Ganciclovir, sold under the brand name Cytovene among others, is an

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...

used to treat cytomegalovirus (CMV) infections. Ganciclovir was patented in 1980 and approved for medical use in 1988.

Medical use

Ganciclovir is indicated for:Rossi S, editor.

Australian Medicines Handbook Australian Medicines Handbook (AMH) is a peer-reviewed medicines prescribing guide for Australian health professionals. The handbook is available in paper and digital formats and is supplemented by the ''AMH Aged Care Companion'' and the ''AMH C ...

2006. Adelaide: Australian Medicines Handbook; 2006. * Sight-threatening CMV retinitis in severely

immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

people * CMV

pneumonitis Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris (e.g., animal dander), aspiration, herbicide ...

bone marrow transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

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. Ganciclovir has also been used with some success in treating ''

Human herpesvirus 6 Human herpesvirus 6 (HHV-6) is the common collective name for '' human betaherpesvirus 6A'' (HHV-6A) and '' human betaherpesvirus 6B'' (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their prim ...

'' infections. Ganciclovir has also been found to be an effective treatment for herpes simplex virus epithelial keratitis.

Adverse effects

Ganciclovir is commonly associated with a range of serious haematological adverse effects. Common

adverse drug reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...

s (≥1% of patients) include:

granulocytopenia Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

, neutropenia,

anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

, fever, nausea, vomiting,

dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

, diarrhea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and

phlebitis Phlebitis (or Venitis) is inflammation of a vein, usually in the legs. It most commonly occurs in superficial veins. Phlebitis often occurs in conjunction with thrombosis and is then called thrombophlebitis or superficial thrombophlebitis. Unlike ...

at injection site (due to high pH), sweating, rash, itch, increased serum

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an importa ...

and blood

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

concentrations.

Toxicity

Ganciclovir is considered a potential human

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...

, teratogen, and mutagen. It is also considered likely to cause inhibition of spermatogenesis. Thus, it is used judiciously and handled as a

cytotoxic drug Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

in the clinical setting.Roche Products Pty Ltd. Cymevene (Australian Approved Product Information). Dee Why (NSW): Roche; 2005.

Mechanism of action

Ganciclovir is a synthetic analogue of 2′-deoxy-

guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosphate ...

. It is first

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells. Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP) incorporation into DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. In addition, ganciclovir triphosphate serves as a poor substrate for chain elongation, thereby disrupting viral DNA synthesis by a second route.

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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

of about 50% of the plasma level. About 90% of plasma ganciclovir is eliminated unchanged in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellular ...

, with a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of 2–6 hours, 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 The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humor ...

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 of acute herpes simplex keratitis.

References

External links

* * {{Portal bar , Medicine Anti-herpes virus drugs Cell culture reagents Purines Ethers Diols Hoffmann-La Roche brands