Composition
1 fl. contains acyclovir 250 mg
Pharmacological action
Pharmaceutical group:
antiviral agent.
Pharmaceutical action: Â
Zovirax is an antiviral drug, a synthetic analog of purine nucleoside, which has the ability to inhibit in vitro and in vivo replication of Herpes simplex viruses type 1 and 2, Varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the most pronounced antiviral activity against Herpes simplex type 1, followed by Herpes simplex type 2, Varicella zoster, EBV and CMV in descending order of activity.
The effect of acyclovir on viruses is highly selective. Acyclovir is not a substrate for the enzyme thymidine kinase in uninfected cells, so it is low toxic to mammalian cells. Thymidine kinase of cells infected with Herpes simplex viruses type 1 and 2, Varicella zoster, EBV and CMV converts acyclovir to acyclovir monophosphate-a nucleoside analog, which is then sequentially converted to diphosphate and triphosphate by cellular enzymes. The inclusion of acyclovir triphosphate in the viral DNA chain 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 formation of resistant strains, and therefore further treatment with acyclovir may not be effective. Most of the isolated strains with reduced sensitivity to acyclovir showed a relatively low content of viral thymidine kinase, a violation of the structure of viral thymidine kinase or DNA polymerase.
Acyclovir exposure to Herpes simplex virus strains in vitro can also lead to the formation of less sensitive strains. There is no correlation between the sensitivity of Herpes simplex virus strains to acyclovir in vitro and the clinical efficacy of the drug.
It has been shown that intravenous use of Zovirax in high doses reduces the frequency of occurrence and delays the development of cytomegalovirus infection. If such infusion therapy is followed by high-dose oral acyclovir treatment for 6 months, mortality and the incidence of viremia are reduced.
Pharmacokinetics:
Distribution
In adults, the mean Cmax of acyclovir 1 h after infusion at 2.5 mg/kg,5 mg / kg,10 mg / kg, and 15 mg / kg was 22.7 mmol (5.1 mcg / ml),43.6 mmol (9.8 mcg/ml),92 mcmol (20.7 mcg/ml), and 105 mcmol (23.6 mcg/ml), respectively. Cmin of the drug in plasma 7 hours after infusion was 2.2 mmol (0.5 mcg/ml),3.1 mmol (0.7 mcg/ml),10.2 mmol (2.3 mcg/ml) and 8.8 mmol (2.0 mcg/ml), respectively. The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its plasma concentration.
Acyclovir is slightly bound to plasma proteins (9-33%).
Deduction
In adults, after intravenous use of acyclovir, T1/2 from plasma is about 2.9 hours. Most of the drug is excreted unchanged by the kidneys. Renal clearance of acyclovir significantly exceeds creatinine clearance, which indicates that acyclovir is eliminated 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 in the urine.
When acyclovir was administered 1 h after taking 1 g of probenecid, acyclovir T1/2 and AUC increased by 18 and 40%, respectively.
Pharmacokinetics in special clinical cases
In children older than 1 year, Cmax and Cmin values corresponding to those in adults were observed when Zovirax was administered at a dose of 250 mg / m2 instead of 5 mg / kg (adult dose) and at a dose of 500 mg/m2 instead of 10 mg/kg (adult dose).
In newborns (from 0 to 3 months) who received acyclovir as an infusion lasting more than 1 hour every 8 hours, Cmax was 61.2 mmol (13.8 mcg/ml), Cmin was 10.1 mmol (2.3 mcg/ml), and T1/2 was 3.8 hours.
In the elderly, acyclovir clearance decreases with age in parallel with a decrease in creatinine clearance, but acyclovir T1/2 changes slightly.
In patients with chronic renal failure, the acyclovir T1/2 averaged 19.5 hours, and during hemodialysis, the T1 / 2 averaged 5.7 hours, the plasma concentration of acyclovir decreased by approximately 60%.
Indications
- Prevention of herpes simplex virus infections in immunodeficient patients
- Treatment of infections caused by the herpes simplex virus
- Treatment of chickenpox and herpes zoster infections
- Treatment of infections caused by the herpes simplex virus in newborns
- Prevention of CMV infections in recipients of bone marrow transplants.
High doses of intravenous Zovirax have been shown to reduce the incidence and delay the development of CMV infection. If a high dose of Zovirax infusion therapy is followed by treatment If Zovirax is taken orally at a high dose for 6 months, then mortality and the incidence of viremia are reduced.
Use during pregnancy and lactation
Analysis of women treated with acyclovir during pregnancy did not reveal an 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 evaluating the intended benefit to the mother and the possible risk to the fetus.
Contraindications
Zovirax is contraindicated in case of hypersensitivity to acyclovir or valacyclovir and during lactation.
It should be used with caution in case of dehydration, renal failure, neurological disorders, during the development of reactions to cytotoxic drugs (with their intravenous use) and in the presence of such in the anamnesis, during pregnancy.
Side effects
Gastrointestinal tract: Â nausea, vomiting; if taken orally-diarrhea, abdominal pain.
Blood system: Â anemia, leukopenia, and thrombocytopenia.
Hypersensitivity reactions and skin:  rash, photosensitivity, urticaria, pruritus, fever; rarely — shortness of breath, angioedema, anaphylaxis; with intravenous use-severe local inflammatory reactions leading to skin necrosis, when Zovirax solution gets under the skin.
Kidneys: Â rarely-increased levels of urea and creatinine in the blood. It is believed that this complication is associated with the value of Cmax in plasma and the state of the patient’s water balance. To avoid such phenomena, instead of intravenous bolus injection, a slow infusion should be prescribed for 1 hour. Patients ‘ water balance should be maintained. Renal failure that develops during treatment with Zovirax for intravenous infusions is usually quickly stopped by rehydrating patients and / or reducing the dose of the drug or canceling it. Progression to acute renal failure occurs in exceptional cases.
Liver: Â reversible increase in bilirubin levels and liver enzyme activity; with intravenous use-hepatitis and jaundice (very rare).
Central Nervous System: Â when administered intravenously, reversible neurological disorders such as confusion, hallucinations, agitation, tremor, drowsiness, psychosis, convulsions, and coma were usually observed in patients with predisposing conditions; when taken orally, headache; rarely, reversible neurological disorders.
Other: Â rapid fatigue; rarely-rapid diffuse hair loss (no association with acyclovir has been established).
Interaction
No clinically significant interactions were observed with Zovirax.
Acyclovir is excreted unchanged in the urine by active tubular secretion. All drugs with a similar elimination 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 intravenous Zovirax, caution should be exercised when prescribing concomitant medications that compete for the elimination route due to the potential increase in plasma levels of one, both drugs or their metabolites. The combined use of acyclovir and mycophenolate mofetil leads to an increase in the AUC for acyclovir and the inactive metabolite mycophenolate mofetil.
With caution, intravenous use of Zovirax should be combined (monitoring of renal function is necessary) with drugs that violate renal function (for example, cyclosporine, tacrolimus).
How to take it, course of use and dosage
Adults
In obese patients, the recommended dosage is similar to that of normal-weight adults.
Treatment of infections caused by HSV (with the exception of herpetic encephalitis) and VZV. Intravenous infusions at a dose of 5 mg / kg every 8 hours.
Treatment of VZV infections and herpetic encephalitis in immunodeficient patients. Intravenous infusions at a dose of 10 mg / kg every 8 hours with normal renal function.
Prevention of CMV infection in bone marrow transplantation 500 mg / m2 intravenously 3 times a day with an interval of 8 hours. The duration of treatment is from 5 days before transplantation and up to 30 days after transplantation.
Children
Doses of Zovirax for intravenous infusions in children aged 3 months to 12 years are calculated depending on the body surface area.
In newborns, doses are calculated depending on body weight. For HSV-related infections, a dose of 10 mg/kg every 8 hours is recommended.
Treatment of infections caused by HSV (except for herpetic encephalitis) and VZV. Intravenous infusions at a dose of 250 mg / m2 every 8 hours.
Treatment of herpetic encephalitis and VZV infections in children with immunodeficiency. Intravenous infusions at a dose of 500 mg / m2 every 8 hours with normal renal function.
Prevention of CMV infection in children over 2 years of age. Few data suggest that children over 2 years of age who have undergone bone marrow transplantation may be prescribed an adult dosage of intravenous Zovirax.
In children with reduced renal function, dose adjustment is required according to the degree of renal failure.
Elderly patients
In the elderly, acyclovir clearance in the body decreases in parallel with a decrease in creatinine clearance. Special attention should be paid to reducing the dose of Zovirax in elderly patients with reduced creatinine clearance.
Kidney failure
Intravenous infusions of Zovirax should be administered with caution in patients with renal insufficiency. The following scheme of dose adjustment depending on the degree of decrease in creatinine clearance is proposed.
Creatinine clearance |
Doses |
25-50 ml / min |
5-10 mg / kg or 500 mg/m2 every 12 hours |
10-25 ml / min |
5-10 mg / kg or 500 mg/m2 every 24 hours |
0( anuria)- 10 ml / min |
With continuous outpatient peritoneal dialysis of 2.5-5 mg / kg or 250 mg/m2 every 24 hours. With hemodialysis 2.5-5 mg / kg or 250 mg / m2 every 24 hours and after dialysis. |
The course of treatment with Zovirax in the form of intravenous infusions is usually 5 days, but may vary depending on the patient’s condition and response to therapy. The duration of treatment for herpetic encephalitis and HSV infections in newborns is usually 10 days.
The duration of prophylactic use of Zovirax for intravenous infusions is determined by the duration of the period when there is a risk of infection.
Preparation of the solution and method of use
The recommended dose of Zovirax should be given as a slow intravenous infusion for more than 1 hour.
The following volumes of water for injection or sodium chloride solution for injection (0.9%) are used to prepare a Zovirax solution containing 25 mg of acyclovir in 1 ml of the resulting solution.
Zovirax dose in 1 ampoule |
Volume of dilution solution |
125 mg |
5 ml |
250 mg |
10 ml |
500 mg |
20 ml |
The recommended volume of dilution solution should be added to the ampoule with Zovirax powder, gently shake until the contents of the ampoule are completely dissolved.
After dilution, the Zovirax solution can be administered as an intravenous infusion using a special infusion pump that regulates the rate of drug use.
Another method of infusion use is possible, when the prepared Zovirax solution is further diluted to obtain an acyclovir concentration not exceeding 5 mg / ml (0.5%).
- To do this, add the prepared solution to the selected infusion solution, which is recommended below, and shake well to completely mix the solutions.
- For children and newborns who need to observe the minimum volume of infusions, it is recommended to add 4 ml of the prepared Zovirax solution (100 mg acyclovir) to 20 ml of the infusion solution.
For adults, it is recommended to use infusion solutions in packs of 100 ml, even if this will give the concentration of acyclovir significantly lower than 0.5%. Thus, a single 100 ml infusion solution can be used for any dose of acyclovir between 250 mg and 500 mg (10 and 20 ml of diluted solution). For doses between 500 and 1000 mg of acyclovir, a second infusion solution of this volume should be used.
Zovirax for intravenous infusions is compatible with the following infusion solutions and remains stable when diluted with them for 12 hours at room temperature (from 15° C to 25°C):
- Sodium chloride for intravenous infusions (0.45% and 0.9%)
- Sodium chloride (0.18%) and glucose (4% ) for intravenous infusions
- Sodium chloride (0.45%) and glucose (2.5% ) for intravenous infusions
- Hartmann’s Solution
Since no antibacterial preservative is included in the composition of the solutions, dissolution and dilution must be carried out completely under aseptic conditions immediately before use of the drug, and the unused solution is destroyed.
If the solution becomes cloudy or crystals fall out, it should be destroyed.
Overdose
Symptoms:Â when administered intravenously-increased serum creatinine, blood urea nitrogen, renal failure, neurological symptoms (confusion, hallucinations, agitation, convulsions and coma).
Treatment:Â hemodialysis significantly enhances the elimination of acyclovir from the blood and may be the optimal treatment for overdose.
Form of production
Lyophilizate for the preparation of a solution for intravenous use.
Storage conditions
At temperatures below 30 °C
Shelf life
5 years
Active ingredient
Acyclovir
Conditions of release from pharmacies
By prescription
Dosage form
infusion solution
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Side effects of Zovirax, 250mg vials, 5pcs.
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