Imiquimod, sold under the brand name Aldara among others, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

that acts as an immune response modifier that is used to treat

genital wart Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...

s, superficial

basal cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...

, and

actinic keratosis Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...

. Scientists at 3M's pharmaceuticals division discovered the drug and 3M obtained the first FDA approval in 1997. As of 2015, imiquimod is generic and is available worldwide under many brands.

Medical uses

Imiquimod is a patient-applied cream prescribed to treat

s, Bowens disease ( squamous cell carcinoma in situ), and, secondary to surgery, for

, as well as

. Imiquimod 5% cream is indicated for the topical treatment of: * external genital and perianal warts (condylomata acuminata) in adults; * small superficial basal-cell carcinomas (sBCCs) in adults; * clinically typical, non-hyperkeratotic, non-hypertrophic actinic keratoses (AKs) on the face or scalp in immunocompetent adults when size or number of lesions limit the efficacy and / or acceptability of cryotherapy and other topical treatment options are contraindicated or less appropriate. Imiquimod 3.75% cream is indicated for the topical treatment of clinically typical, non-hyperkeratotic, non-hypertrophic, visible or palpable actinic keratosis of the full face or balding scalp in immunocompetent adults when other topical treatment options are contraindicated or less appropriate.

Side effects

Side effects include local inflammatory reactions, such as blisters, a burning sensation, skin redness, dry skin, itching, skin breakdown, skin crusting or scabbing, skin drainage, skin flaking or scaling, skin ulceration, sores, swelling, as well as systemic reactions, such as fever, "flu-like" symptoms, headache, and tiredness. People who have had an

organ transplant Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...

and are taking immune-suppressing drugs should not use imiquimod.European Medicines Agency. First published Sept 14,2009, updated March 25, 2015
EMA Summary of Product Characteristics
/ref>

Mechanism of action

Imiquimod yields profound antitumoral activity by acting on several immunological levels synergistically. Imiquimod stimulates the innate immune system by activating

toll-like receptor 7 Toll-like receptor 7, also known as TLR7, is a protein that in humans is encoded by the ''TLR7'' gene. Orthologs are found in mammals and birds. It is a member of the toll-like receptor (TLR) family and detects single stranded RNA. Function T ...

(TLR7), commonly involved in pathogen recognition. Cells activated by imiquimod via TLR-7 secrete

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

(primarily

interferon-α The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyto ...

(IFN-α),

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

(IL-6), and

tumor necrosis factor-α Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

(TNF-α)). There is evidence that imiquimod, when applied to skin, can lead to the activation of

Langerhans cells A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in t ...

, which subsequently migrate to local lymph nodes to activate the

adaptive immune system The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

. Other cell types activated by imiquimod include

natural killer cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

and

B-lymphocytes B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

. Imiquimod exerts its effect by increasing levels of the

opioid growth factor receptor Opioid growth factor receptor, also known as OGFr or the ζ-opioid receptor, is a protein which in humans is encoded by the ''OGFR'' gene. The protein encoded by this gene is a Receptor (biochemistry), receptor for opioid growth factor (OGF), al ...

(OGFr). In experiments, blocking OGFr function with

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...

technology resulted in loss of any antiproliferative effect of imiquimod.

History

Scientists at 3M's pharmaceutical division discovered imiquimod as part of a program to discover inhibitors of

herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...

replication based on a known

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...

derivative. 3M obtained the first FDA approval for it in 1997 as a treatment for external genital and perianal warts under the brand, "Aldara". In 2004, 3M obtained FDA approval to market imiquimod as a treatment for superficial

. In 2006, 3M sold its pharmaceutical business in the Americas to Graceway Pharmaceuticals, its European pharmaceutical business to

Meda AB Meda AB is a specialty pharmaceutical company, headquartered in Solna, Sweden. Meda imports and markets pharmaceuticals, nutritional, and health-care products, and offers services including clinical research, registration, and logistics. At the ...

, and its pharmaceutical business in other territories to two

private equity In the field of finance, the term private equity (PE) refers to investment funds, usually limited partnerships (LP), which buy and restructure financially weak companies that produce goods and provide services. A private-equity fund is both a ty ...

firms. Graceway declared bankruptcy in 2011, after the expiration of the patents on imiquimod, and its assets, including the rights to imiquimod branding and approvals in the Americas, were purchased by

Medicis Pharmaceutical Medicis Pharmaceutical is a medical cosmetics company based in Bridgewater, New Jersey. It is a subsidiary of Valeant Pharmaceuticals, which acquired the company in 2012. Medicis is known for products such as Solodyn and Ziana for treating acne, ...

. Imiquimod 5% was approved for medical use in the European Union in September 1998. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Imiquimod 3.75% was approved for medical use in the European Union in August 2012. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. As of 2015, imiquimod is generic and is available worldwide under many brands.Drugs.co
Drugs.com international listings for imiquimod
Page accessed June 14, 2015

Research

One randomized double-blind Phase III clinical study found clearance of genital warts (an FDA-approved indication) improved from 9% with placebo to 24.9% with 3.75% imiquimod cream applied for up to eight weeks. Imiquimod has been tested for treatment of

molluscum contagiosum Molluscum contagiosum (MC), sometimes called water warts, is a viral infection of the skin that results in small raised pink lesions with a dimple in the center. They may become itchy or sore, and occur singularly or in groups. Any area of the sk ...

. 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. These disprove earlier anecdotal claims and smaller, less reliable studies. Imiquimod has also been tested for treatment of

vulvar intraepithelial neoplasia Vulvar intraepithelial neoplasia (VIN) refers to particular changes that can occur in the skin that covers the vulva. VIN is an intraepithelial neoplasia, and can disappear without treatment. VINs are benign but if the changes become more severe, t ...

vaginal intraepithelial neoplasia Vaginal intraepithelial neoplasia (VAIN) is a condition that describes premalignant histological findings in the vagina characterized by dysplastic changes. The disorder is rare and generally has no symptoms. VAIN can be detected by the presence ...

common warts Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...

(a 2012 Cochrane review found no randomized controlled trials),

plantar wart A plantar wart, or verruca vulgaris, is a wart occurring on the sole (foot), bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may r ...

s, warts in people with suppressed immune systems, flat warts on face and neck, and warts under and around fingernails and toenails. As of 2014, insufficient evidence exists to recommend treatment of warts (other than genital warts) with imiquimod, due to the small size of and lack of controls in existing studies.

References

External links

* * {{Portal bar , Medicine Antiviral drugs Antineoplastic drugs Imidazoquinolines