Ganciclovir
Encyclopedia
Ganciclovir INN
(icon) 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.
. 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
.
It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.
adverse effects. Common adverse drug reaction
s (≥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.
, 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.
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).
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.
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
(icon) is an antiviral medication used to treat or prevent cytomegalovirus
Cytomegalovirus
Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
(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
Bausch & Lomb
Bausch & Lomb, an American company based in Rochester, New York, is one of the world's leading suppliers of eye health products, such as contact lenses and lens care products today. In addition to this main activity, in recent years the area of medical technology has been developed...
). A prodrug form with improved oral bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
(valganciclovir
Valganciclovir
Valganciclovir hydrochloride is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir...
) has also been developed.
Mechanism of action
Ganciclovir is a synthetic analogue of 2'-deoxy-guanosineGuanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
. It is first phosphorylated
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
to a deoxyguanosine triphosphate (dGTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
) analogue. This competitively inhibits the incorporation of dGTP by viral DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
, resulting in the termination of elongation of viral DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
.
Indications
Ganciclovir is indicated for:- Sight-threatening CMV retinitisCytomegalovirus retinitisCytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the eye's retina that can lead to blindness.-Presentation:...
in severely immunocompromised people - CMV pneumonitisPneumonitisPneumonitis or pulmonitis is a general term that refers to inflammation of lung tissue.Pneumonia is pneumonitis combined with consolidation and exudation...
in bone marrow transplantBone marrow transplantHematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
recipients - Prevention of CMV disease in bone marrow and solid organ transplantOrgan transplantOrgan transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
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 haematologicalHematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...
adverse effects. Common adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (≥1% of patients) include: granulocytopenia, neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, anaemia, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, fever, nausea, vomiting, dyspepsia
Dyspepsia
Dyspepsia , also known as upset stomach or indigestion, refers to a condition of impaired digestion. It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating...
, diarrhoea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and phlebitis
Phlebitis
Phlebitis is an inflammation of a vein, usually in the legs.When phlebitis is associated with the formation of blood clots , usually in the deep veins of the legs, the condition is called thrombophlebitis...
at injection site (due to high pH), sweating, rash, itch, increased serum creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
and blood urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
concentrations.
Toxicity
Ganciclovir is considered a potential human carcinogenCarcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
, teratogen, and mutagen
Mutagen
In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are therefore also likely to be carcinogens...
. It is also considered likely to cause inhibition of spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting.
Pharmacokinetics
Absorption of the oral form is very limited - about 5% fasting, about 8% with food. It achieves a concentration in the central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
of about 50% of the plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
level. About 90% of plasma ganciclovir is eliminated unchanged in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, with a half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of 2-6 hrs, depending on renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
(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
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
of the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
, as treatment for CMV retinitis
Cytomegalovirus retinitis
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the eye's retina that can lead to blindness.-Presentation:...
(associated with HIV infection).
A topical ophthalmic gel preparation of ganciclovir was recently approved for the treatment acute herpes simplex keratitis.
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.