Aciclovir-Akrikhin (Tablets, Ointment) Instructions for Use

ATC Code

J05AB01 (Aciclovir)

Active Substance

Aciclovir (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleosides and nucleotides, excluding reverse transcriptase inhibitors

Pharmacological Action

An antiviral drug, a synthetic analogue of an acyclic purine nucleoside, which has a highly selective effect on herpes viruses. In infected cells containing viral thymidine kinase, phosphorylation and conversion to acyclovir monophosphate occurs.

Under the influence of guanylate cyclase, acyclovir monophosphate is converted to diphosphate and, under the action of several cellular enzymes, to triphosphate.

Acyclovir triphosphate is incorporated into the viral DNA chain and blocks its synthesis through competitive inhibition of viral DNA polymerase. The specificity and very high selectivity of action is also due to its predominant accumulation in cells affected by the herpes virus.

Highly active against Herpes simplex virus types 1 and 2; the virus causing varicella and herpes zoster (Varicella zoster); Epstein-Barr virus. Moderately active against cytomegaloviruses.

In herpes, it prevents the formation of new elements, reduces the likelihood of skin dissemination and visceral complications, accelerates crust formation, and reduces pain in the acute phase of herpes zoster.

Pharmacokinetics

Absorption and Distribution

When taken orally, bioavailability is 15-30%. C_max in blood plasma after oral administration of the drug at a dose of 200 mg 5 times/day is 0.7 µg/ml. The time to reach C_max in blood plasma is 1.5-2 hours.

Plasma protein binding is 9-33%. Aciclovir penetrates well into all organs and tissues of the body; the concentration in the cerebrospinal fluid is 50% of the concentration in blood plasma. It penetrates the blood-brain barrier and placental barrier, and is excreted in breast milk.

Metabolism and Excretion

It is metabolized in the liver to form a pharmacologically inactive metabolite – 9-carboxymethoxymethylguanine.

T_1/2 when taken orally is 2-3 hours. It is excreted by the kidneys unchanged (about 84%) and in the form of a metabolite (about 14%). Less than 2% is excreted through the gastrointestinal tract; trace amounts are detected in exhaled air.

Pharmacokinetics in Special Clinical Cases

In patients with severe renal failure, T_1/2 is 20 hours, during hemodialysis – 5.7 hours (while the concentration of acyclovir in plasma decreases to 60% of the initial value).

Indications

• Treatment of infections of the skin and mucous membranes caused by Herpes simplex viruses types 1 and 2, both primary and secondary, including genital herpes;
• Prevention of exacerbations of recurrent infections caused by Herpes simplex viruses types 1 and 2 in patients with normal immune status;
• Prevention of primary and recurrent infections caused by Herpes simplex viruses types 1 and 2 in patients with immunodeficiency;
• As part of complex therapy in patients with severe immunodeficiency: in HIV infection (AIDS stage, early clinical manifestations and advanced clinical picture) and in patients who have undergone bone marrow transplantation;
• Treatment of primary and recurrent infections caused by Varicella zoster virus (chickenpox, herpes zoster).

ICD codes

Dosage Regimen

Ointment

For external use. The drug is applied with clean hands or a cotton swab 5 times/day (every 4 hours) in a thin layer to the affected areas of the skin and areas bordering them.

Therapy should be continued until crusts form on the blisters or until they are completely healed. The duration of therapy is on average 5 days, maximum – 10 days.

If there is no effect, it is necessary to consult a doctor.

Tablets

The drug is taken orally, during or immediately after a meal, with a sufficient amount of water.

The dosage regimen is set individually depending on the severity of the disease.

For treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2, adults are prescribed 200 mg 5 times/day (every 4 hours during waking hours, excluding night sleep) for 5 days; for treatment of genital herpes – 10 days. If necessary, the duration of treatment can be extended.

As part of complex therapy for severe immunodeficiency, including advanced clinical picture of HIV infection (including early clinical manifestations of HIV infection and AIDS stage), after bone marrow transplantation, 400 mg 5 times/day is prescribed.

For prevention of relapses of infections caused by Herpes simplex viruses types 1 and 2, in patients with normal immune status, adults are prescribed 200 mg 4 times/day every 6 hours. The course duration is from 6 to 12 months.

For prevention of infections caused by Herpes simplex viruses types 1 and 2, in patients with immunodeficiency, adults are prescribed 200 mg 4 times/day every 6 hours, the maximum dose is up to 400 mg of acyclovir 5 times/day depending on the severity of the infection.

For treatment of herpes zoster – 800 mg 5 times/day (every 4 hours during waking hours, excluding night sleep) for 7-10 days.

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

For treatment of chickenpox, adults and children over 6 years of age are prescribed 800 mg 4 times/day; children aged 3-6 years – 400 mg 4 times/day. The dose can be more accurately determined at the rate of 20 mg/kg. The course of treatment is 5 days.

In patients with impaired renal function, dose adjustment and dosage regimen are necessary depending on the CC value and the type of infection. For treatment of infection caused by Herpes simplex, with CC less than 10 ml/min, the daily dose of the drug should be reduced to 400 mg, dividing it into 2 doses (with intervals between them of at least 12 hours, i.e. 200 mg 2 times/day). For treatment of infections caused by Varicella zoster, and for maintenance therapy in patients with severe immunodeficiency – patients with CC 10-25 ml/min are prescribed the drug 800 mg 3 times/day at 8-hour intervals, with CC less than 10 ml/min – 800 mg 2 times/day at 12-hour intervals.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea, abdominal pain; rarely – reversible increase in bilirubin content and activity of liver enzymes.

From the hematopoietic system very rarely – anemia, leukopenia, thrombocytopenia.

From the urinary system rarely – increased blood urea and creatinine levels; very rarely – acute renal failure.

From the CNS headache, weakness, dizziness, increased fatigue, confusion, hallucinations, drowsiness, paresthesia, convulsions, decreased concentration, agitation.

Allergic reactions itching, rash, Lyell’s syndrome, urticaria, multiforme exudative erythema, including Stevens-Johnson syndrome, angioedema, anaphylaxis.

Other fever, lymphadenopathy, peripheral edema, visual impairment, myalgia, alopecia.

Contraindications

• Children under 3 years of age;
• Lactation period;
• Hypersensitivity to acyclovir, ganciclovir, valacyclovir or auxiliary components of the drug.

With caution, the drug should be prescribed for dehydration, renal failure, neurological disorders or neurological reactions to the use of cytotoxic drugs (including in the anamnesis), pregnancy, and elderly patients.

Use in Pregnancy and Lactation

The use of the drug during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Use in Renal Impairment

The drug should be prescribed with caution in case of renal failure.

Pediatric Use

The use of the drug is contraindicated in children under 3 years of age.

Geriatric Use

Prescribe with caution to elderly patients.

Special Precautions

When taking the drug, renal function should be monitored (blood urea and plasma creatinine levels).

When using the drug, it is necessary to ensure sufficient fluid intake.

Long-term or repeated treatment with acyclovir of patients with reduced immunity can lead to the emergence of virus strains that are insensitive to its action. Most isolated strains of viruses insensitive to acyclovir show a relative lack of viral thymidine kinase; strains with altered thymidine kinase or altered DNA polymerase have been isolated. In vitro, the effect of acyclovir on isolated strains of Herpes simplex virus can cause the emergence of less sensitive strains.

Aciclovir does not prevent the sexual transmission of herpes, so during treatment it is necessary to refrain from sexual intercourse, even in the absence of clinical manifestations.

Effect on ability to drive vehicles and mechanisms

During treatment, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms agitation, coma, convulsions, lethargy. Precipitation of acyclovir in the renal tubules is possible if its concentration exceeds the solubility in the renal tubules (2.5 mg/ml).

Treatment symptomatic therapy.

Drug Interactions

Simultaneous use with probenecid leads to an increase in the average T_1/2 and a decrease in the clearance of acyclovir.

With simultaneous use with nephrotoxic drugs, the risk of impaired renal function increases.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 4 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.