Valtrex 500mg N10 coated pills
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Valaciclovir
Release form
Pills
Composition
Valaciclovir hydrochloride 556 mg, which corresponds to the content of valaciclovir 500 mg Supplementary substances: microcrystalline cellulose - 70 mg, crospovidone - 28 mg, povidone K90 - 22 mg, magnesium stearate - 4 mg, silicon colloidal dioxide - 2 mg. The composition of the film shell: opadry white - about 14 mg (hypromellose - 9.48 mg, titanium dioxide - 3.26 mg, macrogol 400 - 1.12 mg, polysorbate 80 - 0.14 mg). Composition of polishing: carnauba wax - about 0.016 mg.
Pharmacological effect
Valacyclovir is an antiviral agent, is an L-valine ester of acyclovir. Acyclovir is an analogue of the purine nucleoside (guanine). In the human body, valaciclovir 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 (HSV) (Herpes simplex) 1 and 2, varicella-zoster virus (VZV) Varicella zoster, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpes virus type 6. Acyclovir inhibits the synthesis of viral DNA immediately after f osphorylation and transformation into the active form - acyclovir triphosphate. The first stage of phosphorylation requires the activity of virus-specific enzymes. For HSV, VZV and EBV, this enzyme is viral thymidine kinase, which is present only in the cells affected by the virus. Partial selectivity of phosphorylation is maintained in cytomegalovirus indirectly through the gene product of the phosphotransferase UL97. This need for acyclovir activation 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. Aciclovir triphosphate competitively inhibits viral DNA polymerase and, being an analogue of a nucleoside, is inserted into viral DNA, which leads to an obligate breaking of the chain, stopping the synthesis of DNA and, therefore, blocking viral replication Resistance to acyclovir is usually caused by a deficiency of thymidine kinase, which leads to an excessive spread of the virus in the host.In rare cases, the decrease in sensitivity to acyclovir is due to the appearance of virus strains with a violation of the structure of viral thymidine kinase or DNA polymerase. The virulence of these types of virus resembles that of its wild strain. According to an extensive study of strains of HSV and VZV taken from patients who received acyclovir therapy or used for prophylaxis, it was found that viruses with reduced sensitivity to valacyclovir are extremely rare, but can be rarely found in patients with severe impaired immunity, for example, bone marrow or organ transplant recipients, patients receiving chemotherapy for malignant diseases and HIV-infected neoplasms. Valaciclovir contributes to the relief of pain: reduces its duration and reduces the percentage of patients with pain caused by herpes zoster, including acute postherpetic neuralgia.
Pharmacokinetics
Absorption After oral ingestion, valaciclovir is well absorbed from the gastrointestinal tract, quickly and almost completely turning into acyclovir and valine. This transformation is probably carried out by the enzyme liver valacyclovirhydralase. When taking valacyclovir in a dose of 1000 mg, the bioavailability of acyclovir is 54% and does not decrease from food intake. The pharmacokinetics of valaciclovir is not dose-dependent. The rate and extent of absorption decreases with increasing dose, leading to a less proportional increase in Cmax in plasma but compared with the therapeutic dose range and reduced bioavailability at doses above 500 mg. Distribution Valaciclovir binding to plasma proteins is very low (15%). The degree of penetration into the cerebrospinal fluid (CSF) is defined as the ratio of AUC in CSF to AUC in plasma and is about 25% for acyclovir and 8-hydroxyacyclovir metabolite (8-OH-ACV); about 2.5% for the metabolite 9- (carboxymethoxy) methyl guanine (CMMG). Metabolism After oral administration, valaciclovir is converted to acyclovir and L-valine by means of first-pass metabolism in the intestine and / or liver metabolism. Acyclovir turns into small metabolites: CMMG under the influence of ethyl alcohol and aldehyde dehydrogenase; 8-OH-ACV under the influence of aldehyde oxidase.Approximately 88% of the total cumulative effect on blood plasma accounts for acyclovir, 11% for CMMG and 1% for 8-OH-ACV. Valaciclovir and acyclovir are not metabolized by cytochrome P450 system isoenzymes. Expecting patients with normal renal function T1 / 2 acyclovir from blood plasma after a single or multiple dose of valaciclovir is about 3 hours. Less than 1% of the dose of valacyclovir is eliminated by the kidneys unchanged. Valaniclovir is excreted by the kidneys mainly in the form of acyclovir (more than 80% of the dose taken) and the metabolite of acyclovir - CMMG. Specific patient groups Patients with impaired renal function. Adiclovir excretion correlates with renal function, and exposure to acyclovir increases with increasing severity of renal failure. In patients with end-stage renal disease, the mean T1 / 2 of acyclovir after administration of valacyclovir is about 14 hours compared to about 3 hours with normal renal function. Exposure of acyclovir and its metabolites CMMG and 8-OH-ACV in plasma and CSF was evaluated in a stable condition after repeated administration of valaciclovir in 6 patients with normal renal function (average QA 111 ml / min, range 91-144 ml / min) who received 2000 mg every 6 hours, and in 3 patients with severe renal failure (average QC 26 ml / min, range 17-31 l / min), treated with 1500 mg every 12 hours. With severe renal failure compared with normal renal function in plasma, as well as in CSF, the concentrations of acyclovir, CMMG and 8-OH-ACV were 2, 4 and 5-6 times higher, respectively. There was no difference in the degree of penetration of acyclovir into CSF (defined as the ratio of AUC in CSF to plasma AUC), CMMG or 8-GH-ACV between two populations with severe renal insufficiency and normal renal function. Patients with impaired liver function. Pharmacokinetic data show that in patients with hepatic insufficiency, the rate of conversion of valacyclovir to acyclovir decreases, but not the degree of this transformation. T1 / 2 acyclovir does not depend on liver function. Pregnancy. The study of the pharmacokinetics of valaciclovir and acyclovir in late pregnancy showed an increase in the daily AUC in a stable state with daily intake of valacyclovir at a dose of 1000 mg per day, which is approximately 2 times higher than the AUC when ingesting acyclovir at a dose of 1200 mg per day. Infection .In patients with HIV infection, the distribution and pharmacokinetic characteristics of acyclovir after oral administration of one or more doses of 1000 mg or 2000 mg of valaciclovir remain unchanged compared with healthy volunteers. Organ transplantation. Cmax of acyclovir in patients after transplantation of organs receiving 2000 mg of valaciclovir 4 times / day was comparable or higher than Cmax observed in healthy volunteers who received the same dose. The established daily AUC values can be characterized as markedly higher.
Indications
Adults and adolescents aged 12 to 18 years - 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 the recurrence of skin infections 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 ophthalmic herpes zoster.
Contraindications
- hypersensitivity to valacyclovir, acyclovir and any other component of the drug; - children up to 12 years; - children up to 18 years in the treatment of herpes zoster and ophthalmic herpes zoster. With caution: in patients with renal failure; patients with clinically significant forms of HIV infection; while taking nephrotoxic drugs.
Precautionary measures
Application for violations of renal function When renal failure, the dosing regimen is set depending on creatinine clearance and indications. Use in children Contraindications: - Children under 12 years old - Children under 18 years in the treatment of herpes zoster and ophthalmic shingles Herpes. Use in elderly patientsPatients of the elderly dose adjustment is not required, except in cases of significant renal dysfunction. It is necessary to maintain an adequate water-electrolyte balance.
Use during pregnancy and lactation
Fertility In animal studies, valaciclovir had no effect on fertility.However, the use of high doses of acyclovir when administered parenterally caused testicular effects in rats and dogs. Studies of the effect of valacyclovir on fertility in humans have not been conducted. However, there were no changes in the number, mobility, and morphology of spermatozoa in 20 patients after 6 months of daily use of valaciclovir in doses from 400 mg to 1000 mg. Pregnancy There are limited data on the use of the drug Valtrex during pregnancy. The drug should be used during pregnancy only if the potential benefit to the mother exceeds the potential risk to the fetus. Pregnancy outcomes of women who took Valtrex or other drugs containing acyclovir (acyclovir is an active metabolite of Valtrex), 111 and 1246 observations, respectively (of which 29 and 756 took drugs in the first trimester of pregnancy), were the outcomes of pregnancy, which were 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, nor for any of the malformations revealed specificity or patterns 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 valacyclovir during pregnancy. After taking valaciclovir 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 of acyclovir in breast milk to AUC in maternal serum ranged from 1.4 to 2.6 (mean 2.2). The average concentration of acyclovir in breast milk was 2.24 µg / ml (9.95 µmol / l). When a mother takes valaciclovir at a dose of 500 mg 2 times / day, children who are breastfed are exposed to the same effects of acyclovir as when taken orally at a dose of about 0.61 mg / kg / day.T1 / 2 acyclovir from breast milk is the same as from blood plasma. Valaciclovir in unchanged form was not detected in the mother's blood plasma, breast milk, or the urine of a child. Valtrex should be prescribed with caution to women during breastfeeding. However, acyclovir for iv administration is used to treat HSV in infants at a dose of 30 mg / kg / day.
Dosage and administration
The drug Valtrex can be taken regardless of the meal, the pills should be washed down 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 age from 12 to 18 years. The recommended dose is 500 mg 2 times / day. In case of relapse, treatment should last 3 or 5 days. In the case of primary herpes, which can occur in a more severe form, treatment should begin as early as possible, and its duration should be increased from 5 to 10 days. When recurrent HSV is considered the most correct, the appointment of the drug Valtrex in the prodromal period or immediately after the first symptoms of the disease. The use of valaciclovir can prevent the development of a lesion if it is used at the first sign of symptoms of recurrence caused by HSV. As an alternative treatment for labial herpes, the administration of the drug 2000 mg 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 dosing regimen, the duration of treatment should not exceed 1 day, since exceeding the duration of this treatment does not lead to additional clinical benefits. Therapy should be started when the earliest symptoms of labial herpes appear (ie, tingling, itching, burning). Prevention (suppression) of recurrences of infections of the skin and mucous membranes caused by HSV, including genital herpes, incl. in adults with immunodeficiency immunocompetent adults and adolescents between the ages of 12 and 18 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. Adults with immunodeficiency In adult patients with immunodeficiency are recommended, the 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 years The recommended dose is 2000 mg 4 times a day, is prescribed as soon as possible after transplantation. The dose should be reduced depending on the clearance of creatinine. The duration of treatment is usually 90 days, but in high-risk patients, the treatment can be extended. Treatment of herpes zoster (Herpes zoster) and ophthalmic herpes zoster The Adults Recommended dose is 1000 mg 3 times / day for 7 days. Special patient groups Children Efficiency of Valtrex treatment children were not investigated. Patients of advanced age It is necessary to take into account possible impairment of renal function in elderly patients, the dose of the drug Valtrex should be properly adjusted ektirovana. It is necessary to maintain an adequate water-electrolyte balance. Patients with impaired liver function Based on a study using a single dose of valaciclovir 1000 mg in adult patients with mild or moderate liver cirrhosis (with preserved synthetic liver function), dose adjustment of Valtrex is not required. adult patients with severe abnormal liver function (decompensated cirrhosis), with impaired synthetic liver function and the presence of portocaval Anastomoses also do not indicate the need to adjust the dose of Valtrex, however, clinical experience with these pathologies is limited. Information on doses of more than 4000 mg / day for patients with infections caused by HSV and CMV is indicated in the Special Instructions section.
Side effects
On the part of the nervous system: often - a headache. On the part of the digestive system: often - nausea. Post-marketing research data. On the part of the blood system and blood-forming organs: very rarely - leukopenia, thrombocytopenia. Basically, leukopenia was observed in patients with reduced immunity. For the immune system: very rarely - anaphylaxis. For the nervous system and psyche: rarely - dizziness, confusion, hallucinations, depression of consciousness; very rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma. The above symptoms are mostly reversible and are usually observed in patients with impaired renal function or in comparison with other predisposing conditions.In adult patients with a transplanted organ receiving high doses (8 g / day) of Valtrex for the prevention of CMV infection, neurological reactions develop more often than when taking lower doses. From the respiratory system and mediastinal organs: infrequently - shortness of breath. digestive system: rarely - abdominal discomfort, vomiting, diarrhea. From the side of the liver and biliary tract: very rarely - reversible functional liver function tests, which are sometimes regarded as manifestations of hepatitis. From the skin and subcutaneous o-adipose tissue: rarely - rash, 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 deposition of acyclovir crystals in the lumen of the renal tubules have been reported. Adequate drinking regimen must be observed during treatment. Others: in patients with severe impaired immunity, especially in adult patients with advanced HIV infection, receiving high doses of valacyclovir (8 g / day) for a long period of time, there have been cases of renal failure , microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). Similar complications were noted in patients with the same primary and / or concomitant diseases, but not receiving valacyclovir.
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 doses of valaciclovir higher than recommended. Similar conditions were more common in patients with impaired renal function and elderly patients who received repeated higher than recommended doses of valaciclovir, due to non-compliance with the dosing regimen. Treatment: patients should be under close medical supervision. Hemodialysis contributes significantly to the removal of acyclovir from the blood and can be considered the method of choice when managing patients with an overdose of Valtrex.
Interaction with other drugs
Clinically significant interactions have not been established. Acyclovir is excreted by the kidneys, mostly unchanged through active renal secretion. The combined use of drugs with this mechanism of elimination can lead to an increase in plasma acyclovir concentration. After administering Valtrex at a dose of 1000 m and drugs cimetidine and probenecid, which are eliminated in the same way as Valtrex, an increase in AUC of acyclovir is observed and, thus, , renal clearance of acyclovir decreases. However, due to the wide therapeutic index of acyclovir, dose adjustment of the drug Valtrex is not required. When treating labial herpes, preventing and treating diseases caused by CMV, care must be taken in the case of simultaneous use of the drug Valtrex at higher doses (4000 mg / day and ) and drugs that compete with acyclovir for the route of elimination, since there is a potential threat of an increase in the blood 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 simultaneous use of these drugs. Care must also be taken (monitoring kidney function) with a combination of Valtrex at higher doses (4 g / day and above ) with drugs that affect other kidney functions (for example, cyclosporin, tacrolimus). Simultaneous use of the drug Valtrex with nephrotoxic drugs, including aminoglycosides, platinum organic compounds, iodinated contrast agent, methotrexate, pentamidine, foscarnet, cyclosporine and tacrolimus should be carried out with caution, especially in patients with impaired renal function, and requires regular monitoring of renal function.
special instructions
Hydration Patients at risk of dehydration, especially in elderly patients, need to ensure adequate water and electrolyte balance. Use in patients with impaired renal function and in elderly patients Because acyclovir is eliminated by the kidneys, it is necessary to reduce the dose of the drug Valtrex in patients with impaired renal function.Elderly patients may experience dysfunctional nights, therefore, a dose reduction should be considered for this group of patients. Both elderly patients and patients with impaired renal function are at increased risk of developing neurological complications, such patients should be provided with careful medical supervision. As a rule, these reactions are mainly reversible in the event of drug withdrawal. Treatment of labial herpes and prevention of CMV infections and diseases Use of high doses of the drug Valtrex in violation of the functions of the liver and after liver transplantation. There are no data on the use of the drug Valtrex in high doses (4000 mg / day and above) in patients with liver disease, therefore, such patients high doses of the drug Valtrex should be administered with caution. Special studies on the effect of the drug Valtrex during liver transplantation have not been conducted. However, it was found that prophylactic administration of high doses of acyclovir reduces manifestations of CMV infection and disease. Use in genital herpesPatients should be advised not to have sexual intercourse in the presence of symptoms, even if Valtrex treatment has already been started. Suppressive therapy with Valtrex reduces the risk of transmitting genital herpes, but does not completely eliminate the risk of infection and does not lead to a complete cure. Therapy with Valtrex is recommended in combination with reliable means of barrier contraception. Effect on the ability to drive vehicles and control mechanisms It is necessary to take into account the clinical condition of the patient and the adverse reaction profile of valacyclovir when assessing the patient's ability to drive a car or moving mechanisms.