Tablet zovirax

General characteristics. Structure:

Tablets are white, round, biconvex, with a text of "GXCL3" on the one hand.

Active ingredient: acyclovir of 200 mg

Excipients: lactoses monohydrate, starch sodium glycollate, K30 povidone, magnesium stearate, cellulose microcrystallic.

Pharmacological properties:

Antiviral drug, synthetic analog of a purine nucleoside which possesses ability to inhibit in vitro and in vivo replication of the Herpes simplex viruses of type 1 and 2, the Varicella zoster virus, Epstein-Burra's (EBV) virus and a cytomegalovirus (CMV). In culture of cells the acyclovir has the most expressed antiviral activity concerning Herpes simplex of type 1, further in decreasing order of activity follow: Herpes simplex of type 2, Varicella zoster, EBV and CMV.

Action of an acyclovir on viruses has high-selective character. The acyclovir is not substrate for enzyme of a thymidinekinase of not infected cells therefore it малотоксичен for cells of mammals. The thymidinekinase of the cells infected with the Herpes simplex viruses of type 1 and 2, Varicella zoster, EBV and CMV turns an acyclovir in an acyclovir monophosphate - an analog of a nucleoside which then consistently turns into diphosphate and triphosphate under the influence of cellular enzymes. Inclusion of an acyclovir of triphosphate in a chain of virus DNA and the subsequent break of a chain block further replication of virus DNA.

At patients with the expressed immunodeficiency long or repeated courses of therapy by an acyclovir can lead to formation of resistant strains and therefore further treatment by an acyclovir can be inefficient. At the majority of the allocated strains with a hyposensitivity to an acyclovir rather low maintenance of a virus thymidinekinase, disturbance of structure of a virus thymidinekinase or DNA polymerase was noted. Impact of an acyclovir on virus strains of Herpes simplex in vitro can also lead to formation of strains, less sensitive to it. Correlation between sensitivity of virus strains of Herpes simplex to an acyclovir in vitro and clinical performance of drug is not established.

 

Pharmacokinetics. Absorption

At intake the acyclovir is only partially absorbed from intestines. At reception of 200 mg of an acyclovir each 4 h average CSSmax in plasma made 3.1 µmol (0.7 mkg/ml), and average CSSmin - 1.8 µmol (0.4 mkg/ml). At reception of 400 mg and 800 mg of an acyclovir 5.3 µmol (1.2 mkg/ml) and 8 µmol (1.8 mkg/ml) respectively, an average CSSmin - 2.7 µmol (0.6 mkg/ml) and 4 µmol (0.9 mkg/ml) respectively made each 4 hours of CSSmax.

Distribution

Concentration of an acyclovir in cerebrospinal fluid makes about 50% of its plasma concentration. The acyclovir in insignificant degree (9-33%) contacts proteins of a blood plasma.

Metabolism and removal

The main metabolite of an acyclovir is the 9-карбоксиметокси-methylguanine to which share in urine about 10-15% of the entered drug dose fall.

T1/2 makes 2.5-3.3 h. The most part of drug is removed by kidneys in not changed look. The renal clearance of an acyclovir considerably exceeds clearance of creatinine that demonstrates removal of an acyclovir not only by means of glomerular filtering, but also canalicular secretion. At purpose of an acyclovir in 1 h after reception of 1 g of a probenetsid of T1/2 and AUC increased by 18 and 40% respectively.

Pharmacokinetics in special clinical cases

At patients with a chronic renal failure of T1/2 of an acyclovir averaged 19.5 h; when carrying out a hemodialysis respectively 5.7 h, and concentration of an acyclovir in plasma decreased approximately by 60%.

At elderly people the clearance of an acyclovir decreases in parallel with decrease in clearance of creatinine with age, however T1/2 of an acyclovir changes slightly.

At simultaneous introduction of an acyclovir and zidovudine to HIV-positive patients pharmacokinetic characteristics of both drugs practically did not change.

Indications to use:

— treatment of infections of skin and the mucous membranes caused by the Herpes simplex virus of type 1 and 2 including primary and recurrent genital herpes;

— prevention of a recurrence of the infections caused by the Herpes simplex virus of type 1 and 2 at patients with the normal immune status;

— prevention of the infections caused by the Herpes simplex virus of type 1 and 2 at patients with an immunodeficiency;

— treatment of the infections caused by the Varicella zoster virus (chicken pox and the surrounding herpes);

— treatment of patients with a heavy immunodeficiency, mainly with HIV infection (number of cells of CD4+<200/мкл), with early clinical displays of HIV infection and with the developed clinical picture AIDS), transferred transplantation of marrow.

Route of administration and doses:

The adult for treatment of the infections caused by the Herpes simplex virus of type 1 and 2, the recommended dose of Zovirax makes 200 mg of 5 times / each 4 h (except for the period of a night dream). Usually the course of treatment makes 5 days, but can be prolonged at heavy primary infections.

At the expressed immunodeficiency (for example, after transplantation of marrow) or at disturbance of absorption from intestines the Zovirax dose for intake is increased to 400 mg the 5th time / Treatment needs to be begun as soon as possible after developing of an infection; at a recurrence it is already recommended to appoint drug in a prodromal stage or at emergence of the first elements of rash.

For prevention of a recurrence of the infections caused by the Herpes simplex virus of type 1 and 2 at patients with the normal immune status the recommended dose of Zovirax makes 200 mg 4 (each 6 h). Many patients suit more convenient scheme of therapy: on 400 mg 2 (each 12 h). In some cases there are effective lower doses of Zovirax: on 200 mg 3 (each 8 h) or 2 (each 12 h). Treatment by Zovirax should be interrupted periodically for 6-12 months for identification of possible changes during a disease.

For prevention of developing of the infections caused by the Herpes simplex virus of type 1 and 2 at patients with an immunodeficiency the recommended dose of Zovirax makes 200 mg 4 (each 6 h). At the expressed immunodeficiency (for example, after transplantation of marrow) or at disturbance of absorption from intestines the Zovirax dose for intake can be increased to 400 mg of 5 times/Duration of a preventive course of therapy is defined by duration of the period of existence of risk of infection.

For treatment of chicken pox and the surrounding herpes the recommended dose of Zovirax makes 800 mg of 5 times/, drug is accepted by each 4 h, except for the period of a night dream. The course of treatment makes 7 days.

It is necessary to appoint drug as soon as possible after the beginning of an infection since in this case treatment is more effective.

For treatment of patients with the expressed immunodeficiency the recommended dose of Zovirax makes 800 mg 4 (each 6 h).

The patients who transferred transplantation of marrow before purpose of Zovirax inside are usually recommended to conduct a course in/in therapy by an acyclovir within 1 month. At conduct of clinical trials the maximum duration of a course of treatment of recipients of a transplant of marrow made 6 months (from 1st to the 7th month after transplantation). At patients with the developed clinical picture of HIV infection the course of treatment Zovirax made 12 months, however there are bases to believe that at such patients more long courses of therapy can be effective.

Treatment and prevention of the infections caused by the Herpes simplex viruses at children with an immunodeficiency aged from 2 years are also more senior - the same doses, as for adults; 2 years - a half of a dose for adults are aged younger.

For treatment of chicken pox to children 6 years drug are more senior appoint 800 mg in a single dose; from 2 to 6 years - 400 mg; 2 years - 200 mg are younger. Frequency rate of reception 4 More precisely a single dose can be defined at the rate of 20 mg/kg of body weight (but no more than 800 mg). The course of treatment makes 5 days.

Data on use of Zovirax for prevention of a recurrence of the infections caused by the Herpes simplex viruses and at treatment of the surrounding herpes at children with normal indicators of immunity are absent.

According to the available very limited data for treatment of children 2 years with the expressed immunodeficiency are more senior it is possible to apply the same doses of Zovirax, as to treatment of adults.

At purpose of Zovirax patients of advanced age should consider a possibility of decrease in clearance of an acyclovir in parallel with decrease in clearance of creatinine. In the presence of symptoms of a renal failure it is necessary to resolve an issue of the Zovirax dose decline. Patients of advanced age have to receive enough liquid against the background of Zovirax reception inside in high doses.

Patients with a renal failure have a reception of an acyclovir inside in the recommended doses for the purpose of treatment and prevention of the infections caused by the Herpes simplex viruses is not led to cumulation of drug to the concentration exceeding the established safe levels. However at patients with KK less than 10 ml/min. a dose of Zovirax are recommended to be reduced to 200 mg 2 (each 12 h). For treatment of chicken pox, the surrounding herpes, and also for treatment of patients with the expressed immunodeficiency at KK less than 10 ml/min. the recommended doses of Zovirax make 800 mg 2 each 12 h; at KK of 10-25 ml/min. 800 mg 3 each 8 h.

Zovirax of a tablet can be accepted during food as meal does not break substantially its absorption. Tablets should be washed down with a full glass of water.

Features of use:

The patients accepting inside Zovirax in high doses have to receive enough liquid.

Side effects:

From the alimentary system: nausea, vomiting, diarrhea, abdominal pains; seldom - reversible increase in level of bilirubin and activity of liver enzymes.

From system of a hemopoiesis: very seldom - anemia, a leukopenia, thrombocytopenia.

From an urinary system: seldom - increase in level of urea and creatinine in blood; very seldom - an acute renal failure.

From TsNS: headache; seldom - reversible neurologic disturbances, such as dizziness, confusion of consciousness, a hallucination, drowsiness, spasms, a coma. Usually these side effects were observed at patients with a renal failure who accepted drug in the doses exceeding recommended.

Allergic reactions: rash, photosensitization, urticaria, itch; seldom - an asthma, a Quincke's disease, an anaphylaxis.

Others: bystry fatigue; seldom - a bystry diffusion hair loss. As such type of an alopecia is observed at various diseases and at therapy by many medicines, its connection with reception of an acyclovir is not established.

At the patients receiving anti-retrovirus drugs, additional reception of Zovirax did not cause significant strengthening of toxic effects.

Interaction with other medicines:

Clinically significant interactions of Zovirax with other medicines were not noted.

Blockers of calcium channels and Cimetidinum increase AUC of an acyclovir and reduce its renal clearance (correction of the mode of dosing of Zovirax is not required).

At simultaneous use of Zovirax with the drugs which are removed by active canalicular secretion increase in concentration of active agents or their metabolites in plasma is possible (care at purpose of such combinations is necessary).

The combined use of an acyclovir and mikofenolat of a mofenil, the immunosuppressant which is applied at organ transplantation leads to increase in an indicator of AUC of an acyclovir and inactive metabolite of a mikofenolat of a mofenil.

Contraindications:

— hypersensitivity to an acyclovir or a valatsiklovir.

With care appoint at dehydration and a renal failure.

Tablet drug ZOVIRAKS® use at pregnancy and feeding by a breast
Purpose of Zovirax at pregnancy and in the period of a lactation (breastfeeding) demands care and it is possible only after assessment of estimated advantage for mother and potential risk for a fruit and the child.

Increase in number of inborn defects at children whose mothers received Zovirax during pregnancy, in comparison with the general population is not revealed.

After Zovirax reception inside in a dose of 200 mg the 5th time / acyclovir was defined in breast milk in the concentration making 0.6-4.1% of plasma concentration. At such concentration in breast milk the children who are on breastfeeding can receive an acyclovir in a dose to 300 mkg/kg /

Use at renal failures
Patients with a renal failure have a reception of an acyclovir inside in the recommended doses for the purpose of treatment and prevention of the infections caused by the Herpes simplex viruses is not led to cumulation of drug to the concentration exceeding the established safe levels. However at patients with KK less than 10 ml/min. a dose of Zovirax are recommended to be reduced to 200 mg 2 (each 12 h). For treatment of chicken pox, the surrounding herpes, and also for treatment of patients with the expressed immunodeficiency at KK less than 10 ml/min. the recommended doses of Zovirax make 800 mg 2 each 12 h; at KK of 10-25 ml/min. 800 mg 3 each 8 h.

Use for elderly patients
Patients of advanced age have to receive enough liquid against the background of Zovirax reception inside in high doses.

Use for children
Treatment and prevention of the infections caused by the Herpes simplex viruses at children with an immunodeficiency aged from 2 years are also more senior - the same doses, as for adults; 2 years - a half of a dose for adults are aged younger.

For treatment of chicken pox to children 6 years drug are more senior appoint 800 mg in a single dose; from 2 to 6 years - 400 mg; 2 years - 200 mg are younger. Frequency rate of reception 4 More precisely a single dose can be defined at the rate of 20 mg/kg of body weight (but no more than 800 mg). The course of treatment makes 5 days.

Data on use of Zovirax for prevention of a recurrence of the infections caused by the Herpes simplex viruses and at treatment of the surrounding herpes at children with normal indicators of immunity are absent.

According to the available very limited data for treatment of children 2 years a svyrazhenny immunodeficiency are more senior it is possible to apply the same doses of Zovirax, as to treatment of adults.

Overdose:

At an accidental single dose of an acyclovir inside in doses to 20 g toxic effects are not registered.

Symptoms: disturbances from a GIT (nausea, vomiting) and neurologic disturbances (a headache and confusion of consciousness); sometimes - short wind, diarrhea, a renal failure, a lethargy, spasms, a coma.

Treatment: careful medical observation for the purpose of identification of possible symptoms of intoxication. Use of a hemodialysis is possible.

Storage conditions:

List B. Drug should be stored in the place, dry, unavailable to children, at a temperature not above 25 °C. Validity term – 5 years.

Issue conditions:

According to the recipe

Packaging:

5 - planimetric strip packagings (5) - packs cardboard.