Ganciclovir 82410-32-0

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:*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.

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 dayStable 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).