Valtrex 500mg N42 coated pills
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Active ingredients
Valaciclovir
Release form
Pills
Composition
Active ingredient: Valaciclovir (Valaciclovir) Active ingredient concentration (mg): 500
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 varieties of virus resembles that of its wild strain. According to the results of an extensive study of strains of HSV and VZV, taken from patients who received therapy with acyclovir or used it for prevention,It has been found that viruses with reduced sensitivity to valaciclovir are extremely rare, but can be rarely found in patients with severe immunity disorders, for example, bone marrow or organ transplant recipients, patients receiving chemotherapy for malignant neoplasms, and HIV-infected. 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 ve 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
Neurasthenia and neurotic reactions accompanied by irritability, anxiety, fear, fatigue, confusion. Manager’s syndrome (state of constant mental stress). Insomnia (mild forms). Headaches caused by nervous tension. Migraine. Functional diseases of the gastrointestinal tract (dyspeptic syndrome, irritable bowel syndrome). As a symptomatic remedy for neurocirculatory dystonia and menopausal syndrome. Dermatitis (atopic and seborrheic eczema, beer-house), due to psychological stress.
Contraindications
Children under 12 years of age in the prevention of cytomegalovirus (CMV) infection after transplantation; children's age up to 18 years for all other indications; Hypersensitivity to valacyclovir, acyclovir, and any other component that makes up the drug. With caution: in patients with renal insufficiency; patients with clinically significant forms of HIV infection; while taking nephrotoxic drugs; with clinically expressed forms of HIV infection.
Use during pregnancy and lactation
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.
Dosage and administration
It is taken regardless of the meal, the pills should be washed down with water.
Side effects
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.
Overdose
Headache, nausea, anaphylaxis, dizziness, confusion, hallucinations, depression of consciousness; very rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, convulsions, encephalopathy, coma, shortness of breath, abdominal discomfort, vomiting, diarrhea, rashes, including photosensitivity manifestations; itching; urticaria, angioedema.
Interaction with other drugs
Precautionary measures
special instructions
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.