Description
Acyclovir Pharmacodynamics
Acyclovir is a synthetic analog of purine nucleoside, which has the ability to inhibit in vitro and in vivo 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.
The inhibitory effect of acyclovir against herpes viruses (HAV-1, HAV-2, VZV, EBV and CMV) is highly selective. Acyclovir is not a substrate for thymidine kinase enzyme of uninfected cells, so acyclovir is low toxic to mammalian cells. However, thymidine kinase of cells infected with HBV, EVD, EBV and CMV converts acyclovir into acyclovir monophosphate, a nucleoside analog, which is then sequentially converted into diphosphate and triphosphate under the action of cellular enzymes. Incorporation of acyclovir triphosphate into the chain of viral DNA and subsequent breaking of the chain blocks further replication of viral DNA.
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 showed relatively low viral thymidine kinase content, as well as disruption of viral thymidine kinase or DNA polymerase structure. Exposure of herpes simplex virus (HPV) 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 (HPV) strains to acyclovir in vivo and the clinical efficacy of the drug.
Indications
– Treatment of skin and mucous membrane infections caused by herpes simplex virus, 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 immunodeficient patients;
– 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)
– Treatment of skin and mucous membrane infections caused by herpes simplex virus, 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 immunodeficient patients;
– 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)
Contraindications
Hypersensitivity to acyclovir, ganciclovir, valacyclovir or components of the drug, children under 3 years of age.
Caution
Pregnancy, breast-feeding, old age, renal insufficiency, dehydration, concomitant use with other nephrotoxic drugs.
Usage during pregnancy and breast feeding period
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 administration of acyclovir orally at a dose of up to 1 g per day for 6 months had no clinically significant effect on sperm count, motility or morphology.
Pregnancy
The post-registration pregnancy registry for acyclovir treatment collected data on pregnancy outcomes in women who took 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.
However, caution should be exercised when prescribing Acyclovir-Acrichine to women during pregnancy and the anticipated benefit to the mother and possible risk to the fetus should be evaluated.
Breast-feeding period
After oral administration of Acyclovir-Acrichin in 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-Acrichin to breastfeeding women.
Hypersensitivity to acyclovir, ganciclovir, valacyclovir or components of the drug, children under 3 years of age.
Caution
Pregnancy, breast-feeding, old age, renal insufficiency, dehydration, concomitant use with other nephrotoxic drugs.
Usage during pregnancy and breast feeding period
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 administration of acyclovir orally at a dose of up to 1 g per day for 6 months had no clinically significant effect on sperm count, motility or morphology.
Pregnancy
The post-registration pregnancy registry for acyclovir treatment collected data on pregnancy outcomes in women who took 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.
However, caution should be exercised when prescribing Acyclovir-Acrichine to women during pregnancy and the anticipated benefit to the mother and possible risk to the fetus should be evaluated.
Breast-feeding period
After oral administration of Acyclovir-Acrichin in 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-Acrichin to breastfeeding women.
Dosage and administration
Acyclovir-Acrihin 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
– Treatment of infections caused by the herpes simplex virus
For the treatment of infections caused by herpes simplex virus, the recommended dose of Acyclovir-Acrichin is 200 mg orally five times a day (every four 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 in case of intestinal absorption disorders, the dose of Acyclovir-Acrichin tablets may be increased to 400 mg.
Treatment should be started as soon as possible after the onset of infection; for relapses, the drug should be administered as early as in the prodromal period or when the first rash elements appear.
– Prevention of recurrence of infections caused by herpes simplex virus in patients with normal immune status
For prophylaxis of recurrence of infections caused by herpes simplex virus in patients with normal immune status, the recommended dose of Acyclovir-Acrichin is 200 mg orally 4 times a day (every 6 hours).
Many patients find the more convenient therapy regimen of 400 mg orally 2 times a day (every 12 hours) suitable.
In some cases, lower doses of Acyclovir-Acrihin 200 mg orally 3 times daily (every 8 hours) or 200 mg orally 2 times daily (every 12 hours) may be effective.
Some patients may experience an exacerbation of the infection when taking a total daily dose of 800 mg.
Treatment with Acyclovir-Acrichine should be periodically interrupted 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 prophylaxis of herpes simplex virus infections in immunodeficient patients, the recommended dose of Acyclovir-Acrichin is 200 mg orally four times daily (every 6 hours).
In case of severe immunodeficiency (e.g., after bone marrow transplantation) or in case of impaired intestinal absorption, the drug dose may be increased up to 400 mg orally.
The duration of prophylactic therapy is determined by the duration of the period when there is a risk of infection.
– Treatment of chickenpox and herpes zoster
For treatment of chicken pox and herpes zoster, the recommended dose of the drug Acyclovir-Acrichine is 800 mg orally 5 times a day (every 4 hours, except for bedtime). The course of treatment is 7 days.
Treatment of herpes zoster should be started as early as possible from the time of the first manifestations of the disease, because then the treatment will be more effective.
Treatment of chicken pox in patients with normal immune status should be started within 24 hours from the onset of symptoms.
Special patient groups
Children 3 years of age and older
– Treatment of infections caused by herpes simplex virus; prevention of infections caused by herpes simplex virus in immunodeficient patients
– Aged 3 years and older – same doses as for adults.
– Treatment of chickenpox
– 6 years of age and older – 800 mg orally four times a day;
– Ages 3 to 6 years old – 400 mg orally 4 times a day.
A more precise dosage can be determined at the rate of 20 mg/kg 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
No data are available on the dosing regimen.
Elderly patients
The possibility of renal impairment in elderly patients should be considered; doses should be adjusted according to the degree of renal impairment (see subsection “Patients with impaired renal function”).
It is necessary to ensure that adequate water balance is maintained.
Patients with impaired renal function
Caution should be exercised when prescribing Acyclovir-Acrichin in patients with impaired renal function.
It is necessary to ensure adequate water balance.
In patients with renal insufficiency, 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 reduce the dose of Acyclovir-Acrichin to 200 mg orally twice daily (every 12 hours).
In the treatment of chicken pox and herpes zoster, the recommended doses of the drug Acyclovir-Acrihin, 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).
Acyclovir-Acrihin 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
– Treatment of infections caused by the herpes simplex virus
For the treatment of infections caused by herpes simplex virus, the recommended dose of Acyclovir-Acrichin is 200 mg orally five times a day (every four 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 in case of intestinal absorption disorders, the dose of Acyclovir-Acrichin tablets may be increased to 400 mg.
Treatment should be started as soon as possible after the onset of infection; for relapses, the drug should be administered as early as in the prodromal period or when the first rash elements appear.
– Prevention of recurrence of infections caused by herpes simplex virus in patients with normal immune status
For prophylaxis of recurrence of infections caused by herpes simplex virus in patients with normal immune status, the recommended dose of Acyclovir-Acrichin is 200 mg orally 4 times a day (every 6 hours).
Many patients find the more convenient therapy regimen of 400 mg orally 2 times a day (every 12 hours) suitable.
In some cases, lower doses of Acyclovir-Acrihin 200 mg orally 3 times daily (every 8 hours) or 200 mg orally 2 times daily (every 12 hours) may be effective.
Some patients may experience an exacerbation of the infection when taking a total daily dose of 800 mg.
Treatment with Acyclovir-Acrichine should be periodically interrupted 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 prophylaxis of herpes simplex virus infections in immunodeficient patients, the recommended dose of Acyclovir-Acrichin is 200 mg orally four times daily (every 6 hours).
In case of severe immunodeficiency (e.g., after bone marrow transplantation) or in case of impaired intestinal absorption, the drug dose may be increased up to 400 mg orally.
The duration of prophylactic therapy is determined by the duration of the period when there is a risk of infection.
– Treatment of chickenpox and herpes zoster
For treatment of chicken pox and herpes zoster, the recommended dose of the drug Acyclovir-Acrichine is 800 mg orally 5 times a day (every 4 hours, except for bedtime). The course of treatment is 7 days.
Treatment of herpes zoster should be started as early as possible from the time of the first manifestations of the disease, because then the treatment will be more effective.
Treatment of chicken pox in patients with normal immune status should be started within 24 hours from the onset of symptoms.
Special patient groups
Children 3 years of age and older
– Treatment of infections caused by herpes simplex virus; prevention of infections caused by herpes simplex virus in immunodeficient patients
– Aged 3 years and older – same doses as for adults.
– Treatment of chickenpox
– 6 years of age and older – 800 mg orally four times a day;
– Ages 3 to 6 years old – 400 mg orally 4 times a day.
A more precise dosage can be determined at the rate of 20 mg/kg 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
No data are available on the dosing regimen.
Elderly patients
The possibility of renal impairment in elderly patients should be considered; doses should be adjusted according to the degree of renal impairment (see subsection “Patients with impaired renal function”).
It is necessary to ensure that adequate water balance is maintained.
Patients with impaired renal function
Caution should be exercised when prescribing Acyclovir-Acrichin in patients with impaired renal function.
It is necessary to ensure adequate water balance.
In patients with renal insufficiency, 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 reduce the dose of Acyclovir-Acrichin to 200 mg orally twice daily (every 12 hours).
In the treatment of chicken pox and herpes zoster, the recommended doses of the drug Acyclovir-Acrihin, 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).
