Ganciclovir

Ganciclovir

Systematic (IUPAC) name
2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one
Clinical data
Trade names	Cytovene
AHFS/Drugs.com	monograph
MedlinePlus	a605011
Pregnancy cat.	D (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	IV, oral, intravitreal
Pharmacokinetic data
Bioavailability	5% (oral)
Metabolism	guanylate kinase (CMV UL97 gene product)
Half-life	2.5–5 hours
Excretion	Renal
Identifiers
CAS number	82410-32-0 Y
ATC code	J05AB06 S01AD09
PubChem	CID 3454
DrugBank	APRD00263
ChemSpider	3336 Y
UNII	P9G3CKZ4P5 Y
KEGG	D00333 Y
ChEBI	CHEBI:465284 Y
ChEMBL	CHEMBL182 Y
Chemical data
Formula	C9H13N5O4
Mol. mass	255.23 g/mol
SMILES	eMolecules & PubChem
InChI InChI=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) Y Key:IRSCQMHQWWYFCW-UHFFFAOYSA-N Y
N(what is this?)  (verify)

Ganciclovir INN ( /ɡænˈsaɪkləvɪər/) is an antiviral medication used to treat or prevent cytomegalovirus (CMV) infections.Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene (Roche). Ganciclovir for ocular use is marketed under the trade name Vitrasert (Bausch & Lomb). A prodrug form with improved oral bioavailability (valganciclovir) has also been developed.

Mechanism of action

Ganciclovir is a synthetic analogue of 2'-deoxy-guanosine. It is first phosphorylated to a deoxyguanosine triphosphate (dGTP) analogue. This competitively inhibits the incorporation of dGTP by viral DNA polymerase, resulting in the termination of elongation of viral DNA.

Clinical use

Indications

Ganciclovir is indicated for:^[1]

• Sight-threatening CMV retinitis in severely immunocompromised people
• CMV pneumonitis in bone marrow transplant recipients
• Prevention of CMV disease in bone marrow and solid organ transplant 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.

Adverse effects

Ganciclovir is commonly associated with a range of serious haematological adverse effects. Common adverse drug reactions (≥1% of patients) include: granulocytopenia, neutropenia, anaemia, thrombocytopenia, fever, nausea, vomiting, dyspepsia, diarrhoea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and phlebitis at injection site (due to high pH), sweating, rash, itch, increased serum creatinine and blood urea concentrations.^[1]

Toxicity

Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. It is also considered likely to cause inhibition of spermatogenesis. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting.^[1][2]

Pharmacokinetics

Absorption of the oral form is very limited - about 5% fasting, about 8% with food. It achieves a concentration in the central nervous system of about 50% of the plasma level. About 90% of plasma ganciclovir is eliminated unchanged in the urine, with a half-life of 2-6 hrs, depending on renal function (elimination takes over 24 hours in end-stage renal disease).

Administration

Acute infections are treated in two phases:

• induction phase, 5 mg per kilogram intravenously every 12 hours for 14–21 days, the intravenous dose given as a 1 hour infusion
• maintenance phase, 5 mg per kg intravenously every day

Stable disease is treated with 1000 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 vitreous humour of the eye, as treatment for CMV retinitis (associated with HIV infection).

A topical ophthalmic gel preparation of ganciclovir was recently approved for the treatment acute herpes simplex keratitis.

References

1. ^ ^{a b c} Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
2. ^ Roche Products Pty Ltd. Cymevene (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.

Further reading

• 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
• Spector SA. Oral ganciclovir. Adv Exp Med Biol. 1999;458:121-7
• Couchoud C. Cytomegalovirus prophylaxis with antiviral agents for solid organ transplantation. Cochrane Database Syst Rev. 2000;(2):CD001320.