Imiquimod

Imiquimod

Clinical data
Trade names	Aldara, others
Other names	1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine
AHFS/Drugs.com	Monograph
MedlinePlus	a698010
License data	EU EMA: by INN US DailyMed: Imiquimod
Pregnancy category	AU: B1
Routes of administration	Topical
ATC code	D06BB10 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: WARNINGRx-only EU: Rx-only
Pharmacokinetic data
Elimination half-life	30 hours (topical dose), 2 hours (subcutaneous dose)
Identifiers
IUPAC name 3-(2-Methylpropyl)-3,5,8-triazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,7,10,12-hexaen-7-amine
CAS Number	99011-02-6 Y
PubChem CID	57469
IUPHAR/BPS	5003
DrugBank	DB00724 Y
ChemSpider	51809 Y
UNII	P1QW714R7M
KEGG	D02500 Y
ChEBI	CHEBI:36704 Y
ChEMBL	ChEMBL1282 Y
CompTox Dashboard (EPA)	DTXSID7041047
ECHA InfoCard	100.131.047
Chemical and physical data
Formula	C14H16N4
Molar mass	240.310 g·mol−1
3D model (JSmol)	Interactive image
SMILES n3c1ccccc1c2c(ncn2CC(C)C)c3N
InChI InChI=1S/C14H16N4/c1-9(2)7-18-8-16-12-13(18)10-5-3-4-6-11(10)17-14(12)15/h3-6,8-9H,7H2,1-2H3,(H2,15,17) Y Key:DOUYETYNHWVLEO-UHFFFAOYSA-N Y
(verify)

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. In 2021, it was the 290th most commonly prescribed medication in the United States, with more than 600,000 prescriptions.

Imiquimod is a patient-applied cream prescribed to treat genital warts, Bowens disease (squamous cell carcinoma in situ), and, secondary to surgery, for basal cell carcinoma, as well as actinic keratosis.

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 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 and are taking immune-suppressing drugs should not use imiquimod.

Imiquimod yields profound antitumoral activity by acting on several immunological levels synergistically. Imiquimod stimulates the innate immune system by activating toll-like receptor 7 (TLR7), commonly involved in pathogen recognition. Cells activated by imiquimod via TLR-7 secrete cytokines (primarily interferon-α (IFN-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.

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.

Scientists at 3M's pharmaceutical division discovered imiquimod as part of a program to discover inhibitors of herpes simplex virus replication based on a known adenine derivative.^{: 369–372} 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 basal cell carcinoma.

In 2006, 3M sold its pharmaceutical business in the Americas to Graceway Pharmaceuticals, its European pharmaceutical business to Meda AB, and its pharmaceutical business in other territories to two private equity 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.

Imiquimod 5% was approved for medical use in the European Union in September 1998. Imiquimod 3.75% was approved for medical use in the European Union in August 2012.

As of 2015, imiquimod is generic and is available worldwide under many brands.

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. 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, vaginal intraepithelial neoplasia, common warts (a 2012 Cochrane review found no randomized controlled trials), plantar warts, 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.