Acyclovir - instructions for use, dose, side effects, contraindications

Excipients: povidone (polyvinylpyrrolidone low molecular weight medical (12600 ± 2700), povidone K 17) - 72.0 mg; calcium stearate - 8.2 mg; silicon dioxide colloid (aerosil) - 8.2 mg; talc - 24.6 mg; cellulose microcrystalline 282.4 mg; crospovidone CL-M) - 24.6 mg.

Description:Tablets are white or almost white in color, oval in shape with a risk.

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

S.01.A.D Antiviral drugs

Pharmacodynamics:

Acyclovir is a synthetic analogue of a purine nucleoside, which has the ability to inhibit in vitro and in vivo herpes simplex viruses, including herpes simplex virus (HSV) of the 1st and 2nd types, the virus of varicella and herpes zoster (varicella-zoster virus, Varicella zoster virus (VZV)), the Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture acyclovir has the most pronounced antiviral activity against HSV-1, then in order of decreasing activity follows: HSV-2, VZV, EBV and CMV.

The inhibitory effect of acyclovir on herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV) is highly selective. Acyclovir is not a substrate for the enzyme thymidine kinase of uninfected cells, therefore acyclovir low toxicity for mammalian cells. Thymidine kinase of cells infected with HSV, VDV, EBV and CMV viruses converts acyclovir in acyclovir monophosphate - an analogue of a nucleoside, which is then subsequently converted into a diphosphate and triphosphate under the action of cellular enzymes. Inclusion of acyclovir triphosphate in the chain of viral DNA and subsequent chain termination block further replication of the viral DNA.

In patients with severe immunodeficiency, prolonged or repeated courses of therapy with acyclovir may lead to the emergence of resistant strains, so further treatment with acyclovir may not be effective. In most isolated strains with reduced sensitivity to acyclovir, a relatively low content of viral thymidine kinase was observed, a disruption in the structure of viral thymidine kinase or DNA polymerase. The effect of acyclovir on strains of the herpes simplex virus (HSV) in vitro can also lead to the formation of less sensitive strains. There was no correlation between the sensitivity of strains of the herpes simplex virus (HSV) to acyclovir in vitro and clinical efficacy of the drug.

Pharmacokinetics:

Suction

Acyclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the average maximum equilibrium concentration in the plasma (Css_max) was 3.1 μM (0.7 μg / ml), and the mean equilibrium minimum plasma concentration (Css_min) was 1.8 μM (0.4 μg / ml). When taking 400 mg and 800 mg of acyclovir every 4 hours Css_max was 5.3 μM (1.2 μg / ml) and 8 μM (1.8 μg / ml), respectively, a Css_min2.7 μM (0.6 μg / ml) and 4 μM (0.9 μg / ml), respectively.

Distribution

The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its concentration in the blood plasma.

With blood plasma proteins acyclovir is bound to an insignificant degree (9-33%), therefore, drug interactions due to displacement from the binding sites with plasma proteins are unlikely.

Excretion

In adults, after taking acyclovir, the half-life of plasma is about 3 hours. Most of the drug is excreted by the kidneys unchanged. Renal clearance of acyclovir significantly exceeds the creatinine clearance, which indicates the excretion of acyclovir by not only glomerular filtration, but also tubular secretion. The main metabolite of acyclovir is 9-carboxymethoxy-methylguanine, which accounts for about 10-15% of the dose administered in urine. In the appointment of acyclovir 1 h after receiving 1 g of probenecid, the half-life of acyclovir and AUC (area under the pharmacokinetic curve "concentration-time") increased by 18 and 40%, respectively.

Special patient groups

In patients with chronic renal failure, the half-life of acyclovir averaged 19.5 hours. During hemodialysis, the mean half-life of acyclovir was 5.7 hours.The concentration of acyclovir in the blood plasma during dialysis was reduced by approximately 60%.

In elderly patients, the clearance of acyclovir decreases with age, in parallel with the decrease in creatinine clearance, but the half-life of acyclovir changes insignificantly.

With simultaneous administration of acyclovir and zidovudine to HIV-infected patients, the pharmacokinetic characteristics of both drugs remained virtually unchanged.

Indications:

- Treatment of infections of the skin and mucous membranes caused by the herpes simplex virus, including primary and recurrent genital herpes;

- Pthe prevention of recurrence of infections caused by the herpes simplex virus in patients with normal immune status;

- Pthe prevention of infections caused by the herpes simplex virus in patients with immunodeficiency;

- lTreatment of varicella and herpes zoster (early treatment of herpes zoster with acyclovir has an analgesic effect and can reduce the incidence of postherpetic neuralgia).

Contraindications:

- Hypersensitivity to acyclovir, ganciclovir, valaciclovir or any auxiliary substance of the drug;

- children under 3 years.

Carefully:

Pregnancy, the period of breastfeeding, advanced age, renal failure, dehydration, concomitant use with other nephrotoxic drugs.

Pregnancy and lactation:

Fertility

There is no evidence of the effect of acyclovir on female fertility. In a study involving 20 male patients with a normal sperm count, it was found that the use of acyclovir orally at a dose of up to 1 g per day for 6 months had no clinically significant effect on the number, motility, or morphology of spermatozoa.

Pregnancy

In the post-registration register of pregnancies in the treatment with acyclovir, data on pregnancy outcomes in women who received acyclovir in different dosage forms. When analyzing the registry data, there was no increase in the number of birth defects in newborns whose mothers were taking acyclovir during pregnancy, compared with the general population. Identified birth defects were not distinguished by uniformity or regularity, suggesting a common cause of their occurrence.

However, care should be taken when prescribing the drug Acyclovir women during pregnancy and evaluate the estimated benefit to the mother and the possible risk to the fetus.

Breastfeeding period

After taking the drug Acyclovir Inside at a dose of 200 mg 5 times a day acyclovir is defined in breast milk in a concentration ranging from 60 to 410% plasma concentration. At such concentrations in breast milk, breastfed infants may receive acyclovir in a dose of 0.3 mg / kg / day. Given this, care should be taken when prescribing the drug to lactating women.

Dosing and Administration:

A drug Acyclovir, tablets, can be used during meals, as eating does not violate its absorption to a large extent. Tablets should be washed down with a full glass of water.

Application in adults

Treatment of infections caused by the herpes simplex virus

For the treatment of infections caused by the herpes simplex virus, the recommended dose is 200 mg 5 times a day (every 4 hours, except during the night sleep). The course of treatment is 5 days, but can be prolonged with severe primary infections.

In case of severe immunodeficiency (for example, after bone marrow transplantation) or if absorption is violated from the intestine, the dose of the drug can be increased to 400 mg.Alternatively, the possibility of using acyclovir in a dosage form - a lyophilizate for the preparation of a solution for infusions - can be considered.

Treatment should be started as soon as possible after the onset of infection; with relapses the drug is recommended to be prescribed already in the prodromal period or with the appearance of the first elements of the rash.

Prevention of recurrence of infections, caused by the herpes simplex virus, in patients with normal immune status

To prevent the recurrence of infections caused by the herpes simplex virus, in patients with normal immune status, the recommended dose of the drug is 200 mg 4 times a day (every 6 hours). A more convenient therapy scheme for 400 mg twice a day (every 12 hours) is suitable for many patients.

In some cases, lower doses of the drug are effective - 200 mg 3 times a day (every 8 hours) or 200 mg twice a day (every 12 hours).

Some patients may experience an exacerbation of the infection with a total daily dose of 800 mg.

Treatment with the drug should be interrupted periodically for 6-12 months to identify possible changes in the course of the disease.

Prevention of infections, caused by the herpes simplex virus, in patients with immunodeficiency

To prevent infections caused by the herpes simplex virus, in immunocompromised patients the recommended dose is 200 mg 4 times a day (every 6 hours).

In case of severe immunodeficiency (for example, after bone marrow transplantation) or if absorption is violated from the intestine, the dose of the drug can be increased to 400 mg. Alternatively, the possibility of using acyclovir in a dosage form - a lyophilizate for the preparation of a solution for infusions - can be considered. The duration of the preventive course of therapy is determined by the length of the period when there is a risk of infection.

Treatment of varicella and herpes zoster

For the treatment of varicella and herpes zoster, the recommended dose of the drug is 800 mg 5 times a day (every 4 hours, except during the night sleep). The course of treatment is 7 days.

In patients with severe immunodeficiency (eg, after bone marrow transplantation) or with intestinal absorption, consideration should be given to the possibility of administering acyclovir in a dosage form - lyophilizate for the preparation of a solution for infusions.

The drug should be prescribed as soon as possible after the onset of infection, since in this case the treatment is more effective.

Special patient groups

Children aged 3 years and over

Treatment of infections caused by the herpes simplex virus; infection prevention, caused by the herpes simplex virus, in patients with immunodeficiency

- at the age of 3 years and older - the same dose as for adults.

Treatment of chicken pox

- at the age of 6 years and older - 800 mg 4 times a day;

- at the age of 3 to 6 years - 400 mg 4 times a day.

More precisely, the dose can be determined from the calculation of 20 mg / kg body weight (but not more than 800 mg) 4 times a day. The course of treatment is 5 days.

Prevention of recurrence of infections caused by the herpes simplex virus in patients with normal immune status: treatment of herpes zoster

There is no data on the dosage regimen.

Elderly patients

It is necessary to take into account the likelihood of renal failure in elderly patients, the dose should be adjusted in accordance with the degree of renal failure (see subsection "Patients with impaired renal function"). It is necessary to ensure the maintenance of an adequate water balance.

Patients with impaired renal function

Care should be taken when prescribing the drug to patients with impaired renal function.

It is necessary to ensure the maintenance of an adequate water balance.

In patients with renal insufficiency, taking acyclovir orally at the recommended doses for the treatment and prevention of infections caused by the herpes simplex virus does not result in cumulation of the drug to concentrations exceeding the established safe levels. However, in patients with creatinine clearance less than 10 ml / min, the dose of the drug is recommended to be reduced to 200 mg twice a day (every 12 hours).

In the treatment of varicella zoster and herpes zoster, recommended doses of the drug are:

- when creatinine clearance is less than 10 ml / min - 800 mg twice a day (every 12 hours);

- with the clearance of creatinine 10-25 ml / min - 800 mg 3 times a day (every 8 hours).

Side effects:

The below listed categories of the frequency of undesired reactions are estimated. For most undesirable reactions, the necessary data for determining the frequency of occurrence are absent. In addition, the frequency of occurrence of unwanted reactions can vary depending on the indication.

The undesirable reactions presented below are listed according to the frequency of occurrence, defined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100 ), rarely (> 1/10 000 and <1/1000), very rarely (<1/10 000).

Frequency of occurrence of undesirable reactions:

Violations of the blood and lymphatic system:

Rarely: anemia, leukopenia, thrombocytopenia.

Immune system disorders:

Rarely: anaphylaxis.

Violations from the nervous system and mental status:

Often: headache, dizziness.

Rarely: stimulation, confusion, tremor, ataxia, dysarthria, hallucinations, 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 and were, in general, reversible (see section "Special instructions").

Onrespiratory system, organs of the chest and mediastinum:

Rarely: dyspnea.

Disorders from the gastrointestinal tract:

Often: nausea, vomiting, diarrhea, abdominal pain.

Disturbances from the liver and bile ducts:

Rarely: reversible increase in the concentration of bilirubin and "hepatic" enzymes in the blood.

Rarely: hepatitis, jaundice.

Disturbance of the skin and subcutaneous tissues:

Often: itching, rash, including photosensitivity.

Infrequently: hives, rapid diffuse hair loss.

Since rapid diffuse hair loss is observed in various diseases and in the treatment of many drugs, its association with aciclovir is not established.

Rarely: angioedema.

Rarely: toxic epidermal necrolysis, multiforme exudative erythema.

Disorders from the kidneys and urinary tract:

Rarely: increase in the concentration of urea and creatinine in the blood.

Rarely: acute renal failure, renal colic.

Renal colic can be associated with renal insufficiency and crystalluria.

General disorders and disorders at the site of administration:

Often: fatigue, fever.

Overdose:

Symptoms

Acyclovir is only partially absorbed in the gastrointestinal tract. At a random single dose of acyclovir in a dose of up to 20 g toxic effects are not recorded. With repeated oral administration for several days, in doses exceeding the recommended,there were violations of the gastrointestinal tract (nausea, vomiting) and the nervous system (headache and confusion).

Treatment

Symptomatic. Patients need careful medical supervision to identify possible symptoms of intoxication. Acyclovir is excreted from the body by hemodialysis, therefore hemodialysis can be used in the treatment of overdose.

Interaction:

No clinically significant interactions were observed with the use of the drug.

Acyclovir is excreted unchanged in urine by active tubular secretion. All drugs with a similar elimination route can increase the plasma concentration of acyclovir.

Probenecid and cimetidine increase the AUC (area under the concentration-time curve) of acyclovir and reduce its renal clearance.

An increase in the indicator was noted AUC in plasma for acyclovir and an inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplantology, while using both drugs simultaneously. However, dose adjustment is not required due to the wide therapeutic index of acyclovir.

Acyclovir increases AUC theophylline by approximately 50% with simultaneous administration. It is recommended to measure plasma concentrations of theophylline with simultaneous administration of acyclovir.

Special instructions:

Hydration status

Patients taking high doses of the drug Acyclovir inside, should receive a sufficient amount of liquid.

Older patients and patients with impaired renal function

Because the acyclovir is excreted by the kidneys, correction of the dose of the drug in patients with impaired renal function is necessary (see section "Method of administration and dose").

Elderly patients may have impaired renal function, so this category of patients need a dose adjustment.

Both elderly patients and patients with impaired renal function are at increased risk of developing side effects from the nervous system (usually such reactions are reversible in response to drug withdrawal) and, accordingly, must be closely monitored.

The risk of developing kidney failure increases with simultaneous use with other nephrotoxic drugs.

Transmission of infection

All patients, especially in the presence of clinical manifestations, should be careful to avoid the potential for transmission of the virus, and patients should be informed of cases of asymptomatic virus. Long or repeated courses of treatment with acyclovir in patients with severe immunodeficiency can lead to the emergence of strains of the virus with reduced sensitivity to acyclovir, which do not respond to the continuation of therapy with acyclovir.

Available data from clinical studies are not sufficient to conclude that the use of acyclovir reduces the risk of chickenpox in immunocompetent patients.

Effect on the ability to drive transp. cf. and fur:

When assessing a patient's ability to drive vehicles or mechanisms, the patient's clinical condition and available evidence of side effects of acyclovir should be taken into account. Studies of the effect of acyclovir on the ability to drive vehicles or mechanisms have not been carried out. In addition, it is not possible to predict the adverse effect of acyclovir on these activities on the basis of the pharmacological properties of the active substancepossible.

Form release / dosage:

Tablets, 400 mg.

Packaging:

5, 7 or 10 tablets in a planar cell pack from a polyvinyl chloride film and aluminum foil printed lacquered.

By 10, 20, 25, 30, 35, 70 tablets in cans of polymeric.

Each bank, 5 or 7 contiguous cell packs of 5 tablets, 5 contour cell packs of 7 tablets, 1, 2, 3 contourcell packs of 10 tablets with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004048

Date of registration:27.12.2016

Expiration Date:27.12.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp26.01.2017

Illustrated instructions

Instructions

Acyclovir (Aciclovir)