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{{Short description|Antiviral drug}}
{{linkrot|date=June 2019}}
{{Drugbox
{{Drugbox
| verifiedrevid = 477165826
| verifiedrevid = 477165826
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| tradename = Vistide
| tradename = Vistide
| Drugs.com = {{drugs.com|monograph|cidofovir}}
| Drugs.com = {{drugs.com|monograph|cidofovir}}
| licence_EU = yes
| licence_US = Cidofovir
| pregnancy_AU = D
| pregnancy_AU = D
⚫
| routes_of_administration = [[Intravenous]]
| pregnancy_US = C
⚫
| ATC_prefix = J05
⚫
| ATC_suffix = AB12
⚫
| ATC_supplemental =

| legal_AU = S4
| legal_AU = S4
| legal_CA = Rx-only
| 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=[[Health Canada]] | 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_UK = POM
| legal_US = Rx-only
| legal_US = Rx-only
⚫
| routes_of_administration = [[Intravenous|IV]]


<!--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)
| elimination_half-life = 2.6 hours (active metabolites: 15–65&nbsp;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): 127-43.</ref>
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-->
| 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[C@H](OCP(=O)(O)O)CO)N
| smiles = O=C1/N=C(\C=C/N1C[C@H](OCP(=O)(O)O)CO)N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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}}
}}


'''Cidofovir''' (brand name '''Vistide''') is an injectable [[Antiviral drug|antiviral]] medication primarily used as a treatment for [[cytomegalovirus]] (CMV) [[retinitis]] (an infection of the retina of the eye) in people with [[AIDS]].<ref name = MSR/><ref name =TGA/>
'''Cidofovir''', brand name '''Vistide''', is a [[topical]] or [[injectable]] [[Antiviral drug|antiviral]] medication primarily used as a treatment for [[cytomegalovirus]] (CMV) [[retinitis]] (an infection of the retina of the eye) in people with [[AIDS]].<ref name = MSR/><ref name =TGA/>


Cidofovir was approved for medical use in 1996.<ref>{{cite book|last1=Long|first1=Sarah S.|last2=Pickering|first2=Larry K.|last3=Prober|first3=Charles G.|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>
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==
==Medical use==


===DNA virus===
===DNA virus===
Its only indication that has received regulatory approval worldwide is [[cytomegalovirus]] retinitis.<ref name = MSR/><ref name = TGA/> Cidofovir has also shown efficacy in the treatment of [[aciclovir]]-resistant [[herpes simplex virus|HSV]] infections.<ref>{{cite journal|last=Chilukuri|first=S|author2=Rosen, T|title=Management of acyclovir-resistant herpes simplex virus.|journal=Dermatologic Clinics|date=Apr 2003|volume=21|issue=2|pages=311–20|doi=10.1016/S0733-8635(02)00093-1|pmid=12757254}}</ref> Cidofovir has also been investigated as a treatment for [[progressive multifocal leukoencephalopathy]] 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=Ann Pharmacother |volume=35 |issue=6 |pages=741–4 |date=June 2001 |pmid=11408993 |doi= 10.1345/aph.10338|url=http://www.theannals.com/cgi/pmidlookup?view=long&pmid=11408993}}</ref> Despite this, the drug failed to demonstrate any efficacy in controlled studies.<ref>{{Cite journal
Its only indication that has received regulatory approval worldwide is [[cytomegalovirus]] retinitis.<ref name = MSR/><ref name = TGA/> Cidofovir has also shown efficacy in the treatment of [[aciclovir]]-resistant [[herpes simplex virus|HSV]] 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 [[progressive multifocal leukoencephalopathy]] 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-[[smallpox]] efficacy and might be used on a limited basis in the event of a [[bioterror]] 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> [[Brincidofovir]], 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 [[aciclovir]].<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-[[BK virus]] 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 [[papillomatosis]] caused by [[HPV]].<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>
| pmid = 23737811
| pmc = 3659475
| year = 2013
| author1 = De Gascun
| first1 = C. F.
| title = Human polyomavirus reactivation: Disease pathogenesis and treatment approaches
| journal = Clinical and Developmental Immunology
| volume = 2013
| pages = 1–27
| last2 = Carr
| first2 = M. J.
| doi = 10.1155/2013/373579
}}</ref> Cidofovir might have anti-[[smallpox]] efficacy and might be used on a limited basis in the event of a [[bioterror]] incident involving smallpox cases.<ref name="pmid12076747">{{cite journal |author=De Clercq E |title=Cidofovir in the treatment of poxvirus infections|journal=Antiviral Res. |volume=55 |issue=1 |pages=1–13 |date=July 2002 |pmid=12076747 |doi= 10.1016/S0166-3542(02)00008-6|url=http://linkinghub.elsevier.com/retrieve/pii/S0166354202000086}}</ref> [[Brincidofovir]], a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.<ref>{{cite journal|last=Bradbury|first=J|title=Orally available cidofovir derivative active against smallpox.|journal=Lancet|date=March 2002|volume=359|issue=9311|pages=1041|doi=10.1016/S0140-6736(02)08115-1|pmid=11937193}}</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 [[aciclovir]].<ref>{{cite journal|last=Magee|first=WC|author2=Hostetler, KY |author3=Evans, DH |title=Mechanism of Inhibition of Vaccinia Virus DNA Polymerase by Cidofovir Diphosphate|journal=Antimicrobial Agents and Chemotherapy|date=August 2005|volume=49|issue=8|pages=3153–3162|doi=10.1128/AAC.49.8.3153-3162.2005|pmid=16048917|pmc=1196213}}</ref> Cidofovir shows anti-[[BK virus]] 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=Pediatr Transplant |volume=10 |issue=1 |pages=32–7 |date=February 2006|pmid=16499584 |doi=10.1111/j.1399-3046.2005.00391.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1397-3142&date=2006&volume=10&issue=1&spage=32|archive-url=https://archive.today/20130105093701/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1397-3142&date=2006&volume=10&issue=1&spage=32|dead-url=yes|archive-date=2013-01-05}}</ref> Cidofovir is being investigated as a complementary intralesional therapy against [[papillomatosis]] caused by [[HPV]].<ref name="pmid18458927">{{cite journal |vauthors=Broekema FI, Dikkers FG |title=Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis |journal=Eur Arch Otorhinolaryngol |volume=265 |issue=8 |pages=871–9 |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=Curr Opin Otolaryngol Head Neck Surg |volume=16 |issue=1 |pages=86–90 |date=February 2008 |pmid=18197029|doi=10.1097/MOO.0b013e3282f43408|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00020840-200802000-00019}}</ref>


It first received [[Food and Drug Administration|FDA]] approval on 26 June 1996,<ref name = drugs.com>{{cite web|title=Cidofovir Monograph for Professionals - Drugs.com|work=Drugs.com|publisher=American Society of Health-System Pharmacists|accessdate=5 February 2014|url=https://www.drugs.com/monograph/cidofovir.html}}</ref> [[Therapeutic Goods Administration|TGA]] approval on 30 April 1998<ref name = TGA/> and [[European Medicines Agency|EMA]] 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|accessdate=5 February 2014|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000121/WC500052072.pdf}}</ref>
It first received [[Food and Drug Administration|FDA]] 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> [[Therapeutic Goods Administration|TGA]] approval on 30 April 1998<ref name = TGA/> and [[European Medicines Agency|EMA]] 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 [[warts]].<ref>{{cite journal|last=Fernández-Morano|first=T|author2=del Boz J|author3=González-Carrascosa M|title=Topical cidofovir for viral warts in children|journal=J Eur Acad Dermatol Venereol.|date=2011|volume=25|issue=12|pages=1487–9|doi=10.1111/j.1468-3083.2010.03961.x|pmid=21261749}}</ref>
It has been used topically to treat [[warts]].<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===
===Other===
It has been suggested as an antitumour agent, due to its suppression of [[FGF2]].<ref name="pmid17158200">{{cite journal |vauthors=Liekens S, Gijsbers S, Vanstreels E, Daelemans D, De Clercq E, Hatse S |title=The nucleotide analog cidofovir suppresses basic fibroblast growth factor (FGF2) expression and signaling and induces apoptosis in FGF2-overexpressing endothelial cells |journal=Mol. Pharmacol.|volume=71|issue=3 |pages=695–703 |date=March 2007 |pmid=17158200|doi=10.1124/mol.106.026559|url=http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17158200}}</ref><ref name="pmid18669159">{{cite journal|author=Liekens S |title=Regulation of cancer progression by inhibition of angiogenesis and induction of apoptosis|journal=Verh. K. Acad. Geneeskd. Belg. |volume=70 |issue=3 |pages=175–91 |year=2008 |pmid=18669159 |doi= |url=}}</ref>
It has been suggested as an antitumour agent, due to its suppression of [[FGF2]].<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==
==Administration==
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with [[probenecid]] which decreases side effects to the kidney.<ref name="gilead.com">http://www.gilead.com/~/media/Files/pdfs/medicines/other/vistide/vistide.pdf</ref> Probenecid mitigate nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.<ref>Lacy, S. "Effect of Oral Probenecid Coadministration on the Chronic Toxicity and Pharmacokinetics of Intravenous Cidofovir in Cynomolgus Monkeys.</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"/>
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with [[probenecid]] 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==
==Side effects==
The major dose-limiting side effect of cidofovir is nephrotoxicity (that is, kidney damage).<ref name="AMH">{{cite book | editor = 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|accessdate=4 February 2014|url=http://reference.medscape.com/drug/vistide-cidofovir-342606#showall}}</ref><ref name = AMH/>
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}}
{{div col|colwidth=18em}}
* Nausea
* Nausea
Line 103: Line 90:
* [[Iritis]]
* [[Iritis]]
{{div col end}}
{{div col end}}
Whereas uncommon side effects include: [[anaemia]] and elevated liver enzymes and rare side effects include: [[tachycardia]] and [[Fanconi syndrome]].<ref name = AMH/> [[Probenecid]] (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= [[package insert]] |date=September 2010 |publisher=[[Gilead Sciences]] |pages= DOSAGE AND ADMINISTRATION: Dosage |nopp= yes}}</ref>
Whereas uncommon side effects include: [[anaemia]] and elevated liver enzymes and rare side effects include: [[tachycardia]] and [[Fanconi syndrome]].<ref name = AMH/> [[Probenecid]] (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= [[package insert]] |date=September 2010 |publisher=[[Gilead Sciences]] |pages= Dosage and Administration: Dosage |no-pp= yes}}</ref>


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


===Interactions===
== Interactions ==
It is known to interact with nephrotoxic agents (e.g. [[amphotericin B]], [[foscarnet]], IV [[aminoglycosides]], IV pentamide, [[vancomycin]], [[tacrolimus]], 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|accessdate=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/>
It is known to interact with nephrotoxic agents (e.g. [[amphotericin B]], [[foscarnet]], IV [[aminoglycosides]], IV pentamide, [[vancomycin]], [[tacrolimus]], 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==
==Mechanism of action==
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral [[DNA polymerases]].<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/>
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral [[DNA polymerases]].<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|last=Safrin|first=S|author2=Cherrington, J |author3=Jaffe, HS |title=Clinical uses of cidofovir|journal=Reviews in Medical Virology|date=September 1997|volume=7|issue=3|pages=145–156|doi=10.1002/(SICI)1099-1654(199709)7:3<145::AID-RMV196>3.0.CO;2-0|pmid=10398479}}</ref>
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 [[herpesviruses]]
* [[Human herpesviruses]]
* [[Adenoviruses]]
* [[Adenoviruses]]
* Human [[poxviruses]] (including the [[smallpox]] virus)
* Human [[poxviruses]] (including the [[smallpox]] virus)
Line 121: Line 108:


==History==
==History==
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by [[Antonín Holý]], and developed by [[Gilead Sciences]]<ref name="titlePress Releases: Gilead">{{cite web |url=http://www.gilead.com/pr_881577 |title=Press Releases: Gilead|accessdate=2007-12-05 |format= |website=}}</ref> and is marketed with the brand name '''Vistide''' by Gilead in the USA, and by [[Pfizer]] elsewhere.
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by [[Antonín Holý]], and developed by [[Gilead Sciences]]<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 [[Pfizer]] elsewhere.


==Synthesis==
==Synthesis==
Cidofovir can be synthesized from a pyrimidone [[derivative (chemistry)|derivative]] and a [[protecting group|protected]] derivative of [[glycidol]].<ref>{{Cite journal|doi=10.1016/S0040-4039(00)76875-4|title=A practical synthesis of (S)-HPMPC|year=1994|last1=Brodfuehrer|first1=P|journal=Tetrahedron Letters|volume=35|pages=3243|last2=Howell|first2=Henry G.|last3=Sapino|first3=Chester|last4=Vemishetti|first4=Purushotham|issue=20}}</ref>
Cidofovir can be synthesized from a pyrimidone [[derivative (chemistry)|derivative]] and a [[protecting group|protected]] derivative of [[glycidol]].<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>


:[[File:Cidofovir syn.png|600px]]
:[[File:Cidofovir syn.png|600px]]


== See also==
== See also ==
* [[Brincidofovir]], a novel prodrug of cidofovir that can be taken orally
* [[Brincidofovir]], a prodrug of cidofovir


==References==
== References ==
{{reflist|2}}
{{reflist}}


{{Antivirals}}
{{Antivirals}}

Latest revision as of 05:27, 1 July 2024

Cidofovir
Clinical data
Trade namesVistide
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: D
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilitycomplete
Protein binding<6%
Elimination half-life2.6 hours (active metabolites: 15–65 hours)
Excretionrenal The above pharmacokinetic parameters are measured for cidofovir used in conjunction with probenecid.[3]
Identifiers
  • ({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.166.433 Edit this at Wikidata
Chemical and physical data
FormulaC8H14N3O6P
Molar mass279.189 g·mol−1
3D model (JSmol)
Specific rotation-97.3
Melting point260 °C (500 °F)
  • O=C1/N=C(\C=C/N1C[C@H](OCP(=O)(O)O)CO)N
  • InChI=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 checkY
  • Key:VWFCHDSQECPREK-LURJTMIESA-N checkY
  (verify)

Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis (an infection of the retina of the eye) in people with AIDS.[4][5]

Cidofovir was approved for medical use in 1996.[6]

Medical use

[edit]

DNA virus

[edit]

Its only indication that has received regulatory approval worldwide is cytomegalovirus retinitis.[4][5] Cidofovir has also shown efficacy in the treatment of aciclovir-resistant HSV infections.[7] Cidofovir has also been investigated as a treatment for progressive multifocal leukoencephalopathy with successful case reports of its use.[8] Despite this, the drug failed to demonstrate any efficacy in controlled studies.[9] Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of a bioterror incident involving smallpox cases.[10] Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.[11] 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 aciclovir.[12] Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients.[13] Cidofovir is being investigated as a complementary intralesional therapy against papillomatosis caused by HPV.[14][15]

It first received FDA approval on 26 June 1996,[16] TGA approval on 30 April 1998[5] and EMA approval on 23 April 1997.[17]

It has been used topically to treat warts.[18]

Other

[edit]

It has been suggested as an antitumour agent, due to its suppression of FGF2.[19][20][21]

Administration

[edit]

Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with probenecid which decreases side effects to the kidney.[22] Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.[23] In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir.[22]

Side effects

[edit]

The major dose-limiting side effect of cidofovir is nephrotoxicity (i.e., kidney damage).[24] Other common side effects (occurring in >1% of people treated with the drug) include:[4][24]

Whereas uncommon side effects include: anaemia and elevated liver enzymes and rare side effects include: tachycardia and Fanconi syndrome.[24] Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.[25]

Contraindications

[edit]

Hypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity).[4]

Interactions

[edit]

It is known to interact with nephrotoxic agents (e.g. amphotericin B, foscarnet, IV aminoglycosides, IV pentamide, vancomycin, tacrolimus, non-steroid anti-inflammatory drugs, etc.) to increase their nephrotoxic potential.[4][5] 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.[5]

Mechanism of action

[edit]

Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral DNA polymerases.[5] It also inhibits human polymerases, but this action is 8–600 times weaker than its actions on viral DNA polymerases.[5] It also incorporates itself into viral DNA, hence inhibiting viral DNA synthesis during reproduction.[5]

It possesses in vitro activity against the following viruses:[26]

History

[edit]

Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences[27] and is marketed with the brand name Vistide by Gilead in the US, and by Pfizer elsewhere.

Synthesis

[edit]

Cidofovir can be synthesized from a pyrimidone derivative and a protected derivative of glycidol.[28]

See also

[edit]

References

[edit]
  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada. 14 October 2020. Retrieved 17 April 2024.
  3. ^ Cundy, Kenneth C. "Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir." Clinical Pharmacokinetics 36.2 (1999): 127–143.
  4. ^ a b c d e "Vistide (cidofovir) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 4 February 2014.
  5. ^ a b c d e f g h "Product Information VISTIDE®". TGA eBusiness Services. Gilead Sciences Pty Ltd. 3 September 2013. Retrieved 5 February 2014.
  6. ^ Long SS, Prober CG, Fischer M (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN 978-1437727029.
  7. ^ Chilukuri S, Rosen T (April 2003). "Management of acyclovir-resistant herpes simplex virus". Dermatologic Clinics. 21 (2): 311–320. doi:10.1016/S0733-8635(02)00093-1. PMID 12757254.
  8. ^ Segarra-Newnham M, Vodolo KM (June 2001). "Use of cidofovir in progressive multifocal leukoencephalopathy". The Annals of Pharmacotherapy. 35 (6): 741–744. doi:10.1345/aph.10338. PMID 11408993. S2CID 32026770.[permanent dead link‍]
  9. ^ De Gascun CF, Carr MJ (2013). "Human polyomavirus reactivation: disease pathogenesis and treatment approaches". Clinical & Developmental Immunology. 2013: 373579. doi:10.1155/2013/373579. PMC 3659475. PMID 23737811.
  10. ^ De Clercq E (July 2002). "Cidofovir in the treatment of poxvirus infections". Antiviral Research. 55 (1): 1–13. doi:10.1016/S0166-3542(02)00008-6. PMC 9533828. PMID 12076747.
  11. ^ Bradbury J (March 2002). "Orally available cidofovir derivative active against smallpox". Lancet. 359 (9311): 1041. doi:10.1016/S0140-6736(02)08115-1. PMID 11937193. S2CID 22903225.
  12. ^ Magee WC, Hostetler KY, Evans DH (August 2005). "Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate". Antimicrobial Agents and Chemotherapy. 49 (8): 3153–3162. doi:10.1128/AAC.49.8.3153-3162.2005. PMC 1196213. PMID 16048917.
  13. ^ Araya CE, Lew JF, Fennell RS, Neiberger RE, Dharnidharka VR (February 2006). "Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy". Pediatric Transplantation. 10 (1): 32–37. doi:10.1111/j.1399-3046.2005.00391.x. PMID 16499584. S2CID 24131709.
  14. ^ Broekema FI, Dikkers FG (August 2008). "Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis". European Archives of Oto-Rhino-Laryngology. 265 (8): 871–879. doi:10.1007/s00405-008-0658-0. PMC 2441494. PMID 18458927.
  15. ^ Soma MA, Albert DM (February 2008). "Cidofovir: to use or not to use?". Current Opinion in Otolaryngology & Head and Neck Surgery. 16 (1): 86–90. doi:10.1097/MOO.0b013e3282f43408. PMID 18197029. S2CID 22895067.
  16. ^ "Cidofovir Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 5 February 2014.
  17. ^ "Vistide : EPAR – Product Information" (PDF). European Medicines Agency. Gilead Sciences International Ltd. 7 November 2013. Archived from the original (PDF) on 22 February 2014. Retrieved 5 February 2014.
  18. ^ Fernández-Morano T, del Boz J, González-Carrascosa M, Tortajada B, de Troya M (December 2011). "Topical cidofovir for viral warts in children". Journal of the European Academy of Dermatology and Venereology. 25 (12): 1487–1489. doi:10.1111/j.1468-3083.2010.03961.x. PMID 21261749. S2CID 32295082.
  19. ^ Kern ER (January 2003). "In vitro activity of potential anti-poxvirus agents". Antiviral Research. 57 (1–2): 35–40. doi:10.1016/s0166-3542(02)00198-5. PMC 9628899. PMID 12615301. S2CID 23136929.
  20. ^ Andrei G, Snoeck R (December 2010). "Cidofovir Activity against Poxvirus Infections". Viruses. 2 (12): 2803–2830. doi:10.3390/v2122803. PMC 3185586. PMID 21994641.
  21. ^ "Interim Clinical Guidance for the Treatment of Monkeypox". U.S. Centers for Disease Control and Prevention. 26 May 2022.
  22. ^ a b "Details" (PDF). www.gilead.com. Retrieved 2019-06-05.
  23. ^ Lacy SA, Hitchcock MJ, Lee WA, Tellier P, Cundy KC (August 1998). "Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys". Toxicological Sciences. 44 (2): 97–106. doi:10.1006/toxs.1998.2481. PMID 9742650.
  24. ^ a b c Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  25. ^ "Vistide (cidofovir)" (PDF) (package insert). Gilead Sciences. September 2010. Dosage and Administration: Dosage.
  26. ^ Safrin S, Cherrington J, Jaffe HS (September 1997). "Clinical uses of cidofovir". Reviews in Medical Virology. 7 (3): 145–156. doi:10.1002/(SICI)1099-1654(199709)7:3<145::AID-RMV196>3.0.CO;2-0. PMID 10398479. S2CID 32366514.
  27. ^ "Press Releases: Gilead". Archived from the original on 2013-02-08. Retrieved 2007-12-05.
  28. ^ Brodfuehrer PR, Howell HG, Sapino Jr C, Vemishetti P (1994). "A practical synthesis of (S)-HPMPC". Tetrahedron Letters. 35 (20): 3243. doi:10.1016/S0040-4039(00)76875-4.
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