keratosisLesions clinically atypical for AK or suspicious for malignancy should be biopsied to determine appropriate treatment.Imiquimod has not been evaluated for the treatment of actinic keratoses on the eyelids, the inside of the nostrils or ears, or the lip area inside the vermilion border.There are very limited data available on the use of imiquimod for the treatment of actinic keratoses in anatomical locations other than the face and scalp. The available data on actinic keratosis on the forearms and hands do not support efficacy in this indication and therefore such use is not recommended.Imiquimod is not recommended for the treatment of AK lesions with marked hyperkeratosis or hypertrophy as seen in cutaneous horns.During therapy and until healed, affected skin is likely to appear noticeably different from normal skin. Local skin reactions are common but these reactions generally decrease in intensity during therapy or resolve after cessation of imiquimod cream therapy. There is an association between the complete clearance rate and the intensity of local skin reactions (e.g. erythema). These local skin reactions may be related to the stimulation of local immune response. If required by the patient's discomfort or the intensity of the local skin reaction, a rest period of several days may be taken. Treatment with imiquimod cream can be resumed after the skin reaction has moderated.Each treatment period should not be extended beyond 4 weeks due to missed doses or rest periods. The clinical outcome of therapy can be determined after regeneration of the treated skin, approximately 4-8 weeks after the end of treatment. No clinical experience exists with the use of imiquimod cream in immunocompromised patients.No data are available on re-treating actinic keratoses that have cleared after one or two courses of treatment and subsequently recur, and any such use is therefore not recommended.Data from an open-label clinical trial suggest that subjects with more than 8 AK lesions showed a decreased rate of complete clearance compared to patients with less than 8 lesions.The skin surface area treated should be protected from solar exposure.