Pharmacotherapeutic group: antiviral drug.
ATX code: J05AB01
Pharmacological properties
Pharmacodynamics
Acyclovir is a synthetic purine nucleoside analog that 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, VHF, EBV and CMV) is highly selective. Acyclovir is not a substrate for thymidine kinase enzyme of uninfected cells, so acyclovir is slightly toxic for mammalian cells. Thymidine kinase of cells infected with HPV, 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 acyclovirtriphosphate into the chain of viral DNA and subsequent chain breakage block 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 levels of viral thymidine kinase, impaired viral thymidine kinase structure or DNA polymerase. 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 vitro and the clinical efficacy of the drug.
Pharmacokinetics
Intake
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 µM (0.7 µg/mg), and the mean equilibrium minimum plasma concentration (Cssmin) was 1.8 µM (0.4 µg/mL). When 400 mg and 800 mg of acyclovir were given every 4 hours, Cssmax was 5.3 µM (1.2 µg/mL) and 8 µM (1.8 µg/mL), respectively, and Cssmin was 2.7 µM (0.6 µg/mL) and 4 µM (0.9 µg/mL), respectively.
Distribution
The concentration of acyclovir in cerebrospinal fluid is approximately 50% of its concentration in plasma.
Aciclovir binds only slightly (9-33%) with plasma proteins, therefore drug interactions due to displacement from binding sites with plasma proteins are unlikely.
Elimation
In adults after oral administration of acyclovir the elimination half-life from the blood plasma is about 3 hours. Most of the drug is excreted unchanged by the kidneys. Renal clearance of acyclovir significantly exceeds creatinine clearance, which indicates excretion of acyclovir not only by glomerular filtration, but also by tubular secretion. The main metabolite of acyclovir is 9-carboxymethoxymethylguanine, 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 AUC (area under the pharmacokinetic curve “concentration-time”) increased by 18% and 40%, respectively.
Special patient groups
In patients with chronic renal failure the half-life of acyclovir averaged 19.5 hours. With hemodialysis, the average half-life of acyclovir was 5.7 hours. The plasma concentration of acyclovir decreased by approximately 60% during dialysis.
In elderly patients, acyclovir clearance decreases with age in parallel with a decrease in creatinine clearance, but the half-life of acyclovir changes only slightly.
The pharmacokinetic characteristics of both drugs were virtually unchanged when acyclovir and zidovudine were administered simultaneously to HIV-infected patients.
Indications
- Treatment of infections of the skin and mucous membranes caused by herpes simplex virus, including primary and recurrent genital herpes;
- prevention of recurrence of infections caused by herpes simplex virus in patients with normal immune status;
- prevention of infections caused by herpes simplex virus in patients with immunodeficiency;
- treatment of infections caused by herpes simplex virus
- prevention of infections caused by herpes simplex virus in immunocompromised patients;
- treatment of varicella and herpes zoster (early treatment of herpes zoster with acyclovir has analgesic effects and may reduce the incidence of post-herpetic neuralgia).
Active ingredient
Acyclovir
Composition
Active substance:
acyclovir – 400,00 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, povidon K 30, magnesium stearate.
How to take, the dosage
Ingestion with a full glass of water.
Acyclovir Reneval can be taken with food because eating does not interfere with its absorption to any great extent.
Adults
Treatment of infections caused by herpes simplex virus
For the treatment of infections caused by herpes simplex virus, the recommended dose of Acyclovir Reneval is 200 mg 5 times a day (every 4 hours, except for bedtime). Usually the course of treatment is 5 days, but it may be prolonged in case of severe primary infections.
In case of severe immunodeficiency (e.g., after a bone marrow transplant) or in case of intestinal absorption disorders, the dose of Acyclovir Reneval for oral administration may be increased to 400 mg. As an alternative, the possibility of using acyclovir in the dosage form lyophilisate for preparation of a solution for infusion may be considered.
Treatment should be started as soon as possible after the onset of infection; for relapses, treatment should be started as early as the prodromal period or when the first elements of the rash appear.
Prevention of recurrent herpes simplex virus infections in patients with normal immune status
Prevention of recurrent infections In patients with normal immune status, the recommended dose of Acyclovir Reneval is 200 mg 4 times daily (every 6 hours) to prevent recurrence of infections caused by herpes simplex virus.
Many patients are able to take the more convenient regimen of 400 mg 2 times daily (every 12 hours).
In some cases, lower doses of Acyclovir Reneval 200 mg 3 times daily (every 8 hours) or 200 mg 2 times daily (every 12 hours) may be effective.
In some patients, an exacerbation of the infection may occur when a total daily dose of 800 mg is taken.
The treatment with Acyclovir Reneval 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 patientswith immunodeficiency
Prevention of infections caused by herpes simplex virus in patientswith immunodeficiency. For prevention of infections caused by herpes simplex virus in immunocompromised patients, the recommended dose of Acyclovir Reneval is 200 mg 4 times daily (every 6 hours).
In case of severe immunodeficiency (e.g., after a bone marrow transplant) or in case of intestinal absorption disorders, the dose of Acyclovir Reneval may be increased to 400 mg orally. As an alternative, the possibility of using acyclovir in the dosage form lyophilisate for preparation of solution for infusion may be considered. The duration of prophylactic therapy is determined by the duration of the period when there is a risk of infection.
Treatment of chicken pox and herpes zoster
For treatment of chicken pox and herpes zoster (shingles) the recommended dose of Acyclovir Reneval is 800 mg 5 times daily (every 4 hours, except for bedtime). The course of treatment is 7 days.
The treatment of herpes zoster should begin as soon as possible after the first symptoms of the disease, because in this case the treatment will be more effective.
Patients with normal immune status should begin treatment for chickenpox within 24 hours of the onset of symptoms.
In patients with severe immunodeficiency (e.g., after a bone marrow transplant) or with impaired intestinal absorption, acyclovir in a lyophilizate form for preparation of a solution for infusion should be considered.
Patient special groups
Children aged 3 years and older
Treatment of infections caused by herpes simplex virus; prevention of infections caused by herpes simplex virus: In patients with immunodeficiency
- Ages 3 years and older use the same doses as for adults.
Treatment of varicella
- Aged 3 to 6 years – 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.
Prevention of recurrent herpes simplex virus infections in patients with normal immune status; treatment of herpes zoster
There are no data on dosing regimen.
Elderly patients
The possibility of renal impairment in elderly patients must be considered; doses must be adjusted according to the degree of renal impairment (see subsection “Patients with impaired renal function”).
The maintenance of adequate water balance must be ensured.
Patients with impaired renal function
Caution should be exercised when Acyclovir Reneval is prescribed to patients with impaired renal function.
Aquivalent water balance must be maintained.
In patients with renal impairment, oral administration of Acyclovir Reneval 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 Reneval to 200 mg twice daily (every 12 hours).
In the treatment of varicella and herpes zoster, the recommended doses of Acyclovir Reneval, tablets are:
- when creatinine clearance is less than 10 ml/min, 800 mg 2 times daily (every 12 hours);
- when creatinine clearance is 10-25 ml/min, 800 mg 3 times daily (every 8 hours).
Interaction
No clinically significant interactions with acyclovir were observed.
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.
Acyclovir increases the AUC of theophylline by approximately 50% when taken simultaneously, so it is recommended to measure plasma concentrations of theophylline when concomitantly administering acyclovir.
Probenecid and cimetidine increase the AUC of acyclovir and decrease its renal clearance.
There was an increase in AUC in plasma for acyclovir and inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplantology, when using both drugs simultaneously.
However, no dose adjustment is required due to the wide therapeutic index of acyclovir.
Special Instructions
The available data from clinical studies are insufficient to conclude that acyclovir reduces the risk of varicella in patients with normal immune status.
The risk of renal failure increases with concomitant use of other nephrotoxic drugs.
Hydration status
Patients taking high doses of Acyclovir Reneval orally should get enough fluids.
Elderly patients and patients with impaired renal function
As acyclovir is excreted by the kidneys, dosage adjustment is necessary in patients with impaired renal function (see section “Dosage and administration”).
In elderly patients with impaired renal function may be observed, so a dose adjustment is necessary for this group of patients. Both elderly patients and patients with impaired renal function are at increased risk of nerve side effects (these reactions are usually reversible in response to discontinuation of the drug) and therefore should be under close medical supervision.
Patients with severe immunodeficiency
Long-term or repeated courses of acyclovir treatment in patients with severe immunodeficiency may lead to the appearance of virus strains with hypersensitivity to acyclovir that will not respond to continued acyclovir therapy.
Transmission
All patients, especially those with clinical manifestations, should be careful to avoid potential transmission, and patients should be informed about asymptomatic cases of viral carriage.
The effect on the ability to drive vehicles, machinery
There have been no studies of the effect of acyclovir on the ability to drive vehicles or machinery. It is not possible to predict the negative effect of acyclovir on these activities based on the pharmacological properties of the active substance, but the side effect profile of acyclovir must be considered.
Synopsis
Dosage 400 mg Oval biconvex tablets white or almost white with a rib.
Contraindications
Hypersensitivity to acyclovir, valacyclovir or any other component of the drug; lactase deficiency, lactose intolerance, glucose-galactose malabsorption; children under 3 years of age.
With caution
Pregnancy, breast-feeding, elderly, renal failure, dehydration, concomitant use with other nephrotoxic agents.
Side effects
The following criteria were used to assess the frequency of adverse reactions (ARs): “very common” (> 1/10); “common” (≥1/100, < 1/10); “infrequent” (≥1/1000, < 1/100); “rare” (≥1/10000, < 1/1000); “very rare” (< 1/10000). HPs are grouped according to the system-organ classes of the MedDRA Regulatory Medical Dictionary as well as the World Health Organization recommendations.
Blood and lymphatic system involvement: very rarely – anemia, leukopenia, thrombocytopenia.
From the immune system: rarely – anaphylaxis.
From the central nervous system:often – headache, dizziness; very rarely – agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, seizures, somnolence, encephalopathy, coma.
These side effects were generally seen in patients with renal impairment or in the presence of other triggering factors and were mostly reversible.
Injuries to the respiratory system, thoracic and mediastinal organs: frequently, dyspnea.
Digestive system disorders:often – nausea, vomiting, diarrhea, abdominal pain.
Hepatic and biliary tract disorders: rarely – reversible increase in bilirubin and liver enzymes in the blood; very rarely – hepatitis, jaundice.
Skin and subcutaneous tissue:often – itching, rash, including photosensitization; infrequently – urticaria, rapid diffuse hair loss. Since this type of alopecia is observed in various diseases and during therapy with many medications, its connection with taking acyclovir has not been established; rarely – angioedema; very rarely – toxic epidermal necrolysis, erythema multiforme.
Urinary system disorders: Rarely – increased serum concentrations of urea and creatinine; very rare – acute renal failure, renal colic. Renal colic may be associated with renal failure and crystalluria.
Others: often – fatigue, fever.
Overdose
Symptoms
Acyclovir is only partially absorbed in the gastrointestinal tract. Generally, no toxic effects have been reported with an occasional single dose of acyclovir up to 20 g. When repeated oral doses exceeding the recommended doses over several days, gastrointestinal (nausea, vomiting) and nervous system disorders (headache and confusion) have been observed. Sometimes neurological effects such as seizures, coma may be observed.
Treatment
Patients need close medical monitoring to detect possible symptoms of intoxication. Acyclovir is excreted by hemodialysis, so hemodialysis may be used to treat overdose.
Pregnancy use
Fertility
There are no data on the effect of acyclovir on female fertility. In a study involving 20 male patients with normal sperm counts, oral acyclovir at a dose of up to 1 g per day for 6 months was found to have no clinically significant effect on sperm count, motility, or morphology.
Pregnancy
The post-registration pregnancy registry 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.
But caution should be exercised when prescribing acyclovir to women during pregnancy and assess the anticipated benefit to the mother and the possible risk to the fetus.
Breastfeeding
After oral administration of acyclovir at 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 Reneval to breastfeeding women.
Similarities
Zovirax, Vivorax, Acyclovir-Acri, Acyclovir, Herperax, Acyclovir Belupo, Acyclovir Sandoz
Weight | 0.035 kg |
---|---|
Shelf life | 4 years. Do not use after the expiration date. |
Conditions of storage | At a temperature not higher than 25 ° C. Keep out of reach of children. |
Manufacturer | Update PFC AO, Russia |
Medication form | pills |
Brand | Update PFC AO |
Other forms…
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