Valtrex tablets 500mg, No. 42

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.

ValtrexЃ can be taken with or without food, the tablets should be taken with water.

Treatment of infections of the skin and mucous membranes caused by HSV, including newly diagnosed and recurrent genital herpes (Herpes genitalis) and labial herpes (Herpes labialis)

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.

In case of recurrence of HSV, the most correct is the appointment of ValtrexЃ in the prodromal period or immediately after the first symptoms of the disease appear. Valacyclovir can prevent lesions when given at the first sign of symptoms of HSV-related recurrence.

As an alternative treatment for labial herpes, the administration of the drug ValtrexЃ at a dose of 2000 mg 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 HSV, including genital herpes, incl. in adults with immunodeficiency

Immunocompetent adults and adolescents aged 12 to 18 years

In immunocompetent patients, the recommended dose is 500 mg 1 time / day. After 6-12 months of treatment, it is necessary to evaluate the effectiveness of therapy.

Immunocompromised Adults

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 CMV and diseases after transplantation of parenchymal organs

Adults and adolescents aged 12 to 18

The recommended dose is 2000 mg 4 times / day, given as early as possible after transplantation. The dose should be reduced depending on the creatinine clearance. The duration of treatment is usually 90 days, but in high-risk patients, treatment may be extended.

Herpes zoster and herpes zoster ophthalmic treatment

Adults

The recommended dose is 1000 mg 3 times / day for 7 days.

Special patient groups

Children

The effectiveness of treatment with ValtrexЃ in children has not been studied.

Elderly patients

It is necessary to take into account the possible impairment of renal function in elderly patients, the dose of ValtrexЃ should be adjusted accordingly. It is necessary to maintain an adequate water and electrolyte balance.

White film-coated tablets, oblong, biconvex, without lines, engraved with 'GX CF1' on one side; the core is white to almost white.

1 tab.

valacyclovir hydrochloride * 556 mg,

which corresponds to the content of valacyclovir 500 mg

Excipients **: microcrystalline cellulose - 70 mg, crospovidone - 28 mg, povidone K90 - 22 mg, magnesium stearate - 4 mg, colloidal silicon dioxide - 2 mg.

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

• children under 12 years of age;

• children under 18 years of age in the treatment of herpes zoster and herpes zoster ophthalmic.

• Precautions: in patients with renal insufficiency; patients with clinically expressed forms of HIV infection; while taking nephrotoxic drugs.

pharmachologic effect

Mechanism of action

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 is a specific inhibitor of herpes viruses with in vitro activity against herpes simplex viruses (Herpes simplex) types 1 and 2, varicella zoster virus (VZV) Varicella zoster, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and the virus human herpes type 6. Acyclovir inhibits the synthesis of viral DNA immediately after phosphorylation and conversion into the active form - acyclovir triphosphate. The first stage of phosphorylation requires the activity of virus-specific enzymes. For HSV,VZV and EBV such an 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. This 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. Acyclovirtriphosphate competitively inhibits viral DNA polymerase and, being a nucleoside analogue, is incorporated into viral DNA, which leads to 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 HSV and VZV strains 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 severely impaired immunity. for example, bone marrow or organ transplant recipients, patients receiving chemotherapy for malignant neoplasms, and HIV-infected individuals.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 digestive system: often - nausea.

Post-marketing research data

On the part of the blood system and hematopoietic organs: 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 (8 g / day) of ValtrexЃ for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses.

From the respiratory system: infrequently - shortness of breath.

From the digestive system: 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 severe immunity disorders, especially in adult patients with advanced stage of HIV infection, receiving high doses of valacyclovir (8 g / day) 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

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 fertility have not been conducted in humans. 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 1000 mg.

Pregnancy

There are limited data on the use of ValtrexЃ during pregnancy. The drug should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Pregnancy registers documented pregnancy outcomes in women who took ValtrexЃ or other drugs containing acyclovir (acyclovir is an active metabolite of ValtrexЃ), 111 and 1246 cases, respectively (of which 29 and 756 took drugs in the first trimester of pregnancy), represented are pregnancy outcomes recorded 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 baby's urine. ValtrexЃ 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.

Application for violations of liver function

In adult patients with mild to moderate liver cirrhosis (with preserved synthetic liver function), dose adjustment is not required. Pharmacokinetic data in adult patients with severe liver dysfunction (decompensated cirrhosis), with impaired liver synthetic function and the presence of portocaval anastomoses also do not indicate the need for dose adjustment, however, clinical experience with these pathologies is limited.

Application for impaired renal function

The drug should be used with caution in patients with renal insufficiency.

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 do not need dose adjustment, except in cases of significant renal dysfunction.

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 ValtrexЃ in patients with impaired renal function. In elderly patients, dysfunction of the nights may be observed, 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 CMV infections and diseases

The use of high doses of ValtrexЃ in case of liver dysfunction and after liver transplantation. There is no data on the use of ValtrexЃ in high doses (4000 mg / day and above) in patients with liver disease, therefore, high doses of ValtrexЃ should be prescribed with caution to such patients. Special studies to study the effect of ValtrexЃ in liver transplantation have not been carried out. However, it was found that prophylactic administration of acyclovir in high doses reduces the manifestations of CMV infection and disease.

Use for genital herpes

Patients should be advised to refrain from sexual intercourse if symptoms are present, even if treatment with the antiviral drug ValtrexЃ has already been started. Suppressive therapy with ValtrexЃ 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. ValtrexЃ therapy is recommended in combination with reliable barrier contraception.

Influence on the ability to drive vehicles and use mechanisms

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

Symptoms: acute renal failure and neurological disorders, including confusion, hallucinations, agitation, depression of consciousness and coma, as well as nausea and vomiting, were observed in patients who received higher than recommended doses of valacyclovir. Such conditions were more often observed in patients with impaired renal function and in elderly patients who received repeated exceeding the recommended doses of valacyclovir due to non-compliance with the dosage regimen. Treatment: patients should be under close medical supervision. Hemodialysis significantly contributes to the elimination of acyclovir from the blood and can be considered the method of choice in the management of patients with an overdose of ValtrexЃ.

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 the drug ValtrexЃ at a dose of 1000 m and the drugs cimetidine and probenecid, which are excreted in the same way as the drug ValtrexЃ, an increase in acyclovir AUC is observed and, thus, the renal clearance of acyclovir decreases. However, due to the wide therapeutic index of acyclovir, dose adjustment of ValtrexЃ is not required. In the treatment of labial herpes, prevention and treatment of diseases caused by CMV,care must be taken in the case of simultaneous use of the drug ValtrexЃ in higher doses (4000 mg / day and above) and drugs that 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. Simultaneous use of ValtrexЃ with nephrotoxic drugs, incl. aminoglycosides, organic platinum compounds, iodinated contrast media, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be handled with caution,especially in patients with impaired renal function, and requires regular monitoring of renal function.