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Revision as of 11:15, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 473573534 of page Cidofovir for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 05:27, 1 July 2024 edit InternetArchiveBot (talk | contribs)Bots, Pending changes reviewers5,382,165 edits Rescuing 1 sources and tagging 0 as dead.) #IABot (v2.0.9.5) (Whywhenwhohow - 20275 
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{{Short description|Antiviral drug}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Drugbox {{Drugbox
| verifiedrevid = 443523497 | verifiedrevid = 477165826
| IUPAC_name = ({oxy}methyl)phosphonic acid | IUPAC_name = ({oxy}methyl)phosphonic acid
| image = Cidofovir Structural Formulae.png | image = Cidofovir.svg
| width = 163 | width = 225


<!--Clinical data--> <!--Clinical data-->
| tradename = Vistide | tradename = Vistide
| Drugs.com = {{drugs.com|monograph|cidofovir}} | Drugs.com = {{drugs.com|monograph|cidofovir}}
| legal_status = | pregnancy_AU = D
| routes_of_administration = intravenous | routes_of_administration = ]
⚫ | ATC_prefix = J05
⚫ | ATC_suffix = AB12
⚫ | ATC_supplemental =

| legal_AU = S4
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Drug and medical device highlights 2018: Helping you maintain and improve your health | website=] | date=14 October 2020 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | access-date=17 April 2024}}</ref>
| legal_UK = POM
| legal_US = Rx-only


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = complete | bioavailability = complete
| protein_bound = 6% | protein_bound = <6%
⚫ | elimination_half-life = 2.6 hours (active metabolites: 15–65&nbsp;hours)
| metabolism =
⚫ | elimination_half-life = 2.4 to 3.2 hours
| excretion = renal | excretion = renal
The above pharmacokinetic parameters are measured for cidofovir used in conjunction with probenecid.<ref>Cundy, Kenneth C. "Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir." Clinical Pharmacokinetics 36.2 (1999): 127–143.</ref>


<!--Identifiers--> <!--Identifiers-->
⚫ | CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 113852-37-2 | CAS_number = 113852-37-2
⚫ | ATC_prefix = J05
⚫ | ATC_suffix = AB12
⚫ | ATC_supplemental =
| PubChem = 60613 | PubChem = 60613
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 768M1V522C | UNII = 768M1V522C
⚫ | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C06909
| ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 3696 | ChEBI = 3696
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<!--Chemical data--> <!--Chemical data-->
| C=8 | H=14 | N=3 | O=6 | P=1 | C=8 | H=14 | N=3 | O=6 | P=1
| molecular_weight = 279.187 g/mol
| smiles = O=C1/N=C(\C=C/N1C(OCP(=O)(O)O)CO)N | smiles = O=C1/N=C(\C=C/N1C(OCP(=O)(O)O)CO)N
| InChI = 1/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1
| InChIKey = VWFCHDSQECPREK-LURJTMIEBI
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1 | StdInChI = 1S/C8H14N3O6P/c9-7-1-2-11(8(13)10-7)3-6(4-12)17-5-18(14,15)16/h1-2,6,12H,3-5H2,(H2,9,10,13)(H2,14,15,16)/t6-/m0/s1
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| specific_rotation = -97.3 | specific_rotation = -97.3
}} }}

'''Cidofovir''', brand name '''Vistide''', is a ] or ] ] medication primarily used as a treatment for ] (CMV) ] (an infection of the retina of the eye) in people with ].<ref name = MSR/><ref name =TGA/>

Cidofovir was approved for medical use in 1996.<ref>{{cite book|vauthors = Long SS, Prober CG, Fischer M |title=Principles and Practice of Pediatric Infectious Disease|date=2012|publisher=Elsevier Health Sciences|isbn=978-1437727029|page=1502|url=https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA1502|language=en}}</ref>

==Medical use==

===DNA virus===
Its only indication that has received regulatory approval worldwide is ] retinitis.<ref name = MSR/><ref name = TGA/> Cidofovir has also shown efficacy in the treatment of ]-resistant ] infections.<ref>{{cite journal | vauthors = Chilukuri S, Rosen T | title = Management of acyclovir-resistant herpes simplex virus | journal = Dermatologic Clinics | volume = 21 | issue = 2 | pages = 311–320 | date = April 2003 | pmid = 12757254 | doi = 10.1016/S0733-8635(02)00093-1 }}</ref> Cidofovir has also been investigated as a treatment for ] with successful case reports of its use.<ref name="pmid11408993">{{cite journal | vauthors = Segarra-Newnham M, Vodolo KM | title = Use of cidofovir in progressive multifocal leukoencephalopathy | journal = The Annals of Pharmacotherapy | volume = 35 | issue = 6 | pages = 741–744 | date = June 2001 | pmid = 11408993 | doi = 10.1345/aph.10338 | s2cid = 32026770 }}{{Dead link|date=July 2019 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Despite this, the drug failed to demonstrate any efficacy in controlled studies.<ref>{{cite journal | vauthors = De Gascun CF, Carr MJ | title = Human polyomavirus reactivation: disease pathogenesis and treatment approaches | journal = Clinical & Developmental Immunology | volume = 2013 | pages = 373579 | year = 2013 | pmid = 23737811 | pmc = 3659475 | doi = 10.1155/2013/373579 | doi-access = free }}</ref> Cidofovir might have anti-] efficacy and might be used on a limited basis in the event of a ] incident involving smallpox cases.<ref name="pmid12076747">{{cite journal | vauthors = De Clercq E | title = Cidofovir in the treatment of poxvirus infections | journal = Antiviral Research | volume = 55 | issue = 1 | pages = 1–13 | date = July 2002 | pmid = 12076747 | doi = 10.1016/S0166-3542(02)00008-6 | pmc = 9533828 }}</ref> ], a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.<ref>{{cite journal | vauthors = Bradbury J | title = Orally available cidofovir derivative active against smallpox | journal = Lancet | volume = 359 | issue = 9311 | pages = 1041 | date = March 2002 | pmid = 11937193 | doi = 10.1016/S0140-6736(02)08115-1 | s2cid = 22903225 }}</ref> It has inhibitory effects on varicella-zoster virus replication ''in vitro'' although no clinical trials have been done to date, likely due to the abundance of safer alternatives such as ].<ref>{{cite journal | vauthors = Magee WC, Hostetler KY, Evans DH | title = Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 8 | pages = 3153–3162 | date = August 2005 | pmid = 16048917 | pmc = 1196213 | doi = 10.1128/AAC.49.8.3153-3162.2005 }}</ref> Cidofovir shows anti-] activity in a subgroup of transplant recipients.<ref name="pmid16499584">{{cite journal | vauthors = Araya CE, Lew JF, Fennell RS, Neiberger RE, Dharnidharka VR | title = Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy | journal = Pediatric Transplantation | volume = 10 | issue = 1 | pages = 32–37 | date = February 2006 | pmid = 16499584 | doi = 10.1111/j.1399-3046.2005.00391.x | s2cid = 24131709 }}</ref> Cidofovir is being investigated as a complementary intralesional therapy against ] caused by ].<ref name="pmid18458927">{{cite journal | vauthors = Broekema FI, Dikkers FG | title = Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis | journal = European Archives of Oto-Rhino-Laryngology | volume = 265 | issue = 8 | pages = 871–879 | date = August 2008 | pmid = 18458927 | pmc = 2441494 | doi = 10.1007/s00405-008-0658-0 }}</ref><ref name="pmid18197029">{{cite journal | vauthors = Soma MA, Albert DM | title = Cidofovir: to use or not to use? | journal = Current Opinion in Otolaryngology & Head and Neck Surgery | volume = 16 | issue = 1 | pages = 86–90 | date = February 2008 | pmid = 18197029 | doi = 10.1097/MOO.0b013e3282f43408 | s2cid = 22895067 }}</ref>

It first received ] approval on 26 June 1996,<ref name = drugs.com>{{cite web|title=Cidofovir Monograph for Professionals |work=Drugs.com|publisher=American Society of Health-System Pharmacists|access-date=5 February 2014|url=https://www.drugs.com/monograph/cidofovir.html}}</ref> ] approval on 30 April 1998<ref name = TGA/> and ] approval on 23 April 1997.<ref>{{cite web|title=Vistide : EPAR – Product Information|work=European Medicines Agency|publisher=Gilead Sciences International Ltd.|date=7 November 2013|access-date=5 February 2014|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000121/WC500052072.pdf|archive-date=22 February 2014|archive-url=https://web.archive.org/web/20140222052403/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000121/WC500052072.pdf|url-status=dead}}</ref>

It has been used topically to treat ].<ref>{{cite journal | vauthors = Fernández-Morano T, del Boz J, González-Carrascosa M, Tortajada B, de Troya M | title = Topical cidofovir for viral warts in children | journal = Journal of the European Academy of Dermatology and Venereology | volume = 25 | issue = 12 | pages = 1487–1489 | date = December 2011 | pmid = 21261749 | doi = 10.1111/j.1468-3083.2010.03961.x | s2cid = 32295082 | doi-access = free }}</ref>

===Other===
It has been suggested as an antitumour agent, due to its suppression of ].<ref name="pmid17158200">{{cite journal | vauthors = Kern ER | title = In vitro activity of potential anti-poxvirus agents | journal = Antiviral Research | volume = 57 | issue = 1–2 | pages = 35–40 | date = January 2003 | pmid = 12615301 | doi = 10.1016/s0166-3542(02)00198-5 | s2cid = 23136929 | pmc = 9628899 }}</ref><ref>{{cite journal | vauthors = Andrei G, Snoeck R | title = Cidofovir Activity against Poxvirus Infections | journal = Viruses | volume = 2 | issue = 12 | pages = 2803–2830 | date = December 2010 | pmid = 21994641 | doi = 10.3390/v2122803 | pmc = 3185586 | doi-access = free }}</ref><ref>{{cite web | url = https://www.cdc.gov/poxvirus/monkeypox/treatment.html | title = Interim Clinical Guidance for the Treatment of Monkeypox. | publisher = U.S. Centers for Disease Control and Prevention | date = 26 May 2022 }}</ref>

==Administration==
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with ] which decreases side effects to the kidney.<ref name="gilead.com">{{cite web|url=http://www.gilead.com/~/media/Files/pdfs/medicines/other/vistide/vistide.pdf |title=Details |website=www.gilead.com |access-date=2019-06-05}}</ref> Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.<ref name="pmid9742650">{{cite journal | vauthors = Lacy SA, Hitchcock MJ, Lee WA, Tellier P, Cundy KC | title = Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys | journal = Toxicological Sciences | volume = 44 | issue = 2 | pages = 97–106 | date = August 1998 | pmid = 9742650 | doi = 10.1006/toxs.1998.2481 | doi-access = free }}</ref> In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir.<ref name="gilead.com"/>

==Side effects==
The major dose-limiting side effect of cidofovir is nephrotoxicity (i.e., kidney damage).<ref name="AMH">{{cite book | veditors = Rossi S | isbn = 978-0-9805790-9-3 | title = Australian Medicines Handbook | place = Adelaide | publisher = The Australian Medicines Handbook Unit Trust | year = 2013 | edition = 2013 }}</ref> Other common side effects (occurring in >1% of people treated with the drug) include:<ref name = MSR>{{cite web|title=Vistide (cidofovir) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=4 February 2014|url=http://reference.medscape.com/drug/vistide-cidofovir-342606#showall}}</ref><ref name = AMH/>
{{div col|colwidth=18em}}
* Nausea
* Vomiting
* ]
* Hair loss
* Weakness
* Headache
* Chills
* Decreased intraocular pressure
* ]
* ]
{{div col end}}
Whereas uncommon side effects include: ] and elevated liver enzymes and rare side effects include: ] and ].<ref name = AMH/> ] (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.<ref name="vistide">{{cite web |title= Vistide (cidofovir) |url=http://www.gilead.com/~/media/Files/pdfs/medicines/other/vistide/vistide.pdf |type= ] |date=September 2010 |publisher=] |pages= Dosage and Administration: Dosage |no-pp= yes}}</ref>

===Contraindications===
Hypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity).<ref name = MSR/>

== Interactions ==
It is known to interact with nephrotoxic agents (e.g. ], ], IV ], IV pentamide, ], ], non-steroid anti-inflammatory drugs, etc.) to increase their nephrotoxic potential.<ref name = MSR/><ref name = TGA>{{cite web|title=Product Information VISTIDE®|work=TGA eBusiness Services|publisher=Gilead Sciences Pty Ltd|date=3 September 2013|access-date=5 February 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-01028-3}}</ref> As it must be given concurrently with probenecid it is advised that drugs that are known to interact with probenecid (e.g. drugs that probenecid interferes with the renal tubular secretion of, such as paracetamol, aciclovir, aminosalicylic acid, etc.) are also withheld.<ref name = TGA/>

==Mechanism of action==
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral ].<ref name =TGA/> It also inhibits human polymerases, but this action is 8–600 times weaker than its actions on viral DNA polymerases.<ref name =TGA/> It also incorporates itself into viral DNA, hence inhibiting viral DNA synthesis during reproduction.<ref name = TGA/>

It possesses ''in vitro'' activity against the following viruses:<ref>{{cite journal | vauthors = Safrin S, Cherrington J, Jaffe HS | title = Clinical uses of cidofovir | journal = Reviews in Medical Virology | volume = 7 | issue = 3 | pages = 145–156 | date = September 1997 | pmid = 10398479 | doi = 10.1002/(SICI)1099-1654(199709)7:3<145::AID-RMV196>3.0.CO;2-0 | s2cid = 32366514 }}</ref>
* ]
* ]
* Human ] (including the ] virus)
* ]

==History==
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by ], and developed by ]<ref name="titlePress Releases: Gilead">{{cite web |url=http://www.gilead.com/pr_881577 |title=Press Releases: Gilead |access-date=2007-12-05 |archive-date=2013-02-08 |archive-url=https://web.archive.org/web/20130208114649/http://www.gilead.com/pr_881577 |url-status=dead }}</ref> and is marketed with the brand name '''Vistide''' by Gilead in the US, and by ] elsewhere.

==Synthesis==
Cidofovir can be synthesized from a pyrimidone ] and a ] derivative of ].<ref>{{Cite journal | vauthors = Brodfuehrer PR, Howell HG, Sapino Jr C, Vemishetti P |doi=10.1016/S0040-4039(00)76875-4|title=A practical synthesis of (S)-HPMPC|year=1994 |journal=Tetrahedron Letters|volume=35|page=3243|issue=20}}</ref>

:]

== See also ==
* ], a prodrug of cidofovir

== References ==
{{reflist}}

{{Antivirals}}

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