Acyclovir

General characteristics. Structure:

Active ingredient: 250 mg, 500 mg or 1000 mg of an acyclovir.

Pharmacological properties:

Pharmacodynamics. The acyclovir highly selectively suppresses process of replication of a virus of a herpes simplex (Herpes simplex) of type 1 and 2, a virus of shingles (Varicella zoster), and also Epstein-Burra's virus. The cytomegalovirus is less sensitive to action of an acyclovir.

The molecular and biological mechanism of antiviral activity of an acyclovir is caused by competitive interaction with a virus thymidinekinase and consecutive phosphorylation with education mono - di - and triphosphate. Triphosphate of an acyclovir is built in instead of a deoxyguanosine virus DNA, inhibits a DNA polymerase of the last and suppresses replication process.

Pharmacokinetics. At adults after 1-hour infusion of an acyclovir in doses of 2,5 mg/kg, 5 mg/kg and 10 mg/kg of Css max makes 5,1 mkg/ml, 9,8 mkg/ml and 20,7 mkg/ml, respectively. 7 hours later the indicator of Css min makes 0,5 mkg/ml, 0,7 mkg/ml and 2,3 mkg/ml, respectively.

At newborns and babies aged up to 3 months at introduction of an acyclovir in a dose of 10 mg/kg for one hour with 8-hour intervals of Css max makes 13,8 mkg/ml, Css min makes 2,3 mkg/ml.

The acyclovir gets through hematoencephalic and placental barriers. Concentration of an acyclovir in cerebrospinal liquid makes 50% of its concentration in plasma. It is found in breast milk. In insignificant degree contacts proteins of plasma (9-33%). The main metabolite of an acyclovir is 9-karboksimetoksimetilguanin.

At adults after intravenous administration of an acyclovir plasma elimination half-life makes about 2,9 hours. The most part of drug is removed by kidneys in not changed look and in the form of a 9-karboksimetoksimetilguanin (10-15%). The renal clearance of an acyclovir considerably exceeds clearance of creatinine that demonstrates elimination of drug by glomerular filtering and canalicular secretion. At elderly patients the acyclovir elimination half-life slightly increases.

At patients with a chronic renal failure the elimination half-life of an acyclovir makes 19,5 hours, in case of a hemodialysis – 5,37 hours (at the same time concentration in plasma decreases to 60% of a reference value).

At children aged up to 3 months at administration of drug intravenously kapelno within 1 hour 3 times a day the elimination half-life is equal in a dose of 10 mg/kg 3,8 hours.

Indications to use:

Drug is used at the severe forms of infections of skin and mucous membranes caused by viruses of a herpes simplex of 1 or 2 types (including genital and rectal herpes); for the prevention of infections of skin and mucous membranes caused by viruses of a herpes simplex of 1 or 2 types in patients with disturbances of immune system; as a part of complex therapy of patients with the expressed immunodeficiency, including at the developed clinical picture of HIV infection (number of cells of CD4+ less than 200/mm3), and at the patients who transferred transplantation of marrow; at the infections caused by viruses of the surrounding herpes, chicken pox; for prevention of a Cytomegaloviral infection after transplantation of marrow.

Route of administration and doses:

The adult for treatment of the infections caused by the Herpes Simplex virus of types 1 and 2 at the expressed immunodeficiency including after transplantation of marrow, or disturbance of absorption from intestines, appoint intravenously in a dose 5 mg/kg 3 times a day with an interval of 8 hours.

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

At a herpetic encephalomeningitis each 8 hours (provided that function of kidneys is not broken) enter in a dose 10 mg/kg, treatment should be begun as soon as possible after developing of a disease.

For prevention of the infections caused by the Herpes Simplex virus of types 1 and 2 at the expressed immunodeficiency including after transplantation of marrow, or disturbance of absorption from intestines, appoint intravenously in a dose 5 mg/kg 3 times a day with an interval of 8 hours.

At the infections caused by Varicella zoster 3 times a day with an interval of 8 hours enter intravenously in a dose 5 mg/kg. To patients with an immunodeficiency of a dose increase up to 10 mg/kg each 8 hours (provided that function of kidneys is not broken). Treatment needs to be begun as soon as possible after developing of rash.

For prevention of a Cytomegaloviral infection the drug is administered intravenously in a dose of 500 mg/sq.m by 3 times a day (each 8 hours), for 5 days before transplantation of marrow and within 30 days after transplantation.

As a part of complex therapy at the expressed immunodeficiency by the adult conduct a therapy course an acyclovir intravenously within 1 month, in the subsequent pass to reception of an acyclovir inside.

The maximum dose for adults – 30 mg/kg/days.

To children aged from 3 months up to 12 years usually apply in the dose equal to a half dose to adults (250 mg/sq.m 3 times a day, each 8 hours).

For treatment of the infections caused by Herpes simplex of types 1 and 2 and also for the purpose of prevention of the infections caused by the Herpes simplex virus of types 1 and 2 in children with an immunodeficiency appoint in a dose 250 mg/sq.m 3 times a day (each 8 hours).

For treatment of chicken pox at children применябт in a dose of 250 mg/sq.m 3 times a day (each 8 hours).

For treatment of chicken pox at children with an immunodeficiency and treatments of a herpetic meniigoentsefalit the dose recommended for intravenous administration makes 500 mg/sq.m 3 times a day (each 8 hours) provided that function of kidneys is not broken.

For prevention of a Cytomegaloviral infection at children at the age of 2 years is also more senior the same doses, as for adults are recommended (500 mg/sq.m 3 times a day, each 8 hours, for 5 days before transplantation of marrow and within 30 days after transplantation).

Doses of drug define according to values of clearance of creatinine: at clearance of creatinine of 25-50 ml/min. appoint 5-10 mg/kg or 500 mg/sq.m 2 times a day (each 12 hours), at clearance of creatinine of 10-25 ml/min. appoint 5-10 mg/kg or 500 mg/sq.m of 1 times a day, at clearance of creatinine appoint less than 10 ml/min. on 2,5-5 mg/kg or 250 mg/sq.m of 1 times a day, on condition of carrying out a hemodialysis or continuous out-patient peritoneal dialysis.

Duration of a course of treatment depends on a condition of the patient and the response to the carried-out therapy. The drug is administered intravenously usually for 5 – 7 days. At a herpetic encephalomeningitis duration of a course of treatment makes usually 10 days.

Rules of preparation and administration of infusion solution for intravenous administration

For intravenous administration contents of 1 bottle containing 0,25 g are dissolved in 10 ml of sterile water for injections or in sterile 0,9% chloride sodium solution. Solution can be entered in the form of an injection slowly (within an hour) or to apply kapelno for what the received solution (25 mg in 1 ml) is dissolved in addition in 40 ml of solvent (the total volume of the received solution of 50 ml, contains in 1 ml 5 mg).

For intravenous administration contents of 1 bottle containing 0,5 g are dissolved in 20 ml of sterile water for injections or in sterile 0,9% chloride sodium solution. Solution can be entered in the form of an injection slowly (within an hour) or to apply kapelno for what the received solution (25 mg in 1 ml) is dissolved in addition in 80 ml of solvent (the total volume of the received solution of 100 ml, contains in 1 ml 5 mg).

For intravenous administration contents of 1 bottle containing 1,0 g are dissolved in 40 ml of sterile water for injections or in sterile 0,9% chloride sodium solution. Solution can be entered in the form of an injection slowly (within an hour) or to apply kapelno for what the received solution (25 mg in 1 ml) is dissolved in addition in 160 ml of solvent (the total volume of the received solution of 200 ml, contains in 1 ml 5 mg).

It is necessary to achieve full dissolution of crystals of drug. It is necessary to apply freshly cooked solutions.

Adults in case of use of an acyclovir in doses to 500 mg need to administer the drug in volume of liquid not less than 100 ml. In need of administration of drug in high doses (from 500 mg to 1000 mg) the volume of the entered liquid should be increased.

Intravenous administration is carried out slowly, kapelno, within 1 hour, irrespective of a drug dose. The drug can be administered by means of the injection pump with adjustable giving.

The solution prepared for intravenous administration should be stored at a temperature of 15-25 °C no more than 12 watch. In case of opacification, crystallization at cultivation, introduction or storage, use of solution is excluded.

Features of use:

At pregnancy and a lactation the acyclovir is appointed only according to vital indications; feeding by a breast for treatment is stopped.

At patients with an immunodeficiency emergence of resistance of viruses to an acyclovir, especially in case of carrying out repeated repeated courses of treatment is possible.

Drug is not appointed to children at chicken pox if the disease proceeds benign. Use of an acyclovir for children with normal indicators of immunity for prevention of a recurrence of the infections caused by the Herpes simplex virus and for treatment of the infections caused by a virus of the surrounding herpes is not recommended due to the lack of clinical data.

Purpose of an acyclovir intravenously within 1 month before transplantation of marrow with the subsequent administration of drug inside leads to decrease in a lethality.

During treatment it is necessary to carry out adequate rehydration therapy, especially at elderly patients and at use of high doses of an acyclovir. At elderly patients with a renal failure it is necessary to appoint drug in lower doses.

Drug does not influence ability to manage vehicles and the machine equipment.

Side effects:

At use of drug the headache, increased fatigue, increase in content in blood serum of bilirubin, urea and creatinine, tranzitorny increase in activity of hepatic transaminases, hypostases, a limfoadenopatiya are possible.

In isolated cases neurologic disturbances, drowsiness, nausea, vomiting, diarrhea, intestinal colic can be noted. Skin allergic reactions (quickly pass after drug withdrawal), urticaria, an itch, fever are possible, it is rare - an asthma, a Quincke's disease, an anaphylaxis, a leukopenia, thrombocytopenia. In rare instances (usually at an ekstravazation) emergence of a local inflammation, phlebitis in an injection site is possible.

At course intravenous administration in high doses development of a renal failure is possible.

Side effects from the central nervous system usually have reversible character, are shown preferential at administration of drug in high doses, and also at patients with a renal failure and AIDS.

Interaction with other medicines:

At simultaneous use пробенецид reduces canalicular secretion of an acyclovir and by that increases concentration in a blood plasma and T1/2 of an acyclovir.

At simultaneous use of an acyclovir with nephrotoxic drugs the risk of development of nephrotoxic action increases (especially at patients with an impaired renal function).

Strengthening of effect of an acyclovir is noted at co-administration of immunostimulators.

When mixing solutions it is necessary to consider alkali reaction of an acyclovir for in/in introductions (рН 11).

Contraindications:

Hypersensitivity to an acyclovir and a valatsiklovir; at in introduction - a lactation (breastfeeding).

Issue conditions:

Without recipe

Packaging:

The powder lyophilized for preparation of solution for infusions on 250 mg in bottles with a capacity of 20 ml; on 500 mg or 1000 mg in bottles glass with a capacity of 50 ml or 100 ml, respectively.