Valacyclovir Tab n / a film about 500mg 50 pieces Izvarino Pharma

Description

Composition
Active substance:
1 tablet contains: valaciclovir hydrochloride – 556.2 mg (converted to 500.0 mg Valacyclovir).
Excipients:
Microcrystalline Cellulose – 84.3 mg Hypromellose – 42.0 mg Crospovidone – 7.0 mg magnesium stearate – 7.0 mg colloidal silica 3,5 mg. shell tablet: Opadry II White (33G28435) – 25,0 mg (Hypromellose – 40.0%, titanium dioxide – 25.0%, macrogol 3350 – 8.0%, lactose monohydrate – 21.0%, triacetin – 6, 0%).
Description:
Tablets oval, biconvex, film-coated with a white line on one side and engraved “f” to another. A cross section of the core of a white or nearly white.
Product form:
Tablets, film-coated, 500 mg.
10 tablets in blisters made of PVC film and aluminum foil printed patent.
1, 2, 3, 4, 5 or 6, the contour of cellular packaging together with instructions for medical application is placed in a pile of cardboard boxed.
Contraindications
Hypersensitivity to valaciclovir, aciclovir and any other component, part of the drug;
HIV infection in CD4 + lymphocytes content of less than 100 in 1 mm;
Children up to age 12 years;
Children up to age 18 years in the treatment of herpes zoster and ophthalmic zoster.
Carefully
Renal impairment, advanced age, patients at risk of dehydration, concomitant use of nephrotoxic drugs, pregnancy, lactation, symptomatic forms of HIV patients.
Dosage
500 mg
Indications
Adults and adolescents aged 12 to 18 years, treatment of infections of the skin and mucous membranes caused by HSV, including first identified and recurrent genital herpes (Herpes genitalis), as well as labial herpes (Herpes labialis); prevention (suppression) of recurrences of skin infections and mucous membranes caused by HSV, including genital herpes, including adults with immunodeficiency; prophylaxis of infections caused by cytomegalovirus (CMV), and diseases following transplantation of parenchymal organs.
Adults Treatment of shingles (Herpes zoster) and ophthalmic zoster.
Interaction with other drugs
Clinically significant interactions have not been established.
Acyclovir is excreted by the kidneys, in largely unaltered by the active renal secretion. The combined use of drugs with the same mechanism of elimination can lead to increased concentration of acyclovir in plasma.
After assigning Valaciclovir drug in a dose of 1000 mg probenecid and cimetidine, are derived in the same manner as valaciclovir, aciclovir and AUC increased, thus reducing its renal clearance. However, because of the wide therapeutic index of acyclovir, drug dosages Valacyclovir correction in this case is not required.
Care must be taken in the case of simultaneous use of the drug Valaciclovir at higher doses (4000 mg per day or higher) and drugs that compete with acyclovir for road clearance, since there is a potential threat increase in the concentration of blood plasma, one or both drugs or their metabolites . AUC increase was noted acyclovir and inactive metabolite mycophenolate mofetil (immunosuppressant used after organ transplantation) while taking these drugs.
The simultaneous use of valaciclovir with nephrotoxic drugs, including aminoglycosides, organic compounds of platinum, iodinated contrast agent, methotrexate, pentamidine, foscarnet, cyclosporin and tacrolimus, should be carried out with care, particularly in patients with impaired kidney function and require regular monitoring of renal function.
Overdose
symptoms
With an overdose of valacyclovir may cause acute renal failure and the development of neurological symptoms, including confusion, hallucinations, agitation, depression of consciousness and coma, nausea, and vomiting are also marked. To prevent overdose should follow dosing regimen. Many cases of overdose were associated with the use of a drug for treating patients with impaired kidney function and elderly patients due to non-compliance with the dosing regimen (repeatedly received valaciclovir dose exceeding the recommended).
Treatment
Patients subject to careful monitoring for timely diagnosis toxic manifestations. Hemodialysis greatly accelerates the removal of acyclovir from the blood plasma and can be considered an optimal treatment method in the case of overdose.
pharmachologic effect
Pharmacological group:
An antiviral agent.
Pharmacodynamics:
Valaciclovir is the antiviral agent is an L-valine ester of acyclovir. Acyclovir is a nucleoside analogue of a purine (guanine). In humans, valacyclovir is rapidly and almost completely converted to acyclovir and L-valine allegedly under the influence of valatsiklovirgidrolazy enzyme.
Acyclovir in vitro has a specific inhibitory activity against herpes simplex virus (HSV) 1, 2 types (Herpes simplex 1 and 2 types) virus, varicella zoster virus (VZV – varicella-zoster virus, Varicella zoster virus), cytomegalovirus (CMV ), Epstein-Barr virus (EBV) virus and human herpes type 6. Acyclovir inhibits viral DNA synthesis and the phosphorylation immediately after conversion to the active form atsiklovirtrifosfat.
The first stage of phosphorylation takes place with the participation of virus enzymes. For viruses, HSV, VZV and EBV this enzyme is the viral thymidine kinase, which is only present in virus infected cells. Partial selectivity in phosphorylation stored and cytomegalovirus mediated through product phosphotransferase gene UL97. Activation of acyclovir specific viral enzyme largely explains its selectivity.
Acyclovir phosphorylation process (conversion of a mono- triphosphate) is completed by cellular kinases. Atsiklovirtrifosfat competitively inhibits viral DNA polymerase, and being a nucleoside analogue, is incorporated into the viral DNA, which leads to rupture obligate chain termination of DNA synthesis and therefore to block viral replication.
In patients with immunocompetent HSV and VZV with reduced sensitivity to valacyclovir are extremely rare, but can sometimes be found in patients with severely impaired immunity, such as bone marrow transplant patients receiving chemotherapy for malignant tumors and in HIV-infected patients.
Resistance to acyclovir due to deficiency virus thymidine kinase, that leads to excessive proliferation of the virus in the host organism. Sometimes reduction of sensitivity to acyclovir due to the appearance of virus strains with impaired viral thymidine kinase or DNA polymerase structure. The virulence of the virus species resembles that of his wild strain.
Pharmacokinetics:
Suction
After oral administration valaciclovir is well absorbed from the gastrointestinal tract and rapidly and almost completely converted to acyclovir and L-valine. This conversion is catalysed by the enzyme liver – valatsiklovirgidrolazoy.
When receiving a valaciclovir dose of 1000 mg of acyclovir bioavailability is 54% and is independent of food intake. The pharmacokinetics of valaciclovir is dose-rate and extent of absorption decreases with increasing dose, resulting in an increase in the mean maximum concentration (Cmax) in less proportion in a range of therapeutic doses, and also decrease the bioavailability observed at doses above 500 mg. Valaciclovir Cmax in plasma was 4% and the concentration of acyclovir achieved after an average of 30-100 minutes after taking the drug; after 3 h Cmax remains the same or decreases. Valaciclovir and acyclovir have similar pharmacokinetic parameters after single or multiple dose.
Distribution
valaciclovir Binding to plasma proteins is very low (15%). Penetration into the cerebrospinal fluid (CSF), defined as the ratio of AUC in CSF to the AUC in the blood plasma does not depend on renal function and is about 25% for acyclovir and metabolite 8-hydroxy-acyclovir (8-OH-ACV) and about 2 , 5% for metabolite 9- (carboxymethoxy) methylguanine (KMMG).
Metabolism
After oral valacyclovir is converted into acyclovir and L-valine by first-pass metabolism in the intestine and / or liver metabolism. Acyclovir is converted to a small extent into metabolites – 9- (carboxymethoxy) methylguanine with the participation of the alcohol and aldehyde and 8-hydroxy-acyclovir involving aldehyde. Approximately 88% of the combined effects due to plasma acyclovir KMMG 11% and 1% 8-OH-ACV. Neither valaciclovir or acyclovir is not metabolised by cytochrome P450 isozymes system.
breeding
Valaciclovir excreted in the urine, mainly as acyclovir (more than 80% of the dose) and its metabolite KMMG (about 14% of the dose). Metabolite 8-OH-ACV detected in urine only in low amounts (less than 2% of the dose). Less than 1% of an valaciclovir dose excreted by the kidneys in unchanged form. In patients with normal renal function, the half-life of acyclovir from blood plasma after single or repeated application of valaciclovir is approximately 3 hours.
Special patient groups
kidney failure
Excretion of aciclovir is correlated to renal function, and exposure to aciclovir will increase with renal failure. Patients with end-stage renal failure half-life of acyclovir after administration of valacyclovir is on average 14 hours compared with approximately 3 hours at normal renal function.
Effects of acyclovir and its metabolites KMMG and 8-OH-ACV in plasma and cerebrospinal fluid were assessed at steady state after repeated use of valaciclovir in 6 volunteers with normal renal function (mean creatinine clearance 111 ml / min, the range of 91-144 ml / min) receiving 2000 mg every 6 hours, and 3 patients with severe renal failure (creatinine clearance Intermediate 26 ml / min, the range of 17-31 ml / min) receiving 1500 mg every 12 hours. in severe renal insufficiency compared with normal function renal plasma also ka k and cerebrospinal fluid concentration of acyclovir, KMMG and 8-OH-ACV was on average at 2, 4 and 5-6 times higher, respectively.
Liver failure
Pharmacokinetic data indicate that hepatic failure reduces the rate of conversion of valaciclovir acyclovir, but not the extent of the transformation.
Pregnancy and breast-feeding
Pregnancy
There is limited information on the use of valaciclovir and minor details on the use of acyclovir (an active metabolite of valaciclovir) during pregnancy in women. Recorded data on the outcome of pregnancy in women taking valacyclovir or acyclovir, showed no increase in the number of birth defects in their children compared to the general population. Valacyclovir is used only in cases where the potential benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding
Acyclovir, the main metabolite of valaciclovir, is excreted in breast milk. After assigning the valaciclovir 500 mg inwardly Cmax acyclovir in breast milk in 0,5-2,3 times (an average 1.4 times) higher than the corresponding concentration of acyclovir in plasma, maternal blood. The mean value of the concentration of acyclovir in breast milk was 2.24 micrograms / ml (9.95 micromol / L). When receiving the mother valaciclovir 500 mg 2 times a day to the same child is exposed to acyclovir as when administered in a dosage of about 0.61 mg / kg / day. The half-life of acyclovir from breast milk is the same as from the blood plasma.
Valacyclovir in unchanged form was not detected in the plasma of the mother’s blood, breast milk and urine of a child.
The drug Valacyclovir should be used with caution in women during breastfeeding.
Conditions of supply of pharmacies
On prescription.
side effects
frequency category of side effects: very common (> 1/10), common (by> 1/100 to
special instructions
Hydration
In patients at risk of dehydration, especially in elderly patients, in the period of treatment is necessary to ensure adequate fluid replacement.
Use in patients with renal insufficiency and in elderly patients
Because acyclovir is excreted by the kidneys, the dose Valaciclovir should be reduced according to the degree of renal impairment. In patients with renal insufficiency and in elderly patients have an increased risk of neurological complications, these patients must be thoroughly monitored. Typically, these reactions are generally reversible.
The use of high doses of valaciclovir at infringement of the liver and liver transplant
No data on the use of valacyclovir in high doses (4000 mg per day and above) in patients with liver disease, so these patients Valaciclovir high dose should be administered with caution. Special studies on the effect of valaciclovir in liver transplantation have not been conducted. However, it was found that the prophylactic administration of high doses of acyclovir to reduce CMV infection and the manifestation of the disease.
Use in genital herpes
Patients should abstain from sex when symptoms are present even if begun antiviral treatment. Suppressive valacyclovir therapy decreases the risk of transmission of genital herpes, but does not exclude the risk of infection and does not lead to a complete cure. Valaciclovir drug therapy is recommended in conjunction with reliable barrier contraceptive means.
Application of CMV infections
The use of valacyclovir in high doses for the prevention of CMV infections leads to more frequent occurrence of side effects, including disorders of the central nervous system than when used in lower doses for other indications. Careful monitoring of parameters of renal function in those patients with doses adjusted if necessary.
Effects on ability to drive vehicles and mechanisms:
No data on the effect of valacyclovir used in therapeutic doses, the ability to drive vehicles and mechanisms. However, in assessing the patient’s ability to drive a car or moving machinery should be aware that you may experience side effects on the central nervous system, so be careful.
Storage conditions
In the dark place at a temperature not higher than 25 C. Keep out of reach of children.
Dosing and Administration
Inside, regardless of the meal with water.
Treatment of infections of the skin and mucous membranes caused by HSV, including first identified and recurrent genital herpes (Herpes genitalis), as well as labial herpes (Herpes labialis)
Immunocompetent adults and adolescents aged 12 to 18 years
The recommended dose is 500 mg 2 times a day.
In the case of relapse, treatment should continue for 3 or 5 days. In the case of a primary herpes, which can flow more severe, treatment should start as early as possible, and its duration should be increased from 5 to 10 days. At most HSV recurrent appointment is considered the best valaciclovir prodromal period or immediately after the first symptoms. The use of valaciclovir can prevent the development of lesions, if applied at the first signs and symptoms of relapse caused by HSV.
Alternatively, treatment of labial herpes effective assignment valaciclovir 2000 mg 2 times a day for 1 day. The second dose should be taken about 12 hours (but not earlier than 6 hours) after the first dose. By using such dosing regimen duration of treatment should not exceed 1 day, so as exceeding the duration of this treatment does not lead to additional clinical benefits.
Therapy should be initiated with the appearance of the earliest symptoms of herpes labialis (eg tingling, itching, burning).
Prevention (suppression) of recurrences of skin infections and mucous membranes caused by HSV, including genital herpes, including adults with immunodeficiency
Immunocompetent adults and adolescents aged 12 to 18 years
In immunocompetent patients recommended dose is 500 mg 1 time per day.
6-12 months of treatment should be to evaluate the effectiveness of therapy.
Immunocompromised Adults
In adult patients with immunodeficiency recommended dose is 500 mg 2 times a day.
6-12 months of treatment should be to evaluate the effectiveness of therapy.
Prevention of infections caused by CMV, and diseases following transplantation of parenchymal organs
Adults and adolescents aged 12 to 18 years
The recommended dose is 2000 mg four times a day, is assigned as soon as possible after transplantation. The dose should be reduced according to creatinine clearance.
Duration of treatment is usually 90 days, but in patients at high risk of treatment can be extended.
Treatment of shingles (Herpes zoster) and ophthalmic zoster
Adults
The recommended dose is 1000 mg 3 times daily for 7 days.
Special patient groups
Patients with impaired renal function
Valaciclovir dose recommended to reduce in patients with severe renal impairment. These patients need to maintain an adequate fluid and electrolyte balance.
Valacyclovir should be used after dialysis in patients undergoing periodic hemodialysis.
It is often necessary to determine the creatinine clearance, particularly at a time when kidney function is changing rapidly, for example, immediately after transplantation or engraftment, the valaciclovir dose adjusted according to the creatinine clearance.
Patients with impaired liver function
According to reports on the application of single dose valaciclovir 1000 mg, in adult patients with cirrhosis of the light and moderate hepatic (when stored synthetic liver function) correction dose is not required Valaciclovir preparation. Pharmacokinetic data in adult patients with severe liver function abnormalities (decompensated cirrhosis) with impaired liver synthetic function and presence portocaval anastomoses also indicate the need for dose adjustment Valaciclovir drug, but clinical experience with these pathologies limited.
Children under the age of 12 years
There are no data on the use of valaciclovir in children up to 12 years.
Elderly patients
It is necessary to consider the possible impairment of renal function in elderly patients, a dose Valaciclovir drug should be appropriately adjusted. Необходимо поддерживать адекватный водно-электролитный баланс.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist