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Active ingredients
Acyclovir
Release form
Pills
Composition
1 tablet contains: Active ingredient: acyclovir 200 mg. Auxiliary substances: lactose monohydrate, sodium starch glycolate, povidone K30, magnesium stearate, microcrystalline cellulose.
Pharmacological effect
Antiviral drug, a synthetic analogue of the purine nucleoside, which has the ability to inhibit in vitro and in vivo replication of Herpes simplex type 1 and 2 viruses, Varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the most pronounced antiviral activity against Herpes simplex type 1, then in order of decreasing activity follow: Herpes simplex type 2, Varicella zoster, EBV and CMV. The effect of acyclovir on viruses has a highly selective character. Acyclovir is not a substrate for the enzyme thymidine kinase of uninfected cells; therefore, it is of low toxicity to mammalian cells. Thymidine kinase of cells infected with Herpes simplex type 1 and 2 viruses, Varicella zoster, EBV and CMV, turns acyclovir into acyclovir monophosphate, a nucleoside analogue, which is then sequentially converted to diphosphate and triphosphate under the action of cellular enzymes. Inclusion of acyclovir triphosphate in the viral DNA chain and subsequent chain termination block further viral DNA replication. In patients with severe immunodeficiency, long or repeated courses of therapy with acyclovir can lead to the formation of resistant strains, and therefore further treatment with acyclovir can be ineffective. Most of the isolated strains with reduced sensitivity to acyclovir showed a relatively low content of viral thymidine kinase, a violation of the structure of viral thymidine kinase or DNA polymerase. The effect of acyclovir on Herpes simplex virus strains in vitro can also lead to the formation of less sensitive strains. The correlation between the sensitivity of Herpes simplex virus strains to acyclovir in vitro and the clinical efficacy of the drug has not been established.
Pharmacokinetics
Absorption When ingested, acyclovir is only partially absorbed from the intestine. When taking 200 mg of acyclovir every 4 hours, the average CSSmax in plasma was 3.1 μmol (0.7 μg / ml) and the average CSSmin was 1.8 μmol (0.4 μg / ml). When taking 400 mg and 800 mg of acyclovir every 4 hours, CSSmax was 5.3 μmol (1.2 μg / ml) and 8 μmol (1.8 μg / ml), respectively, and the average CSSmin was 2.7 μmol (0.6 μg / ml) and 4 μmol (0.9 μg / ml), respectively. Distribution The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its plasma concentration.Acyclovir to a small extent (9-33%) binds to plasma proteins. Metabolism and excretion The main metabolite of acyclovir is 9-carboxymethoxy-methylguanine, which accounts for about 10-15% of the administered dose in the urine. 2.5 / 3.3 hours Most of the drug is excreted by the kidneys in unchanged form. The renal clearance of acyclovir significantly exceeds creatinine clearance, which indicates the removal of acyclovir not only by means of glomerular filtration, but also by tubular secretion. When prescribing acyclovir 1 h after ingestion, 1 g of probenecid T1 / 2 and AUC increased by 18 and 40%, respectively. Pharmacokinetics in special clinical cases of patients with chronic renal failure T1 / 2 acyclovir averaged 19.5 h; during hemodialysis, respectively, 5.7 hours, and the concentration of acyclovir in plasma decreased by approximately 60%. In older people, the clearance of acyclovir decreases with age, along with a decrease in creatinine clearance, however, T1 / 2 of acyclovir changes slightly. in patients, the pharmacokinetic characteristics of both drugs remained virtually unchanged.
Indications
Acute and chronic diarrhea (diarrhea); regulation of stool in patients with ileostomy.
Contraindications
Zovirax is contraindicated in case of hypersensitivity to acyclovir or valacyclovir. Zovirax should be used with caution in dehydration and renal failure. Zovirax in tablet dosage form is not used in children under 3 years of age.
Use during pregnancy and lactation
Appointment of Zovirax during pregnancy and lactation (breastfeeding) requires caution and is possible only after assessing the intended benefits to the mother and the potential risk to the fetus and child. There is no increase in the number of birth defects in children whose mothers received Zovirax during pregnancy, compared to with the general population. After ingestion of Zovirax orally at a dose of 200 mg 5 times / day, acyclovir was determined in breast milk at concentrations of 0.6–4.1% of plasma concentrations. At such concentrations in breast milk, babies who are breastfed can receive acyclovir at a dose of up to 300 mcg / kg / day.
Dosage and administration
Zovirax pills can be taken with meals, since eating does not significantly affect its absorption. Tablets should be taken with a full glass of water. Adults Treatment of infections caused by the herpes simplex virus For the treatment of infections caused by the herpes simplex virus, the recommended dose of Zovirax is 200 mg 5 times a day every 4 hours, except during the nighttime sleep. Usually, the course of treatment is 5 days, but it can be prolonged with severe primary infections. In case of severe immunodeficiency (for example, after bone marrow transplantation) or if the intestinal absorption is impaired, the dose of Zovirax for oral administration can be increased to 400 mg 5 times a day . Treatment should begin as soon as possible after the onset of infection; in case of relapses, it is recommended to prescribe it in the prodromal period or when the first elements of the rash appear. Prevention of recurrence of infections caused by the herpes simplex virus day (every 6 hours). A more convenient 400 mg regimen 2 times a day (every 12 hours) is suitable for many patients. In some cases, lower doses of the drug are effective that Zovirax 200 mg 3 times a day (every 8 hours) or 2 times a day (every 12 hours). In some patients, interruption of infection may occur when taking a total daily dose of 800 mg. Treatment with Zovirax should be periodically interrupted for 6-12 months to identify possible changes in the course of the disease. Prevention of infections caused by the herpes simplex virus in immunocompromised patients: For the prevention of infections, caused by the herpes simplex virus, in immunocompromised patients, the recommended dose of Zovirax is 200 mg 4 times a day (every 6 hours). In case of marked immunodeficiency (for example, measures, after bone marrow transplantation) or in violation of the absorption from the intestine, the dose of Zovirax for oral administration can be increased to 400 mg 5 times a day. The duration of the prophylactic course of therapy is determined by the duration of the period when there is a risk of infection. Treatment of chicken pox and herpes zoster: For the treatment of chicken pox and herpes zoster, the recommended dose of Zovirax is 800 mg 5 times a day; the drug is taken every 4 hours, except during the period of night sleep. The course of treatment is 7 days.The drug should be prescribed as soon as possible after the start of infection, as in this case the treatment is more effective. Treatment of patients with severe immunodeficiency: For treatment of patients with severe immunodeficiency, the recommended dose of Zovirax is 800 mg 4 times a day (every 6 hours). Patients who have undergone bone marrow transplantation, before prescribing Zovirax for oral administration, it is usually recommended to conduct a course of intravenous therapy with Zovirax for 1 month. When conducting clinical studies The maximum duration of treatment for bone marrow transplant recipients was 6 months (from the 1st to the 7th month after transplantation). Patients with an expanded clinical picture of HIV infection treated with Zovirax for 12 months, but there is reason to believe that longer courses of therapy may be effective in such patients. Children aged 3 years and older Treatment and prevention of infections caused by the herpes simplex virus , in children with immunodeficiency and normal immune status: 3 years and older - the same doses as for adults; Treatment of chickenpox older than 6 years - 800 mg 4 times a day, from 3 to 6 years - 400 mg 4 times a day; More precisely the dose can limit the rate of 20 mg / kg body weight (but not more than 800 mg) 4 times per day. The course of treatment is 5 days. There are no data on preventing the recurrence of infections caused by the herpes simplex virus and the treatment of herpes zoster in children with normal immunity indicators. There is limited treatment of children with marked immunodeficiency According to very limited information, for the treatment of children over 3 years old with with a pronounced immunodeficiency, the same doses of Zovirax can be used as for the treatment of adults with immunodeficiency (i.e. 800 mg 4 times a day every 6 hours). Sulfur age causes a decrease in the clearance of acyclovir in the body in parallel with a decrease in creatinine clearance. Elderly patients should receive a sufficient amount of fluid while receiving high doses of Zovirax orally, in case of renal failure they need to resolve the issue of reducing the dose of Zovirax. Patients with renal insufficiency use caution when prescribing Zovirax to patients with renal insufficiency. Patients with renal insufficiency receive acycles Dr. orally in recommended doses for the treatment and prevention of infections caused by the herpes simplex virus,does not lead to cumulation of the drug to concentrations in excess of the established safe levels. However, in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), it is recommended to reduce the dose of Zovirax to 200 mg 2 times a day (every 12 hours). When treating varicella, herpes zoster, and in the treatment of patients with severe immunodeficiency, the recommended doses of Zovirax are: severe renal failure (creatinine clearance less than 10 ml / min) 800 mg 2 times a day every 12 hours, moderate renal failure (creatinine clearance 10-25 ml / min) 800 mg 3 times a day every 8 hours
Side effects
The following classification of undesirable reactions depending on the frequency of occurrence was used: very often (more than 1/10), often (more than 1/100, less than 1/10), sometimes (more than 1/1000, less than 1/100), rarely (more than 1 / 10,000, less than 1/1000 ), very rarely (less than 1 / 10,000). From the side of hematopoiesis and lymphatic system: Very rarely: Anemia, leukopenia, thrombocytopenia. From the immune system: Rarely: Anaphylaxis. Mental status: Often: Headache, dizziness. Very rarely: Excitement, confusion consciousness, tremor, ataxia, dysarthria, hallucin tion, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma. Usually, these side effects were observed in patients with renal insufficiency or in the presence of other provoking factors, were mostly reversible. On the part of the respiratory system, chest organs and mediastinum: Rarely: Dyspnea. On the part of the gastrointestinal tract: Often: Nausea, vomiting, diarrhea, abdominal pain. From the side of the liver and biliary tract: Rarely: Reversible increase in bilirubin and liver enzymes in the blood. Very rarely: Hepatitis, jaundice. On the skin and subcutaneous tissue: Often: Itching, rash, including photosensitization. Sometimes: Urticaria, rapid diffuse hair loss. Because this type of alopecia is observed in various diseases and with many drugs, its connection with the use of acyclovir has not been established. Rare: Angioedema levels of urea and creatinine in the blood. Very rarely: Acute renal failure, renal colic. Renal colic may be associated with renal insufficiency. atochnostyu.Drugie: Common: Fatigue, fever.
Overdose
In case of a single dose of acyclovir ingested in doses of up to 20 g, no toxic effects were recorded. Symptoms: disorders of the gastrointestinal tract (nausea, vomiting) and neurological disorders (headache and confusion); sometimes - shortness of breath, diarrhea, renal dysfunction, lethargy, convulsions, coma. Treatment: careful medical observation to identify possible symptoms of intoxication. Perhaps the use of hemodialysis.
Interaction with other drugs
No clinically significant interactions of Zovirax with other drugs were noted. Calcium channel blockers and cimetidine increase AUC of acyclovir and reduce its renal clearance (correction of Zovirax dosing regimen is not required). With simultaneous use of Zovirax with drugs eliminated by active tubular secretion, it is possible to increase active substances or their metabolites in plasma (caution is needed in the appointment of such combinations). The combined use of acyclovir and mycophenolate mofenila, immunosuppressant employed during organ transplantation, increases the parameter AUC of acyclovir and mycophenolate mofenila inactive metabolite.
special instructions
Patients taking Zovirax in high doses should receive a sufficient amount of liquid.