Valacyclovir tablets 500mg, No. 10

• Treatment and prevention of infectious diseases caused by Herpes zoster.

• Prevention of cytomegalovirus infection that develops during organ transplantation.

When administered orally, a single dose for adults is 0.25-2 g. The frequency of administration and the duration of treatment depend on the indications. Patients with severe renal impairment require adjustment of the dosage regimen.

Film-coated tablets

1 tab.

valacyclovir

Hypersensitivity to valacyclovir, acyclovir.

pharmachologic effect

Antiviral agent of the group of nucleoside analogs. Valacyclovir is the L-valine ester of acyclovir, thus being a prodrug. After absorption into the blood, valacyclovir is almost completely converted to acyclovir under the influence of the hepatic enzyme valacyclovir hydrolase. The acyclovir formed from valacyclovir, in turn, penetrates the cells affected by the virus, where, under the influence of the viral enzyme thymidine kinase, it turns into monophosphate, then, under the influence of cellular kinases, into diphosphate and active triphosphate. Acyclovir triphosphate inhibits DNA polymerase and thus disrupts viral DNA replication. In addition, a violation of viral DNA replication may result from the incorporation of acyclovir into its structure. Thus, the high selectivity of valacyclovir in relation to tissues affected by the virus is explained by the fact thatthat stage I of the phosphorylation chain is mediated by an enzyme produced by the virus itself. Active against Herpes simplex viruses types 1 and 2, Varicella zoster, cytomegalovirus, Epstein-Barr virus, human herpes virus 6.

Pharmacokinetics

After oral administration, valacyclovir is well absorbed from the gastrointestinal tract, rapidly and almost completely converted into acyclovir and L-valine under the action of the enzyme valacyclovir hydrolase. After a single dose of 0.25-2 g of valacyclovir Cmax of acyclovir in healthy volunteers with normal renal function averages 10-37 ?mol (2.2-8.3 ?g / ml) and is achieved after 1-2 hours. The bioavailability of acyclovir when taken from 1 g of valacyclovir is 54 % and does not depend on food intake. Cmax of valacyclovir in plasma is only 4% of the level of acyclovir and is achieved on average 30-100 minutes after taking the drug; after 3 hours, the Cmax level remains the same or decreases. The binding of valacyclovir to plasma proteins is very low - 15%. In patients with normal renal function, T1 / 2 of acyclovir is about 3 hours. Valacyclovir is excreted in the urine,mainly in the form of acyclovir (more than 80% of the dose) and its metabolite 9-carboxymethoxymethylguanine, less than 1% of the drug is excreted unchanged. In patients with end-stage renal failure, T1 / 2 of acyclovir is approximately 14 hours. In late pregnancy, the stable daily AUC after taking 1 g of valacyclovir was approximately 2 times more than that when taking acyclovir at a dose of 1.2 g / day. In organ transplant recipients receiving valacyclovir at a dose of 2 g 4 times / day, the Cmax of acyclovir is equal or higher than that in healthy volunteers receiving the same dose of valacyclovir, and their daily AUC values ??are significantly higher.In patients with end-stage renal failure, T1 / 2 of acyclovir is approximately 14 hours. In late pregnancy, the stable daily AUC after taking 1 g of valacyclovir was approximately 2 times more than that when taking acyclovir at a dose of 1.2 g / day. In organ transplant recipients receiving valacyclovir at a dose of 2 g 4 times / day, the Cmax of acyclovir is equal or higher than that in healthy volunteers receiving the same dose of valacyclovir, and their daily AUC values ??are significantly higher.In patients with end-stage renal failure, T1 / 2 of acyclovir is approximately 14 hours. In late pregnancy, the stable daily AUC after taking 1 g of valacyclovir was approximately 2 times more than that when taking acyclovir at a dose of 1.2 g / day. In organ transplant recipients receiving valacyclovir at a dose of 2 g 4 times / day, the Cmax of acyclovir is equal or higher than that in healthy volunteers receiving the same dose of valacyclovir, and their daily AUC values ??are significantly higher.Cmax of acyclovir is equal to or exceeds that in healthy volunteers receiving the same dose of valacyclovir, and their daily AUC values ??are significantly higher.Cmax of acyclovir is equal to or exceeds that in healthy volunteers receiving the same dose of valacyclovir, and their daily AUC values ??are significantly higher.

Side effect

From the digestive system: nausea, discomfort, abdominal pain, vomiting, diarrhea, anorexia; rarely - a transient increase in liver function tests. From the side of the central nervous system: headache, fatigue, dizziness, confusion, hallucinations; rarely - impaired consciousness; in some cases - coma (usually in patients with impaired renal function or other predisposing factors). Allergic reactions: rarely - rash, urticaria, itching, angioedema, anaphylaxis. Others: rarely - thrombocytopenia, shortness of breath, renal dysfunction, photosensitivity.

Application during pregnancy and lactation

Adequate and strictly controlled studies of the safety of valacyclovir use during pregnancy and lactation have not been conducted. Application in this category of patients is possible in cases where the expected benefit of therapy to the mother outweighs the potential risk to the fetus or infant. It is known that acyclovir, which is a metabolite of valacyclovir, is excreted in breast milk at concentrations 0.6-4.1 times higher than its plasma concentration. T1 / 2 of acyclovir from breast milk is 2.8 hours, which is comparable to T1 / 2 from blood plasma.

Application for violations of liver function

Use with caution in patients with liver disease.

Application for impaired renal function

Patients with renal insufficiency have an increased risk of developing neurological complications when taking valacyclovir.

Application in children

There is no clinical experience with children.

Use in elderly patients

Elderly patients during the treatment period need to increase the volume of fluid intake.

special instructions

Elderly patients during the treatment period need to increase the volume of fluid intake. Patients with renal insufficiency have an increased risk of developing neurological complications when taking valacyclovir. Use with caution in patients with liver disease. There is no clinical experience with children.

Drug interactions

Acyclovir enters the urine unchanged as a result of active tubular secretion. Any drugs that are prescribed simultaneously with it and compete for this elimination mechanism can cause an increase in the plasma concentration of valacyclovir. Cimetidine and drugs that block tubular secretion, when administered after taking valacyclovir at a dose of 1 g, increase the AUC for acyclovir and decrease its renal clearance. With the simultaneous administration of acyclovir and an inactive metabolite of mycophenolate mofetil (an immunosuppressant used in transplantation), an increase in the AUC of acyclovir and mycophenolate mofetil was observed. With the simultaneous use of valacyclovir with drugs that impair renal function (including cyclosporine, tacrolimus), renal function may deteriorate.