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Revision as of 13:40, 22 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,074 edits Saving copy of the {{drugbox}} taken from revid 456932064 of page Imiquimod for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:12, 16 July 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,324 edits update refs 
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{{Short description|Chemical compound}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use dmy dates|date=January 2024}}
{{Drugbox
{{Infobox drug
⚫ | verifiedrevid = 443870391
| Watchedfields = changed
⚫ | IUPAC_name = 3-(2-methylpropyl)-3,5,8-triazatricyclotrideca-1(9),2(6),4,7,10,12-hexaen-7-amine
⚫ | verifiedrevid = 461936187
| image = Imiquimod.svg | image = Imiquimod.svg
| width = 180px | width = 180


<!--Clinical data--> <!--Clinical data-->
| tradename = Aldara | tradename = Aldara, others<ref name=drugnames/>
| Drugs.com = {{drugs.com|monograph|imiquimod}} | Drugs.com = {{drugs.com|monograph|imiquimod}}
| MedlinePlus = a698010 | MedlinePlus = a698010
| licence_EU = Aldara | licence_EU = yes
| licence_US = Imiquimod | DailyMedID = Imiquimod
| pregnancy_AU = B1 | pregnancy_AU = B1
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Imiquimod topical Use During Pregnancy | website=Drugs.com | date=29 May 2019 | url=https://www.drugs.com/pregnancy/imiquimod-topical.html | access-date=14 July 2020}}</ref>
| pregnancy_US = C
| pregnancy_category = | pregnancy_category =
⚫ | routes_of_administration = ]
⚫ | ATC_prefix = D06
⚫ | ATC_suffix = BB10

| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = POM | legal_UK = POM
| legal_US = Rx-only | legal_US = Rx-only
| legal_EU = Rx-only
| legal_status = | legal_status =
⚫ | routes_of_administration = ]


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
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<!--Identifiers--> <!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 99011-02-6 | CAS_number = 99011-02-6
⚫ | ATC_prefix = D06
⚫ | ATC_suffix = BB10
| PubChem = 57469 | PubChem = 57469
| IUPHAR_ligand = 5003
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00724 | DrugBank = DB00724
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<!--Chemical data--> <!--Chemical data-->
⚫ | IUPAC_name = 3-(2-Methylpropyl)-3,5,8-triazatricyclotrideca-1(9),2(6),4,7,10,12-hexaen-7-amine
| C=14 | H=16 | N=4 | C=14 | H=16 | N=4
⚫ | SMILES = n3c1ccccc1c2c(ncn2CC(C)C)c3N
| molecular_weight = 240.304 ]/]
⚫ | smiles = n3c1ccccc1c2c(ncn2CC(C)C)c3N
| InChI = 1/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)
| InChIKey = DOUYETYNHWVLEO-UHFFFAOYAF
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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) | StdInChI = 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)
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| synonyms = 1-isobutyl-1''H''-imidazoquinolin-4-amine | synonyms = 1-isobutyl-1''H''-imidazoquinolin-4-amine
}} }}

'''Imiquimod''', sold under the brand name '''Aldara''' among others, is a ] that acts as an ] that is used to treat ]s, superficial ], and ].<ref>{{cite web |title=Imiquimod Topical |url=https://medlineplus.gov/druginfo/meds/a698010.html |website=MedlinePlus |publisher=] |access-date=2 June 2021 }}</ref>

Scientists at ]'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.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Imiquimod - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Imiquimod | access-date = 14 January 2024}}</ref>

==Medical uses==
Imiquimod is a patient-applied cream prescribed to treat ]s, Bowens disease (] in situ), and, secondary to surgery, for ],<ref>{{cite web | quote = Imiquimod should be used for treatment of only when surgery is medically less appropriate | work = U.S. Food And Drug Administration | title = FDA Approval for Imiquimod | url = http://www.cancer.gov/cancertopics/druginfo/fda-imiquimod | archive-url = https://web.archive.org/web/20150406010920/http://www.cancer.gov/cancertopics/druginfo/fda-imiquimod | archive-date= 6 April 2015 | date = 1 January 2011 | access-date = 19 October 2012 }}</ref><ref>{{cite web | title = Imiquimod Cream | publisher = American Cancer Society | work = Guide To Cancer Drugs | url = http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/imiquimod-cream | archive-url = https://web.archive.org/web/20150207152913/http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/imiquimod-cream | archive-date = 7 February 2015 | access-date = 28 April 2014 }}</ref> as well as ].<ref name=EMA/>

Imiquimod 5% cream is indicated for the topical treatment of:
* external genital and perianal warts (condylomata acuminata) in adults;<ref name="Aldara EPAR" />
* small superficial basal-cell carcinomas (sBCCs) in adults;<ref name="Aldara EPAR" />
* 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.<ref name="Aldara EPAR" />

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.<ref name="Zyclara EPAR" />

==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.<ref name=EMA/><ref>PDR Health </ref>

People who have had an ] and are taking immune-suppressing drugs should not use imiquimod.<ref name=EMA>European Medicines Agency. First published 14 September 2009, updated 25 March 2015. {{Webarchive|url=https://web.archive.org/web/20170925001832/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000179/WC500023122.pdf |date=25 September 2017 }}</ref>

==Mechanism of action==

Imiquimod yields profound antitumoral activity by acting on several immunological levels synergistically.<ref>{{cite journal | vauthors = Schön MP, Schön M | title = Imiquimod: mode of action | journal = The British Journal of Dermatology | volume = 157 | issue = Suppl 2 | pages = 8–13 | date = December 2007 | pmid = 18067624 | doi = 10.1111/j.1365-2133.2007.08265.x | s2cid = 36643157 }}</ref> Imiquimod stimulates the innate immune system by activating ] (TLR7), commonly involved in pathogen recognition.<ref name="pmid23463003">{{cite journal | vauthors = Walter A, Schäfer M, Cecconi V, Matter C, Urosevic-Maiwald M, Belloni B, Schönewolf N, Dummer R, Bloch W, Werner S, Beer HD, Knuth A, van den Broek M | display-authors = 6 | title = Aldara activates TLR7-independent immune defence | journal = Nature Communications | volume = 4 | pages = 1560 | year = 2013 | pmid = 23463003 | doi = 10.1038/ncomms2566 | doi-access = free | bibcode = 2013NatCo...4.1560W }}</ref><ref name="Evans">{{cite journal | vauthors = Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S | display-authors = 6 | title = Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway | journal = Nature Immunology | volume = 3 | issue = 2 | pages = 196–200 | date = February 2002 | pmid = 11812998 | doi = 10.1038/ni758 | s2cid = 1694900 }}</ref> Cells activated by imiquimod via TLR-7 secrete ] (primarily ] (IFN-α), ] (IL-6), and ] (TNF-α)).<ref name="Sauder">{{cite journal | vauthors = Bilu D, Sauder DN | title = Imiquimod: modes of action | journal = The British Journal of Dermatology | volume = 149 | issue = Suppl 66 | pages = 5–8 | date = November 2003 | pmid = 14616337 | doi = 10.1046/j.0366-077x.2003.05628.x | s2cid = 41274637 }}</ref> There is evidence that imiquimod, when applied to skin, can lead to the activation of ], which subsequently migrate to local lymph nodes to activate the ].<ref name="Miller">{{cite journal | vauthors = Miller RL, Gerster JF, Owens ML, Slade HB, Tomai MA | title = Imiquimod applied topically: a novel immune response modifier and new class of drug | journal = International Journal of Immunopharmacology | volume = 21 | issue = 1 | pages = 1–14 | date = January 1999 | pmid = 10411278 | doi = 10.1016/s0192-0561(98)00068-x }}</ref> Other cell types activated by imiquimod include ], ] and ].<ref name="Miller"/>

Imiquimod exerts its effect by increasing levels of the ] (OGFr). In experiments, blocking OGFr function with ] technology resulted in loss of any antiproliferative effect of imiquimod.<ref>{{cite journal | vauthors = Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ | title = Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function | journal = Experimental Biology and Medicine | volume = 233 | issue = 8 | pages = 968–979 | date = August 2008 | pmid = 18480416 | doi = 10.3181/0802-RM-58 | s2cid = 35164284 }}</ref>

==History==
Scientists at 3M's pharmaceutical division discovered imiquimod as part of a program to discover inhibitors of ] replication based on a known ] derivative.<ref>Randall L. Halcomb. TLR-7 Agonists for the Treatment of Viral Hepatitis. Chapter 10 in Successful Strategies for the Discovery of Antiviral Drugs. Issue 32 of RSC drug discovery series. Eds Manoj C. Desai and Nicholas A. Meanwell. Royal Society of Chemistry, 2013. {{ISBN|9781849736572}}</ref>{{rp|369–372}} 3M obtained the first FDA approval for it in 1997 as a treatment for external ] under the brand "Aldara".<ref>Centerwatch. Page accessed 14 June 2015</ref> In 2004, 3M obtained FDA approval to market imiquimod as a treatment for superficial ].<ref>{{cite web | work = National Cancer Institute | date = 3 July 2013 | url = http://www.cancer.gov/about-cancer/treatment/drugs/fda-imiquimod | title = NCI: FDA Approval for Imiquimod | archive-url = https://web.archive.org/web/20180123191957/https://www.cancer.gov/about-cancer/treatment/drugs/fda-imiquimod | archive-date = 23 January 2018 }}</ref>

In 2006, 3M sold its pharmaceutical business in the Americas to ], its European pharmaceutical business to ], and its pharmaceutical business in other territories to two ] firms.<ref>{{cite web | work = 3M | date = 9 November 2006 | url = https://news.3m.com/press-release/company/3m-reaches-agreements-sell-its-pharmaceuticals-business | title = Press release: 3M Reaches Agreements to Sell its Pharmaceuticals Business] | archive-url = https://web.archive.org/web/20190821065048/https://news.3m.com/press-release/company/3m-reaches-agreements-sell-its-pharmaceuticals-business | archive-date = 21 August 2019 }}</ref>

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 ].<ref>{{cite web | title = Medicis buys Graceway Pharmaceuticals for $455M | url = https://www.bizjournals.com/phoenix/news/2011/11/29/medicis-buys-graceway-pharmaceuticals.html?page=all | vauthors = Johnson JA | work = The Phoenix Business Journal | date = 29 November 2011 }}</ref>

Imiquimod 5% was approved for medical use in the European Union in September 1998.<ref name="Aldara EPAR">{{cite web | title=Aldara EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/aldara | access-date=14 July 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Imiquimod 3.75% was approved for medical use in the European Union in August 2012.<ref name="Zyclara EPAR">{{cite web | title=Zyclara EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zyclara | access-date=14 July 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>

As of 2015, imiquimod is generic and is available worldwide under many brands.<ref name=drugnames>Drugs.com Page accessed 14 June 2015</ref>

==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.<ref>{{ClinicalTrialsGov|NCT00735462|Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts}}</ref>

Imiquimod has been tested for treatment of ]. 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.<ref>{{cite web |archive-url=https://web.archive.org/web/20131102194852/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7fccca4e-fb8f-42b8-9555-8f78a5804ed3 |url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=7fccca4e-fb8f-42b8-9555-8f78a5804ed3 |archive-date=2 November 2013 |title=Aldara (imiquimod) cream for topical use. Prescribing information. |url-status=dead }}</ref> These disprove earlier anecdotal claims and smaller, less reliable studies.<ref>{{EMedicine|article|910570|Molluscum Contagiosum|treatment}}</ref><ref>{{cite journal | vauthors = Theos AU, Cummins R, Silverberg NB, Paller AS | title = Effectiveness of imiquimod cream 5% for treating childhood molluscum contagiosum in a double-blind, randomized pilot trial | journal = Cutis | volume = 74 | issue = 2 | pages = 134–8, 141–2 | date = August 2004 | pmid = 15379366 }}</ref><ref>{{cite journal | vauthors = Bayerl C, Feller G, Goerdt S | title = Experience in treating molluscum contagiosum in children with imiquimod 5% cream | journal = The British Journal of Dermatology | volume = 149 | issue = Suppl 66 | pages = 25–29 | date = November 2003 | pmid = 14616342 | doi = 10.1046/j.0366-077x.2003.05631.x | s2cid = 23728783 }}</ref><ref>{{cite journal | vauthors = Arican O | title = Topical treatment of molluscum contagiosum with imiquimod 5% cream in Turkish children | journal = Pediatrics International | volume = 48 | issue = 4 | pages = 403–405 | date = August 2006 | pmid = 16911087 | doi = 10.1111/j.1442-200X.2006.02229.x | s2cid = 2867793 }}</ref>

Imiquimod has also been tested for treatment of ],<ref name= "pmid18385498">{{cite journal | vauthors = van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ | display-authors = 6 | title = Treatment of vulvar intraepithelial neoplasia with topical imiquimod | journal = The New England Journal of Medicine | volume = 358 | issue = 14 | pages = 1465–1473 | date = April 2008 | pmid = 18385498 | doi = 10.1056/NEJMoa072685 | doi-access = free }}</ref> ],<ref name="pmid17051086">{{cite journal | vauthors = Buck HW, Guth KJ | title = Treatment of vaginal intraepithelial neoplasia (primarily low grade) with imiquimod 5% cream | journal = Journal of Lower Genital Tract Disease | volume = 7 | issue = 4 | pages = 290–293 | date = October 2003 | pmid = 17051086 | doi = 10.1097/00128360-200310000-00011 | s2cid = 44649376 }}</ref> ] (a 2012 Cochrane review found no randomized controlled trials),<ref>{{cite journal | vauthors = Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R | title = Topical treatments for cutaneous warts | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 9 | pages = CD001781 | date = September 2012 | pmid = 22972052 | pmc = 8101088 | doi = 10.1002/14651858.CD001781.pub3 }}</ref> ]s,<ref name="dpic">{{cite web|url=http://www.dpic.org/article/professional/imiquimod-non-genital-cutaneous-warts|title=Imiquimod for non-genital cutaneous warts|website=www.dpic.org}}</ref> warts in people with suppressed immune systems,<ref>{{cite journal | vauthors = Harwood CA, Perrett CM, Brown VL, Leigh IM, McGregor JM, Proby CM | title = Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals | journal = The British Journal of Dermatology | volume = 152 | issue = 1 | pages = 122–129 | date = January 2005 | pmid = 15656812 | doi = 10.1111/j.1365-2133.2005.06322.x | s2cid = 42369353 }}</ref> flat warts on face and neck,<ref name="dpic"/> and warts under and around fingernails and toenails.<ref name="dpic"/> 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.<ref>{{cite journal | vauthors = Ahn CS, Huang WW | title = Imiquimod in the treatment of cutaneous warts: an evidence-based review | journal = American Journal of Clinical Dermatology | volume = 15 | issue = 5 | pages = 387–399 | date = October 2014 | pmid = 25186654 | doi = 10.1007/s40257-014-0093-5 | s2cid = 26624740 }}</ref><ref name="dpic"/>

== References ==
{{Reflist}}

== External links ==
* {{DermNet|treatments/imiquimod}}

{{Antibiotics and chemotherapeutics for dermatological use}}
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Misplaced Pages:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Imiquimod: Difference between pages Add topic