Valvir pills p o. 500mg N10
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Valaciclovir
Release form
Pills
Composition
1 tablet contains: Active substances: valaciclovir hydrochloride hydrate - 611.7 mg. Adjuvants: microcrystalline cellulose - 59.6 mg, povidone K30 - 24.5 mg, magnesium stearate - 4.2 mg. Composition of the film shell: white opadry Y-5-7068 (hypromellose 3cP - 7.35 mg, hyprolosis - 6.3 mg, titanium dioxide - 4.2 mg, macrogol / PEG 400 - 2.1 mg, hypromellose 50cP - 1.05 mg) - 21 mg.
Pharmacological effect
Antiviral drug. In humans, valaciclovir is rapidly and completely converted to acyclovir and L-valine under the influence of valacyclovir hydrolase. In vitro acyclovir has a specific inhibitory activity against Herpes simplex types 1 and 2 viruses, Varicella zoster and Epstein-Barr, a cytomegalovirus (CMV) and human herpes virus 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 the viruses Herpes simplex, Varicella zoster and Epstein-Barr, this enzyme is viral thymidine kinase, which is present in virus-infected cells. Partial selectivity of phosphorylation is retained in CMV and is mediated through the UL 97 phosphotransferase gene product. Activation of acyclovir with a specific viral enzyme explains its selectivity to a great extent. The process of phosphorylation of acyclovir (conversion from mono to triphosphate) ends with cell kinases. Acyclovir triphosphate competitively inhibits viral DNA polymerase and, being an analogue of a nucleoside, integrates into viral DNA, which leads to an obligate (complete) breaking of the chain, cessation of DNA synthesis and, therefore, blocking viral replication. In patients with immunity, Herpes simplex viruses and Varicella zoster with reduced sensitivity to valaciclovir is extremely rare (less than 0.1%), but can sometimes be found in patients with severe immunity disorders, for example, with a bone marrow transplant in those receiving chemotherapy. treatment for malignant neoplasms and those infected with HIV. The resistance is caused by a deficiency of thymidine kinase of the virus, which leads to an excessive spread of the virus in the host.Sometimes 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.
Pharmacokinetics
Valacyclovir and acyclovir have similar pharmacokinetic parameters after oral administration. Absorption After oral administration, valacyclovir is well absorbed from the gastrointestinal tract, quickly and almost completely converted into acyclovir and L-valine. This conversion is catalyzed by the enzyme valaciclovirhydrolase, isolated from human liver. After a single dose of 0.25-2 g valaciclovir Cmax acyclovir in healthy volunteers with normal renal function averages 10-37 mcmol / L (2.2-8.3 mcg / ml), and the median time to reach 1-2 h of this concentration. When taking valaciclovir in a dose of 1 g, the bioavailability of acyclovir is 54% and does not depend on food intake. Cmax of valaciclovir in plasma is only 4% of the concentration of acyclovir and is reached on average 30-100 minutes after taking prepa ata; after 3 hours, the Cmax level remains the same or decreases. DistributionThe degree of binding of acyclovir to plasma proteins is very low — about 15%. Acyclovir is rapidly distributed throughout the body’s tissues, especially to the liver, kidneys, muscles, and lungs. It also penetrates the vaginal secretions, cerebrospinal fluid, and herpetic vesicle fluid. Expelling patients with normal renal function T1 / 2 acyclovir after a single dose and repeated use is approximately 3 hours. Valaciclovir is excreted in the urine, mainly in the form of acyclovir (more than 80 % of the dose) and its 9-carboxymethoxymethylguanine metabolite, less than 1% of the drug is excreted unchanged. Pharmacokinetics in special clinical situations in patients with end-stage renal failure T1 / 2 acyclovir comp. approximately 14 hours. The pharmacokinetics of acyclovir are not significantly impaired in patients infected with the Herpes simplex and Varicella zoster viruses, as well as in elderly patients and patients with liver cirrhosis. Patients with severe impaired renal function have a Cmax value of acyclovir approximately 2 times more than with healthy patients and T1 / 2 acyclovir is increased 5 times. Aciclovir, the main metabolite of valaciclovir, is excreted in breast milk.After administration of valacyclovir orally at a dose of 500 mg Cmax of acyclovir in breast milk, 0.5–2.3 times (on average 1.4 times) exceeded its corresponding concentrations in the mother’s plasma. The ratio of AUC of acyclovir, found in breast milk, to AUC of acyclovir in the mother's plasma was 1.4-2.6 (average 2.2). The average concentration of acyclovir in breast milk is 2.24 mcg / ml. When prescribing the mother of valaciclovir at a dose of 500 mg, 2 times a day, the child will be exposed to the same effect 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 is not detected in the plasma of the mother, breast milk, or the baby’s urine. In the late stages of pregnancy, the steady daily AUC after taking 1 g of valaciclovir was about 2 times greater than that when taking acyclovir at a dose of 1.2 g / day. During pregnancy, the pharmacokinetic characteristics of valaciclovir do not change. Taking valaciclovir at a dose of 1 g and 2 g does not disrupt the distribution and pharmacokinetic indicators of valacyclovir in HIV-infected patients compared with healthy individuals. Organ transplant recipients receiving valcyclovir at a dose of 2 g 4 times / day The Cmax of acyclovir is equal to or greater than that of healthy volunteers receiving the same dose of the drug, and their daily AUC values are much higher.
Indications
- treatment of herpes zoster; - treatment and prevention of recurrences of infections of the skin and mucous membranes caused by the herpes simplex virus (including newly diagnosed and recurrent genital herpes); - treatment of labial herpes; - reduction of infection by genital herpes of a healthy partner if taken as a suppressive therapy in combination with safe sex; - prevention of cytomegalovirus infection that occurs during organ transplantation (reduces the severity of the reaction of acute transplant rejection in patients with kidney transplants, the development of opportunistic infections and other viral infections caused by the viruses Herpes simplex and Varicella zoster) in adults and children over 12 years.
Contraindications
- hypersensitivity to valacyclovir, acyclovir and other components of the drug; - clinically expressed forms of HIV infection with a CD4 + lymphocyte content of less than 100 / μl; - bone marrow transplantation; - kidney transplantation; - children's age (up to 12 years with CMV,up to 18 years old - for other indications). With caution in patients with renal insufficiency; in patients with clinically significant forms of HIV infection; while taking nephrotoxic drugs.
Use during pregnancy and lactation
Use during pregnancy is possible if the expected effect of therapy for the mother outweighs the potential risk to the fetus (information about the use during pregnancy is not enough). Aciclovir, the main metabolite of valacyclovir, is excreted in breast milk. With valacyclovir therapy, breastfeeding is possible if the expected effect of therapy for the mother outweighs the potential risk to the baby.
Dosage and administration
The drug is prescribed for adults inside. For herpes zoster, 1000 mg 3 times / day for 7 days. For herpes simplex, 500 mg 2 times / day. In case of relapse, the course should be 3 or 5 days. In the first episode with a severe course, the duration of treatment can be extended up to 10 days (with relapses, it is ideal to prescribe Valvir in the prodromal period or when the first symptoms of the disease appear, ie, tingling, itching, burning). For treatment of labial herpes, the administration of the drug is effective in a dose 2 g 2 times within 1 day: the second dose should be taken approximately 12 hours (but not earlier than 6 hours) after the first dose (do not use this dosing regimen for more than 1 day, because, as shown, this does not give additional clinical pre property). Prevention of recurrence of infections caused by the herpes simplex virus: in patients with preserved immunity - 500 mg 1 time / day; with very frequent relapses (10 or more per year) - 250 mg 2 times / day; for adult patients with immunodeficiency - 500 mg 2 times / day. Course duration - 4-12 months. Prevention of infection with genital herpes of a healthy partner: infected heterosexual adults with preserved immunity and with the number of exacerbations up to 9 per year are prescribed 500 mg 1 time / day for 1 year or more, every day with regular sex life , in case of irregular sexual contacts, Valvir reception should be started 3 days before the intended sexual contact (data on infection prevention in other patient populations are not available). Prevention of cytomegalovirus infection: adults and adolescents over 12 years - 2 g 4 times / day (as soon as possible after transplantation).The course duration is 90 days, but in patients with a high risk, treatment may be longer. Valvir dose is recommended to be reduced in patients with a significant reduction in kidney function. Patients on hemodialysis are advised to use Valvir immediately after the end of the hemodialysis session in the same dose as Patients with QC less than 15 ml / min. Patients on dialysis should be prescribed Valvir after the end of the hemodialysis session. It is often necessary to determine QC, especially during periods when renal function changes rapidly, for example ep immediately after transplant or transplant engraftment. In this case, the dose of Valvira is adjusted in accordance with the indicators of CC. Violation of the liver: with mild and moderate liver cirrhosis (the synthetic function of the liver is preserved), no dose adjustment is required. Pharmacokinetic data in patients with severe cirrhosis of the liver (with impaired synthetic liver function and the presence of shunts between the portal system and the general vascular bed) also do not indicate the need for dose adjustment Valvira, but experience with its clinical use in this pathology is limited. In elderly people dose adjustment not required, with the exception of significant renal dysfunction. It is necessary to maintain an adequate water-electrolyte balance.
Side effects
The most common adverse reactions with valaciclovir are: headache and nausea, more serious adverse reactions: thrombotic thrombocytopenic purpura / hemolytic-uremic syndrome, acute renal failure and neurological disorders. frequency of occurrence: very often (≥ 1/10); often (≥1 / 100 or <1/10); infrequently (≥1 / 1000 or <1/100); rarely (≥1 / 10,000 or <1/1000); very rarely (<1/10 000). From the digestive system: often - nausea; rarely - abdominal discomfort, incl. abdominal pain, vomiting, diarrhea; very rarely - reversible violations of the functional hepatic tests, which are sometimes regarded as manifestations of hepatitis. From the blood and lymphatic system: very rarely - leukopenia (mainly in immunocompromised patients),thrombocytopenia. For the immune system: very rarely - anaphylaxis. For the nervous system and psyche: often - headache; infrequently - agitation, including aggressive behavior; rarely - dizziness, confusion, hallucinations, mental decline; very rarely - agitation, tremor, ataxia, dysarthria, psychotic symptoms, including mania, depression, seizures, encephalopathy, coma. These symptoms are reversible and are usually observed in patients with impaired renal function or on the background of other diseases. In patients with a transplanted organ, receiving valaciclovir in high doses (8 g / day) for the prevention of CMV infection, neurological reactions develop more often than when taken in lower doses. From the side of the respiratory system: rarely - dyspnea. From the skin and subcutaneous cellulose: infrequently - rashes, including manifestations of photosensitivity; rarely - itching. Allergic reactions: 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 (may be associated with impaired renal function). Possible deposition of acyclovir crystals in the lumen of the renal tubules. Adequate drinking regimen must be observed during treatment. Others: in patients with severe immunity disorders, especially in patients with advanced stage of acquired immune deficiency syndrome, receiving valacyclovir in high doses (8 g / day) for a long time, there have been cases of renal failure , microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination). Similar complications were observed in patients with the same diseases, but not receiving valacyclovir. It is not possible to establish the frequency of manifestations of certain adverse reactions. From the sensory organs: impaired vision. From the hematopoietic organs: neutropenia, aplastic anemia, leukoplastic vasculitis, thrombotic thrombocytopenic purpura. On the skin side: erythema multiforme. On the laboratory side: decreased hemoglobin, hypercreatininemia. Other: dismene aurea, arthralgia, nasopharyngitis, respiratory tract infections, swelling of the face, increased blood pressure, tachycardia, fatigue; in addition in children - fever, dehydration, rhinorrhea.
Overdose
Currently, there is insufficient data on overdose with valaciclovir. 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 ingestion of acyclovir for several days, nausea, vomiting, headache, confusion developed in ultra-high doses; with a / in the introduction - an increase in the concentration of serum creatinine, the development of renal failure, confusion, hallucinations, agitation, convulsions, coma. Treatment: patients should be under close medical supervision to identify signs of toxic effects. Hemodialysis significantly enhances the removal of acyclovir from the blood and can be considered the method of choice when managing patients with an overdose of valacyclovir.
Interaction with other drugs
The simultaneous use of valaciclovir 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 require regular monitoring of renal function. There is no clinically significant interaction. 1 g of valaciclovir increases the AUC of acyclovir, reducing its renal clearance (however, dose adjustment of valaciclovir is not required due to the wide therapeutic range acyclovir). Care must be taken in the case of simultaneous use of valacyclovir in high doses (4 g / day) and drugs that compete with acyclovir for the elimination pathway (the latter is eliminated with the urine unchanged as a result of active tubular secretion), since there is a potential the threat of an increase in plasma concentration of one or both drugs or their metabolites. With simultaneous use of acyclovir with mycophenolate mofetil, an increase in the AUC of acyclovir and inactive is noted th metabolite of mycophenolate mofetil.
special instructions
Taking the drug in high doses for a long time in conditions accompanied by severe immunodeficiency (bone marrow transplantation, clinically expressed forms of HIV infection, kidney transplantation) led to the development of thrombocytopenic purpura and hemolytic uremic syndrome, up to a fatal outcome. In case of side effects from the central nervous system (includingagitation, hallucinations, confusion, delirium, seizures and encephalopathy) the drug is canceled. Patients at risk of dehydration, especially for elderly patients, during treatment with Valvir, ensure adequate hydration of the body. Patients with renal insufficiency have an increased risk of developing neurological complications. In patients with impaired liver function, patients with mild or moderate liver cirrhosis (synthetic liver function is preserved) do not require dose adjustment of Valvir. In the study of pharmacokinetics in patients with severe cirrhosis of the liver (with a violation of the synthetic function of the liver and the presence of shunts between the portal system and the general vascular bed), there is also no evidence of the need to correct the dosage regimen; however, clinical experience with the use of the drug Valvir in this category of patients is organic. There is no data on the use of the drug Valvir in high doses (4 g / day or more) in patients with liver diseases, therefore, it should be prescribed with caution in high doses of this category of patients. Elderly patients do not need dose adjustment, except for cases of significant dysfunction the kidneys. It is necessary to maintain an adequate water-electrolyte balance. Special studies have not been conducted to study the effect of Valvir in patients with liver transplants. However, it was shown that prophylactic administration of acyclovir in high doses reduces cytomegalovirus infection. Suppressive therapy with Valvir reduces the risk of transmitting genital herpes, but does not exclude it completely and does not lead to complete cure. During treatment with Valvir, the patient should take measures to ensure the safety of the partner during sexual intercourse. Use in pediatrics There is no experience with clinical use of the drug in children. Effect on the ability to drive vehicles and control mechanisms Care should be taken in case of adverse reactions that affect the speed of psychomotor reactions.