an antiviral agent.
Zovirax is an antiviral drug, a synthetic analog of the purine nucleoside, which has the ability to inhibit in vitro and in vivo replication of Herpes simplex virus types 1 and 2, Varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture acyclovir has the most expressed antiviral activity against Herpes simplex type 1, followed in descending order of activity by Herpes simplex type 2, Varicella zoster, EBV and CMV.
The action of acyclovir on viruses is highly selective. Acyclovir is not a substrate for thymidine kinase enzyme of uninfected cells, so it is low toxic to mammalian cells. Thymidine kinase of cells infected with Herpes simplex virus types 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. 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 can lead to the formation of resistant strains, and therefore further treatment with acyclovir may not be effective. Most of the acyclovir-resistant strains isolated had relatively low levels of viral thymidine kinase, disruption of viral thymidine kinase or DNA polymerase.
Exposure of acyclovir to Herpes simplex virus strains in vitro can also lead to the formation of less sensitive strains. No correlation has been established between the sensitivity of Herpes simplex virus strains to acyclovir in vitro and the clinical efficacy of the drug.
Injection of Zovirax in high doses has been shown to reduce the incidence and delay 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 viraemia are reduced.
In adults, the mean Cmax of acyclovir is 1 h after infusion at a dose of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, and 15 mg/kg were 22.7 µmol (5.1 µg/ml), 43.6 µmol (9.8 µg/ml), 92 µmol (20.7 µg/ml), and 105 µmol (23.6 µg/ml), respectively. The Cmin of the drug in plasma 7 h after infusion was 2.2 µmol (0.5 µg/ml), 3.1 µmol (0.7 µg/ml), 10.2 µmol (2.3 µg/ml) and 8.8 µmol (2.0 µg/ml), respectively.
The concentration of acyclovir in the cerebrospinal fluid is approximately 50% of its plasma concentration.
Aciclovir is slightly bound to plasma proteins (9-33%).
In adults after intravenous administration of acyclovir the t1/2 from plasma is about 2.9 h. Most of the drug is excreted unchanged by kidneys. Renal clearance of acyclovir significantly exceeds creatinine clearance, indicating 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 of the drug in the urine.
When acyclovir was administered 1 h after administration of 1 g of probenecid, the T1/2 of acyclovir and AUC increased by 18 and 40%, respectively.
Pharmacokinetics in special clinical cases
In children over 1 year of age, Cmax and Cmin values consistent with 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 infants (0 to 3 months) who received acyclovir as an infusion of more than 1 h every 8 h, the Cmax was 61.2 μmol (13.8 μg/mL), the Cmin was 10.1 μmol (2.3 μg/mL), and the T1/2 was 3.8 h.
In the elderly, acyclovir clearance decreases with age in parallel with a decrease in creatinine clearance, but the T1/2 of acyclovir changes only slightly.
In patients with chronic renal impairment, the T1/2 of acyclovir averaged 19.5 h, and with hemodialysis the T1/2 averaged 5.7 h, the plasma concentration of acyclovir decreased by approximately 60%.
- Prevention of herpes simplex virus infections in immunodeficient patients
- Treatment of herpes simplex virus infections
- Treatment of herpes simplex virus infections.Treatment of infections caused by varicella zoster virus and herpes zoster
- Treatment of infections caused by herpes simplex virus in newborns
- Prevention of CMV infections in bone marrow transplant recipients.
High doses of intravenous Zovirax have been shown to reduce the incidence and delay the development of CMV infection. If high-dose Zovirax infusion therapy is followed by high-dose oral Zovirax treatment for 6 months, mortality and the incidence of viraemia are reduced.
1 bottle contains acyclovir 250 mg.
How to take, the dosage
The doses recommended in obese patients are the same as in adults of normal body weight.
The treatment of infections caused by HPV (except herpetic encephalitis) and VZV.
Intravenous infusions at a dose of 5 mg/kg every 8 hours.
The treatment of infections caused by CHD and herpetic encephalitis in immunodeficient patients.
Intravenous infusions at a dose of 10 mg/kg every 8 hours if renal function is normal.
The prevention of CMV infection in bone marrow transplants
500 mg/m2 intravenously 3 times a day at 8-hour intervals. The duration of treatment is from 5 days before transplantation and up to 30 days after transplantation.
Doses of Zovirax for intravenous infusions in children aged 3 months to 12 years are calculated according to body surface area.
In newborns, doses are calculated according to body weight. In infections caused by HPV, a dose of 10 mg/kg every 8 hours is recommended.
The treatment of infections caused by HPV (except herpetic encephalitis) and VZV.
Intravenous infusions at a dose of 250 mg/m2 every 8 hours.
The treatment of herpetic encephalitis and infections caused by VZV in immunodeficient children.
Intravenous infusions at a dose of 500 mg/m2 every 8 hours with normal renal function.
Preventing CMV infection in children older than 2 years.
Few data suggest that children older than 2 years who have undergone a bone marrow transplant may be prescribed an adult dose of intravenous Zovirax.
In children with decreased renal function, dose adjustments are required according to the degree of renal failure.
Patients in the elderly
In the elderly, the clearance of acyclovir in the body decreases in parallel with a decrease in creatinine clearance. Particular attention should be given to reducing doses of Zovirax in the elderly with decreased creatinine clearance.
Intravenous infusions of Zovirax should be administered with caution in patients with renal impairment. The following dosage adjustment scheme has been suggested depending on the degree of decrease in creatinine clearance.
5-10 mg/kg or 500 mg/m2 every 12 hours
5-10 mg/kg or 500 mg/m2 every 24 hours
0( anuria)-10 mL/min
In continuous ambulatory peritoneal dialysis, 2.5-5 mg/kg or 250 mg/m2 every 24 hours.
In hemodialysis, 2.5-5 mg/kg or 250 mg/m2 every 24 hours and after dialysis.
The course of treatment with Zovirax as intravenous infusions is usually 5 days, but may vary depending on the patient’s condition and response to therapy. The duration of treatment of herpetic encephalitis and HPV infections in infants is usually 10 days.
The duration of prophylactic use of Zovirax for intravenous infusions is determined by the length of time there is a risk of infection.
Preparation of solution and method of administration
The recommended dose of Zovirax should be administered as a slow intravenous infusion over 1 hour.
The following volumes of water for injection or sodium chloride solution for injection (0.9%) are used to prepare Zovirax solution with 25 mg of acyclovir in 1 ml of the resulting solution.
Dose of Zovirax in 1 ampoule
Volume of dilution solution
Add the recommended volume of dilution solution to the ampoule with Zovirax powder, shake gently until the contents of the ampoule are completely dissolved.
After dilution, Zovirax solution can be administered as intravenous infusions using a special infusion pump to regulate the rate of administration of the drug.
An alternative method of infusion is possible when the prepared Zovirax solution is further diluted to obtain a concentration of acyclovir not exceeding 5 mg/ml (0.5%).
- To do this, add the prepared solution to the selected infusion solution recommended below and shake well to mix the solutions completely.
- For children and newborns in whom minimum infusion volumes must be observed, we recommend adding 4 ml of prepared Zovirax solution (100 mg acyclovir) to 20 ml of infusion solution.
For adults, it is recommended to use infusion solutions in packages of 100 ml, even if this would give an acyclovir concentration significantly below 0.5%. Thus, one 100 ml infusion solution can be used for any dose of acyclovir between 250 mg and 500 mg (10 and 20 ml diluted solution). For doses between 500 and 1000 mg of acyclovir a second infusion solution of this volume must be used.
Zovirax for intravenous infusion is compatible with the following infusion solutions and remains stable for 12 hours at room temperature (15°C to 25°C) when diluted:
- Natrium chloride for intravenous infusion ( 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 infusion
- Hartman’s solution
. Since no antibacterial preservative is included in the solutions, dissolution and dilution must be performed completely under aseptic conditions immediately prior to administration, and the unused solution is destroyed.
If the solution becomes cloudy or crystals precipitate, they must be destroyed.
No clinically significant interactions have been observed with Zovirax.
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 IV, caution is required when prescribing 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 mycophenolate mofetil.
Cautiously combine intravenous administration of Zovirax (renal function should be monitored) with drugs that impair renal function (e.g., cyclosporine, tacrolimus).
Zovirax is contraindicated in cases of hypersensitivity to acyclovir or valacyclovir and during lactation.
With caution should be used with dehydration, renal failure, neurological disorders, during the development of reactions to cytotoxic drugs (when administered intravenously) and in the presence of such in the history, pregnancy.
Gastrointestinal tract: nausea, vomiting; if ingested – diarrhea, abdominal pain.
Blood system: anemia, leukopenia and thrombocytopenia.
Hypersensitivity reactions and skin: rash, photosensitization, urticaria, itching, fever; rarely – shortness of breath, angioedema, anaphylaxis; when administered intravenously – severe local inflammatory reactions leading to necrosis of the skin when Zovirax solution gets under the skin.
Kidney: rarely – increase in urea and creatinine levels in the blood. It is believed that this complication is related to the Cmax value in plasma and the state of the patient’s water balance. To avoid these phenomena, instead of an IV bolus injection, a slow infusion of 1 h should be administered. The patient’s water balance should be maintained. Renal failure that develops during treatment with Zovirax for IV infusion is usually rapidly resolved by rehydrating patients and/or reducing the dose of the drug or cancelling it. Progression to acute renal failure occurs in exceptional cases.
Liver: reversible increase in bilirubin levels and liver enzyme activity; hepatitis and jaundice (very rare) when administered intravenously.
CNS: when administered by injection – reversible neurological disorders such as confusion, hallucinations, agitation, tremor, somnolence, psychosis, seizures and coma usually observed in patients with predisposing conditions; when administered orally – headache; rarely – reversible neurological disorders.
Others: rapid fatigue; rarely, rapid diffuse hair loss (no association with acyclovir intake has been established).
Symptoms: when administered intravenously – increased serum creatinine, blood urea nitrogen, renal failure, neurological symptoms (confusion, hallucinations, agitation, seizures and coma).
Treatment: hemodialysis significantly enhances excretion of acyclovir from the blood and may be the optimal treatment for overdose.
An analysis of acyclovir treatment of women during pregnancy showed no increase in birth defects in their children compared to the general population.
But caution should be exercised when prescribing Zovirax to women during pregnancy and assess the expected benefit to the mother and the possible risk to the fetus.
Vivorax, Acyclovir-Acri, Acyclovir, Herperax, Acyclovir Belupo, Acyclovir Sandoz
|Conditions of storage|
At temperatures below 30 °C
GlaxoSmithKlein Manufacturing S.p.A., Italy
GlaxoSmithKlein Manufacturing S.p.A.
Buy Zovirax, lyophilizate 250 mg 5 pcs with delivery to USA, UK, Europe and over 120 other countries.