Aciclovir tablets 200 mg

Composition:

Per one tablet:

Active ingredient:

Acyclovir - 200.0 mg.

Excipients:

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.

Description:

Round, biconvex white or almost white tablets with a bevel and a score line.

Pharmacotherapeutic group: Antiviral agent.

ATC code: J05AB01

Pharmacological properties

Pharmacodynamics

Mechanism of action

Acyclovir is a synthetic analogue of a purine nucleoside which has the ability to inhibit human herpes viruses in vitro and in vivo, including Herpes Simplex Virus (HSV) types 1 and 2, 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 in descending order of activity by HSV-2, VZV, EBV and CMV.

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 thymidine kinase enzyme of uninfected cells, therefore acyclovir has low toxicity to mammalian cells. However, the thymidine kinase of cells infected with HSV, VZV, EBV and CMV viruses converts acyclovir into acyclovir monophosphate - a nucleoside analogue, which is then sequentially converted into diphosphate and triphosphate by cellular enzymes. The incorporation of acyclovir triphosphate into the viral DNA chain and the subsequent chain termination block further replication of the viral DNA.

In patients with severe immunodeficiency, long-term or repeated courses of acyclovir therapy can lead to the emergence of resistant strains, so further treatment with acyclovir may be ineffective. Most isolated strains with reduced sensitivity to acyclovir showed relatively low thymidine kinase content, as well as impaired viral thymidine kinase or DNA polymerase structure. Exposure of Herpes Simplex Virus (HSV) strains to acyclovir in vitro can also lead to the formation of less sensitive strains. No correlation has been established 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 (Css_max) was 3.1 µM (0.7 µg/ml), and the mean minimum steady-state plasma concentration (Css_min) was 1.8 µM (0.4 µg/ml). When taking 400 mg and 800 mg of acyclovir orally every 4 hours, the Css_max was 5.3 µM (1.2 µg/ml) and 8 µM (1.8 µg/ml), respectively, and the Css_min was 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 plasma.

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

Elimination

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

Indications for use

- Treatment of skin and mucous membrane infections caused by Herpes Simplex Virus, including primary and recurrent genital herpes;

- prevention of recurrences of Herpes Simplex Virus infections in patients with normal immune status;

- prevention of Herpes Simplex Virus infections in immunocompromised patients;

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

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, breastfeeding, elderly age, renal failure, dehydration, simultaneous use with other nephrotoxic drugs.

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 normal sperm count, it was found that oral administration of acyclovir at doses up to 1 g per day for 6 months had no clinically significant effect on sperm count, motility or morphology.

Pregnancy

A post-marketing pregnancy registry has collected data on pregnancy outcomes in women who took acyclovir in various dosage forms. Analysis of the registry data did not show an increase in the number of birth defects in newborns whose mothers took acyclovir during pregnancy compared to the general population. The identified birth defects were not uniform or patterned in a way that would suggest a common cause.

However, caution should be exercised when prescribing Acyclovir to pregnant women and the intended benefit to the mother should be weighed against the potential risk to the fetus.

Breastfeeding period

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

Dosage and administration

Acyclovir tablets can be taken with meals, as food does not significantly impair its absorption. The tablets should be taken with a full glass of water.

Adults

Treatment of skin and mucous membrane infections 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, omitting the night dose). The course of treatment is 5 days, but may be extended for severe primary infections.

In cases of severe immunodeficiency (e.g., after bone marrow transplantation) or impaired intestinal absorption, the dose of Acyclovir may be increased to 400 mg. Alternatively, the use of acyclovir in the form of a lyophilisate for the preparation of an infusion solution may be considered.

Treatment should be started as early as possible after the onset of infection; for recurrences, the drug is recommended to be prescribed in the prodromal period or when the first elements of the rash appear.

Prevention of recurrences of Herpes Simplex Virus infections in patients with normal immune status

For the prevention of recurrences of Herpes Simplex Virus infections in patients with normal immune status, the recommended dose of Acyclovir is 200 mg orally 4 times a day (every 6 hours).

Many patients find the more convenient therapy regimen of 400 mg orally twice a day (every 12 hours) suitable.

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

In some patients, exacerbation of the infection may occur when taking a total daily dose of 800 mg.

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

Prevention of Herpes Simplex Virus infections in immunocompromised patients

For the prevention of Herpes Simplex Virus infections in immunocompromised patients, the recommended dose of Acyclovir is 200 mg orally 4 times a day (every 6 hours).

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

The duration of the prophylactic 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, omitting the night dose). 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, as in this case the treatment will be more effective.

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

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

Special patient groups

Children aged 3 years and older

Treatment of infections caused by Herpes Simplex Virus; prevention of infections caused by Herpes Simplex Virus in immunocompromised patients

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

Treatment of chickenpox

- aged 6 years and older — 800 mg orally 4 times a day;

- aged 3 to 6 years — 400 mg orally 4 times a day.

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

Prevention of recurrences of Herpes Simplex Virus infections in patients with normal immune status; treatment of herpes zoster

Data on the dosage regimen are not available.

Elderly patients

The likelihood of renal failure in elderly patients should be considered; doses should be adjusted according to the degree of renal failure (see subsection "Patients with impaired renal function").

Adequate hydration should be maintained.

Patients with impaired renal function

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

Adequate hydration should be maintained.

In patients with renal failure, oral administration of acyclovir in recommended doses for the treatment and prevention of Herpes Simplex Virus infections does not lead to accumulation of the drug to concentrations exceeding established safe levels. However, in patients with creatinine clearance less than 10 ml/min, the dose of Acyclovir is recommended to be reduced to 200 mg orally twice a day (every 12 hours).

For the treatment of chickenpox and herpes zoster, the recommended doses of Acyclovir tablets are:

- with creatinine clearance less than 10 ml/min — 800 mg orally twice a day (every 12 hours);

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

Side effects

The frequency categories of adverse reactions provided below are estimates. For most adverse reactions, the data necessary to determine the frequency of occurrence are lacking. In addition, the frequency of adverse reactions may vary depending on the indication.

The adverse reactions listed below are presented by frequency of occurrence, defined as follows: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1000 and <1/100), rare (>1/10000 and <1/1000), very rare (<1/10,000).

Frequency of adverse reactions

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia.

Disorders of the immune system

Rare: anaphylaxis.

Disorders of the nervous system and mental status

Common: headache, dizziness.

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

These side effects were usually observed in patients with renal failure or in the presence of other provoking factors and were mainly reversible (see section "Special instructions").

Disorders of the respiratory system, thoracic and mediastinal organs

Rare: shortness of breath.

Gastrointestinal disorders

Common: nausea, vomiting, diarrhea, abdominal pain.

Disorders of the liver and biliary tract

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

Very rare: hepatitis, jaundice.

Disorders of the skin and subcutaneous tissues

Common: itching, rash, including photosensitivity.

Uncommon: urticaria, rapid diffuse hair loss.

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

Rare: angioedema.

Very rare: toxic epidermal necrolysis, exudative erythema multiforme.

Disorders of the kidneys and urinary tract

Rare: 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 administration site conditions

Common: fatigue, fever.

Overdose

Acyclovir is only partially absorbed in the gastrointestinal tract. As a rule, no toxic effects were recorded after a single accidental intake of acyclovir in doses up to 20 g. With repeated oral administration over several days of doses exceeding the recommended ones, disorders of the gastrointestinal tract (nausea, vomiting) and nervous system (headache and confusion) were noted. Neurological effects such as seizures and coma may sometimes be observed.

Patients require careful medical supervision to detect possible symptoms of intoxication. Acyclovir is removed from the body by hemodialysis, so hemodialysis can be used to treat overdose.

Dosage form

Tablets, 200 mg

10 tablets in a blister strip made of polyvinyl chloride film and printed lacquered aluminum foil.

1, 2 or 3 blister packs, together with the instructions for use, are placed in a cardboard carton. Shelf life

3 years. Do not use after the expiration date.

Storage conditions

In a dry place, protected from light and moisture, at a temperature not exceeding 25°C.

Keep out of reach of children.

Prescription status

By prescription.