indication

Valganciclovir is an antiviral medication used for the treatment of cytomegalovirus infections.

pharmacology

Valganciclovir is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases. After this, it (being an analogue of guanosine) gets incorporated into DNA and thus cannot be properly read by DNA polymerase. This results in the termination of the elongation of viral DNA.

mechanism of action

Valganciclovir is a prodrug of ganciclovir that exists as a mixture of two diastereomers. After administration, these diastereomers are rapidly converted to ganciclovir by hepatic and intestinal esterases. In cytomegalovirus (CMV)-infected cells, ganciclovir is initially phosphorylated to the monophosphate form by viral protein kinase, then it is further phosphorylated via cellular kinases to produce the triphosphate form. This triphosphate form is slowly metabolized intracellularly. The phosphorylation is dependent upon the viral kinase and occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to the inhibition of viral DNA synthesis by ganciclovir triphosphate. Ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.

toxicity

It is expected that an overdose of valganciclovir could also possibly result in increased renal toxicity.

biotransformation

Rapidly hydrolyzed in the intestinal wall and liver to ganciclovir. No other metabolites have been detected.

absorption

Valganciclovir is well absorbed from the gastrointestinal tract and the absolute bioavailability from valganciclovir tablets (following administration with food) is approximately 60%.

half life

Approximately 4.08 hours. Increased in patients with renal function impairment.

route of elimination

The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion.

drug interactions

Abacavir: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.

Adefovir Dipivoxil: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Adefovir Dipivoxil, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.

Cilastatin: Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)

Didanosine: The adverse/toxic effects of Didanosine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.

Emtricitabine: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Emtricitabine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.

Imipenem: Generalized convulsions have been reported in patients taking Ganciclovir and Imipenem-cilastatin. Concomitant therapy should be avoided. (Note: Valganciclovir is converted to Ganciclovir in vivo)

Lamivudine: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Lamivudine, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.

Mycophenolate mofetil: The excretion rates of Valganciclovir and/or Mycophenolate mofetil may decrease. Monitor for increased serum concentrations and toxicity of both agents.

Mycophenolic acid: The excretion rates of Valganciclovir and/or Mycophenolic acid may decrease. Monitor for increased serum concentrations and toxicity of both agents.

Probenecid: Probenecid may decrease excretion of Valganciclovir. Monitor for increased serum concentration and toxicity of Valganciclovir.

Tenofovir: The excretion rates of Valganciclovir and/or Tenofovir may decrease as both drugs are eliminated by active tubular secretion. Monitor for increased serum concentrations and toxicity of both agents.

Zidovudine: The adverse/toxic effects of Zidovudine, a reverse transcriptase inhibitor (nucleoside), may be enhanced by Valganciclovir. There is a significant risk of hematologic toxicity. Concomitant therapy should be avoided.