Imiquimod (INN) is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals, and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by FarmacoquÃmica Médica (FQM) in Brazil as Ixium. It is also referred to as R-837. Due to the bankruptcy of Graceway in 2011, Medicis Pharmaceutical Corporation is the current owner of these products.
History
The original FDA approval was on February 27, 1997, FDA Application No. (NDA) 020723, by 3M. Imiquimod is approved for the uses described below under Uses. Adverse side effects have been reported, in some cases serious and systemic, resulting in the revision of warning labels.
Uses
Imiquimod is a patient-applied cream used to treat certain diseases of the skin, including skin cancers (basal cell carcinoma, Bowen's disease, superficial squamous cell carcinoma, some superficial malignant melanomas, and actinic keratosis) as well as genital warts (condylomata acuminata). However, Imiquimod is generally secondary to surgery, because surgery has a better chance to effectively treat at least some forms of skin cancer.
Imiquimod has been tested for treatment of molluscum contagiosum. Two large randomized controlled trials, however, found no evidence of effectiveness of imiquimod in treating children with molluscum contagiosum, and concerning adverse effects were also noted.
Imiquimod has also been tested for treatment of vulvar intraepithelial neoplasia, common warts that have proven difficult to treat, and vaginal intraepithelial neoplasia.
Outstanding cosmetic result has resulted from the treatment of both large superficial basal cell carcinoma and squamous cell carcinoma in-situ, but the morbidity and discomfort of the treatment can be severe, and can very occasionally result in some degree of permanent mild scarring. Focal recurrence of tumor has been seen after imiquimod treatment, but appear to be amenable to surgical excision.
Imiquimod can also cause subclinical lesions to become visible and to be killed by the immune system. Photographs of actinic keratosis and superficial basal cell carcinomas before, during and after treatment show the unmasking of subclinical disease. The more-concentrated (5%) Imiquimod cream needs to be applied on and off for 4 months, while the less concentrated (3.75%) Imiquimod cream needs to be applied on and off for a number of months to be determined by the doctor.
Imiquimod is more likely to cure skin disease that is identified earlier.
Mechanism of action
It is known that imiquimod signals to the innate arm of the immune system through the toll-like receptor 7 (TLR7), commonly involved in pathogen recognition. Cells activated by imiquimod via TLR-7 secrete cytokines (primarily interferon-α (INF-α), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). There is evidence that imiquimod, when applied to skin, can lead to the activation of Langerhans cells, which subsequently migrate to local lymph nodes to activate the adaptive immune system. Other cell types activated by imiquimod include natural killer cells, macrophages and B-lymphocytes.
New research has shown that imiquimod has anti-proliferative effects in vitro that are independent of immune system activation or function. However, those effects do not apply to skin cancer cells.
Imiquimod exerts its effect by increasing levels of the opioid growth factor receptor (OGFr). In experiments, blocking OGFr function with siRNA technology resulted in loss of any antiproliferative effect of imiquimod.
Disadvantages
Nonspecific inflammation and dermatitis can occur during use of imiquimod for genital warts and molluscum. This often occurs where the skin is traumatized from scratching or between skin folds. Blisters, bloody dry eschar, pain, and discomfort often follows the use of imiquimod for skin cancers and precancerous growths. During the treatment of large superficial basal cell carcinoma or squamous cell cancer in situ, areas of black dried crust often form. Many individuals with extensive actinic keratoses cannot tolerate the resulting reaction. Despite frequent significant inflammation, the areas treated generally heal well with no scarring.
Recurrence of skin cancer can occur with imiquimod, but often appears to be localized. It is more common when there are deeply penetrating nests of tumor cells such as in nodular basal cell carcinoma. However, nodular basal cell carcinomas should generally not be treated with imiquimod. Recurrence of superficial basal cell carcinomas can be treated by repeat courses of imiquimod, surgically by simple local excision or by Mohs' micrographic surgery. The recurrence rate depends on the condition being treated and the frequency of topical imiquimod application. A 6-week study on 99 patients with superficial basal cell carcinomas found success rates of 100%, 88%, 73% and 70% for twice daily, once daily, 6 times weekly and 3 times weekly application, respectively.
Other side effects include headaches, back pain, muscle aches, tiredness, flu-like symptoms, swollen lymph nodes, diarrhea, and fungal infections.
Synthesis
Imiquimod can be prepared from 4-chloro-3-nitroquinoline.
See also
- Resiquimod
References
External links
- MedlinePlus DrugInfo medmaster-a698010
- DermNet treatments/imiquimod
- NPS RADAR
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