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Revision as of 09:11, 7 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,071 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit		Latest revision as of 18:29, 28 August 2024 edit undoJay Hodec (talk | contribs)Extended confirmed users5,833 edits →Mechanism of action: Corrected wikilink.Tag: Visual edit
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			{{Short description|Chemical compound}}
	{{Drugbox		{{Drugbox
	| verifiedrevid = 443832770		| verifiedrevid = 459429712
	| IUPAC_name = 2-amino-9-{methyl}-6,9-dihydro-3''H''-purin-6-one		| IUPAC_name = 2-Amino-9-(1,3-dihydroxypropan-2-yloxymethyl)-3''H''-purin-6-one
	| image = Ganciclovir Structural Formulae V.1.svg		| image = Ganciclovir structure.svg
			| width = 195
			| alt =
			| image2 = Ganciclovir ball-and-stick.png
			| alt2 =
	<!--Clinical data-->		<!-- Clinical data -->
			| pronounce = {{IPAc-en|ɡ|æ|n|ˈ|s|aɪ|k|l|ə|v|ɪər}}
	| tradename = Cytovene		| tradename = Cytovene; Cymevene; Vitrasert
			| synonyms = gancyclovir; DHPG; 9-(1,3-dihydroxy-2-propoxymethyl)guanine
	| Drugs.com = {{drugs.com|monograph|cytovene}}		| Drugs.com = {{drugs.com|monograph|cytovene}}
	| MedlinePlus = a605011		| MedlinePlus = a605011
			| DailyMedID = Ganciclovir
	| pregnancy_category = D <small>(])</small>, C <small>(])</small>
			| pregnancy_AU = D
	| legal_status = S4 <small>(Au)</small>, POM <small>(])</small>, ℞-only <small>(U.S.)</small>
	| routes_of_administration = ], oral, intravitreal		| routes_of_administration = ], ], intravitreal
		⚫	| ATC_prefix = J05
		⚫	| ATC_suffix = AB06
		⚫	| ATC_supplemental = {{ATC|S01|AD09}}
			| legal_AU = S4
⚫	<!--Pharmacokinetic data-->
			| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
			| legal_CA = Rx-only
			| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=] | date=7 July 2016 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=13 July 2024}}</ref>
			| legal_UK = POM
			| legal_US = Rx-only
		⚫	<!-- Pharmacokinetic data -->
	| bioavailability = 5% (oral)		| bioavailability = 5% (oral)
	| metabolism = ]		| metabolism = guanylate kinase (CMV UL97 gene product)
	| elimination_half-life = 2.5–5 hours		| elimination_half-life = 2.5–5 hours
	| excretion = ]		| excretion = ]
	<!--Identifiers-->		<!-- Identifiers -->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 82410-32-0		| CAS_number = 82410-32-0
⚫	| ATC_prefix = J05
⚫	| ATC_suffix = AB06
⚫	| ATC_supplemental = {{ATC|S01|AD09}}
	| PubChem = 3454		| PubChem = 3454
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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	| ChEMBL = 182		| ChEMBL = 182
	<!--Chemical data-->		<!-- Chemical data -->
	| C=9 | H=13 | N=5 | O=4		| C=9 | H=13 | N=5 | O=4
	| molecular_weight = 255.23 g/mol
	| smiles = O=C2/N=C(\Nc1n(cnc12)COC(CO)CO)N		| smiles = O=C2/N=C(\Nc1n(cnc12)COC(CO)CO)N
	| InChI = 1/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)
	| InChIKey = IRSCQMHQWWYFCW-UHFFFAOYAM
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)		| StdInChI = 1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17)
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = IRSCQMHQWWYFCW-UHFFFAOYSA-N		| StdInChIKey = IRSCQMHQWWYFCW-UHFFFAOYSA-N
			| melting_point = 250
			| melting_notes = (dec.)
	}}		}}
			'''Ganciclovir''', sold under the brand name '''Cytovene''' among others, is an ] used to treat ] (CMV) infections.
	'''Ganciclovir''' ] ({{IPAc-en|icon|ɡ|æ|n|ˈ|s|aɪ|k|l|ə|v|ɪər}}) is an ] used to treat or prevent ] (CMV) infections.'''Ganciclovir sodium''' is marketed under the trade names '''Cytovene''' and '''Cymevene''' (]). Ganciclovir for ocular use is marketed under the trade name '''Vitrasert''' (]). A prodrug form with improved oral ] (]) has also been developed.
			Ganciclovir was patented in 1980 and approved for medical use in 1988.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=504 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA504 }}</ref>
⚫	==Mechanism of action==
	Ganciclovir is a synthetic analogue of 2'-deoxy-]. It is first ] to a deoxyguanosine triphosphate (d]) analogue. This competitively inhibits the incorporation of dGTP by viral ], resulting in the termination of elongation of viral ].
	==Clinical use==		==Medical use==
		⚫	Ganciclovir is indicated for:<ref name="AMH2006">{{cite book | veditors = Rossi S | title = ] | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook | isbn = 0-9757919-2-3 }}</ref>
	===Indications===
		⚫	* Sight-threatening ] in severely ] people
⚫	Ganciclovir is indicated for:<ref name="AMH2006">Rossi S, editor. ] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
		⚫	* CMV ] in ] recipients
⚫	*Sight-threatening ] in severely ] people
	*CMV ] in ] recipients		* Prevention of CMV disease in bone marrow and ] recipients
		⚫	* Confirmed CMV retinitis in people with AIDS (intravitreal implant)
⚫	*Prevention of CMV disease in bone marrow and ] recipients
⚫	*Confirmed CMV retinitis in people with AIDS (intravitreal implant)
	It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.		It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.{{medcn|date=September 2020}}
			Ganciclovir has also been used with some success in treating '']'' infections.<ref>{{cite journal | vauthors = Nakano K, Nishinaka K, Tanaka T, Ohshima A, Sugimoto N, Isegawa Y | title = Detection and identification of U69 gene mutations encoded by ganciclovir-resistant human herpesvirus 6 using denaturing high-performance liquid chromatography | journal = Journal of Virological Methods | volume = 161 | issue = 2 | pages = 223–230 | date = November 2009 | pmid = 19559728 | doi = 10.1016/j.jviromet.2009.06.016 }}</ref>
⚫	===Adverse effects===
⚫	Ganciclovir is commonly associated with a range of serious ] adverse effects. Common ]s (≥1% of patients) include: ], ], ], ], fever, nausea, vomiting, ], diarrhoea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and ] at injection site (due to high pH), sweating, rash, itch, increased serum ] and blood ] concentrations.<ref name="AMH2006" />
			Ganciclovir has also been found to be an effective treatment for ].<ref>{{cite journal | vauthors = Wilhelmus KR | title = Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD002898 | date = January 2015 | issue = 1 | pmid = 25879115 | pmc = 4443501 | doi = 10.1002/14651858.CD002898.pub5 }}</ref>
⚫	====Toxicity====
⚫	Ganciclovir is considered a potential human ], ], and ]. It is also considered likely to cause inhibition of ]. Thus, it is used judiciously and handled as a ] in the clinical setting.<ref name="AMH2006" /><ref name="Cymevene PI">Roche Products Pty Ltd. Cymevene (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.</ref>
			==Veterinary use ==
⚫	===Pharmacokinetics===
			Ganciclovir (in gel form) appears to be effective for treating the ophthalmic ] (FHV-1) virus infection in cats.<ref>{{cite journal | vauthors = Ledbetter EC, Badanes ZI, Chan RX, Donohue LK, Hayot NL, Harman RM, Van de Walle GR, Mohammed HO | display-authors = 6 | title = Comparative Efficacy of Topical Ophthalmic Ganciclovir and Oral Famciclovir in Cats with Experimental Ocular Feline Herpesvirus-1 Epithelial Infection | journal = Journal of Ocular Pharmacology and Therapeutics | volume = 38 | issue = 5 | pages = 339–347 | date = June 2022 | pmid = 35613418 | pmc = 9242719 | doi = 10.1089/jop.2022.0001 }}</ref>
	Absorption of the oral form is very limited - about 5% fasting, about 8% with food. It achieves a concentration in the ] of about 50% of the ] level. About 90% of plasma ganciclovir is eliminated unchanged in the ], with a ] of 2-6 hrs, depending on ] (elimination takes over 24 hours in end-stage renal disease).
		⚫	==Adverse effects==
		⚫	Ganciclovir is commonly associated with a range of serious ] adverse effects. Common ]s (≥1% of patients) include: ], ], ], ], fever, nausea, vomiting, ], diarrhea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and ] at injection site (due to high pH), sweating, rash, itch, increased serum ] and blood ] concentrations.<ref name="AMH2006" />
		⚫	===Toxicity===
		⚫	Ganciclovir is considered a potential human ], ], and ]. It is also considered likely to cause inhibition of ]. Thus, it is used judiciously and handled as a ] in the clinical setting.<ref name="AMH2006" /><ref name="Cymevene PI">{{cite web | title = Cymevene® (ganciclovir) Australian Approved Product Information | url = https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2019-PI-01802-1&d=20230921172310101 | work = Pharmaco (Australia) Ltd | publisher = Australian Therapeutic Goods Administration | date = 4 November 2022 }}</ref>
		⚫	==Mechanism of action==
			Ganciclovir (9-guanine) is a potent inhibitor of viruses of the ], including cytomegalovirus (CMV), that are pathogenic for humans and animals. The primary mechanism of ganciclovir action against CMV is inhibition of the replication of viral DNA by ganciclovir-5'-triphosphate (ganciclovir-TP). This inhibition includes a selective and potent inhibition of the viral ]. Ganciclovir is metabolized to the triphosphate form by primarily three cellular enzymes: (1) a deoxyguanosine kinase induced by CMV-infected cells; (2) guanylate kinase; and (3) phosphoglycerate kinase. Other nucleotide-metabolizing enzymes may be involved as well. The selective antiviral response associated with ganciclovir treatment is achieved because of the much weaker inhibition of cellular DNA polymerases by ganciclovir-TP. Activity and selectivity are also amplified by the accumulation of ganciclovir-TP in CMV-infected cells.
		⚫	==Pharmacokinetics==
			{{unreferenced section|date=September 2020}}
	===Administration===		===Administration===
	Acute infections are treated in two phases:		Acute infections are treated in two phases:
	*induction phase, 5&nbsp;mg per kilogram intravenously every 12 hours for 14–21 days, the intravenous dose given as a 1 hour infusion		* induction phase, 5&nbsp;mg per kilogram intravenously every 12 hours for 14–21 days, the intravenous dose given as a 1-hour infusion
	*maintenance phase, 5&nbsp;mg per kg intravenously every day		* maintenance phase, 5&nbsp;mg per kg intravenously every day
	Stable disease is treated with 1000&nbsp;mg orally three times daily. Similar dosing is used to prevent disease in high-risk patients, such as those infected with human immunodeficiency virus (HIV) or those with organ transplants.		Stable disease is treated with 1000&nbsp;mg orally three times daily. Similar dosing is used to prevent disease in high-risk patients, such as those infected with human immunodeficiency virus (HIV) or those with organ transplants.
	Ganciclovir is also available in slow-release formulations for insertion into the ] of the ], as treatment for ] (associated with HIV infection).		Ganciclovir is also available in slow-release formulations for insertion into the ] of the ], as treatment for ] (associated with HIV infection).
	A topical ophthalmic gel preparation of ganciclovir was recently approved for the treatment acute herpes simplex keratitis.		A topical ophthalmic gel preparation of ganciclovir was recently{{when|date=September 2020}} approved for the treatment of acute herpes simplex keratitis.{{cn|date=September 2020}}
	==References==		== See also ==
			] – the ] of ganciclovir
			== References ==
	{{reflist}}		{{reflist}}
	===Further reading===		== Further reading ==
			{{refbegin}}
	* Noble S, Faulds D. Ganciclovir. An update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs. 1998;56(1):115-46		* {{cite journal | vauthors = Noble S, Faulds D | title = Ganciclovir. An update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients | journal = Drugs | volume = 56 | issue = 1 | pages = 115–146 | date = July 1998 | pmid = 9664203 | doi = 10.2165/00003495-199856010-00012 }}
	* Spector SA. Oral ganciclovir. Adv Exp Med Biol. 1999;458:121-7
			* {{cite book | vauthors = Spector SA | chapter = Oral Ganciclovir | title = Antiviral Chemotherapy 5 | volume = 458 | pages = 121–7 | year = 1999 | pmid = 10549384 | doi = 10.1007/978-1-4615-4743-3_11 | isbn = 978-1-4613-7150-2 | series = Advances in Experimental Medicine and Biology }}
	* Couchoud C. Cytomegalovirus prophylaxis with antiviral agents for solid organ transplantation. Cochrane Database Syst Rev. 2000;(2):CD001320.
			* {{cite journal | vauthors = Couchoud-Heyer C | title = WITHDRAWN: Cytomegalovirus prophylaxis with antiviral agents for solid organ transplantation | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD001320 | date = July 2007 | volume = 1998 | pmid = 17636667 | doi = 10.1002/14651858.cd001320.pub2 | pmc = 10734368 }}
			{{refend}}
	{{Antivirals}}		{{Antivirals}}
			{{Ophthalmological anti-infectives}}
			{{Portal bar | Medicine}}
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