Cyclovir (Tablets) Instructions for Use

Marketing Authorization Holder

Cadila Healthcare Ltd. (India)

ATC Code

J05AB01 (Aciclovir)

Active Substance

Aciclovir (Rec.INN registered by WHO)

Dosage Form

Cyclovir

Tablets 200 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – non-cell contour packs (1) – cardboard packs.
10 pcs. – non-cell contour packs (2) – cardboard packs.
10 pcs. – cell contour packs (1) – cardboard packs.
10 pcs. – cell contour packs (2) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Antiviral agent

Pharmacological Action

Antiviral agent, a synthetic analogue of a purine nucleoside.

It has the ability to inhibit in vitro and in vivo Herpes simplex virus types 1 and 2, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. In cell culture, Aciclovir has the most pronounced antiviral activity against Herpes simplex virus type 1, followed in descending order of activity by: Herpes virus type 2, Varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. The inhibitory effect of acyclovir on these viruses is characterized by high selectivity.

Aciclovir is not a substrate for the thymidine kinase enzyme of uninfected cells, therefore Aciclovir has low toxicity for mammalian cells. The high selectivity of action and low toxicity for humans are due to the absence of the necessary enzyme for the formation of acyclovir triphosphate in intact cells of the macroorganism.

Thymidine kinase of cells infected with Herpes simplex viruses types 1 and 2, Varicella zoster virus, Epstein-Barr virus, or cytomegalovirus converts Aciclovir into Aciclovir monophosphate – a nucleoside analogue, which is then sequentially converted into diphosphate and triphosphate under the action of cellular enzymes. Acyclovir triphosphate is incorporated into the viral DNA chain and blocks its synthesis through competitive inhibition of viral DNA polymerase. Thus, “defective” viral DNA is formed, which leads to the suppression of the replication of new generations of viruses.

Pharmacokinetics

Aciclovir is only partially absorbed from the intestine. After taking 200 mg of acyclovir every 4 hours, the average C_ss,max was 0.7 µg/ml, and the average C_ss,min was 0.4 µg/ml. Aciclovir binds to plasma proteins to a small extent (9-33%). The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of the concentration in plasma. In adults after oral administration of acyclovir, T_1/2 from plasma is about 3 hours. Most of the drug is excreted unchanged in the urine. The renal clearance of acyclovir significantly exceeds the creatinine clearance, which indicates that acyclovir is excreted 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.

Indications

Treatment of infections of the skin and mucous membranes caused by Herpes simplex virus types 1 and 2, including primary and recurrent genital herpes; prevention of recurrences of infections caused by Herpes simplex virus types 1 and 2 in patients with normal immune status; prevention of infections caused by Herpes simplex virus types 1 and 2 in patients with immunodeficiency; 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).

ICD codes

Dosage Regimen

Take orally. The dosage regimen is set individually based on the diagnosis, severity of the disease, and the patient’s renal function.

For treatment of herpes simplex infections in adults and children over 2 years: take 200 mg five times daily, approximately every four hours, omitting the night dose. The typical treatment course is 5 days, but may be extended for severe primary infections.

For severe primary genital herpes, extend the treatment course to 10 days.

For suppression of recurrent genital herpes in immunocompetent patients: take 200 mg four times daily or 400 mg twice daily. Long-term therapy may be reassessed at 6-12 month intervals.

For prevention of herpes simplex in immunocompromised patients: take 200 mg four times daily.

For treatment of herpes zoster (shingles): take 800 mg five times daily for 7 days. Initiate therapy at the earliest sign or symptom.

For treatment of chickenpox in adults and children over 2 years weighing over 40 kg: take 800 mg four times daily for 5 days. For children aged 2 years and older weighing 40 kg or less, the dose is 20 mg/kg (up to 800 mg) four times daily for 5 days. Start treatment at the earliest sign or symptom.

Adjust the dosage in patients with renal impairment. For creatinine clearance above 25 ml/min, use standard dosing. For creatinine clearance of 10-25 ml/min, use twice-daily dosing. For creatinine clearance below 10 ml/min, use once-daily dosing. Refer to specific dosing tables for each indication.

For hemodialysis patients, administer the dose after the dialysis session.

In elderly patients, consider age-related renal function decline and adjust the dose accordingly. Ensure adequate hydration during treatment, especially with high-dose regimens.

Adverse Reactions

From the immune system rarely – anaphylaxis.

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

From the nervous system often – headache, dizziness; very rarely – agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.

From the respiratory system rarely – dyspnea.

From the digestive system often – nausea, vomiting, diarrhea, abdominal pain.

From the liver and biliary tract rarely – transient increase in the concentration of bilirubin in the blood and activity of liver enzymes; very rarely – hepatitis, jaundice.

From the urinary system rarely – increase in the concentration of urea, creatinine in blood plasma; very rarely – acute renal failure, renal colic.

From the skin and subcutaneous tissues often – itching, rash, incl. photosensitivity; infrequently – urticaria, rapid diffuse hair loss; rarely – angioedema; very rarely – toxic epidermal necrolysis, multiforme exudative erythema, incl. Stevens-Johnson syndrome.

Other often – fever, fatigue.

Contraindications

Hypersensitivity to acyclovir or valacyclovir; children under 3 years of age.

With caution pregnancy, period of breastfeeding, elderly age, renal failure, dehydration, simultaneous use with other nephrotoxic drugs.

Use in Pregnancy and Lactation

Caution should be exercised when prescribing acyclovir to women during pregnancy and breastfeeding, and the intended benefit to the mother and the possible risk to the fetus or child should be assessed.

Use in Renal Impairment

Aciclovir should be prescribed with caution in renal failure.

Pediatric Use

Contraindicated for use in children under 3 years of age.

Geriatric Use

The likelihood of renal failure in elderly patients should be taken into account; doses should be adjusted according to the degree of renal failure.

Special Precautions

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

Patients taking Aciclovir in high doses should receive sufficient fluids.

Since Aciclovir is excreted in the urine, doses should be reduced for patients with renal failure. In elderly patients, renal 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 and, accordingly, should be under close medical supervision.

Long-term or repeated courses of treatment with acyclovir in patients with severe immunodeficiency may lead to the emergence of virus strains with reduced sensitivity to acyclovir, which will not respond to continued acyclovir therapy.

Drug Interactions

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

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

Probenecid and cimetidine increase the AUC of acyclovir and reduce its renal clearance.

An increase in the plasma AUC for acyclovir and the inactive metabolite of mycophenolate mofetil was observed with the simultaneous use of both drugs.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.