Acуclovir frozen-dried powder 0,25 g, 0,5 gand 1,0 g

For preparation of solution for infusions

Acуclovir 0,25, 0,5 et 1.0 g.

 

International nonproprietary name

Acуclovir.

Acyclovir.

Pharmacotherapeutic group

Antiviral preparations for systemic application. Acуclovir.

Composition of the preparation

1 vial (bottle) contains 0,25 g, either 0,5 gor 1,0 gacуclovir.

Pharmacological action

Pharmacodynamics

Acуclovirhighly selectively inhibits replication process virus of herpes simplex (Herpes simplex) 1 and 2 types, shingles virus (Varicella zoster), and also Epstein-Barra virus. Cytomegalovirus is less sensitive to acyclovir action.

The molecular and biological mechanism of acyclovir antiviral activity is due to competitive interaction with virus thymidine kinase and step-by-step phosphorylation with formation of mono-, di- and triphosphate. Acyclovir triphosphate is built in instead of deoxyguanosine in virus DNA, inhibits DNA-polymerase of the last and suppresses replication process.

Pharmakokinetics

In adults after 1-hour infusion of acyclovir in doses of 2,5 mg/kg, 5 mg/kg and 10 mg/kg Css max is 5,1 mkg/ml, 9,8 mkg/ml and 20,7 mkg/ml, respectively. After 7 hours Css min parameter is 0,5 mkg/ml, 0,7 mkg/ml and 2,3 mkg/ml, respectively.

In newborns and babies in the age under 3 months at introduction of acyclovir in a dose of 10 mg/kg during one hour with 8-hour intervals Css max ish 13,8 mkg/ml, Css min is 2,3 mkg/ml.

Acyclovir passes through hematoencephalic and placental barriers. Acyclovir concentration in cerebrospinal liquid is 50 % of its concentration in plasma. It is found out in breast milk. It binds to a certain extent with plasma proteins (9-33 %). The basic acyclovir metabolite is 9-carboxymethoxymethylguanin.

In adults after acyclovir intravenous introduction the period of half-elimination from plasma is about 2,9 hours. The most part of the preparation is eliminated by kidneys in not changed form and in the form of 9- carboxymethoxymethylguanin (10-15 %). The acyclovir renal clearance considerably exceeds creatinine clearance that testifies about elimination of the preparation by glomerular filtration and tubular secretion. In elderly patients the period of acyclovir half-eliminationis slightly increased. 

In patients with chronic renal failure the period of acyclovir half-elimination is 19,5 hours, in case of hemodialysis is 5,37 hours (thus concentration in plasma decreases up to 60 % from initial value).

In children in the age under 3 months the period of half-elimination is 3,8 hours at introduction of the preparation intravenously dropwisely in a dose of 10 mg/kg within 1 hour 3 times a day.

Indications 

The preparation is indicated at serious forms of skin and the mucosa infections caused by viruses of herpes simplex of 1 or 2 types (including genital and rectal herpes); for prophylaxis of skin and the mucosa infections caused by viruses of herpes simplex of 1 or 2 types in patients with immune system disorders; in structure of complex therapy of patients with the expressed immunodeficiency, including at the developed clinical picture of HIV-infection (number of CD4 + cells  is less than 200/mm3), and in the patients who have endured marrow transplantation; at the infections caused by shingles viruses, chicken pox; for prophylaxis of cytomegalovirus infections after marrow transplantation.

Dosage and method of administration

To the adultsfor treatment of the infections caused by virus Herpes Simplex of 1 and 2types at expressed immunodeficiency, including after marrow transplantation, or intestinal absorption dysfunction should be administrated intravenously in a dose of 5 mg/kg 3 times a day with an interval of 8 hours.

At the infections caused Herpes simplex of 1 and 2 types (except for герпетическогоa meningocephalitis)enter intravenously in a dose of 5 mg/kg 3 times into day with an interval of 8 hours.

At herpetic meningoencephalitis should be administrated  in a dose of 10 mg/kg each 8 hours (provided that function of kidneys is not impaired), treatment should be started as soon as possible after disease onset.

For prophylaxis of the infections caused by Herpes Simplex virus of 1 and 2 types  at expressed immunodeficiency, including after marrow transplantation, or intestinal absorption dysfunction, should be administrated intravenously in a dose of 5 mg/kg 3 times a day with an interval of 8 hours.

At the infections caused by Varicella zoster,should be administrated intravenously in a dose of 5 mg/kg 3 times a day with an interval of 8 hours. The doses are increased to 10 mg/kg each 8 h to patients with immunodeficiency (provided that function of kidneys is not impaired). Treatment is necessary to start as soon as possible after eruption appearance.

Forprophylaxis  of cytomegalovirus infectionsthe preparation should be administrated intravenously in a dose of 500 mg/m23 times a day (each 8 hours), during 5 days before marrow transplantation and within 30 days after transplantation.

In structure ofcomplex therapy at the expressed immunodeficiencythe adults are indicated acyclovir therapy course intravenously during 1 month, further the doses are indicated per orally.

The maximal dose for adults is 30 mg/kg/day.

To the children in the age from 3 months till 12 years the preparation is usually applied in a half dose in comparison with a dose for adults (250 mg/m23 times a day, each 8 hours).

For treatment of the infectionscaused Herpes simplex of 1 and 2 types, and also with the purpose of prophylaxis of infections, caused Herpes simplex virus of 1 and 2types in children with an immunodeficiency, should be administrated in a dose of 250 mg/m23 times a day (each 8 hours).

For treatmentof chicken poxin children should be administrated in a dose of 250 mg/m23 times a day (each 8 hours).

For treatmentof chicken poxin children with an immunodeficiency and treatment ofherpetic meningoencephalitis the dose recommended for intravenous introduction is 500 mg/m23 times a day (each 8 hours) provided that function of kidneys is not impaired.

The same doses as for adults are recommended forprophylaxis of cytomegalovirus infectionsin children in the age of 2 years and elder (500 mg/m23 times a day, each 8 hours, during 5 days before marrow transplantation and within 30 days after transplantation).     

Doses of a preparation are determined in compliance with values of creatinine clearance: at creatinine clearance of 25-50 ml/min 5-10 mg/kg or 500 mg/m22 times a day (each 12 hours) should be indicated, at creatinine clearance of 10-25 ml/min 5-10 mg/kg or 500 mg/m2 1 time a day should be indicated, at creatinine clearance less than 10 ml/min 2,5-5 mg/kg or 250 mg/m2 1 time a day should be indicated, under condition of hemodialysis carrying out or continuous out-patient peritoneal dialysis.

Duration of course of treatment depends on patient condition and response to carried out therapy. The preparation is introduced intravenously usually during 5 - 7 days. At herpetic meningocephalitis duration the course of treatment is usually 10 days.

Rules of infusion solution for intravenous introduction preparation and introduction

For intravenous introduction contentsof 1 vial containing 0,25 g should be dissolved in 10 ml of sterile water for injections or in sterile 0,9 % sodium chloride solution. The solution can be introduced in the form of injection slowly (within an hour) or could be entered dropwisely, for what the received solution (25 mg in 1 ml) is additionally diluted in 40 ml of a solvent (the total volume of the received solution is 50 ml, 5 mg in 1 ml).

For intravenous introduction contentsof 1 vial containing 0,5 g should be dissolved in 20 ml of sterile water for injections or in sterile 0,9 % sodium chloride solution. The solution can be introduced in the form of injection slowly (within an hour) or could be entered dropwisely, for what the received solution (25 mg in 1 ml) is additionally diluted in 80 ml of a solvent (the total volume of the received solution is 100 ml, 5 mg in 1 ml).

For intravenous introduction contentsof 1 vial containing 1,0 g should be dissolved in 40 ml of sterile water for injections or in sterile 0,9 % sodium chloride solution. The solution can be introduced in the form of injection slowly (within an hour) or could be entered dropwisely, for what the received solution (25 mg in 1 ml) is additionally diluted in 160 ml of a solvent (the total volume of the received solution is 200 ml, 5 mg in 1 ml).

It is necessary to achieve full dissolution of the preparation crystals and apply freshly diluted solutions.

In case of acyclovir application in doses up to 500 mg it is necessary for adults to introduce the preparation in volume of a liquid not less than 100 ml. If introductions of the preparation in high doses are necessary (from 500 mg up to 1000 mg) the volume of introduced liquid should be increased.

Intravenous introduction is carried out slowly, dropwisely, within 1 hour, irrespective of a dose of a preparation. The preparation can be entered by means of injection pump with variable delivery.

The solution prepared for intravenous introduction  is necessary to store at a temperature of 15-25°С no more than 12 hours. In case of opacification and crystallization at dilution, introduction or storage the application of the solution is prohibited.

Special indications

At pregnancy and lactation the acyclovir is administrated only under vital indications; breast-feeding  should be stopped a for the period of treatment.

The development if viruses resistance to acyclovir is possible in patients with immunodeficiency, especially in case of treatment repeated courses carrying out.

The preparation should not be administrated to children with chicken pox if disease proceeds in mild form. Acyclovir indication in children with normal parameters of immunity for prophylaxis of relapses of infections caused by Herpes simplex virus, and for treatment of the infections caused by shingles virus is not recommended in connection with clinical data absence.

The acyclovir administration intravenously within 1 month before marrow with the subsequent per orally preparation intake results to lethality decrease.

It is necessary to carry out adequate rehydration therapy during treatment, especially in elderly patients and at application of high acyclovir doses. In elderly patients with renal failure it is necessary to administrate the preparation in lower doses.

 The preparation does not influence on ability to control vehicles and the machine equipment.

Side effects

Headache, undue fatigability, increase of contents bilirubin, urea and creatinine in blood serum, transitional increase of hepatic transaminases activity, edemas, lymphoadenopathy are possible at application of the preparation.

In single cases neurological disturbances, sleepiness, nausea, vomiting, diarrhea, intestinal colic can be noted. Dermal allergic reactions (quickly pass after the preparation canceling), urticaria, itch, fever are possible, in rare cases - dyspnea, Quincke's disease, anaphylaxis, leukopenia, thrombocytopenia. Local inflammation, phlebitis in a place of introduction are possible in rare cases (usually at extravasation).

The development of a renal failure is possible at intravenous introduction in high doses.

Side effects of the central nervous system usually have reversible character, and are shown mainly at introduction of the preparation in high doses, and also in patients with renal failure and AIDS.

Contraindications

Hypersensitivity to acyclovir or valacyclovir.

The form of release

Frozen-driedpowder for preparation of solution for infusions per 0,25 gin 20 ml vials; per 0,5 gor 1,0 gin 50 ml or 100 ml glass bottles, respectively.