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

An antiviral (antiherpetic) agent is a synthetic analogue of a purine nucleoside, which has the ability to inhibit in vitro and in vivo virus replication Herpes simplex type 1 and 2, the virus Varicella zoster, the Epstein-Barr virus and cytomegalovirus.

Highly active against viruses Herpes simplex 1 and 2 types; a virus that causes varicella and shingles (Varicella zoster); of the Epstein-Barr virus (virus types are listed in order of increasing 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 guanylyl cyclase acyclovir, monophosphate is converted to diphosphate and under the influence of several cellular enzymes - into triphosphate. High selectivity of the action is for viruses and low toxicity for humans due to the fact that acyclovir is not a substrate for the thymidine kinase enzyme of uninfected cells, so it is low-toxic for mammalian cells.

Acyclovir triphosphate inhibits the synthesis (replication) of the virus DNA by three mechanisms: 1) competitively replaces deoxyguanosine triphosphate in DNA synthesis; 2) "embedded" in the synthesized DNA chain and stops its elongation; 3) inhibits the enzyme DNA polymerase of the virus.As a result, the multiplication of the virus in the human body is blocked. The specificity and very high selectivity of the action of acyclovir is also due to its predominant accumulation in cells infected with viruses.

When herpes infection prevents the formation of new elements of the rash, reduces the likelihood of skin dissemination and visceral complications, accelerates the formation of crusts, reduces pain in the acute phase of herpes zoster. It has an immunostimulating effect.

Pharmacokinetics:

After ingestion, it is partially absorbed into the intestine, because of low lipophilicity, absorption after oral intake of 200 mg to 20% (15-30%), but at the same time dose-related concentrations are created sufficient to effectively treat viral diseases. Food has no significant effect on the absorption of acyclovir. As the dose increases, bioavailability decreases.

Maximum concentration (C_max) after the administration of 200 mg 5 times a day - 0.7 μg / ml, the minimum concentration (C_m_in) - 0,4 mkg / ml, the time to reach the maximum concentration - 1,5-2 hours. The connection with plasma proteins is 9-33%.

Penetrates through the blood-brain barrier. Well penetrates into organs and tissues (incl.the brain, kidneys, lungs, liver, watery moisture, tear fluid, intestines, muscles, spleen, breast milk, uterus, mucous membrane and vaginal secretion, sperm, amniotic fluid, the contents of herpetic vesicles); concentration in the cerebrospinal fluid - 50% of that in the blood. Acyclovir penetrates the placenta, with breast milk excreted in low concentrations. After oral administration at a dose of 200 mg 5 times a day acyclovir is defined in breast milk in concentrations of 0.6-4.1% of plasma concentrations (at such concentrations in breast milk, infants fed breastfed can receive acyclovir with milk of mother in a dose to 0.3 mg / kg / day). Metabolised in the liver with the formation of a metabolite - 9-carboxymethoxymethylguanine.

It is excreted by the kidneys through glomerular filtration and tubular secretion: when ingested, most of it is unchanged (62-91% of dose) and metabolite (14% on average). Less than 2% is excreted through the gastrointestinal tract; trace amounts are determined in the exhaled air.

With a single hemodialysis session for 6 hours, the concentration of acyclovir in the plasma decreases by approximately 60%; At peritoneal dialysis, the clearance of acyclovir does not change significantly.

Half-life (T_1/2) with oral administration in adults - 3.3 hours, in children and adolescents from 1 to 18 years - 2.6 hours. The rate of excretion slows down with age, but T_1/2 of active drug increases slightly

In patients with severe chronic renal insufficiency T_1/2- up to 20 hours. T_1/2 with renal insufficiency (in adults, depending on the values of creatinine clearance (CC)): with SC 80 ml / min - 2.5 h, 50-80 ml / min - 3 h, 15-50 ml / min - 3.5 h ; at anuria - 19.5 h, during the hemodialysis - 5.7 h, with constant outpatient peritoneal dialysis - 14-18 h.

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

Indications:

Treatment and prevention of infections caused by viruses Herpes simplex types 1 and 2 and Varicella zoster:

1 herpes simplex skin and mucous membranes (primary and recurrent);

2 genital herpes (primary and recurrent);

3 shingles (herpes zoster);

4 Chicken pox (in the first 24 hours after the appearance of a typical rash);

5 in patients with severe immunodeficiency (including after transplantation, with the reception of immunosuppressive drugs, in HIV-infected patients, against chemotherapy).

Contraindications:

Hypersensitivity to acyclovir (incl.to valacyclovir), children under 3 years old.

Carefully:

Pregnancy, lactation, dehydration and kidney failure.

Pregnancy and lactation:

The use of the drug during pregnancy is possible in the event that the intended use for the mother exceeds the potential risk to the fetus.

Dosing and Administration:

Inside, regardless of food intake, drink a full glass of water.

Adults for treatment herpes simplex skin and mucous membranes - 200 mg 5 times a day (every 4 hours during waking hours, excluding night sleep) during 5 days, if necessary, the duration of treatment can be extended. In the treatment of patients with immunodeficiency, a single dose of the drug should be increased to 400 mg, the duration of the course is 10 days or more.

Adults for treatment genital herpes - 200 mg 5 times a day (every 4 hours during wakefulness, except for night sleep) for 10 days, if necessary, the duration of treatment can be extended. In the treatment of patients with immunodeficiency, a single dose of the drug should be increased to 400 mg.

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.

For prevention of recurrence of infections caused by the herpes simplex virus (including in patients with immunodeficiency), the drug is prescribed at 200 mg 4 times a day (every

6 hours). Patients with normal immune status for the prevention of herpes simplex skin and mucous membranes may be prescribed 400 mg twice a day (every 12 hours). In the case of severe immunodeficiency (after bone marrow transplantation or when intestinal absorption is violated), 400 mg 5 times a day.

Recurrent genital herpes (less than 6 episodes a year): intermittent therapy - 200 mg 5 times a day for 5 days. Recurrent genital herpes (more

6 episodes a year): prolonged suppressive therapy - 400 mg twice a day or 200 mg 3-5 times a day (duration of the course up to 12 months).

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

In the treatment shingles (herpes zoster) - 800 mg 5 times a day (every 4 hours during waking hours, except for a night's sleep) for 7-10 days. The maximum single dose for admission is 800 mg.

Patients taking high doses orally should receive a sufficient amount of fluid.

Children over the age of 3 years of age are prescribed the drug at the same dose as adults.

Treatment chicken pox: adults and children over 6 years - 800 mg 4 times a day; children 3-6 years - 400 mg 4 times a day. More precisely, the dose can be determined from the calculation of 20 mg / kg, but not more than 800 mg 4 times a day. The course of treatment is 5 days.

In patients with impaired renal function, dose adjustments and dosing regimens are required, depending on the amount of creatinine clearance and the type of infection. For the treatment of infection caused by Herpes simplex, when the creatinine clearance is less than 10 ml / min, the daily dose of the drug should be reduced to 400 mg, dividing it into 2 divided doses (with intervals of at least 12 hours, ie 200 mg twice a day). In the treatment of infections caused by Varicella zoster, and with maintenance therapy of patients with severe immunodeficiency, patients with a creatinine clearance of 10-25 ml / min are prescribed a drug at a dose of 2.4 g / day in 3 divided doses at an interval of 8 h (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, the frequency of administration is 2 times a day with an interval of 12 hours (800 mg twice a day).

Side effects:

From the digestive system: nausea, vomiting, diarrhea, abdominal pain; rarely - a reversible increase in the level of bilirubin and activity of liver enzymes.

On the part of the hematopoiesis system: very rarely - anemia, leukopenia, thrombocytopenia.

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

From the side of the central nervous system: headache; rarely - reversible neurological disorders, such as dizziness, confusion, hallucinations, drowsiness, paresthesia, convulsions, coma. Usually these side effects were observed in patients with renal insufficiency, who took the drug in doses exceeding the recommended ones.

Allergic reactions: rash, photosensitivity, urticaria, pruritus; rarely - shortness of breath, angioedema, anaphylaxis.

Fever, lymphadenopathy, peripheral edema, visual impairment, agitation, myalgia.

Other: fast fatiguability; rarely - alopecia.

In patients receiving antiretroviral drugs, an additional dose of acyclovir did not cause a significant increase in toxic effects.

Overdose:Oral administration of 20 g of acyclovir did not lead to the development of specific symptoms.

Interaction:

An increase in the effect is noted with the simultaneous appointment of immunostimulants. Other nephrotoxic drugs are an increased risk of nephrotoxic action.

Special instructions:

Long-term or repeated treatment with acyclovir patients with reduced immunity can lead to the appearance of strains of viruses that are insensitive to its action. The majority of isolated strains of viruses, 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 action of acyclovir on isolated strains of the virus Herpes simplex may cause the appearance of less sensitive strains.

Adequate and strictly controlled clinical studies of the safety of the drug during pregnancy have not been conducted. The application is indicated only in cases where the intended use for the mother exceeds the potential risk to the fetus.

In the course of therapy with high oral doses of the drug, a sufficient supply of fluid to the patient's body should be ensured.

During the lactation period, the drug is prescribed only in case of emergency and a short course, in connection with a slight penetration of acyclovir into breast milk, breastfeeding does not stop, but continues with great care under the strict supervision of the doctor.

Acyclovir does not prevent the transmission of genital herpes, therefore during treatment it is necessary to abstain from sexual intercourse, even in the absence of clinical manifestations.

Form release / dosage:

Tablets of 200 mg.

Packaging:

10 tablets in a planar cell package.

1,2,3 contoured cell packs with instructions for use in packs of cardboard.

Storage conditions:

List B. Store in a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:5 years. The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N001595 / 02

Date of registration:11.09.2008

Expiration Date:Unlimited

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

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp30.09.2017

Illustrated instructions

Instructions

Acyclovir-AKOS (Aciclovir-AKOS)