Aciclovir, tablets 200 mg 20 pcs

Pharmacotherapeutic group: antiviral agent.

Code ATX: J05AB01.

Pharmacological properties:

Pharmacodynamics

Mechanism of Action

. Acyclovir is a synthetic analog of the purine nucleoside that has the ability to inhibit invitroinvivo human herpes viruses, including herpes simplex virus (HPV) 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 HPV-1, followed in descending order of activity by HPV-2, VZV, EBV and CMV.

In patients with severe immunodeficiency, prolonged or repeated courses of acyclovir therapy may lead to the emergence of resistant strains, so further treatment with acyclovir may not be effective. Most isolated strains with reduced sensitivity to acyclovir had relatively low thymidine kinase content, as well as disruption of viral thymidine kinase or DNA polymerase structure. Exposure to acyclovir on herpes simplex virus (HPV) strains invitro can also produce less sensitive strains. No correlation has been established between the sensitivity of herpes simplex virus (HPV) strains to acyclovir invitro and the clinical efficacy of the drug.

Pharmacokinetics

.Absorption

Acyclovir is only partially absorbed from the intestine. After administration of 200 mg of acyclovir every 4 hours, the mean maximum equilibrium plasma concentration (Cs_max) was 3.1 µM (0.7 µg/mL) and the mean equilibrium minimum plasma concentration (Cs_min) was 1.8 µM (0.4 µg/mL). When administered orally, 400 mg and 800 mg of acyclovir every 4 hours, the Cs_max was 5.3 µM (1.2 µg/mL) and 8 µM (1.8 µg/mL), respectively, and Cs_min was 2.7 µM (0.6 µg/mL) and 4 µM (0.9 µg/mL), respectively.

Distribution

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

Aciclovir binds only slightly (9-33%) with blood plasma proteins, therefore drug interactions due to displacement from binding sites with blood plasma proteins are unlikely.

Elimation

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

Special patient groups

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

In elderly patients, the overall clearance of acyclovir decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir does not change significantly.

The pharmacokinetic characteristics of both drugs were virtually unchanged when acyclovir and zidovudine were administered simultaneously to HIV-infected patients.

Indications

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

– Prevention of recurrent herpes simplex virus infections 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 an analgesic effect and may reduce the incidence of post-herpetic neuralgia).

Active ingredient

Acyclovir

Composition

Per tablet:

Active substance:

Aciclovir – 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.

How to take, the dosage

The drug Acyclovir tablets can be taken with food, since eating does not interfere with its absorption to any great extent. The tablets should be washed down with a full glass of water.

Adults

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

.

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

In case of severe immunodeficiency (e.g., after bone marrow transplantation) or if absorption from the intestine is impaired, the dose of Acyclovir may be increased to 400 mg. Alternatively, the possibility of using acyclovir in the dosage form lyophilisate for preparation of a solution for infusion may be considered.

Treatment should be started as soon as possible after the onset of infection; for relapses, it is recommended that the drug be given as early as the prodromal period or the appearance of the first elements of the rash.

In order to prevent recurrent herpes simplex virus infections in patients with normal immune status

In order to prevent recurrent herpes simplex virus infections in patients with normal immune status, the recommended dose of Acyclovir is 200 mg orally 4 times daily (every 6 hours).

Many patients are able to take the more convenient regimen of 400 mg orally 2 times daily (every 12 hours).

In some cases, lower doses of acyclovir may be effective: 200 mg orally 3 times daily (every 8 hours) or 200 mg orally 2 times daily (every 12 hours).

In some patients, the infection may worsen if a total daily dose of 800 mg is taken.

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

Prevention of infections caused by herpes simplex virus in immunodeficient patients

In order to prevent infections caused by herpes simplex virus in immunodeficient patients, the recommended dose of Acyclovir is 200 mg orally 4 times daily (every 6 hours).

In cases of severe immunodeficiency (e.g., after a bone marrow transplant) or with impaired intestinal absorption, the drug dose may be increased to 400 mg orally. Alternatively, the possibility of using acyclovir in the dosage form lyophilisate for preparation of a solution for infusion may be considered.

The duration of prophylactic therapy is determined by the length of time during which there is a risk of infection.

The treatment of chicken pox and herpes zoster

For the treatment of chicken pox and herpes zoster, the recommended dose of acyclovir is 800 mg orally 5 times daily (every 4 hours except for bedtime). The course of treatment is 7 days.

The treatment of herpes zoster should begin as soon as possible after the first symptoms of the disease, because in this case the treatment is more effective.

Patients with normal immune status should begin treatment for chickenpox within 24 hours of the onset of symptoms.

In patients with severe immunodeficiency (e.g., after a bone marrow transplant) or with impaired intestinal absorption, acyclovir in the dosage form lyophilisate for preparation of a solution for infusion should be considered.

Patient Special Groups

Children aged 3 years and older

The treatment of infections caused by herpes simplex virus; Prevention of infections caused by herpes simplex virus in patients with immunodeficiency

Aged 3 years and older, the same doses as for adults.

The treatment of chickenpox

– ages 6 years and older – 800 mg orally 4 times daily;

– ages 3 to 6 years – 400 mg orally 4 times daily.

A more precise dose can be determined at the rate of 20 mg/kg of body weight (but no more than 800 mg) orally 4 times a day. The course of treatment is 5 days.

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

There are no data on dosing regimen.

Elderly patients

The possibility of renal impairment in elderly patients must be considered; doses must be adjusted according to the degree of renal impairment (see subsection “Patients with impaired renal function”).

An adequate water balance must be maintained.

Patients with impaired renal function

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

Aquivalent water balance must be maintained.

In patients with renal impairment, oral administration of acyclovir in recommended doses for the treatment and prevention of infections caused by herpes simplex virus does not lead to cumulation of the drug to concentrations exceeding the established safe levels. However, in patients with creatinine clearance less than 10 ml/min, it is recommended to decrease the dose of Acyclovir to 200 mg orally twice daily (every 12 hours).

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

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

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

Interaction

No clinically significant interactions during the use of Acyclovir were observed.

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

Acyclovir increases the AUC of theophylline by approximately 50% when taken simultaneously, so it is recommended to measure plasma concentrations of theophylline when acyclovir is simultaneously administered.

Probenecid and cimetidine increase the AUC (area under the curve “concentration – time”) of acyclovir and decrease its renal clearance. There was an increase in plasma AUC for acyclovir and the 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 wide therapeutic index of acyclovir.

Special Instructions

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

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

Hydration status

Patients taking high doses of Acyclovir orally should get enough fluids.

Patients in the elderly and patients with impaired renal function

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

In elderly patients, renal function may be reduced; therefore, this group of patients may also require dose reduction. Both elderly patients and patients with impaired renal function are at increased risk of nerve side effects (these reactions are usually reversible in response to discontinuation of the drug) and therefore should be under close medical supervision.

Patients with severe immunodeficiency

Long or repeated courses of acyclovir treatment in patients with severe immunodeficiency may lead to the emergence of acyclovir strains of the virus with hypersensitivity to acyclovir that will not respond to continued acyclovir therapy.

All patients, especially those with clinical manifestations, should use caution to avoid potential transmission. Patients should be informed about cases of asymptomatic viral carriage.

Impact on ability to drive vehicles, machinery:

There have been no studies of the effect of acyclovir on the ability to drive or operate machinery. 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 the side effect profile of acyclovir must be considered.

Synopsis

Round flat cylindrical white or almost white tablets with a bevel and a rib.

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, renal failure, dehydration, concomitant use with other nephrotoxic drugs.

Side effects

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

The undesired reactions presented below are listed according to the frequency of occurrence, defined as follows: very common (>1/10), frequent (>1/100 and <1/10), not commonnot often (>1/10000 and <1/1000), very rarely (<1/10,000).

Frequency of adverse reactions

p> Blood and lymphatic system disorders

Very rare: Anemia, leukopenia, thrombocytopenia.

Disorders of the immune system

Rarely: anaphylaxis.

Nervous system and mental status disorders

Often: headache, dizziness.

Very rarely: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, seizures, somnolence, encephalopathy, coma.

In general, these side effects were observed in patients with renal impairment or other proximate factors and were mostly reversible (see Special Precautions).

Disorders of the respiratory system, thorax and mediastinum

Rarely: dyspnea.

Gastrointestinal tract disorders

Often: 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

Often: itching, rash, including photosensitization.

Infrequent: urticaria, rapid diffuse hair loss.

Because rapid diffuse hair loss is seen in a variety of diseases and with therapy with many drugs, its relationship to taking acyclovir has not been established.

Rarely: angioedema.

very rarely: toxic epidermal necrolysis, erythema multiforme.

Renal and urinary tract disorders

Rarely: increased concentration of urea and creatinine in blood serum.

very rarely: acute renal failure, renal colic.

Renal colic may be associated with renal failure and crystalluria.

General disorders and disorders at the site of administration

Often: fatigue, fever.

Overdose

Acyclovir is only partially absorbed in the gastrointestinal tract.

As a rule, toxic effects have not been reported with occasional single administration of acyclovir in doses up to 20 g.

When repeated oral doses exceeding the recommended doses for several days, gastrointestinal (nausea, vomiting) and nervous system disorders (headache and confusion) were observed.

Sometimes neurological effects such as seizures, coma may be observed.

Patients need careful medical monitoring to identify possible symptoms of intoxication.

Acyclovir is eliminated from the body by hemodialysis, so hemodialysis can be used to treat overdose.

Pregnancy use

Fertility

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

In a study involving 20 male patients with normal sperm counts, oral acyclovir at a dose of up to 1 g per day for 6 months was found to have no clinically significant effect on sperm count, motility or morphology.

Pregnancy

The post-registration pregnancy registry collected data on pregnancy outcomes in women treated with acyclovir in different 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 to the general population. The birth defects detected were not characterized by uniformity or a pattern suggesting a common cause.

But caution should be exercised when prescribing Acyclovir to women during pregnancy and assess the anticipated benefit to the mother and the possible risk to the fetus.

The period of breastfeeding

. After oral administration of Acyclovir at a dose of 200 mg 5 times daily, acyclovir was detected in breast milk at concentrations ranging from 60% to 410% of plasma concentration. At such concentrations in breast milk, breastfed infants can receive acyclovir at doses up to 0.3 mg/kg/day. Taking this into account, caution should be exercised when prescribing Acyclovir to breastfeeding women.

Similarities

Zovirax, Vivorax, Acyclovir-Acri, Acyclovir, Herperax, Acyclovir Belupo, Acyclovir Sandoz