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

Excipientslactose monohydrate (137.0 mg), potato starch (45.0 mg), povidone low molecular weight (7.6 mg), sucrose (16.0 mg), sodium lauryl sulfate (1.4 mg), magnesium stearate (3, 0 mg).

Description:

Round flat cylindrical tablets of white or almost white color, with a facet and a risk.

Pharmacotherapeutic group:Antiviral agent

ATX: & nbsp

S.01.A.D Antiviral drugs

Pharmacodynamics:

Mechanism of action

Acyclovir is a synthetic analogue of the purine nucleoside, which has the ability to inhibit in vitro and in vivo human herpes viruses, including herpes simplex virus type 1 and type 2, varicella zoster virus (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, VCB, EBV and CMV viruses converts acyclovir in acyclovir monophosphate - an analogue of the nucleoside, which is then sequentially 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. Most of the isolated strains with reduced sensitivity to acyclovir showed a relatively low content of thymidine kinase, a disruption of the structure of the viral thymidine kinase or DNA polymerase. The effect of acyclovir on strains of 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 the 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 (C_ssmax) was 3.1 μM (0.7 μg / ml), and the mean equilibrium minimum plasma concentration (C_ssmin) was 1.8 μM (0.4 μg / ml). When taking 400 mg and 800 mg of acyclovir every 4 hours C_ssmax was 5.3 μM (1.2 μg / ml) and 8 μM (1.8 μg / ml), respectively, and C_ssmin 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.

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 administration of acyclovir 1 h after receiving 1 g of probenecid, the half-life of acyclovir and AUC (the 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 average 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;

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

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

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

Contraindications:

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

Carefully:Pregnancy, the period of breastfeeding, old age, renal failure, dehydration, concomitant use with other nephroxic 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 was determined 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 up to 0.3 mg / kg / day. Given this, care should be taken when prescribing the drug Acyclovir nursing women.

Dosing and Administration:

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

Adults

Treatment of infections caused by the herpes simplex virus

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

In the case of severe immunodeficiency (for example, after bone marrow transplantation) or with a violation of absorption from the intestine, the dose of the drug Acyclovir for oral administration can be increased to 400 mg. Alternatively, the possibility of using acyclovir in the dosage form of a lyophilizate for the preparation of a solution for infusions may 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; treatment of herpes zoster.

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

In the case of severe immunodeficiency (for example, after bone marrow transplantation) or with a violation of absorption from the intestine, the dose of the drug Acyclovir for oral administration can be increased to 400 mg 4 times a day. 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 Acyclovir is 800 mg 5 times a day (every 4 hours, except for the night sleep), the course of treatment is 7 days.

Treatment of herpes zoster should be started as soon as possible after the appearance of rashes, since in this case the treatment will be more effective.

Treatment of varicella in patients with normal immune status should be started within 24 hours of the onset of rashes.

In patients with severe immunodeficiency (for example, after bone marrow transplantation) or when there is a violation of absorption from the intestine, consideration should be given to the possibility of prescribing acyclovir in the dosage form of lyophilizate for the preparation of a solution for infusions.

Special patient groups

Children aged 3 years and over

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

- at the age of 3 years and older - the same dose as in 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 consider the likelihood of renal failure in elderly patients, the dose should be adjusted in accordance with the degree of renal failure (see section "Patients with renal insufficiency").

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 Acyclovir 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 Acyclovir it is recommended to reduce to 200 mg twice a day (every 12 hours).

In the treatment of varicella zoster and herpes zoster the recommended dose of the drug Acyclovir, tablets, make up

- with creatinine clearance less than 10 ml / min

-800 mg twice a day (every 12 hours);

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

Side effects:

The following classification of unwanted reactions is used depending on the frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10), sometimes (> 1/1000, <1/100), rarely (> 1 / 10000, <1/1000), very rarely (<10 000).

From the hematopoiesis and lymphatic system:

Very rarely: anemia, leukopenia, thrombocytopenia.

From the immune system:

Rare: anaphylaxis.

From the side of neuro-mental status:

Often: headache, dizziness.

Very rarely: agitation, 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, were mainly reversible.

From the respiratory system, chest and mediastinum:

Rarely: shortness of breath.

From the gastrointestinal tract:

Often: nausea, vomiting, diarrhea, abdominal pain.

From the liver and bile ducts:

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

Very rarely: hepatitis, jaundice.

From the skin and subcutaneous tissue:

Often: itching, rash, including photosensitivity.

Sometimes: urticaria, rapid diffuse hair loss.

Since this type of alopecia is observed in various diseases and in the treatment with many drugs, its association with acyclovir is not established.

Rarely: angioedema.

Very rarely: toxic epidermal necrolysis, multiforme exudative erythema.

From the urinary system:

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

Very rarely: acute renal failure, renal colic.

Renal colic can be associated with renal insufficiency and crystalluria.

Others:

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 of doses exceeding the recommended, there were violations of the gastrointestinal tract (nausea,vomiting) and the nervous system (headache and confusion). Sometimes such neurological effects as convulsive seizures, coma may occur.

Treatment

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 relevant interactions with the drug Acyclovir was not noted.

Acyclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar elimination route can increase the plasma concentration of acyclovir. Probenecid and cimetidineBeing inhibitors of microsomal oxidation increase AUC value (area under the curve "in the plasma concentration - time") of acyclovir, reduce its renal clearance and increased plasma concentration. Increase in AUC was observed for acyclovir and indicator inactive metabolite mycophenolate mofetil, an immunosuppressant in transplantation being applied, while the use of both drugs.However, dose adjustment is not required, due to the wide range of therapeutic doses of acyclovir.

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

Special instructions:

Available data from clinical trials are not sufficient to conclude that the use of acyclovir reduces the risk of chickenpox in patients with normal immune status. The risk of developing kidney failure increases with simultaneous use with other nephrotoxic drugs. The state of hydration.

Patients taking high doses of the drug Acyclovir inside, should receive a sufficient amount of liquid. Patients of advanced age and patients with impaired renal function.

Because the acyclovir is excreted by the kidneys, the doses should be reduced to patients with renal insufficiency (see the section "Dosing and Administration").

In elderly patients, kidney function may be reduced, therefore, a dose reduction may also be required for this group of patients.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.

Patients with severe immunodeficiency.

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.

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.

Effect on the ability to drive transp. cf. and fur:Studies of the effect of acyclovir on the ability to drive vehicles or mechanisms have not been carried out. It is not possible to predict the negative effect of acyclovir on these activities on the basis of the pharmacological properties of the active substance,but it is necessary to take into account the side effects profile of acyclovir.

Form release / dosage:Tablets of 200 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1, 2 or 3 contour mesh packages together with the instruction for use will be prevented in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-001205

Date of registration:15.07.2011 / 05.09.2017

Expiration Date:Unlimited

The owner of the registration certificate:AVVA RUS, OJSC AVVA RUS, OJSC Russia

Manufacturer: & nbsp

AVVA RUS, OJSC Russia

Information update date: & nbsp30.09.2017

Illustrated instructions

Instructions

Acyclovir (Aciclovir)