Valganciclovir
When ATH:
J05AB14
Pharmacological action.
Antiviral agent, L-valyl ester of ganciclovir. It is a prodrug of ganciclovir. Once inside quickly transformed into ganciclovir involving the intestine and liver esterase.
Ganciclovir is a synthetic analogue of guanine. Inside the cells ganciclovir metabolized in a form consistent with the participation of cell monophosphate deoksiguanozinkinazy, then active ganciclovir triphosphate. Acting as a substrate and embedding in DNA, ganciclovir triphosphate competitively inhibits the synthesis of viral DNA. This leads to inhibition of DNA synthesis by inhibiting DNA chain elongation. Ganciclovir inhibits viral DNA polymerase active, than cellular polymerase.
By valganciclovir sensitive human cytomegalovirus, Herpes simplex types 1 and 2, Varicella zoster, Epstein-Barr virus and hepatitis B virus.
Pharmacokinetics
After ingestion is rapidly absorbed from the gastrointestinal tract, in the gut wall and liver converted to gancyclovir. The absolute bioavailability of ganciclovir after his transformation from valganciclovir is approximately 60%. Binding of ganciclovir to plasma proteins is 1-2%.
Write mainly kidneys.
After receiving valganciclovir final T1 / 2 is about ganciclovir 4.2 no.
Testimony
Treatment of CMV retinitis in AIDS.
Dosage regimen
Inside of 450 mg 1-2 times / day in accordance with the treatment.
Patients with impaired renal function, sick, hemodialysis, as well as the inhibition of bone marrow hemopoiesis requires correction mode.
Side effect
Related side effects of ganciclovir.
Contraindications
Hypersensitivity to valganciclovir, ganciclovir.
Not recommended for use when the number of neutrophils in the peripheral blood of less than 500 cells / mm, Platelet – less 25 000/l, Hemoglobin – less 8 g / dl.
Cautions
Comply with special instructions to ganciclovir.
Drug Interactions
Valganciclovir interactions with valacyclovir, didanozinom, nelfinavirom, cyclosporine, omeprazole and Mycophenolate mofetilom not detected.
Interaction, typical of ganciclovir, can be expected when using valganciclovir: imipenem / cilastatin - the risk of seizures. Probenecid decreases on 20% ganciclovir renal clearance and increases AUC by 40%.
Ganciclovir increases the AUC of zidovudine by 17%; AZT significantly reduces the concentration of ganciclovir. The combined use of zidovudine and ganciclovir - increased risk of neutropenia and anemia.
Ganciclovir increases the concentration of didanosine: upon receiving an oral dose of ganciclovir 3 and 6 g per day didanosine AUC increases by 84-124%, and in / in the introduction of ganciclovir at doses of 5-10 mg / kg / day didanosine AUC increased by 38-67%. The reason for this increase may be either increased bioavailability, or inhibition of metabolism. Clinically significant effect on the concentration of ganciclovir not observed. However, given the increase in plasma concentrations of didanosine in the presence of ganciclovir patients should be carefully monitored for the onset of symptoms of toxic action of didanosine.
Mycophenolate mofetil - increasing the concentration of ganciclovir and phenolic glucuronide of mycophenolic acid, however, a significant change in the pharmacokinetics of mycophenolic acid is detected, adjust the dose of mycophenolate mofetil is not required. In patients with chronic renal failure, simultaneously receiving ganciclovir to mycophenolate mofetil, you must observe the correct dose of ganciclovir and conduct close monitoring.
Zalcitabine increases AUC of ganciclovir on 13%.
Of trimethoprim 16,3% reduces the renal clearance of ganciclovir, which is accompanied by a decrease in the terminal elimination rate and corresponding increase in T1 / 2 15%, AUC and Cmax are not changed.
Information about, Ganciclovir that alters the pharmacokinetics of cyclosporine has been received. However, after the start of ganciclovir indicated an insignificant hypercreatininemia.
Simultaneous treatment with ganciclovir, etc.. PM, providing mielotoksicskie or nephrotic action (incl. dapsone, pentamidine, flucytosine, vynkrystyn, vynblastyn, adriamycin, Amphotericin B, nucleoside analogues and hydroxyurea) can enhance their toxic effects.
