Acyclovir pills 200 mg, 20 pcs.

Composition

Per tablet:

Active ingredient:

Acyclovir – 200.0 mg.

Auxiliary substances:

lactose monohydrate – 137.0 mg, potato starch-45.0 mg, sucrose-16.0 mg, povidone K-17-7.6 mg, magnesium stearate-3.0 mg, sodium lauryl sulfate-1.4 mg.

Pharmacological action

Pharmacotherapeutic group: antiviral agent.

ATX code: J05 AB 01.

Pharmacological properties:

Pharmacodynamics

Mechanism of action

Acyclovir is a synthetic purine nucleoside analog that has the ability to inhibit invitro and invivo human herpes viruses, including herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (Varicella zoster virus (VZV)), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the most pronounced antiviral activity against HSV-1, followed by HSV-2, VZV, EBV and CMV in descending order of activity.

The inhibitory effect of acyclovir on herpes viruses (HSV-1, HSV-2, VZV, EBV and CMV) is highly selective. Acyclovir is not a substrate for the enzyme thymidine kinase in uninfected cells, so acyclovir is low toxic to mammalian cells. However, thymidine kinase in cells infected with HSV, VZV, EBV, and CMV viruses converts acyclovir to acyclovir monophosphate, a nucleoside analog that is then sequentially converted to diphosphate and triphosphate by cellular enzymes. The inclusion of acyclovir triphosphate in the viral DNA chain and subsequent chain breakage block further replication of viral DNA.

In patients with severe immunodeficiency, prolonged or repeated courses of acyclovir therapy may lead to the appearance of resistant strains, so further treatment with acyclovir may not be effective. Most of the isolated strains with reduced sensitivity to acyclovir showed a relatively low thymidine kinase content, as well as a violation of the structure of viral thymidine kinase or DNA polymerase. Acyclovir exposure to invitro herpes simplex virus (HSV) strains can also lead to the formation of less sensitive strains. There is no correlation between the sensitivity of herpes simplex virus (HSV) strains to acyclovir in vitro and the clinical efficacy of the drug.

Pharmacokinetics

Absorption

Acyclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the mean maximum steady-state plasma concentration (Ss_max) was 3.1 µm (0.7 µg / ml), and the mean steady – state minimum plasma concentration (Ss_min) was 1.8 µm (0.4 µg/ml). When taking 400 mg and 800 mg acyclovir orally every 4 hours, the Ss_max was 5.3 µm (1.2 µg / ml) and 8 µm (1.8 µg/ml), respectively, and the Ss_minwas 2.7 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.

Acyclovir binds to plasma proteins to a small extent (9-33%), so drug interactions due to displacement from the sites of binding to plasma proteins are unlikely.

Deduction

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

Special patient groups

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

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

When acyclovir and zidovudine were co-administered 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;

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

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

– treatment of varicella and herpes zoster (early treatment of herpes zoster with acyclovir has analgesic effect and may reduce the incidence of postherpetic neuralgia).

Use during pregnancy and lactation

Fertility

There are no data on the effect of acyclovir on female fertility.

In a study involving 20 male patients with a normal sperm count, it was found that oral administration of acyclovir at a dose of up to 1 g per day for 6 months did not have a clinically significant effect on the number, motility or morphology of sperm.

Pregnancy

The post-marketing pregnancy registry for acyclovir treatment contains data on pregnancy outcomes in women who took acyclovir in various dosage forms. When analyzing the registry data, there was no increase in the number of birth defects in newborns whose mothers took acyclovir during pregnancy, compared with the general population. The revealed birth defects did not differ in uniformity or regularity, which allowed us to assume a common cause of their occurrence.

However, caution should be exercised when prescribing Acyclovir to women during pregnancy and evaluating the intended benefit to the mother and the possible risk to the fetus.

Breast-feeding period

After taking Acyclovir orally at a dose of 200 mg 5 times a day, acyclovir was detected in breast milk at a concentration of 60 to 410% of the plasma concentration. At such concentrations in breast milk, children who are breastfed can receive acyclovir at a dose of up to 0.3 mg / kg / day. Given this, caution should be exercised when prescribing Acyclovir to nursing women.

Contraindications

Hypersensitivity to acyclovir or valacyclovir or any other component of the drug; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; children under 3 years of age.

With caution: Pregnancy, breast-feeding, elderly age, renal failure, dehydration, concomitant use with other nephrotoxic drugs.

Side effects

The following categories of frequency of adverse reactions are estimated. For most adverse reactions, the necessary data to determine the frequency of occurrence are not available. In addition, the frequency of adverse reactions may vary depending on the indication.

The adverse reactions listed below are listed according to the frequency of occurrence, defined as: very common (>1/10), >common (>1/100 and ><1/10), uncommon (>1/1000 and ><1/100), rare (>1/10000 and ><1/1000), very rare (

Frequency of adverse reactions

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia.

Immune system disorders

Rare: anaphylaxis.

Disorders of the nervous system and mental status

Often: headache, dizziness.

Very rare: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, seizures, drowsiness, encephalopathy, coma.

Usually, these side effects were observed in patients with renal insufficiency or in the presence of other provoking factors and were mostly reversible (see section“Special instructions”).

Respiratory, thoracic and mediastinal disorders

Rare: shortness of breath.

Gastrointestinal disorders

are common: nausea, vomiting, diarrhea, abdominal pain.

Liver and biliary tract disorders

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

Very rare: hepatitis, jaundice.

Skin and subcutaneous tissue disorders

are common: pruritus, rash, including photosensitization.

Infrequently: hives, rapid diffuse hair loss.

Since rapid diffuse hair loss is observed in various diseases and during therapy with many medications, the relationship between egos and acyclovir intake has not been established.

Rare: angioedema.

Very rare: toxic epidermal necrolysis, erythema multiforme.

Kidney and urinary tract disorders

Rarely: increased serum urea and creatinine concentrations.

Very rare: acute renal failure, renal colic.

Renal colic may be associated with renal failure and crystalluria.

General disorders and disorders at the injection

site Often: fatigue, fever.

Interaction

No clinically significant interactions were observed with Acyclovir. Acyclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar elimination route may increase the plasma concentration of acyclovir. Acyclovir increases the AUC of theophylline by approximately 50% when co-administered, so it is recommended to measure plasma concentrations of theophylline when co-administered with acyclovir. Probenecid and cimetidine increase the AUC (area under the concentration – time curve). acyclovir and reduce its renal clearance. There was an increase in plasma AUC for acyclovir and an inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplantology, when both drugs were used simultaneously. However, no dose adjustment is required due to the broad therapeutic index of acyclovir.

How to take, course of administration and dosage

The drug Acyclovir, tablets can be taken with a meal, since food intake does not significantly interfere with its absorption. Tablets should be washed down with a full glass of water.

Adults

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

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

In the case of severe immunodeficiency (for example, after bone marrow transplantation) or with impaired intestinal absorption, the dose of Acyclovir can be increased to 400 mg. Alternatively, the possibility of using acyclovir in the lyophilizate dosage form to prepare an infusion solution may be considered.

Treatment should be started as early as possible after the infection occurs; in case of relapses, the drug is recommended to be prescribed already in the prodromal period or the appearance of the first elements of the rash.

Prevention of recurrent infections caused by herpes simplex virus in patients with normal immune status

To prevent recurrent infections caused by the herpes simplex virus in patients with normal immune status, the recommended dose of Acyclovir is 200 mg orally 4 times a day (every 6 hours).

For many patients, a more convenient therapy regimen of 400 mg orally 2 times a day (every 12 hours) is suitable.

In some cases, lower doses of Acyclovir are effective: 200 mg orally 3 times a day (every 8 hours) or 200 mg orally 2 times a day (every 12 hours).

Some patients may experience an exacerbation of infection when taking a total daily dose of 800 mg.

Treatment with Acyclovir should be interrupted every 6-12 months to detect possible changes in the course of the disease.

Prevention of herpes simplex virus infections in immunodeficient patients

For the prevention of infections caused by the herpes simplex virus, in patients with immunodeficiency, the recommended dose of Acyclovir is 200 mg orally 4 times a day (every 6 hours).

In the case of severe immunodeficiency (for example, after bone marrow transplantation) or with impaired intestinal absorption, the dose of the drug can be increased to 400 mg orally. Alternatively, the possibility of using acyclovir in the lyophilizate dosage form to prepare an infusion solution may be considered.

The duration of a preventive course of therapy is determined by the duration of the period during which there is a risk of infection.

Treatment of chickenpox and herpes zoster

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

Treatment of herpes zoster should be started as early as possible from the moment of the first manifestations of the disease, since in this case the treatment will be more effective.

Treatment of chickenpox in patients with normal immune status should begin within 24 hours of the appearance of the rash.

In patients with severe immunodeficiency (for example, after bone marrow transplantation) or with impaired intestinal absorption, the possibility of prescribing acyclovir in the dosage form of lyophilizate for the preparation of an infusion solution should be considered.

Special patient groups

Children aged 3 years and older

Treatment of infections caused by the herpes simplex virus; prevention of infections caused by the herpes simplex virus in immunodeficient patients

-aged 3 years and older-the same doses as for adults.

Treatment of chickenpox

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

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

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

Prevention of recurrent infections caused by herpes simplex virus in patients with normal immune status; treatment of herpes zoster

There are no data on the dosage regimen.

Elderly patients

It is necessary to take into account the possibility of renal insufficiency in elderly patients, and doses should be adjusted according to the degree of renal insufficiency (see the subsection “Patients with impaired renal function”).

Adequate water balance must be maintained.

Patients with impaired renal function

Caution should be exercised when prescribing Acyclovir to patients with impaired renal function.

Adequate water balance must be maintained.

In patients with renal insufficiency, oral administration of acyclovir at the recommended doses for the treatment and prevention of infections caused by the herpes simplex virus does not lead to accumulation of the drug to concentrations exceeding the established safe levels. However, in patients with a creatinine clearance of less than 10 ml/min, the dose of Acyclovir is recommended to be reduced to 200 mg orally 2 times a day (every 12 hours).

In the treatment of varicella and herpes zoster recommended dose Acyclovir tablets are:

– in creatinine clearance less than 10 ml/min,800 mg orally 2 times a day (every 12 hours);

– if creatinine clearance 10 to 25 ml/min,800 mg orally 3 times a day (every 8 hours).

Overdose

Acyclovir is only partially absorbed in the gastrointestinal tract. As a rule, no toxic effects were reported with an accidental single dose of acyclovir at a dose of up to 20 g. Repeated oral doses exceeding the recommended dose range for several days were associated with gastrointestinal disorders (nausea, vomiting) and nervous system disorders (headache and confusion). Sometimes there may be neurological effects such as seizures, coma. Patients should be closely monitored for possible symptoms of intoxication. Acyclovir is eliminated from the body by hemodialysis, so hemodialysis can be used to treat overdose.

Description

Round flat-cylindrical tablets of white or almost white color with a chamfer and risk.

Special instructions

The available data obtained from clinical studies are insufficient to conclude that the use of acyclovir reduces the risk of chickenpox in patients with normal immune status.

The risk of developing renal failure increases with concomitant use with other nephrotoxic drugs.

Hydration status

Patients taking high-dose oral Acyclovir should receive sufficient fluids.

Elderly patients and patients with impaired renal function

Since acyclovir is excreted by the kidneys, doses should be reduced in patients with renal insufficiency (see section “Dosage and administration”).

Elderly patients may have reduced renal function, and therefore a dose reduction may also be required for this group of patients. Both elderly patients and patients with impaired renal function are at an increased risk of developing side effects from the nervous system (usually such reactions are reversible in response to drug withdrawal) and, accordingly, should be closely monitored.

Patients with severe immunodeficiency

Long-term or repeated courses of acyclovir treatment in patients with severe immunodeficiency may lead to the appearance of virus strains with reduced sensitivity to acyclovir, which will not respond to continued acyclovir therapy.

Transmission of infection

Caution should be exercised in all patients, especially in the presence of clinical manifestations, to avoid potential transmission of the virus. Patients should be informed about cases of asymptomatic viral transmission.

Influence on the ability to drive vehicles and mechanisms:

Studies of the effect of acyclovir on the ability to drive vehicles or mechanisms have not been conducted. It is not possible to predict the negative impact of acyclovir on these activities based on the pharmacological properties of the Active ingredient, but it is necessary to take into account the side effect profile of acyclovir.

Form of production

Tablets,200 mg

10 tablets in a contour cell package made of polyvinyl chloride film and aluminum foil printed varnished.

1,2 or 3 contour cell packages together with the instructions for use will be placed in a pack of cardboard.

Storage conditions

In a place protected from moisture and light at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Acyclovir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Weight

Weight: 18 gr.