Valvir tablets 1000mg, No. 7

Adults and adolescents aged 12 to 18

• treatment of infections of the skin and mucous membranes caused by HSV, including newly diagnosed and recurrent genital herpes (Herpes genitalis), as well as labial herpes (Herpes labialis);

• prevention (suppression) of recurrent infections of the skin and mucous membranes caused by HSV, including genital herpes, incl. in adults with immunodeficiency;

• prevention of infections caused by cytomegalovirus (CMV), and diseases after transplantation of parenchymal organs.

Adults

treatment of herpes zoster (Herpes zoster) and herpes zoster ophthalmic.

The drug is taken orally, regardless of food intake. The tablets should be taken with water.

Treatment of infections of the skin and mucous membranes caused by the herpes simplex virus, including newly diagnosed and recurrent genital herpes, as well as labial herpes.In immunocompetent adults and adolescents aged 12 to 18 years, the recommended dose is 500 mg 2 times / day. In case of relapses, treatment should be continued for 3 or 5 days. In the case of primary herpes, which may be more severe, treatment should be started as early as possible and its duration should be increased from 5 to 10 days.

With relapses of infections caused by the herpes simplex virus, the most correct is the appointment of the drug Valvir in the prodromal period or immediately after the onset of the first symptoms of the disease.

Valacyclovir can prevent the development of the lesion if it is used at the first symptoms of HSV-induced recurrence. As an alternative treatment for labial herpes, the administration of Valvir at a dose of 2 g 2 times / day for 1 day is effective. The second dose should be taken approximately 12 hours (but not earlier than 6 hours) after taking the first dose. When using such a dosage regimen, the duration of treatment should not exceed 1 day, because exceeding the duration of this course of treatment does not lead to additional clinical benefit. Therapy should be started at the earliest symptoms of herpes labialis (i.e., tingling, itching, burning).

Prevention (suppression) of recurrent infections of the skin and mucous membranes caused by the herpes simplex virus, including genital herpes, incl. in adults with immunodeficiency In immunocompetent adults and adolescents aged 12 to 18 years, the recommended dose is 500 mg 1 time / day. After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy. In adult patients with immunodeficiency, the recommended dose is 500 mg 2 times / day. After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy.

Prevention of infections caused by cytomegalovirus and diseases after transplantation of parenchymal organs In adults and adolescents aged 12 to 18 years, the recommended dose is 2 g 4 times / day, prescribed as early as possible after transplantation. The dose should be reduced depending on the QC. The duration of treatment is usually 90 days, but in high-risk patients, treatment may be extended. Treatment of herpes zoster and ophthalmic herpes zoster In adults, the recommended dose is 1 g 3 times / day for 7 days.

Special patient groups

The effectiveness of treatment with Valvir in children has not been studied. It is necessary to take into account the possible impairment of renal function in elderly patients, the dose of Valvir should be adjusted accordingly. It is necessary to maintain an adequate water and electrolyte balance. The dose of Valvir is recommended to be reduced in patients with severe renal impairment.

1 film-coated tablet contains:

active substance: valacyclovir hydrochloride hydrate 611.70 mg or 1223.40 mg, corresponding to 500 mg or 1000 mg of valacyclovir;

excipients: microcrystalline cellulose 59.60 / 119.20 mg, povidone-K30 24.50 / 49.00 mg, magnesium stearate 4.20 / 8.40 mg; film coating: Opadry white Y-5-7068 (hypromellose ZsR 7.35 / 14.7 mg, hyprolose 6.3 / 12.6 mg, titanium dioxide 4.2 / 8.4 mg, macrogol / PEG 400 2.1 / 4.2 mg, hypromellose 50cP 1.05 / 2.1 mg) - 21/42 mg. in a pack of 7, 10, 14, 28 and 42 tablets

• Hypersensitivity to valacyclovir, acyclovir and any other component of the drug;

• children under 12 years of age;

• children and adolescents up to 18 years of age in the treatment of herpes zoster and herpes zoster ophthalmic.

pharmachologic effect

Valacyclovir is an antiviral agent, it is an L-valine ester of acyclovir. Acyclovir is an analogue of a purine nucleoside (guanine). In the human body, valacyclovir is rapidly and almost completely converted into acyclovir and valine, presumably under the influence of the enzyme valacyclovir hydrolase. Acyclovir in vitro has specific inhibitory activity against Herpes simplex viruses types 1 and 2, Varicella zoster and Epstein-Barr, cytomegalovirus and human herpesvirus type 6.

Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion to the active form of acyclovir triphosphate. The first stage of phosphorylation occurs with the participation of virus-specific enzymes. For Herpes simplex, Varicella zoster and Epstein-Barr viruses, this enzyme is viral thymidine kinase, which is present only in cells affected by the virus. In part, the selectivity of phosphorylation is maintained in cytomegalovirus indirectly through the product of the UL97 phosphotransferase gene. The need to activate acyclovir by a specific viral enzyme largely explains its selectivity. The process of phosphorylation of acyclovir (conversion from mono- to triphosphate) is completed by cellular kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being a nucleoside analog, is incorporated into viral DNA,which leads to an obligate chain break, termination of DNA synthesis and, consequently, blocking of viral replication.

Resistance to acyclovir is usually caused by a deficiency of thymidine kinase, which leads to excessive spread of the virus in the host. In rare cases, a decrease in sensitivity to acyclovir is due to the appearance of viral strains with a violation of the structure of viral thymidine kinase or DNA polymerase. The virulence of these variants of the virus resembles that of its wild strain. According to the results of an extensive study of the strains Herpes simplex and Varicella zoster, selected from patients who received therapy with acyclovir or used it for prophylaxis, it was found that viruses with reduced sensitivity to valacyclovir are extremely rare, but can be detected in rare cases in patients with severe disorders immunity, for example, bone marrow or organ transplant recipients,patients receiving chemotherapy for malignant neoplasms, and HIV-infected.

Valacyclovir contributes to the relief of pain syndrome: it reduces its duration and reduces the percentage of patients with pain caused by herpes zoster, including acute postherpetic neuralgia.

Side effect

From the nervous system: often - headache.

From the gastrointestinal tract: often - nausea.

Post-marketing research data

From the hematopoietic system: very rarely - leukopenia, thrombocytopenia. Basically, leukopenia was observed in patients with reduced immunity.

From the immune system: very rarely - anaphylaxis.

From the nervous system and psyche: rarely - dizziness, confusion, hallucinations, depression of consciousness; very rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma. The symptoms listed above are generally reversible and are usually observed in patients with impaired renal function or other predisposing conditions. In adult patients with a transplanted organ receiving high doses of valacyclovir (8 g / day) for the prevention of cytomegalovirus infection, neurological reactions develop more often than when taken at lower doses.

From the respiratory system: infrequently - shortness of breath.

From the gastrointestinal tract: rarely - abdominal discomfort, vomiting, diarrhea.

From the liver and biliary tract: very rarely - reversible violations of liver function tests, which are sometimes regarded as manifestations of hepatitis.

On the part of the skin and subcutaneous fat: infrequently - rashes, including manifestations of photosensitivity; rarely - itching; very rarely - urticaria, angioedema.

From the urinary system: infrequently - hematuria (often associated with other disorders of the kidneys); rarely - impaired renal function; very rarely - acute renal failure, renal colic. Renal colic may be associated with impaired renal function. Cases of precipitation of crystals of acyclovir in the lumen of the renal tubules have been reported. An adequate drinking regime must be observed during treatment.

Others: in patients with severely impaired immunity, especially in adult patients with advanced stage of HIV infection, receiving high doses of valacyclovir (8 g daily) for a long period of time, cases of renal failure, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combinations). Similar complications have been observed in patients with the same underlying and / or concomitant diseases, but not receiving valacyclovir.

Application during pregnancy and lactation

Pregnancy

There are limited data on the use of Valvir during pregnancy. The drug should be used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus. Pregnancy registers documented pregnancy outcomes in women who took valacyclovir or other drugs containing acyclovir (acyclovir is an active metabolite of valacyclovir), 111 and 1246 observations, respectively (of which 29 and 756 were taking drugs in the first trimester of pregnancy), were outcomes pregnancies registered prospectively. Analysis of the data presented in the register of pregnant women exposed to acyclovir did not reveal an increase in the number of birth defects in their children compared to the general population.no specificity or pattern has been identified for any of the malformations indicating a common cause. Since a small number of women who took valacyclovir during pregnancy were included in the register of pregnant women, it is impossible to make reliable and definite conclusions about the safety of using valacyclovir during pregnancy. Breastfeeding Period Acyclovir, the main metabolite of valacyclovir, passes into breast milk. After taking valacyclovir at a dose of 500 mg orally, Cmax in breast milk was 0.5-2.3 times (on average 1.4 times) higher than the corresponding concentrations of acyclovir in the mother's blood plasma. The ratio of AUC values ??of acyclovir in breast milk to AUC in maternal blood serum ranged from 1.4 to 2.6 (mean value 2.2). The average concentration of acyclovir in breast milk was 2.24 ?g / ml (9.95 ?mol / L). When a mother takes valacyclovir at a dose of 500 mg 2 times / day, breastfed infants are exposed to the same effects of acyclovir as when taken orally at a dose of about 0.61 mg / kg / day. T1 / 2 of acyclovir from breast milk is the same as from blood plasma. Valacyclovir in unchanged form was not detected in the mother's blood plasma, breast milk or child's urine. Valacyclovir should be administered with caution to women during breastfeeding. However, IV acyclovir is used for the treatment of HSV in infants at a dose of 30 mg / kg / day.as from blood plasma. Valacyclovir in unchanged form was not detected in the mother's blood plasma, breast milk or child's urine. Valacyclovir should be administered with caution to women during breastfeeding. However, IV acyclovir is used for the treatment of HSV in infants at a dose of 30 mg / kg / day.as from blood plasma. Valacyclovir in unchanged form was not detected in the mother's blood plasma, breast milk or child's urine. Valacyclovir should be administered with caution to women during breastfeeding. However, IV acyclovir is used for the treatment of HSV in infants at a dose of 30 mg / kg / day.

Fertility

In animal studies, valacyclovir did not affect fertility. However, high-dose parenteral acyclovir produced testicular effects in rats and dogs. Studies of the effect of valacyclovir on human fertility have not been conducted. However, there were no changes in the number, motility and morphology of spermatozoa in 20 patients after 6 months of daily use of valacyclovir in doses from 400 mg to 1 g.

Application for violations of liver function

In patients with liver disease, high doses of Valvir should be prescribed with caution.

Application for impaired renal function

Since acyclovir is excreted by the kidneys, it is necessary to reduce the dose of Valvir in patients with impaired renal function.

Application in children

The use of the drug is contraindicated in children under 12 years of age; under the age of 18 - in the treatment of herpes zoster and herpes zoster ophthalmic.

Use in elderly patients

Elderly patients may experience impaired renal function, therefore, a dose reduction for this group of patients should be considered.

special instructions

Hydration

In patients at risk of dehydration, especially in elderly patients, it is necessary to ensure an adequate water-electrolyte balance.

Use in patients with impaired renal function and in elderly patients

Since acyclovir is excreted by the kidneys, it is necessary to reduce the dose of Valvir in patients with impaired renal function. Elderly patients may experience impaired renal function, therefore, a dose reduction for this group of patients should be considered. Both elderly patients and patients with impaired renal function are at increased risk of developing neurological complications, such patients need to ensure careful medical supervision. As a rule, these reactions are mostly reversible if the drug is discontinued. Treatment of labial herpes and prevention of infections and diseases caused by cytomegalovirus Use of Valvir in high doses in case of liver dysfunction and after liver transplantation.There is no data on the use of Valvir in high doses (4 g / day and above) in patients with liver disease, therefore, high doses of Valvir should be prescribed to such patients with caution. Special studies to study the effect of Valvir in liver transplantation have not been carried out. However, it was found that the prophylactic administration of acyclovir in high doses reduces the manifestations of infection and disease caused by cytomegalovirus. Use for genital herpes Patients should be advised to refrain from sexual intercourse if symptoms are present, even if treatment with the antiviral drug Valvir has already been started. Suppressive therapy with Valvir reduces the risk of transmission of genital herpes, but does not completely eliminate the risk of infection and does not lead to a complete cure.Therapy with Valvir is recommended in combination with reliable barrier contraception. Use in pediatrics There is no experience of clinical use of the drug in children.

Influence on the ability to drive vehicles and use mechanisms

Care should be taken in case of the development of adverse reactions affecting the speed of psychomotor reactions. It is necessary to take into account the clinical condition of the patient and the profile of the adverse reactions of valacyclovir when assessing the patient's ability to drive a car or moving machinery.

Overdose

Currently, there are insufficient data on overdose of valacyclovir. Symptoms: a single dose of acyclovir in an overdose of up to 20 g, which was partially absorbed from the gastrointestinal tract, was not accompanied by the toxic effect of the drug. When acyclovir was taken orally for several days in ultrahigh doses, nausea, vomiting, headache, confusion developed; with intravenous administration - an increase in the concentration of serum creatinine, the development of renal failure, confusion, hallucinations, agitation, convulsions, coma. Treatment: Patients should be closely monitored for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and can be considered the method of choice in the management of patients with overdose of valacyclovir.

Drug interactions

No clinically significant interaction has been established. Acyclovir is excreted by the kidneys, mainly unchanged through active renal secretion. The combined use of drugs with this elimination mechanism can lead to an increase in the concentration of acyclovir in plasma. After the appointment of valacyclovir at a dose of 1 g and the drugs cimetidine and probenecid, which are excreted in the same way, an increase in the AUC of acyclovir is observed and, thus, the renal clearance of acyclovir decreases. However, due to the broad therapeutic index of acyclovir, no dose adjustment of valacyclovir is required. In the treatment of labial herpes, the prevention and treatment of diseases caused by cytomegalovirus, care must be taken in the case of the simultaneous use of valacyclovir in higher doses (4 g / day and above) and drugs,which compete with acyclovir for the elimination route, because there is a potential threat of an increase in the plasma concentration of one or both drugs or their metabolites. An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) was observed with the simultaneous use of these drugs. The simultaneous use of valacyclovir with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodine-containing contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.there is a potential threat of an increase in the plasma concentration of one or both drugs or their metabolites. An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) was observed with the simultaneous use of these drugs. The simultaneous use of valacyclovir with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodine-containing contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.there is a potential threat of an increase in the plasma concentration of one or both drugs or their metabolites. An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) was observed with the simultaneous use of these drugs. The simultaneous use of valacyclovir with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodine-containing contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) was observed with the simultaneous use of these drugs. The simultaneous use of valacyclovir with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodine-containing contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.An increase in the AUC of acyclovir and the inactive metabolite of mycophenolate mofetil (an immunosuppressant used in patients after organ transplantation) was observed with the simultaneous use of these drugs. The simultaneous use of valacyclovir with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodine-containing contrast agents, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be used with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.