Uses of Valcyte: - Cytomegalovirus Infection

Anti-viral drugs

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir, which after oral administration is rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2’-deoxyguanosine, which inhibits replication of herpes viruses in vitro and in vivo. Sensitive human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and -2 (HSV-1 and HSV-2), human herpes virus 6, 7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) and hepatitis B virus.In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir mono-phosphate by the viral protein kinase, UL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly. This has been shown to occur in HSV- and HCMV-infected cells with half-lives of 18 and between 6 and 24 hours respectively after removal of extracellular ganciclovir. As phosphorylation is largely dependent on the viral kinase, the phosphorylation of ganciclovir occurs preferentially in virus-infected cells.The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by: (a) competitive inhibition of incorporation of deoxyguanosine-triphosphate into DNA by viral DNA polymerase and (b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited further viral DNA elongation. Typical antiviral IC 50 against CMV in vitro is in the range 0.08 μM (0.02 μg/ml) to 14 μM (3.5 μg/ml).The clinical antiviral effect of Valganciclovir has been demonstrated in the treatment of AIDS patients with newly diagnosed CMV retinitis (clinical trial WV15376). CMV shedding was decreased from 46% (32/69) of patients at study entry to 7% (4/55) of patients following 4 weeks of Valganciclovir treatment.

How to use Valganciclovir: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Valganciclovir is to be taken with food.

In vivo drug-drug interaction studies were not conducted with valganciclovir. However, because valganciclovir is rapidly and extensively converted to ganciclovir, drug-drug interactions associated with ganciclovir will be expected for Valganciclovir. Drug-drug interaction studies with ganciclovir were conducted in patients with normal renal function. Following concomitant administration of Valganciclovir and other renally excreted drugs, patients with impaired renal function may have increased concentrations of ganciclovir and the coadministered drug. Therefore, these patients should be closely monitored for toxicity of ganciclovir and the coadministered drug.

Valganciclovir is contraindicated in patients with known hypersensitivity to valganciclovir, ganciclovir or to any of the excipients.

Common - Stomach pain - Decreased red blood cell count - Diarrhea - Fever - Vomiting

Pregnancy: The safety of Valganciclovir for use in pregnant women has not been established. However, ganciclovir readily diffuses across the human placenta. The use of Valganciclovir should be avoided in pregnant women unless the benefit to the mother outweighs the potential risk to the fetus. Reprotoxicity studies have not been repeated with valganciclovir because of the rapid and extensive conversion to ganciclovir. In animal studies ganciclovir was associated with reproductive toxicity and teratogenicity (see section 3.3.4 Reproductive Toxicity). The safe use of Valganciclovir during labor and delivery has not been established.Lactation: Peri- and postnatal development has not been studied with valganciclovir or with ganciclovir but the possibility of ganciclovir being excreted in breast milk and causing serious adverse reactions in the nursing infant cannot be discounted. Human data are not available but animal data indicates that ganciclovir is excreted in the milk of lactating rats. Therefore, a decision should be made to discontinue the drug or discontinue nursing taking into consideration the potential benefit of Valganciclovir to the nursing mother.

Store Valganciclovir tablets at 20°C to 25°C; excursions are permitted to 15°C to 30°C

Anti-viral drugs

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir, which after oral administration is rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2’-deoxyguanosine, which inhibits replication of herpes viruses in vitro and in vivo. Sensitive human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and -2 (HSV-1 and HSV-2), human herpes virus 6, 7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus (EBV), varicella-zoster virus (VZV) and hepatitis B virus.In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir mono-phosphate by the viral protein kinase, UL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly. This has been shown to occur in HSV- and HCMV-infected cells with half-lives of 18 and between 6 and 24 hours respectively after removal of extracellular ganciclovir. As phosphorylation is largely dependent on the viral kinase, the phosphorylation of ganciclovir occurs preferentially in virus-infected cells.The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by: (a) competitive inhibition of incorporation of deoxyguanosine-triphosphate into DNA by viral DNA polymerase and (b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited further viral DNA elongation. Typical antiviral IC 50 against CMV in vitro is in the range 0.08 μM (0.02 μg/ml) to 14 μM (3.5 μg/ml).The clinical antiviral effect of Valganciclovir has been demonstrated in the treatment of AIDS patients with newly diagnosed CMV retinitis (clinical trial WV15376). CMV shedding was decreased from 46% (32/69) of patients at study entry to 7% (4/55) of patients following 4 weeks of Valganciclovir treatment.

Pregnancy: The safety of Valganciclovir for use in pregnant women has not been established. However, ganciclovir readily diffuses across the human placenta. The use of Valganciclovir should be avoided in pregnant women unless the benefit to the mother outweighs the potential risk to the fetus. Reprotoxicity studies have not been repeated with valganciclovir because of the rapid and extensive conversion to ganciclovir. In animal studies ganciclovir was associated with reproductive toxicity and teratogenicity (see section 3.3.4 Reproductive Toxicity). The safe use of Valganciclovir during labor and delivery has not been established.Lactation: Peri- and postnatal development has not been studied with valganciclovir or with ganciclovir but the possibility of ganciclovir being excreted in breast milk and causing serious adverse reactions in the nursing infant cannot be discounted. Human data are not available but animal data indicates that ganciclovir is excreted in the milk of lactating rats. Therefore, a decision should be made to discontinue the drug or discontinue nursing taking into consideration the potential benefit of Valganciclovir to the nursing mother.