Pharmacological group: antiviral.
ATX code: [J05AB01].
Mechanism of action
Acyclovir is a synthetic analog of the purine nucleoside, which has the ability to inhibit in vitro and in vivo replication of human herpes viruses, including herpes simplex virus (HSV) types 1 and 2, varicella and shingles virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture acyclovir exhibits the most expressed antiviral activity against HSV-1, followed by HSV-2, VZV, EBV and CMV in descending order of activity.
The activity of acyclovir against herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV) is highly selective. Acyclovir is not a substrate for thymidine kinase enzyme of uninfected cells, so acyclovir is little toxic to mammalian cells. Thymidine kinase of cells infected with HSV, VZV, EBV and CMV transforms acyclovir into acyclovir monophosphate, a nucleoside analog, which is then sequentially transformed into diphosphate and triphosphate by cellular enzymes. Incorporation of acyclovir triphosphate into the viral DNA chain and subsequent chain breakage blocks further replication of viral DNA.
In patients with severe immunodeficiency long-term or repeated courses of acyclovir therapy can lead to the formation of resistant strains, and therefore further treatment with acyclovir may be ineffective. Most acyclovir-resistant strains isolated have relatively low levels of viral thymidine kinase, impaired viral thymidine kinase structure or DNA polymerase). Exposure of HSV strains to acyclovir in vitro may also result in the formation of less sensitive strains. There is no correlation between the sensitivity of HSV strains to acyclovir in vitro and the clinical efficacy of the drug.
Acyclovir is only partially absorbed from the intestine. After administration of 200 mg of acyclovir every 4 hours, the mean maximum equilibrium plasma concentration (Cssmax) was 3.1 µmol (0.7 µg/mL) and the mean equilibrium minimum plasma concentration (Cssmin) was 1.8 µmol (0.4 µg/mL). When 400 mg and 800 mg of acyclovir were taken every 4 hours, Cssmax was 5.3 µmol (1.2 µg/mL) and 8 µmol (1.8 µg/mL), respectively, and Cssmin was 2.7 µmol (0.6 µg/mL) and 4 µmol (0.9 µg/mL), respectively.
Acyclovir half-life is 2.5-3.3 hours. Most of the drug is excreted unchanged by the kidneys. Renal clearance of acyclovir is much higher than creatinine clearance, which indicates excretion of acyclovir not only by glomerular filtration, but also by tubular secretion. The main metabolite of acyclovir is 9-carboxymethoxy-methylguanine, which accounts for about 10-15% of the administered dose of the drug in the urine. When administering acyclovir 1 hour after taking 1 g of probenecid the half-life of acyclovir and the area under the curve “concentration in plasma – time” increased by 18 and 40% respectively.
In elderly patients acyclovir clearance decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir changes slightly.
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 h, and the plasma concentration of acyclovir decreased by approximately 60%.
The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its plasma concentration. Acyclovir binds insignificantly to plasma proteins (9-33%), therefore drug interactions through protein binding mechanism are unlikely.
When concomitant administration of acyclovir and zidovudine to HIV-infected patients pharmacokinetic characteristics of both drugs were virtually unchanged.
Herpes genitalis, herpes zoster, HIV infection, herpes, chickenpox
- 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 herpes simplex virus infectionsPrevention of herpes simplex virus infections in immunocompromised patients
- Treatment of varicella pox and herpes zoster
- Treatment of herpes simplex virus infectionsTreatment of patients with severe immunodeficiency, mainly those with advanced HIV infection (CD4+ cell count less than 200/mm in AIDS patients or severe manifestations of AIDS-associated complex) and patients who have undergone bone marrow transplantation. Studies have proven that combined therapy with Zovirax and antiretroviral drugs (mainly oral zidovudine) significantly reduces mortality in patients with late-stage AIDS and bone marrow transplant patients.
acyclovir 200.0 mg;
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How to take, the dosage
Zovirax tablets can be taken with food, since eating does not interfere with its absorption to any great extent. The tablets should be swallowed with a full glass of water.
Treatment of infections caused by herpes simplex virus
For the treatment of infections caused by herpes simplex virus, the recommended dose of Zovirax is 200 mg 5 times daily every 4 hours, except for bedtime. The course of treatment is usually 5 days, but may be extended in severe primary infections.
In cases of severe immunodeficiency (for example, after a bone marrow transplant) or when absorption from the intestine is impaired, the dose of Zovirax for oral administration may be increased to 400 mg 5 times daily.
The treatment should begin as soon as possible after the onset of infection; for relapses, it is recommended that the drug be started as early as the prodromal period or as soon as the first elements of the rash appear.
Prevention of recurrent herpes simplex virus infections
For prevention of recurrent herpes simplex virus infections in patients with normal immune status, the recommended dose of Zovirax is 200 mg 4 times daily (every 6 hours).
Many patients are comfortable with a regimen of 400 mg 2 times daily (every 12 hours).
In some cases, lower doses of Zovirax 200 mg 3 times daily (every 8 hours) or 2 times daily (every 12 hours) are effective. In some patients, interruption of infection may occur with a total daily dose of 800 mg.
The treatment with Zovirax should be interrupted periodically for 6-12 months to detect possible changes in the course of the disease.
Prevention of infections caused by herpes simplex virus in immunodeficient patients:
For prevention of infections caused by herpes simplex virus in immunodeficient patients the recommended dose of Zovirax is 200 mg 4 times daily (every 6 hours).
In case of severe immunodeficiency (for example, after a bone marrow transplant) or in case of impaired intestinal absorption, the oral dose of Zovirax may be increased to 400 mg 5 times daily. The duration of the prophylactic course of therapy is determined by the duration of the period when there is a risk of infection.
The treatment of chickenpox and herpes zoster:
For the treatment of chickenpox and herpes zoster, the recommended dose of Zovirax is 800 mg 5 times daily; the drug is taken, every 4 hours, except during nighttime sleep. The course of treatment is 7 days. The drug should be prescribed as early as possible after the onset of infection, since treatment is more effective.
The treatment of patients with severe immunodeficiency:
For the treatment of patients with severe immunodeficiency, the recommended dose of Zovirax is 800 mg 4 times daily (every 6 hours).
Patients who have undergone bone marrow transplantation are usually recommended a course of intravenous therapy with Zovirax for 1 month before oral administration of Zovirax.
In clinical trials the maximum duration of treatment of bone marrow transplant recipients was 6 months (from 1 to 7 months after transplantation). In patients with advanced clinical picture of HIV the course of treatment with Zovirax was 12 months, but there is reason to believe that longer courses of therapy can be effective in these patients.
Children 3 years of age and older
The treatment and prevention of herpes simplex virus infections in children who are immunocompromised and have normal immune status: 3 years and older – the same doses as for adults;
The treatment of chickenpox
- six years old – 800 mg 4 times a day;
- From 3 to 6 years old – 400 mg 4 times a day;
A more precise dose can be determined at the rate of 20 mg/kg of body weight (but no more than 800 mg) 4 times a day. The course of treatment is 5 days.
There are no data on prevention of recurrent herpes simplex virus infections or on treatment of herpes zoster in children with normal immune status.
Treatment of severely immunocompromised pediatric patients
According to the very limited information available, the same doses of Zovirax as for adults with immunodeficiency (i.e., 800 mg 4 times daily every 6 hours) can be used for children over 3 years of age with severe immunodeficiency.
Patients in the elderly
In the elderly there is a decrease in the clearance of acyclovir in the body in parallel with a decrease in creatinine clearance.
Patients in the elderly should receive sufficient fluids while taking high doses of oral Zovirax, and if they have renal insufficiency, reduction of the dose of Zovirax should be considered.
Patients with renal impairment
Caution should be exercised when prescribing Zovirax to patients with renal impairment.
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 greater than the established safe levels. However, in patients with significant renal insufficiency (creatinine clearance less than 10 ml/min) the Zovirax dose should be decreased to 200 mg 2 times per day (every 12 hours).
When treating chickenpox, herpes zoster, and when treating patients with severe immunodeficiency, the recommended doses of Zovirax are:
- severe renal failure (creatinine clearance less than 10 ml/min) 800 mg 2 times daily every 12 hours;
- moderate renal failure (creatinine clearance 10-25 ml/min) 800 mg 3 times daily every 8 hours.
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. BCC and cimetidine increase the AUC of acyclovir and decrease its renal clearance (no dose adjustment is required due to the wide range of therapeutic doses of acyclovir).
In patients receiving Zovirax by injection, caution is required when administering drugs competing for the elimination pathway with it due to the potential increase in plasma levels of one, both drugs or their metabolites. Concomitant use of acyclovir and mycophenolate mofetil leads to increased AUC for acyclovir and the inactive metabolite of mycophenolate mofetil. Caution should be exercised when combining intravenous administration of Zovirax (renal function should be monitored) with drugs that impair renal function (e.g., cyclosporine, tacrolimus).
Hydration status: Patients taking high doses of Zovirax orally should get enough fluids. Elderly patients and patients with renal insufficiency: Patients in this group are at increased risk of adverse effects of the nervous system (usually such reactions are reversible in response to drug withdrawal), respectively, should be under close medical supervision.
Transmission: Patients should be informed of the possibility of genital herpes virus transmission during the rash period and of asymptomatic cases of viral carriage.
Impact on Driving Capability
Zovirax is contraindicated in cases of hypersensitivity to acyclovir or valacyclovir.
Zovirax should be used with caution in case of dehydration and renal failure.
Zovirax in tablet form is not used in children under 3 years of age.
The digestive system: nausea, vomiting, diarrhea, abdominal pain, rarely – reversible increase in bilirubin and liver enzymes activity.
The blood system: very rare – anemia, leukopenia, thrombocytopenia.
The urinary system: rare – increased levels of urea and creatinine in the blood, very rare – acute renal failure.
CNS: headache, rare – reversible neurological disorders such as dizziness, confusion, hallucinations, somnolence, seizures, coma. Usually these side effects were observed in patients with renal insufficiency who took the drug in doses higher than recommended.
Allergic reactions: rash, photosensitization, urticaria, itching; rarely – shortness of breath, angioedema, anaphylaxis.
Other: rapid fatigue; rarely – rapid diffuse hair loss. Since this type of alopecia is observed in various diseases and during therapy with many drugs, its relationship with acyclovir intake has not been established.
In patients who received antiretroviral drugs, additional intake of Zovirax did not cause a significant increase in toxic effects.
Acyclovir is only partially absorbed in the gastrointestinal tract. No toxic effects have been reported with occasional single oral doses of acyclovir up to 20 g. Gastrointestinal (nausea, vomiting) and neurological (headache and confusion) disorders were observed when repeated oral doses exceeded the recommended ones over several days.
Sometimes dyspnea, diarrhea, impaired renal function, agitation, confusion, hallucinations, seizures, coma may be observed.
Patients need close medical monitoring to detect possible symptoms of intoxication. Acyclovir is excreted with hemodialysis, so hemodialysis may be used if symptoms of intoxication develop.
Analysis of acyclovir treatment in women during pregnancy showed no increase in the number of birth defects in their children compared to the general population. However, caution should be exercised when prescribing Zovirax to women during pregnancy and the estimated benefit to the mother and possible risk to the fetus should be assessed.
After oral doses of Zovirax 200 mg five 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 Zovirax to breastfeeding women.
Zovirax, Vivorax, Acyclovir-Acri, Acyclovir, Herperax, Acyclovir Belupo, Acyclovir Sandoz
|Conditions of storage|
Store in a dry place at temperatures below 25 ° C. Keep out of reach of children.
Glaxo Wellcome S.A., Spain
Glaxo Wellcome S.A.
Buy Zovirax, tablets 200 mg 25 pcs with delivery to USA, UK, Europe and over 120 other countries.