Acyclovir - instructions for use, reviews, analogs and forms of release (tablets, ointment, cream, eye ointment - acri, hexal, akos) medications for the treatment of oral and genital herpes in adults, children and pregnancy. Admission for pregnant and lactating women
APPROVED
By order of the Chairman of the Committee
Control of medical and
Pharmaceutical activities
Ministry of Health
Republic of Kazakhstan
from "____"___________201 __
№__________________________
Instructions for medical use
Medicine
ACICLOVIR-AKOS
Tradename
ACICLOVIR-AKOS
International nonproprietary name
Acyclovir
Dosage form
Tablets, 0.2 g
Compound
One tablet contains
active substance- acyclovir (in terms of anhydrous substance) 0.2 g,
Excipients: potato starch, magnesium stearate, talc
Description
White flat-cylindrical tablets with chamfer and score
Pharmacotherapeutic group
Antiviral drugs for systemic use. Nucleosides and nucleotides.
ATS code J05АВ01
Pharmacological properties
Pharmacokinetics
After oral administration, it is partially absorbed into the intestine; due to its low lipophilicity, absorption after oral administration of 200 mg is 20% (15 - 30%), however, dose-dependent concentrations are created that are sufficient for the effective treatment of viral diseases. Food does not have a significant effect on the absorption of acyclovir. With increasing dose, bioavailability decreases.
The maximum concentration (Cmax) after oral administration of 200 mg 5 times a day is 0.7 mcg/ml, the minimum concentration (Cmin) is 0.4 mcg/ml, the time to reach maximum concentration is 1.5-2 hours. Communication with blood plasma proteins - 9 - 33%.
Penetrates the blood-brain barrier. Penetrates well into organs and tissues (including the brain, kidneys, lungs, liver, aqueous humor, tear fluid, intestines, muscles, spleen, breast milk, uterus, mucous membrane and vaginal secretions, sperm, amniotic fluid, contents herpetic vesicles); concentration in the cerebrospinal fluid is 50% of that in the blood. Acyclovir crosses the placenta and is excreted in breast milk in small concentrations. After oral administration at a dose of 200 mg 5 times a day, acyclovir is determined in breast milk in concentrations of 0.6 - 4.1% of plasma concentrations (at such concentrations in breast milk, breastfed children can receive acyclovir with mother's milk in a dose of up to 0.3 mg/kg/day).
Metabolized in the liver to form a metabolite - 9-carboxy-methoxymethylguanine.
It is excreted by the kidneys through glomerular filtration and tubular secretion: when taken orally, most of it is unchanged (62 - 91% of the dose) and in the form of a metabolite (on average 14%). Less than 2% is excreted through the gastrointestinal tract; trace amounts are determined in exhaled air.
With a single session of hemodialysis for 6 hours, the concentration of acyclovir in plasma decreases by approximately 60%; During peritoneal dialysis, the clearance of acyclovir does not change significantly.
The half-life (T1/2) when taken orally in adults is 3.3 hours, in children and adolescents from 1 year to 18 years - 2.6 hours. The rate of elimination slows down with age, but T1/2 of the active drug increases slightly.
In patients with severe chronic renal failure T1/2 - up to 20 hours. T1/2 with renal failure (in adults, depending on the values of creatinine clearance (CC)): with CC 80 ml/min - 2.5 hours, 50-80 ml/ min - 3 hours, 15-50 ml/min - 3.5 hours; with anuria - 19.5 hours, during hemodialysis - 5.7 hours, with continuous outpatient peritoneal dialysis - 14-18 hours.
With the simultaneous administration of acyclovir and zidovudine to HIV-infected patients, the pharmacokinetic characteristics of both drugs remain virtually unchanged.
Pharmacodynamics
An antiviral (antiherpetic) agent is a synthetic analogue of a purine nucleoside that has the ability to inhibit in vitro and in vivo the replication of Herpes simplex viruses type 1 and 2, Varicella zoster virus, Epstein-Barr virus and cytomegalovirus.
Highly active against Herpes simplex viruses type 1 and 2; the virus that causes chickenpox and herpes zoster (Varicella zoster); Epstein-Barr virus (types of viruses are listed in increasing order of the minimum inhibitory concentration of acyclovir). Moderately active against cytomegalovirus. In infected cells containing viral thymidine kinase, phosphorylation and conversion of acyclovir to acyclovir monophosphate occurs. Under the influence of acyclovir guanylate cyclase, monophosphate is converted into diphosphate and, under the action of several cellular enzymes, into triphosphate. The high selectivity of action specifically on viruses and low toxicity to humans are due to the fact that acyclovir is not a substrate for the thymidine kinase enzyme of uninfected cells, therefore it is of low toxicity to mammalian cells.
Acyclovir triphosphate inhibits the synthesis (replication) of viral DNA by three mechanisms:
1) competitively replaces deoxyguanosine triphosphate in DNA synthesis;
2) “integrates” into the DNA chain being synthesized and stops its elongation;
3) inhibits the enzyme DNA polymerase of the virus.
As a result, the multiplication of the virus in the body is blocked.
The specificity and very high selectivity of the action of acyclovir are also due to its predominant accumulation in cells affected by viruses. Has an immunostimulating effect.
Indications for use
Herpes simplex of the skin and mucous membranes (primary and recurrent)
Genital herpes (primary and recurrent)
Shingles (herpes zoster)
Chickenpox (in the first 24 hours after the typical rash appears)
In patients with severe immunodeficiency (including after transplantation, when taking immunosuppressive drugs, in HIV-infected patients, during chemotherapy)
Directions for use and doses
Inside, regardless of food intake, take a full glass of water.
For adults, for the treatment of herpes simplex of the skin and mucous membranes - 200 mg 5 times a day (every 4 hours while awake, excluding night sleep) for 5 days, if necessary, the duration of treatment can be extended. When treating patients with immunodeficiency, the single dose of the drug should be increased to 400 mg, the course duration should be 10 days or more.
Adults for the treatment of genital herpes - 200 mg 5 times a day (every 4 hours while awake, excluding night sleep) for 10 days, if necessary, the duration of treatment can be extended. When treating patients with immunodeficiency, the single dose of the drug should be increased to 400 mg.
Treatment should begin as soon as possible after infection occurs; in case of relapses, it is recommended to prescribe the drug already in the prodromal period or when the first elements of the rash appear.
To prevent relapses of infections caused by the herpes simplex virus (including in patients with immunodeficiency), the drug is prescribed 200 mg 4 times a day (every 6 hours). For patients with normal immune status, for the prevention of herpes simplex of the skin and mucous membranes, it is possible to prescribe 400 mg 2 times a day (every 12 hours). In case of severe immunodeficiency (after bone marrow transplantation or in case of impaired absorption from the intestine) - 400 mg 5 times a day.
Recurrent genital herpes (less than 6 episodes per year): intermittent therapy - 200 mg 5 times a day for 5 days. Recurrent genital herpes (more than 6 episodes per year): long-term suppressive therapy - 400 mg 2 times a day or 200 mg 3-5 times a day (course duration up to 12 months).
When treating herpes zoster (herpes zoster): 800 mg 5 times a day (every 4 hours while awake, excluding night sleep) for 7-10 days.
The maximum single dose per reception is 800 mg.
Patients taking high doses orally should receive sufficient fluids.
For children over 3 years of age, the drug is prescribed in the same dose as for adults.
In patients with impaired renal function, dose adjustment and dosage regimen are necessary depending on the magnitude of creatinine clearance and the type of infection. For the treatment of infection caused by Herpes simplex, with creatinine clearance less than 10 ml/min, the daily dose of the drug should be reduced to 400 mg, divided into 2 doses (with intervals between them of at least 12 hours, i.e. 200 mg 2 times a day ). In the treatment of infections caused by Varicella zoster, and in the maintenance therapy of patients with severe immunodeficiency - patients with a creatinine clearance of 10-25 ml/min, the drug is prescribed at a dose of 2.4 g / day in 3 doses with an interval of 8 hours (800 mg 3 times a day ). In patients with creatinine clearance less than 10 ml/min, the daily dose is reduced to 1.6 g, dose frequency 2 times a day with an interval of 12 hours (800 mg 2 times a day).
Side effects
Very rarely
Nausea, vomiting, diarrhea, abdominal pain, reversible increase in bilirubin levels and liver enzymes
Anemia, leukopenia, thrombocytopenia
Acute renal failure
Increased levels of urea and creatinine in the blood
Headache
Allergic reactions: sometimes - rash, photosensitivity, urticaria, itching, rarely - shortness of breath, angioedema, anaphylaxis, fever, lymphadenopathy, peripheral edema, blurred vision, agitation, myalgia
Other: sometimes - fatigue, rarely - alopecia
Contraindications
Hypersensitivity to acyclovir
Prophylactic use of the drug in patients with impaired renal function or anuria
Lactation period
Children under 3 years old
Drug interactions
An enhanced effect is observed with the simultaneous administration of immunostimulants.
Other nephrotoxic drugs - increased risk of nephrotoxicity.
Active substance
Acyclovir
Release form
pills
Primary packaging
contour cell packaging
Amount in a package
Manufacturer
Sintez OJSC
Composition and release form
in a blister pack 10 pcs.; in a cardboard pack of 2 packs or in dark glass jars of 20 pcs.; in a cardboard pack 1 jar.
in aluminum tubes of 5 g; in a cardboard pack 1 tube.
Characteristic
Tablets are white, flat-cylindrical in shape with a chamfer and a score.
The ointment is white or white with a yellowish tint.
Pharmacological actions
Penetrates into virus-infected cells, competitively interacts with viral thymidine kinase and is sequentially phosphorylated to form mono-, di- and triphosphate. Acyclovir triphosphate is integrated into the viral DNA chain, competitively inhibits the viral DNA polymerase and suppresses its replication.
Pharmacokinetics
When taken orally, the bioavailability is 15–30%, Cmax is achieved after 1.5–2 hours. The concentration after oral administration of 200 mg 5 times a day is 0.7 μg/ml. Plasma protein binding is 9–33% and is independent of the concentration of acyclovir in plasma. Penetrates well into all organs and tissues, including the brain and skin. The concentration in the cerebrospinal fluid is 50% of the concentration in plasma. Passes through the placental barrier and accumulates in breast milk. Metabolized in the liver to form a pharmacologically inactive derivative - 9-carboxymethoxymethylguanine. T1/2 in adults with normal renal function - 2-3 hours, in severe renal failure - 20 hours, in patients with hemodialysis - 5.7 hours (at the same time, the concentration of acyclovir in plasma decreases to 60% of the original value). It is excreted by the kidneys (84% unchanged, 14% as a metabolite), less than 2% through the intestines. Renal clearance accounts for 75–80% of the total clearance.
Pharmacodynamics
It has high specificity for herpes simplex virus types I and II, the virus that causes chickenpox and herpes zoster (Varicella zoster), Epstein-Barr virus and cytomegalovirus.
Acyclovir-AKOS: indications
For systemic use:
Treatment of infections of the skin and mucous membranes caused by Herpes simplex viruses type I and II (primary and secondary, including genital herpes);
Prevention of exacerbations of recurrent infections caused by Herpes simplex viruses type I and II in patients with normal immune status;
Prevention of primary and recurrent infections caused by Herpes simplex viruses type I and II in patients with immunodeficiency;
As part of complex therapy for patients with severe immunodeficiency: with HIV infection (stage of AIDS, early clinical manifestations and detailed clinical picture) and in patients who have undergone bone marrow transplantation;
Treatment of primary and recurrent infections caused by the Varicella zoster virus (chickenpox, herpes zoster).
For external use: herpes simplex of the skin, genital herpes (simple and recurrent), labial herpes; herpes zoster and chicken pox.
Acyclovir-AKOS: contraindications
Hypersensitivity, incl. to acyclovir or components of the drug, breastfeeding; with caution - dehydration, renal failure, neurological disorders, incl. in the anamnesis.
Use during pregnancy and breastfeeding
Possibly if the expected effect of therapy exceeds the potential risk to the fetus. Breastfeeding should be stopped during treatment.
Directions for use and doses
Inside during or immediately after a meal, with plenty of water. In the treatment of infections of the skin and mucous membranes caused by Herpes simplex I or II, adults and children over 2 years of age - 200 mg 5 times a day for 5 days at 4 hour intervals during the day and at 8 hour intervals at night (if necessary the course can be extended). As part of complex therapy for severe immunodeficiency (including with a full-blown clinical picture of HIV infection, including early clinical manifestations of HIV infection and AIDS), after bone marrow transplantation - 400 mg 5 times a day.
To prevent relapses of infections caused by Herpes simplex I or II, for patients with normal immune status and in case of relapse of the disease - 200 mg 4 times a day every 6 hours (maximum dose - up to 400 mg 5 times a day, depending on the severity of the infection).
When treating infections caused by Varicella zoster, adults and children weighing more than 40 kg - 800 mg 5 times a day every 4 hours during the day and at 8-hour intervals at night. Duration of treatment is 7–10 days. Children over 2 years old - 20 mg/kg 4 times a day for 5 days.
When treating infections caused by Herpes zoster, adults - 800 mg 4 times a day every 6 hours during the day for 5 days.
If renal function is impaired during the treatment and prevention of infections caused by Herpes simplex, in patients with creatinine Cl less than 10 ml/min, the dose of the drug is reduced to 200 mg 2 times a day with a 12-hour interval.
In the treatment and prevention of infections caused by Varicella zoster, in patients with creatinine Cl less than 10 ml/min, the dose of the drug is reduced to 800 mg 2 times a day with 12 hour intervals, with creatinine Cl up to 25 ml/min - 800 mg 3 times a day day with 8 hour intervals.
Externally, the ointment is applied to the affected surface 5 times a day (every 4 hours). Duration of treatment is 5–10 days.
Acyclovir-AKOS: side effects
When taken orally.
From the nervous system and sensory organs: rarely - headache, weakness; in some cases - tremor, dizziness, increased fatigue, drowsiness, hallucinations.
From the gastrointestinal tract: in isolated cases - abdominal pain, nausea, vomiting, diarrhea.
Allergic reactions: skin rash.
Other: transient increase in liver enzyme activity; rarely - increased levels of urea and creatinine, hyperbilirubinemia, leukopenia, erythropenia, alopecia, fever.
For external use: possible redness, itching, peeling, burning or tingling at the application site; in rare cases - allergic dermatitis.
Interaction
When taken orally: probenecid increases the average half-life and reduces the clearance of acyclovir; nephrotoxic drugs increase the risk of renal dysfunction. For external use: No interaction with other drugs was detected.
Precautionary measures
Prescribe with caution to patients with impaired renal function and elderly patients (due to an increase in T1/2). When using the drug, it is recommended to take a sufficient amount of fluid. During treatment, it is necessary to monitor kidney function (urea and creatinine levels in the blood). The ointment is not recommended to be applied to the mucous membranes of the mouth, eyes, and genitals (local inflammation may develop).
special instructions
Use internally strictly as prescribed by a doctor in adults and children over 2 years of age (to avoid complications).
It is recommended to start treatment when the first signs of the disease appear (the effectiveness will be higher). In patients with immunodeficiency, with multiple repeated courses, viral resistance to acyclovir may develop.
Manufacturer
Joint Stock Kurgan Society of Medical Preparations and Products “Sintez”, Russia.
- Description of the drug ACICLOVIR-AKOS
- Composition of the drug ACICLOVIR-AKOS
- Indications for the drug ACICLOVIR-AKOS
- Storage conditions for the drug ACICLOVIR-AKOS
- Shelf life of the drug ACICLOVIR-AKOS
ATX Code: Dermatology (D) > Antimicrobials for the treatment of skin diseases (D06) > > > Aciclovir (D06BB03) , +
Dermatology (D) > Antimicrobials for the treatment of skin diseases (D06) > Other antimicrobials for topical use (D06B) > Antivirals (D06BB) > Antimicrobials for systemic use (J) > Antivirals for systemic use (J05) > Antivirals direct acting drugs (J05A) > Nucleosides and nucleotides (J05AB) > Aciclovir (J05AB01)
Release form, composition and packaging
tab. 200 mg: 20 pcs.Reg. No.: RK-LS-5-No. 003211 dated 12/12/2011 - Valid
Pills white, flat-cylindrical, with chamfer and notch.
Excipients: potato starch, magnesium stearate, talc.
10 pieces. - contour cell packaging (2) - cardboard packs.
ointment 5%: tubes 5 gReg. No.: RK-LS-5-No. 003223 dated 12/12/2011 - Valid
Ointment 5% for external use, white or white with a yellowish tint.
Excipients: lipocomp (lipid component of poultry fat) or chicken oil, emulsifier No. 1, polyethylene oxide-400, 1,2-propylene glycol, nipagin, nipazole, purified water.
5 g - aluminum tubes (1) - cardboard packs.
Description of active ingredients drug ACICLOVIR-AKOS. The scientific information provided is general and cannot be used to make a decision about the possibility of using a particular drug. Update date: 01/14/2006
Antiviral agent. Thymidine kinase in virus-infected cells actively converts acyclovir through a series of sequential reactions into acyclovir mono-, di- and triphosphate. The latter interacts with the viral DNA polymerase and is integrated into the DNA that is synthesized for new viruses. Thus, “defective” viral DNA is formed, which leads to suppression of the replication of new generations of viruses.
Acyclovir is active against Herpes simplex virus types 1 and 2, Varicella zoster virus, Epstein-Barr virus and cytomegalovirus.
When taken orally, bioavailability is 15-30%. Widely distributed in tissues and body fluids. Plasma protein binding is 9-33%. Metabolized in the liver. T1/2 when taken orally - 3.3 hours, when administered intravenously - 2.5 hours. It is excreted in the urine, and in small quantities - in feces.
For systemic use (orally and intravenously):
- infections caused by Herpes simplex viruses types 1 and 2 and Varicella zoster; prevention of infections caused by Herpes simplex and Varicella zoster viruses (including in patients with reduced immunity);
- as part of complex therapy for severe immunodeficiency (including the clinical picture of HIV infection) and in patients who have undergone bone marrow transplantation;
- prevention of cytomegalovirus infection after bone marrow transplantation.
For topical use in ophthalmology:
- keratitis and other eye lesions caused by the Herpes simplex virus.
For external use:
- skin infections caused by Herpes simplex and Varicella zoster viruses.
Orally for adults and children over 2 years old - 200-400 mg 3-5 times a day, if necessary - 20 mg/kg (up to 800 mg per dose) 4 times a day. In children under 2 years of age, use a dose equal to half the dose for adults. Duration of treatment is 5-10 days. In case of renal failure, adjustment of the dosage regimen is recommended.
IV drip for adults and children over 12 years old - 5-10 mg/kg, interval between injections - 8 hours. Children aged 3 months to 12 years - 250-500 mg/m 2 body surface, interval between injections - 8 hours. For newborns, the dose is 10 mg/kg, the interval between doses is 8 hours.
Apply locally and externally 5 times a day. The dose and duration of treatment depend on the indications and dosage form used.
Maximum doses: for adults with intravenous administration - 30 mg/kg/day.
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Externally. The drug is applied 5 times a day (every 4 hours) in a thin layer to the affected and adjacent areas of the skin. The cream is applied either with a cotton swab or with clean hands to avoid additional infection of the affected areas. Therapy should be continued until a crust forms on the blisters or until they are completely healed. The duration of therapy is on average 5 days and should not exceed 10 days.
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For adults and children eye ointment in the form of a strip 1 cm long is placed in the lower conjunctival sac 5 times a day (every 4 hours) until healing.
Treatment is continued for another 3 days after healing.
When taken orally: nausea, vomiting, diarrhea, abdominal pain, skin rash, headache, dizziness, fatigue, decreased concentration, hallucinations, drowsiness or insomnia, fever;
With intravenous administration: acute renal failure, crystalluria, encephalopathy (confusion, hallucinations, agitation, tremor, convulsions, psychosis, drowsiness, coma), phlebitis or inflammation at the injection site, nausea, vomiting.
For local use: burning sensation at the application site, superficial punctate keratitis, blepharitis, conjunctivitis.
For external use: at the site of application, a burning sensation, skin rash, itching, peeling, erythema, dry skin are possible;
Use during pregnancy and breastfeeding
The use of acyclovir during pregnancy is possible in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
IV use of acyclovir during lactation is contraindicated (excreted in breast milk).
IN experimental studies Animal studies have shown that acyclovir penetrates the placental barrier.
In case of renal failure, adjustment of the dosage regimen is necessary.
It should be taken into account that when using acyclovir, acute renal failure may develop due to the formation of sediment from acyclovir crystals, which is especially likely with rapid intravenous administration, simultaneous use of nephrotoxic drugs, in patients with impaired renal function and with insufficient water load.
It should be taken into account that when using acyclovir, acute renal failure may develop due to the formation of sediment from acyclovir crystals, which is especially likely with rapid intravenous administration, simultaneous use of nephrotoxic drugs, in patients with impaired renal function and with insufficient water load.
When using acyclovir, it is necessary to monitor renal function (determining the level of urea nitrogen in the blood and creatinine in the blood plasma).
Treatment of elderly patients should be carried out with a sufficient increase in water load and under the supervision of a physician, because in this category of patients, T1/2 of acyclovir increases.
When treating genital herpes, you should avoid sexual intercourse or use condoms, because the use of acyclovir does not prevent transmission of the virus to partners.
Acyclovir in the form of dosage forms for external use should not be applied to the mucous membranes of the mouth, eyes, or vagina.
With simultaneous use, probenecid reduces the tubular secretion of acyclovir and thereby increases the plasma concentration and half-life of acyclovir.
When used simultaneously with mycophenolate mofetil, the AUC of acyclovir and the inactive metabolite mycophenolate mofetil increases.
With the simultaneous use of acyclovir with nephrotoxic drugs, the risk of developing nephrotoxicity increases (especially in patients with impaired renal function).
When mixing solutions, it is necessary to take into account the alkaline reaction of acyclovir for intravenous administration (pH 11).
Tablets are white, with a flat-cylindrical surface, with a chamfer and a score.
Pharmacotherapeutic group
Antiviral drugs for systemic use. Direct acting antiviral drugs. Nucleosides and nucleotides. Acyclovir.
ATX code J05AB01
Pharmacological properties
Pharmacokinetics
Acyclovir is only partially absorbed from the gastrointestinal tract. At steady state, the mean maximum concentration (CSSmaks) after taking the drug at a dose of 200 mg every 4 hours is 3.1 μmol/L (0.7 μg/ml), and the corresponding minimum concentration (CSSmin) is 1.8 μmol/L ( 0.4 µg/ml). After taking the drug in doses of 400 mg and 800 mg every 4 hours, CSSmax is 5.3 µmol/l (1.2 µg/ml) and 8 µmol/l (1.8 µg/ml), respectively, and CSSmin is 2 .7 µmol/l (0.6 µg/ml) and 4 µmol/l (0.9 µg/ml).
In adults, after intravenous administration of acyclovir, the half-life in plasma is approximately 2.9 hours. Most of the drug is excreted unchanged by the kidneys. The renal clearance of acyclovir is significantly higher compared to the clearance of creatinine, indicating the participation of tubular secretion in the presence of glomerular filtration in the excretion of the drug by the kidneys. The most significant metabolite of acyclovir is 9-carboxymethoxymethylguanine, which is excreted in the urine in an amount of about 10 - 15% of the administered dose.
Taking 1 g of probenecid 60 minutes before administration of acyclovir prolongs the half-life of acyclovir by 18% and increases the surface area of the plasma concentration/time curve by 40%.
In elderly people, the clearance of acyclovir decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir changes slightly.
In patients with chronic renal failure, the average half-life is approximately 19.5 hours. The average half-life during hemodialysis is 5.7 hours. During hemodialysis, plasma levels of acyclovir drop by approximately 60%.
The concentration of the drug in the cerebrospinal fluid is 50% of the concentration in the serum. Plasma protein binding ranged between 9 and 33%.
Pharmacodynamics
An antiviral (antiherpetic) agent is a synthetic analogue of a purine nucleoside that has the ability to inhibit in vitro and in vivo the replication of Herpes simplex viruses type 1 and 2, Varicella zoster virus, Epstein-Barr virus and cytomegalovirus.
Highly active against Herpes simplex viruses type 1 and 2; the virus that causes chickenpox and herpes zoster (Varicella zoster); Epstein-Barr virus (types of viruses are listed in increasing order of the minimum inhibitory concentration of acyclovir). Moderately active against cytomegalovirus. In infected cells containing viral thymidine kinase, phosphorylation and conversion of acyclovir to acyclovir monophosphate occurs. Under the influence of acyclovir guanylate cyclase, monophosphate is converted into diphosphate and, under the action of several cellular enzymes, into triphosphate. The high selectivity of action specifically on viruses and low toxicity to humans are due to the fact that acyclovir is not a substrate for the thymidine kinase enzyme of uninfected cells, therefore it is of low toxicity to mammalian cells.
Acyclovir triphosphate inhibits the synthesis (replication) of viral DNA by three mechanisms:
1) competitively replaces deoxyguanosine triphosphate in DNA synthesis;
2) “integrates” into the DNA chain being synthesized and stops its elongation;
3) inhibits the enzyme DNA polymerase of the virus.
As a result, the multiplication of the virus in the body is blocked.
The specificity and very high selectivity of the action of acyclovir are also due to its predominant accumulation in cells affected by viruses. Has an immunostimulating effect.
Indications for use
Herpes simplex of the skin and mucous membranes (primary and recurrent)
Genital herpes (primary and recurrent)
Shingles (herpes zoster)
Chickenpox (in the first 24 hours after the typical rash appears)
In patients with severe immunodeficiency (including after transplantation, when taking immunosuppressive drugs, in HIV-infected patients, during chemotherapy)
Directions for use and doses
The drug is taken orally with a sufficient amount of water.
Dosage in adults
Treatment of infections caused by the herpes simplex virus
The drug should be taken at a dose of 200 mg five times a day every 4 hours with a break at night for 5 days. In severe cases, treatment is prolonged.
In patients with reduced immunity (for example, after bone marrow transplantation) or with impaired absorption from the gastrointestinal tract, the dose can be increased to 400 mg (as an option, intravenous administration of the drug may be considered). Treatment should begin as soon as possible, immediately after diagnosis. For recurrent infections, it is especially important to begin treatment in the prodromal period or immediately after the first changes appear on the skin.
Suppressive therapy of herpes simplex virus (Herpes simplex virus) in patients with unimpaired immunity
The drug is prescribed 200 mg four times a day every 6 hours.
For most patients, dosing 400 mg twice daily every 12 hours may be effective and convenient.
Gradually reducing the dose to 200 mg three times daily every 8 hours or even twice daily every 12 hours may also be effective.
In some patients, a reaction to taking the drug occurs after prescribing a total daily dose of the drug product of 800 mg.
Drug therapy may be interrupted every 6 to 12 months in order to monitor possible changes in the course of the disease.
Prevention of herpes simplex virus in patients with intact immunity
The drug is prescribed 200 mg four times a day, every 6 hours.
For patients with reduced immunity (for example, after bone marrow transplantation) or with impaired absorption from the gastrointestinal tract, the dose can be increased to 400 mg.
The duration of preventive treatment is determined by the length of the risk period.
Treatment of infections caused by varicella-zoster virus and herpes zoster virus
The drug is prescribed 800 mg five times a day every 4 hours with a night break. Treatment is continued for 7 days.
Patients with reduced immunity (for example, after bone marrow transplantation) or with impaired absorption from the gastrointestinal tract should consider intravenous administration of the drug. Treatment should begin as soon as possible, immediately after symptoms of infection appear. For both chickenpox and herpes zoster, the best treatment results were observed after taking the drug within the first 24 hours of the onset of the rash.
Dosing in children
Treatment of infections caused by the herpes simplex virus in patients with intact immunity
Children 2 years of age and older should receive the same dose as adults. Children under two years of age are prescribed half the dose for adults.
Treatment of infections caused by varicella zoster virus
Children aged 6 years and older: 800 mg four times daily,
Children aged 2 to 5 years: 400 mg four times daily.
Children under 2 years of age: 200 mg four times daily.
The dose can be set more precisely, at the rate of 20 mg/kg body weight (up to a maximum dose of 800 mg) four times a day. Treatment should be continued for 5 days.
There are no data on the specifics of suppressive therapy for infections caused by herpes simplex virus or chickenpox in children with immunodeficiencies.
Dosing in elderly patients
In elderly patients, the risk of renal impairment should be taken into account and the dose of the drug should be adjusted accordingly (see dosing in patients with renal failure).
Fluid replacement should be monitored in these patients.
Use in patients with impaired renal function
During the treatment of infections caused by the herpes simplex virus, or the prevention of viral infection in patients with moderate to severe renal failure, the use of recommended oral doses does not lead to the accumulation of acyclovir in the body at concentrations higher than those considered safe during intravenous administration of the drug. However, in patients with severe renal impairment (creatinine clearance less than 10 ml/min), it is recommended to reduce the dose to 200 mg twice daily, every 12 hours.
During the treatment of infections caused by the varicella zoster virus and herpes zoster, in patients with moderate renal impairment (creatinine clearance 10-25 ml/min), it is recommended to reduce the dose to 800 mg three times a day every 8 hours, and in patients with severe renal impairment insufficiency (creatinine clearance less than 10 ml/min), a dose reduction to 800 mg twice daily every 12 hours is recommended.
Side effects
Very often (>1/10), often (>1/100,<1/10), нечасто (>1/1,000, <1/100), редко (>1/10,000, <1/1,000), очень редко (<1/10,000). Данные побочные явления выражены в основном у пациентов с почечной недостаточностью.
Headache, dizziness
Nausea, vomiting, diarrhea, abdominal pain
Itching, rash, including photo sensitization
Fatigue, fever
Urticaria, rapid diffuse hair loss (the connection with taking the drug Acyclovir has not been proven, it is more often associated with multiple variations in the course of the disease and a large number of drugs used)
Angioedema
Reversible increase in bilirubin levels and liver enzyme activity
Increased concentrations of urea and creatinine in the blood
Anaphylaxis
Very rarely
Anemia, leukopenia and thrombocytopenia
Hepatitis, jaundice
Acute renal failure, renal pain
Anxiety, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma (these symptoms are reversible and are usually observed in patients with renal failure or other predisposing factors).
Contraindications
The drug Acyclovir-AKOS should not be prescribed to patients who have demonstrated hypersensitivity to acyclovir, valacyclovir.
Drug interactions
Acyclovir is excreted mainly in unchanged form, through active excretion in the renal tubules. Any drugs taken concomitantly that compete for this biotransformation pathway may increase plasma concentrations of acyclovir. Probenecid and cimetidine increase the area under the curve (AUC) of acyclovir and reduce the renal clearance of acyclovir. Increased plasma levels of acyclovir and the inactive metabolite mycophenolate mofetil (an immunosuppressive drug used in organ transplant patients) have been observed during concomitant use of these drugs. However, no dosage changes are necessary given the wide therapeutic range of acyclovir.
special instructions
Use as directed by a doctor.
With caution: pregnancy, lactation, dehydration and renal failure.
Adequate and strictly controlled clinical studies of the safety of the drug during pregnancy have not been conducted.
Long-term or repeated treatment with acyclovir in patients with reduced immunity can lead to the emergence of strains of viruses that are insensitive to its action. Most isolated strains of viruses that are insensitive to acyclovir show a relative lack of viral thymidine kinase; Strains with altered thymidine kinase or with altered DNA polymerase were isolated. In vitro, the effect of acyclovir on isolated strains of the Herpes simplex virus may cause the emergence of less sensitive strains.
Instructions for medical use of the drug
Description of pharmacological action
Penetrates into virus-infected cells, competitively interacts with viral thymidine kinase and is sequentially phosphorylated to form mono-, di- and triphosphate. Acyclovir triphosphate is integrated into the viral DNA chain, competitively inhibits the viral DNA polymerase and suppresses its replication.
Indications for use
For systemic use:
Treatment of infections of the skin and mucous membranes caused by Herpes simplex viruses type I and II (primary and secondary, including genital herpes);
Prevention of exacerbations of recurrent infections caused by Herpes simplex viruses type I and II in patients with normal immune status;
Prevention of primary and recurrent infections caused by Herpes simplex viruses type I and II in patients with immunodeficiency;
As part of complex therapy for patients with severe immunodeficiency: with HIV infection (stage of AIDS, early clinical manifestations and detailed clinical picture) and in patients who have undergone bone marrow transplantation;
Treatment of primary and recurrent infections caused by the Varicella zoster virus (chickenpox, herpes zoster).
For external use: skin herpes simplex, genital herpes (simple and recurrent), labial herpes; herpes zoster and chicken pox.
Release form
tablets 200 mg; dark glass jar (jar) 20, cardboard pack 1;
tablets 200 mg; contour packaging 10, cardboard pack 3;
tablets 200 mg; contour packaging 10, cardboard pack 1;
tablets 200 mg; contour packaging 10, cardboard pack 2;
Pharmacodynamics
It has high specificity for herpes simplex virus types I and II, the virus that causes chickenpox and herpes zoster (Varicella zoster), Epstein-Barr virus and cytomegalovirus.
Pharmacokinetics
When taken orally, bioavailability is 15–30%, Cmax is achieved after 1.5–2 hours. The concentration after oral administration of 200 mg 5 times a day is 0.7 mcg/ml. Plasma protein binding is 9–33% and is independent of the concentration of acyclovir in plasma. Penetrates well into all organs and tissues, including the brain and skin. The concentration in the cerebrospinal fluid is 50% of the concentration in plasma. Passes through the placental barrier and accumulates in breast milk. Metabolized in the liver to form a pharmacologically inactive derivative - 9-carboxymethoxymethylguanine. T1/2 in adults with normal renal function is 2–3 hours, in severe renal failure - 20 hours, in patients with hemodialysis - 5.7 hours (at the same time, the concentration of acyclovir in plasma decreases to 60% of the initial value). It is excreted by the kidneys (84% unchanged, 14% as a metabolite), less than 2% through the intestines. Renal clearance accounts for 75–80% of the total clearance.
Use during pregnancy
Possibly if the expected effect of therapy exceeds the potential risk to the fetus. Breastfeeding should be stopped during treatment.
Contraindications for use
Hypersensitivity, incl. to acyclovir or components of the drug, breastfeeding; with caution - dehydration, renal failure, neurological disorders, incl. in the anamnesis.
Side effects
From the nervous system and sensory organs: rarely - headache, weakness; in some cases - tremor, dizziness, increased fatigue, drowsiness, hallucinations.
From the gastrointestinal tract: in isolated cases - abdominal pain, nausea, vomiting, diarrhea.
Allergic reactions: skin rash.
Other: transient increase in liver enzyme activity; rarely - increased levels of urea and creatinine, hyperbilirubinemia, leukopenia, erythropenia, alopecia, fever.
Directions for use and doses
Orally, during or immediately after a meal, with plenty of water. In the treatment of infections of the skin and mucous membranes caused by Herpes simplex I or II, adults and children over 2 years of age - 200 mg 5 times a day for 5 days at 4 hour intervals during the day and at 8 hour intervals at night (if necessary the course can be extended). As part of complex therapy for severe immunodeficiency (including with a full-blown clinical picture of HIV infection, including early clinical manifestations of HIV infection and AIDS), after bone marrow transplantation - 400 mg 5 times a day.
To prevent relapses of infections caused by Herpes simplex I or II, for patients with normal immune status and in case of relapse of the disease - 200 mg 4 times a day every 6 hours (maximum dose - up to 400 mg 5 times a day, depending on the severity of the infection).
When treating infections caused by Varicella zoster, adults and children weighing more than 40 kg - 800 mg 5 times a day every 4 hours during the day and at 8-hour intervals at night. Duration of treatment is 7–10 days. Children over 2 years old - 20 mg/kg 4 times a day for 5 days.
When treating infections caused by Herpes zoster, adults - 800 mg 4 times a day every 6 hours during the day for 5 days.
If renal function is impaired during the treatment and prevention of infections caused by Herpes simplex, in patients with creatinine Cl less than 10 ml/min, the dose of the drug is reduced to 200 mg 2 times a day with a 12-hour interval.
In the treatment and prevention of infections caused by Varicella zoster, in patients with creatinine Cl less than 10 ml/min, the dose of the drug is reduced to 800 mg 2 times a day with 12 hour intervals, with creatinine Cl up to 25 ml/min - 800 mg 3 times a day day with 8 hour intervals.
Interactions with other drugs
When taken orally: probenecid increases the average T1/2 and reduces the clearance of acyclovir; nephrotoxic drugs increase the risk of renal dysfunction.
Precautions for use
Prescribe with caution to patients with impaired renal function and elderly patients (due to an increase in T1/2). When using the drug, it is recommended to take a sufficient amount of fluid. During treatment, it is necessary to monitor kidney function (urea and creatinine levels in the blood). The ointment is not recommended to be applied to the mucous membranes of the mouth, eyes, and genitals (local inflammation may develop).
Special instructions for use
Use internally strictly as prescribed by a doctor in adults and children over 2 years of age (to avoid complications).
It is recommended to start treatment when the first signs of the disease appear (the effectiveness will be higher). In patients with immunodeficiency, with multiple repeated courses, viral resistance to acyclovir may develop.
Storage conditions
In a dry place, protected from light, at a temperature of 8–15 °C.
Best before date
ATX classification:
** The Drug Directory is intended for informational purposes only. For more complete information, please refer to the manufacturer's instructions. Do not self-medicate; Before starting to use the drug Acyclovir-AKOS, you should consult a doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal. Any information on the site does not replace medical advice and cannot serve as a guarantee of the positive effect of the drug.
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