Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antiviral agent of the group of nucleoside analogues. Valacyclovir is an L-valine ester of acyclovir, thus being a prodrug.
After absorption into the blood, valaciclovir is almost completely converted into acyclovir under the influence of the hepatic enzyme valaciclovir hydrolase.Acyclovir, formed from valaciclovir, in turn penetrates into the cells affected by the virus, where, under the influence of the virus enzyme, thymidine kinase is converted to monophosphate, then, under the influence of cellular kinases, into diphosphate and active triphosphate. Acyclovir triphosphate depresses the DNA polymerase and, thus, disrupts the replication of the DNA of the virus. In addition, the disruption of viral DNA replication may be the result of the incorporation of acyclovir into its structure. Thus, the high selectivity of valacyclovir for tissues affected by the virus is explained by the fact that the first stage of the chain of phosphorylation reactions is mediated by an enzyme produced by the virus itself.
It is active against Herpes simplex virus types 1 and 2, Varicella zoster, cytomegalovirus, Epstein-Barr virus, human herpes virus 6.
PHARMACOKINETICS
After oral administration, valacyclovir is well absorbed from the digestive tract, quickly and almost completely converted to acyclovir and L-valine under the action of the enzyme valacyclovirhydrolase.
After a single dose of 0.25-2 g valacyclovir C max acyclovir in healthy volunteers with normal renal function averages 10-37 Ојmol (2.2-8.3 Ојg / ml) and is achieved in 1-2 hours.
Bioavailability of acyclovir when taken from 1 g of valaciclovir is 54% and does not depend on food intake.
C max valacyclovir in plasma is only 4% of the level of acyclovir and is achieved on average 30-100 min after taking the drug; After 3 hours, the C max level remains the same or decreases.
The binding of valaciclovir to plasma proteins is very low - 15%.
In patients with normal renal function, T 1/2 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 unchanged.
In patients with terminal stage of renal failure, T 1/2 acyclovir is approximately 14 hours.
In late pregnancy, a steady daily AUC after receiving 1 g of valaciclovir was more approximately 2-fold than that of acyclovir at a dose of 1.2 g / day.
In recipients of organ transplants receiving valacyclovir at a dose of 2 g 4 times / day, C max of acyclovir is equal to or greater than that of healthy volunteers receiving the same dose of valacyclovir, and the daily AUC values ​​are significantly higher.
INDICATIONS
Treatment and prevention of infectious diseases caused by Herpes zoster.
Prevention of cytomegalovirus infection, which develops during organ transplantation.
DOSING MODE
When administered orally, a single dose for adults is 0.25-2 grams. The frequency of admission and the duration of treatment depend on the indications.
Patients with severe impairment of kidney function require a correction of the dosing regimen.
SIDE EFFECT
On the part of the digestive system: nausea, discomfort, abdominal pain, vomiting, diarrhea, anorexia; rarely - transient increase in liver function tests.
From the side of the central nervous system: headache, fatigue, dizziness, confusion, hallucinations; rarely - disturbances of consciousness; in some cases - coma (usually in patients with impaired renal function or other predisposing factors).
Allergic reactions: rarely - rashes, hives, itching, angioedema, anaphylaxis.
Other: rarely - thrombocytopenia, dyspnea, renal dysfunction, photosensitivity.
CONTRAINDICATIONS
Hypersensitivity to valacyclovir, acyclovir.
PREGNANCY AND LACTATION
Adequate and strictly controlled studies of the safety of valaciclovir during pregnancy and lactation are not conducted. Use in this category of patients is possible in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus or infant.
It is known that acyclovir, a metabolite of valaciclovir, is excreted in breast milk in concentrations that are 0.6-4.1 times higher than its concentration in plasma. T 1/2acyclovir from breast milk is 2.8 hours, which is comparable to T 1/2 from blood plasma.
In experimental studies, valacyclovir did not have teratogenic effects in rats and rabbits. When administered orally, valaciclovir did not cause fertility disorders in males and female rats.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with renal insufficiency have an increased risk of developing neurological complications with valaciclovir.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in patients with liver disease.
APPLICATION FOR CHILDREN
Clinical experience of use in children is absent.
APPLICATION IN ELDERLY PATIENTS
Older patients in the period of treatment need to increase the amount of fluid consumed.
SPECIAL INSTRUCTIONS
Older patients in the period of treatment need to increase the amount of fluid consumed.
Patients with renal insufficiency have an increased risk of developing neurological complications with valaciclovir.
Use with caution in patients with liver disease.
Clinical experience of use in children is absent.
DRUG INTERACTION
Acyclovir in unchanged form enters the urine as a result of active tubular secretion. Any drugs that are prescribed with it at the same time and compete for this mechanism of elimination, can cause an increase in the concentration of valacyclovir in the plasma. Cimetidine and drugs that block tubular secretion, when prescribed after taking valaciclovir in a dose of 1 g, increase the acyclovir AUC and reduce its kidney clearance.
With the simultaneous administration of acyclovir and an inactive metabolite of mycophenolate mofetil (an immunosuppressant used in transplantation), there was an increase in the aUC of acyclovir and mycophenolate mofetil.
With the simultaneous use of valaciclovir with drugs that disrupt the function of the kidneys (including cyclosporine, tacrolimus), kidney function may worsen.
