Description: Ganciclovir is a synthetic guanine derivative active against cytomegalovirus (CMV). The chemical name for Ganciclovir is 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy] methyl]guanine. 
Pharmacological effects: Ganciclovir is an acyclic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses.  Ganciclovir has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in human clinical studies. To achieve anti-CMV activity, Ganciclovir is phosphorylated first to the monophosphate form by a CMV-encoded (UL97 gene) protein kinase homologue, then to the di- and triphosphate forms by cellular kinases. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected than in uninfected cells, indicating preferential phosphorylation in infected cells. Ganciclovir triphosphate, once formed, persists for days in the CMV-infected cell. Ganciclovir triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation.

Pharmacokinetics: Absorption: At the end of a 1-hour intravenous infusion of 5 mg/kg Ganciclovir, total AUC ranged between 22.1 ± 3.2 (n=16) and 26.8 ± 6.1 mcg·hr/mL (n=16) and Cmax ranged between 8.27 ± 1.02 (n=16) and 9 ± 1.4 mcg/mL (n=16). Distribution: The steady-state volume of distribution of Ganciclovir after intravenous administration was 0.74 ± 0.15 L/kg (n=98).  Cerebrospinal fluid concentrations obtained 0.25 to 5.67 hours postdose in 3 patients who received 2.5 mg/kg Ganciclovir intravenously q8h or q12h ranged from 0.31 to 0.68 mcg/mL representing 24% to 70% of the respective plasma concentrations.  Binding to plasma proteins was 1% to 2% over Ganciclovir concentrations of 0.5 and 51 mcg/mL. Elimination: When administered intravenously, Ganciclovir exhibits linear pharmacokinetics over the range of 1.6 to 5 mg/kg and when administered orally, it exhibits linear kinetics up to a total daily dose of 4 g/day.  Renal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of Ganciclovir. In patients with normal renal function, 91.3 ± 5% (n=4) of intravenously administered Ganciclovir was recovered unmetabolized in the urine.  Systemic clearance of intravenously administered Ganciclovir was 3.52 ± 0.8 mL/min/kg (n=98) while renal clearance was 3.2 ± 0.8 mL/min/kg (n=47), accounting for 91 ± 11% of the systemic clearance (n=47).  Half-life was 3.5 ± 0.9 hours (n=98) following IV administration and 4.8 ± 0.9 hours (n=39) following oral administration.
Indications: Ganciclovir for injection is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS).  Ganciclovir for injection is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease.
Precautions: In clinical studies with Ganciclovir for injection, the maximum single dose administered was 6 mg/kg by intravenous infusion over 1 hour. Larger doses have resulted in increased toxicity.  It is likely that more rapid infusions would also result in increased toxicity.  Administration of Ganciclovir for injection solution should be accompanied by adequate hydration. Initially reconstituted solutions of Ganciclovir for injection have a high pH (pH 11). Despite further dilution in intravenous fluids, phlebitis and/or pain may occur at the site of intravenous infusion. Care must be taken to infuse solutions containing Ganciclovir for injection only into veins with adequate blood flow to permit rapid dilution and distribution. Since Ganciclovir is excreted by the kidneys, normal clearance depends on adequate renal function. IF RENAL FUNCTION IS IMPAIRED, DOSAGE ADJUSTMENTS ARE REQUIRED FOR Ganciclovir FOR INJECTION.  Such adjustments should be based on measured or estimated creatinine clearance values.
Adverse reaction: The following events have been identified during post approval use of the drug. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.  These events have been chosen for inclusion due to either the seriousness, frequency of reporting, the apparent causal connection or a combination of these factors: Acidosis, allergic reaction, anaphylactic reaction, arthritis, bronchospasm, cardiac arrest, cardiac conduction abnormality, cataracts, cholelithiasis, cholestasis, congenital anomaly, dry eyes, dysesthesia, dysphasia, elevated triglyceride levels, encephalopathy, exfoliative dermatitis, extrapyramidal reaction, facial palsy, hallucinations, hemolytic anemia, hemolytic uremic syndrome, hepatic failure, hepatitis, hypercalcemia, hyponatremia, inappropriate serum ADH, infertility, intestinal ulceration, intracranial hypertension, irritability, loss of memory, loss of sense of smell, myelopathy, oculomotor nerve paralysis, peripheral ischemia, pulmonary fibrosis, renal tubular disorder, rhabdomyolysis, Stevens-Johnson syndrome, stroke, testicular hypotrophy, Torsade de Pointes, vasculitis, ventricular tachycardia.