Composition, structure and packing
The tablets are white, round, biconvex, with the inscription "GXCL3" on one side. 1 tab. Acyclovir 200 mg. Excipients: lactose monohydrate, sodium starch glycolate, povidone K30, magnesium stearate, microcrystalline cellulose.
Clinico-pharmacological group: antiviral drugs.
Pharmacological action
Antiviral drug, a synthetic purine nucleoside analogue, which has the ability to inhibit in vitro and in vivo replication of Herpes simplex virus type 1 and type 2, virus, Varicella zoster, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, aciclovir has the most pronounced antiviral activity against Herpes simplex type 1, followed in descending order of activity follows: Herpes simplex type 2, Varicella zoster, EBV and CMV. Effect of acyclovir is highly selective for viruses in nature. Acyclovir is not a substrate for the enzyme thymidine kinase uninfected cells, so it has low toxicity to mammalian cells.
Thymidine kinase cells infected with Herpes simplex virus types 1 and 2, Varicella zoster, EBV and CMV, converts acyclovir into acyclovir monophosphate - nucleoside analogue, which is then successively converted into diphosphate and triphosphate by the action of cellular enzymes. The inclusion of acyclovir triphosphate in the chain of viral DNA and subsequent chain termination block further replication of viral DNA. In patients with severe immunodeficiency prolonged or repeated courses of therapy with acyclovir may lead to the formation of resistant strains, and therefore further treatment with acyclovir may be ineffective.
Most of the strains with reduced sensitivity to acyclovir had relatively low content of viral thymidine kinase, disturbance of viral thymidine kinase or DNA polymerase. Effects of acyclovir on the strains of the virus Herpes simplex in vitro can also lead to the formation of the less sensitive to it strains. No correlation between the sensitivity of strains of Herpes simplex virus to acyclovir in vitro and clinical efficacy of the drug.
Pharmacokinetics
Absorption
When administered acyclovir is only partially absorbed from the intestine. When receiving 200 mg of acyclovir every 4 h average CSSmax in plasma was 3.1 mmol (0.7 mg / ml), and the average CSSmin - 1.8 mmol (0.4 mg / ml). In the 400 mg and 800 mg of acyclovir every 4 hours CSSmax was 5.3 mmol (1.2 mg / ml) and 8 mmol (1.8 mg / ml), respectively, a medium CSSmin - 2.7 mmol (0.6 mg / ml) and 4 mmol (0.9 mg / ml), respectively.
Distribution
The concentration of acyclovir in 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-karboksimetoksi-methylguanine, which share in the urine accounts for about 10-15% of the administered dose. T1 / 2 of 2.5-3.3 h. Most of the drug appears kidneys unchanged.
Renal clearance of acyclovir significantly higher than creatinine clearance, indicating that the withdrawal of acyclovir not only by glomerular filtration and tubular secretion. When administration of acyclovir at 1 h after administration of 1 g probenecid T1 / 2 and AUC increased by 18 and 40% respectively.
Pharmacokinetics in special clinical situations
Patients with chronic renal insufficiency T1 / 2 of acyclovir averaged 19.5 h during hemodialysis, respectively, 5.7 hours, and the concentration of acyclovir in plasma decreased by approximately 60%. Older people clearance of acyclovir decreases with age in parallel with a reduction in creatinine clearance, but the T1 / 2 of acyclovir varies slightly.
When simultaneous administration of acyclovir and zidovudine for HIV patients pharmacokinetic characteristics of the two drugs remained practically unchanged.
Statement
treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2, including the primary and recurrent genital herpes;
prevention of recurrence of infections caused by Herpes simplex virus types 1 and 2, patients with normal immunnnym status;
prevention of infections caused by Herpes simplex virus type 1 and 2, in immunocompromised patients;
treatment of infections caused by the virus Varicella zoster (chickenpox and herpes zoster);
treatment of patients with severe immunodeficiency, mainly with HIV infection (the number of cells CD4 + <200/mkl), with early clinical manifestations of HIV infection and expanded clinical picture of AIDS) who underwent bone marrow transplantation.
Dosage regimen
Adults for the treatment of infections caused by Herpes simplex virus types 1 and 2, the recommended dose is 200 mg Zoviraks 5 times / day every 4 h (except during nighttime sleep). Typically, treatment is 5 days, but can be extended in cases of severe primary infection.
In marked immunodeficiency (eg, after bone marrow transplantation) or in violation of absorption from the intestine Zoviraks dose for oral administration may be increased to 400 mg 5 times / day. Treatment should begin as soon as possible after the onset of infection, when relapses are encouraged to nominate a drug already in the prodromal period or when the first elements of the rash.
To prevent recurrence of infections caused by Herpes simplex virus types 1 and 2, in patients with normal immune status of the recommended dose of 200 mg Zoviraks 4 times / day (every 6 h),. Many patients fit more convenient treatment regimen: 400 mg 2 times / day (every 12 h). In some cases, are effective, lower doses Zoviraks: 200 mg 3 times / day (every 8 h) or 2 times a day (every 12 h).
Treatment Zoviraks should periodically interrupted by 6-12 months to detect possible changes in the course of the disease. For the prevention of infections caused by Herpes simplex virus type 1 and 2, in immunocompromised patients the recommended dose is 200 mg Zoviraks 4 times / day (every 6 h).
In marked immunodeficiency (eg, after bone marrow transplantation) or in violation of absorption from the intestine Zoviraks dose for oral administration may be increased to 400 mg 5 times / day. The duration of preventive therapy is determined by the duration period of the risk of infection. For the treatment of varicella and herpes zoster Zoviraks recommended dose is 800 mg 5 times / day, a drug taken every 4 h, except for a night's sleep. The treatment course is 7 days. The drug should be administered as soon as possible after the start of infection, because In this case, treatment is more effective. For the treatment of patients with severe immunodeficiency Zoviraks recommended dose is 800 mg 4 times / day (every 6 h).
Patients undergoing bone marrow transplantation, before the appointment Zoviraks inside is usually recommended course / in therapy with acyclovir for 1 month. In clinical trials the maximum duration of treatment of bone marrow transplant recipients was 6 months (from 1 st to 7 th month after transplantation).
In patients with a comprehensive clinical picture of HIV infection treatment Zoviraks was 12 months, but there is reason to believe that such patients may be effective for longer courses of therapy. Treatment and prevention of infections caused by viruses of Herpes simplex, in children with immunodeficiency, aged 2 years and older - the same dose as for adults under the age of 2 years - half adult dose. For the treatment of varicella for children older than 6 years of drug administered in a single dose of 800 mg from 2 to 6 years - 400 mg; under 2 years - 200 mg. Multiplicity receive 4 times per day. More precisely, a single dose can be determined from the rate of 20 mg / kg body weight (but not more than 800 mg). The treatment course is 5 days.
Data on the use Zoviraks to prevent recurrent infections caused by viruses of Herpes simplex, and in the treatment of herpes zoster in children with normal immunity are absent. The evidence is very limited information for the treatment of children older than 2 years with marked immunodeficiency can apply the same dose Zoviraks as for the treatment of adults.
In appointing Zoviraks elderly patients should take into account the possibility of reducing the clearance of acyclovir in parallel with a reduction in creatinine clearance. If signs of renal insufficiency should resolve the issue of reducing the dose Zoviraks.
Elderly patients should receive a sufficient amount of fluid in the intake of Zoviraks inside in high doses. In patients with renal failure receiving acyclovir by mouth in recommended doses to treat and prevent infections caused by viruses of Herpes simplex, did not lead to accumulation of the drug to concentrations exceeding the established safe levels. However, patients with CC <10 mL / min dose Zoviraks recommended to reduce to 200 mg 2 times / day (every 12 h).
For the treatment of varicella, herpes zoster, as well as for the treatment of patients with severe immunodeficiency at QC <10 mL / min recommended dose is 800 mg Zoviraks 2 times / day every 12 h and QA 10-25 ml / min 800 mg 3 times / days every 8 hours Zoviraks pills can be taken with food, because food intake does not affect significantly its absorption. Tablets with a full glass of water.
Side effect
On the part of the digestive system: nausea, vomiting, diarrhea, abdominal pain, rarely - a reversible increase in bilirubin and liver enzymes.
On the part of the hemopoietic system: very rarely - anemia, leukopenia, thrombocytopenia.
From the urinary system: rarely - increasing urea and creatinine in blood, very rarely - acute renal failure.
From the side of the central nervous system: headache, rarely - reversible neurological disorders, such as dizziness, confusion, hallucinations, drowsiness, convulsions, coma. Usually, these side effects were observed in patients with renal insufficiency who took the drug in doses exceeding recommended.
Allergic reactions: rash, photosensitivity, urticaria, pruritus, rarely - shortness of breath, angioedema, anaphylaxis.
Other: fatigue; rarely - fast diffuse hair loss. Since this type of alopecia is observed in various diseases and for the treatment of many drugs, its connection with the reception of acyclovir is not installed.
In patients treated with antiretroviral drugs, extra Zoviraks did not cause significant amplification of toxic effects.
Contraindications
Hypersensitivity to acyclovir or valaciclovir.
With caution is prescribed for dehydration and kidney failure.
Pregnancy and lactation
Appointment Zoviraks during pregnancy and lactation (breastfeeding) requires caution and perhaps only after an assessment of anticipated benefits to the mother and the potential risk to the fetus and child. No increase in the number of birth defects in children whose mothers received Zoviraks during pregnancy, compared with the general population.
After receiving Zoviraks oral dose of 200 mg 5 times / day acyclovir was determined in breast milk in concentrations that make up 0.6-4.1% of plasma concentrations. At these concentrations in breast milk, children who are breastfed may receive acyclovir at a dose of 300 mg / kg / day.
Application for violations of renal function
In patients with renal failure receiving acyclovir by mouth in recommended doses to treat and prevent infections caused by viruses of Herpes simplex, does not lead to accumulation of the drug to concentrations that exceed the established safe levels. However, patients with CC <10 mL / min dose Zoviraks recommended to reduce to 200 mg 2 times / day (every 12 h). For the treatment of varicella, herpes zoster, as well as for the treatment of patients with severe immunodeficiency at QC <10 mL / min recommended dose is 800 mg Zoviraks 2 times / day every 12 h and QA 10-25 ml / min 800 mg 3 times / days every 8 hours
Cautions
Patients who are inside Zoviraks in high doses, should receive plenty of fluids.
Overdose
In case of accidental single dose of acyclovir by mouth in doses up to 20 grams of toxic effects are not registered.
Symptoms: violations of the gastrointestinal tract (nausea, vomiting) and neurological disorders (headache and confusion), sometimes - shortness of breath, diarrhea, renal failure, lethargy, convulsions, coma.
Treatment: careful medical monitoring to detect possible symptoms of intoxication. Perhaps the use of hemodialysis.
Drug Interactions
Clinically significant interactions Zoviraks with other drugs have been noted. Calcium channel blockers and cimetidine increase the AUC of acyclovir and reduce its renal clearance (correct dosing regimen Zoviraks required).
With simultaneous application Zoviraks with drugs that are excreted by active tubular secretion may increase the concentration of active substances or their metabolites in plasma (caution is necessary in the appointment of such combinations). The combined use of acyclovir and mycophenolate mofenila, an immunosuppressant that was used in organ transplantation, resulting in an increase in AUC of acyclovir and the inactive metabolite of mycophenolate mofenila.
Terms and Conditions of storage
List B. preparation should be stored in a dry place inaccessible to children, at a temperature not exceeding 25 ° C. Period of validity - 5 years.
The tablets are white, round, biconvex, with the inscription "GXCL3" on one side. 1 tab. Acyclovir 200 mg. Excipients: lactose monohydrate, sodium starch glycolate, povidone K30, magnesium stearate, microcrystalline cellulose.
Clinico-pharmacological group: antiviral drugs.
Pharmacological action
Antiviral drug, a synthetic purine nucleoside analogue, which has the ability to inhibit in vitro and in vivo replication of Herpes simplex virus type 1 and type 2, virus, Varicella zoster, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, aciclovir has the most pronounced antiviral activity against Herpes simplex type 1, followed in descending order of activity follows: Herpes simplex type 2, Varicella zoster, EBV and CMV. Effect of acyclovir is highly selective for viruses in nature. Acyclovir is not a substrate for the enzyme thymidine kinase uninfected cells, so it has low toxicity to mammalian cells.
Thymidine kinase cells infected with Herpes simplex virus types 1 and 2, Varicella zoster, EBV and CMV, converts acyclovir into acyclovir monophosphate - nucleoside analogue, which is then successively converted into diphosphate and triphosphate by the action of cellular enzymes. The inclusion of acyclovir triphosphate in the chain of viral DNA and subsequent chain termination block further replication of viral DNA. In patients with severe immunodeficiency prolonged or repeated courses of therapy with acyclovir may lead to the formation of resistant strains, and therefore further treatment with acyclovir may be ineffective.
Most of the strains with reduced sensitivity to acyclovir had relatively low content of viral thymidine kinase, disturbance of viral thymidine kinase or DNA polymerase. Effects of acyclovir on the strains of the virus Herpes simplex in vitro can also lead to the formation of the less sensitive to it strains. No correlation between the sensitivity of strains of Herpes simplex virus to acyclovir in vitro and clinical efficacy of the drug.
Pharmacokinetics
Absorption
When administered acyclovir is only partially absorbed from the intestine. When receiving 200 mg of acyclovir every 4 h average CSSmax in plasma was 3.1 mmol (0.7 mg / ml), and the average CSSmin - 1.8 mmol (0.4 mg / ml). In the 400 mg and 800 mg of acyclovir every 4 hours CSSmax was 5.3 mmol (1.2 mg / ml) and 8 mmol (1.8 mg / ml), respectively, a medium CSSmin - 2.7 mmol (0.6 mg / ml) and 4 mmol (0.9 mg / ml), respectively.
Distribution
The concentration of acyclovir in 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-karboksimetoksi-methylguanine, which share in the urine accounts for about 10-15% of the administered dose. T1 / 2 of 2.5-3.3 h. Most of the drug appears kidneys unchanged.
Renal clearance of acyclovir significantly higher than creatinine clearance, indicating that the withdrawal of acyclovir not only by glomerular filtration and tubular secretion. When administration of acyclovir at 1 h after administration of 1 g probenecid T1 / 2 and AUC increased by 18 and 40% respectively.
Pharmacokinetics in special clinical situations
Patients with chronic renal insufficiency T1 / 2 of acyclovir averaged 19.5 h during hemodialysis, respectively, 5.7 hours, and the concentration of acyclovir in plasma decreased by approximately 60%. Older people clearance of acyclovir decreases with age in parallel with a reduction in creatinine clearance, but the T1 / 2 of acyclovir varies slightly.
When simultaneous administration of acyclovir and zidovudine for HIV patients pharmacokinetic characteristics of the two drugs remained practically unchanged.
Statement
treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2, including the primary and recurrent genital herpes;
prevention of recurrence of infections caused by Herpes simplex virus types 1 and 2, patients with normal immunnnym status;
prevention of infections caused by Herpes simplex virus type 1 and 2, in immunocompromised patients;
treatment of infections caused by the virus Varicella zoster (chickenpox and herpes zoster);
treatment of patients with severe immunodeficiency, mainly with HIV infection (the number of cells CD4 + <200/mkl), with early clinical manifestations of HIV infection and expanded clinical picture of AIDS) who underwent bone marrow transplantation.
Dosage regimen
Adults for the treatment of infections caused by Herpes simplex virus types 1 and 2, the recommended dose is 200 mg Zoviraks 5 times / day every 4 h (except during nighttime sleep). Typically, treatment is 5 days, but can be extended in cases of severe primary infection.
In marked immunodeficiency (eg, after bone marrow transplantation) or in violation of absorption from the intestine Zoviraks dose for oral administration may be increased to 400 mg 5 times / day. Treatment should begin as soon as possible after the onset of infection, when relapses are encouraged to nominate a drug already in the prodromal period or when the first elements of the rash.
To prevent recurrence of infections caused by Herpes simplex virus types 1 and 2, in patients with normal immune status of the recommended dose of 200 mg Zoviraks 4 times / day (every 6 h),. Many patients fit more convenient treatment regimen: 400 mg 2 times / day (every 12 h). In some cases, are effective, lower doses Zoviraks: 200 mg 3 times / day (every 8 h) or 2 times a day (every 12 h).
Treatment Zoviraks should periodically interrupted by 6-12 months to detect possible changes in the course of the disease. For the prevention of infections caused by Herpes simplex virus type 1 and 2, in immunocompromised patients the recommended dose is 200 mg Zoviraks 4 times / day (every 6 h).
In marked immunodeficiency (eg, after bone marrow transplantation) or in violation of absorption from the intestine Zoviraks dose for oral administration may be increased to 400 mg 5 times / day. The duration of preventive therapy is determined by the duration period of the risk of infection. For the treatment of varicella and herpes zoster Zoviraks recommended dose is 800 mg 5 times / day, a drug taken every 4 h, except for a night's sleep. The treatment course is 7 days. The drug should be administered as soon as possible after the start of infection, because In this case, treatment is more effective. For the treatment of patients with severe immunodeficiency Zoviraks recommended dose is 800 mg 4 times / day (every 6 h).
Patients undergoing bone marrow transplantation, before the appointment Zoviraks inside is usually recommended course / in therapy with acyclovir for 1 month. In clinical trials the maximum duration of treatment of bone marrow transplant recipients was 6 months (from 1 st to 7 th month after transplantation).
In patients with a comprehensive clinical picture of HIV infection treatment Zoviraks was 12 months, but there is reason to believe that such patients may be effective for longer courses of therapy. Treatment and prevention of infections caused by viruses of Herpes simplex, in children with immunodeficiency, aged 2 years and older - the same dose as for adults under the age of 2 years - half adult dose. For the treatment of varicella for children older than 6 years of drug administered in a single dose of 800 mg from 2 to 6 years - 400 mg; under 2 years - 200 mg. Multiplicity receive 4 times per day. More precisely, a single dose can be determined from the rate of 20 mg / kg body weight (but not more than 800 mg). The treatment course is 5 days.
Data on the use Zoviraks to prevent recurrent infections caused by viruses of Herpes simplex, and in the treatment of herpes zoster in children with normal immunity are absent. The evidence is very limited information for the treatment of children older than 2 years with marked immunodeficiency can apply the same dose Zoviraks as for the treatment of adults.
In appointing Zoviraks elderly patients should take into account the possibility of reducing the clearance of acyclovir in parallel with a reduction in creatinine clearance. If signs of renal insufficiency should resolve the issue of reducing the dose Zoviraks.
Elderly patients should receive a sufficient amount of fluid in the intake of Zoviraks inside in high doses. In patients with renal failure receiving acyclovir by mouth in recommended doses to treat and prevent infections caused by viruses of Herpes simplex, did not lead to accumulation of the drug to concentrations exceeding the established safe levels. However, patients with CC <10 mL / min dose Zoviraks recommended to reduce to 200 mg 2 times / day (every 12 h).
For the treatment of varicella, herpes zoster, as well as for the treatment of patients with severe immunodeficiency at QC <10 mL / min recommended dose is 800 mg Zoviraks 2 times / day every 12 h and QA 10-25 ml / min 800 mg 3 times / days every 8 hours Zoviraks pills can be taken with food, because food intake does not affect significantly its absorption. Tablets with a full glass of water.
Side effect
On the part of the digestive system: nausea, vomiting, diarrhea, abdominal pain, rarely - a reversible increase in bilirubin and liver enzymes.
On the part of the hemopoietic system: very rarely - anemia, leukopenia, thrombocytopenia.
From the urinary system: rarely - increasing urea and creatinine in blood, very rarely - acute renal failure.
From the side of the central nervous system: headache, rarely - reversible neurological disorders, such as dizziness, confusion, hallucinations, drowsiness, convulsions, coma. Usually, these side effects were observed in patients with renal insufficiency who took the drug in doses exceeding recommended.
Allergic reactions: rash, photosensitivity, urticaria, pruritus, rarely - shortness of breath, angioedema, anaphylaxis.
Other: fatigue; rarely - fast diffuse hair loss. Since this type of alopecia is observed in various diseases and for the treatment of many drugs, its connection with the reception of acyclovir is not installed.
In patients treated with antiretroviral drugs, extra Zoviraks did not cause significant amplification of toxic effects.
Contraindications
Hypersensitivity to acyclovir or valaciclovir.
With caution is prescribed for dehydration and kidney failure.
Pregnancy and lactation
Appointment Zoviraks during pregnancy and lactation (breastfeeding) requires caution and perhaps only after an assessment of anticipated benefits to the mother and the potential risk to the fetus and child. No increase in the number of birth defects in children whose mothers received Zoviraks during pregnancy, compared with the general population.
After receiving Zoviraks oral dose of 200 mg 5 times / day acyclovir was determined in breast milk in concentrations that make up 0.6-4.1% of plasma concentrations. At these concentrations in breast milk, children who are breastfed may receive acyclovir at a dose of 300 mg / kg / day.
Application for violations of renal function
In patients with renal failure receiving acyclovir by mouth in recommended doses to treat and prevent infections caused by viruses of Herpes simplex, does not lead to accumulation of the drug to concentrations that exceed the established safe levels. However, patients with CC <10 mL / min dose Zoviraks recommended to reduce to 200 mg 2 times / day (every 12 h). For the treatment of varicella, herpes zoster, as well as for the treatment of patients with severe immunodeficiency at QC <10 mL / min recommended dose is 800 mg Zoviraks 2 times / day every 12 h and QA 10-25 ml / min 800 mg 3 times / days every 8 hours
Cautions
Patients who are inside Zoviraks in high doses, should receive plenty of fluids.
Overdose
In case of accidental single dose of acyclovir by mouth in doses up to 20 grams of toxic effects are not registered.
Symptoms: violations of the gastrointestinal tract (nausea, vomiting) and neurological disorders (headache and confusion), sometimes - shortness of breath, diarrhea, renal failure, lethargy, convulsions, coma.
Treatment: careful medical monitoring to detect possible symptoms of intoxication. Perhaps the use of hemodialysis.
Drug Interactions
Clinically significant interactions Zoviraks with other drugs have been noted. Calcium channel blockers and cimetidine increase the AUC of acyclovir and reduce its renal clearance (correct dosing regimen Zoviraks required).
With simultaneous application Zoviraks with drugs that are excreted by active tubular secretion may increase the concentration of active substances or their metabolites in plasma (caution is necessary in the appointment of such combinations). The combined use of acyclovir and mycophenolate mofenila, an immunosuppressant that was used in organ transplantation, resulting in an increase in AUC of acyclovir and the inactive metabolite of mycophenolate mofenila.
Terms and Conditions of storage
List B. preparation should be stored in a dry place inaccessible to children, at a temperature not exceeding 25 ° C. Period of validity - 5 years.
No comments:
Post a Comment