Zovirax Intravenous injection Ref.[4773] Active ingredients: Aciclovir

Route of administration: Slow intravenous infusion over 1 hour.

A course of treatment with Zovirax I.V. usually lasts 5 days, but this may be adjusted according to the patient’s condition and response to therapy. Treatment for herpes encephalitis usually lasts 10 days. Treatment for neonatal herpes infections usually lasts 14 days for mucocutaneous (skin-eye-mouth) infections and 21 days for disseminated or central nervous system disease.

The duration of prophylactic administration of Zovirax I.V. is determined by the duration of the period at risk.

Dosage in adults

Patients with Herpes simplex (except herpes encephalitis) or Varicella zoster infections should be given Zovirax I.V. in doses of 5 mg/kg body weight every 8 hours provided renal function is not impaired (see Dosage in renal impairment).

Immunocompromised patients with Varicella zoster infections or patients with herpes encephalitis should be given Zovirax I.V. in doses of 10 mg/kg body weight every 8 hours provided renal function is not impaired (see Dosage in renal impairment).

In obese patients dosed with intravenous aciclovir based on their actual body weight, higher plasma concentrations may be obtained (see 5.2 Pharmacokinetic properties). Consideration should therefore be given to dosage reduction in obese patients and especially in those with renal impairment or the elderly.

Dosage in infants and children: The dose of Zovirax I.V. for infants and children aged between 3 months and 12 years is calculated on the basis of body surface area.

Infants and children 3 months of age or older with Herpes simplex (except herpes encephalitis) or Varicella zoster infections should be given Zovirax I.V. in doses of 250 mg per square metre of body surface area every 8 hours if renal function is not impaired.

In immunocompromised children with Varicella zoster infections or children with herpes encephalitis, Zovirax I.V. should be given in doses of 500 mg per square metre body surface area every 8 hours if renal function is not impaired.

The dosage of Zovirax I.V. in neonates and infants up to 3 months of age is calculated on the basis of body weight.

The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease, or for 14 days for disease limited to the skin and mucous membranes.

Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Dosage in renal impairment).

Dosage in the elderly

The possibility of renal impairment in the elderly must be considered and dosage should be adjusted accordingly (see Dosage in renal impairment below).

Adequate hydration should be maintained.

Dosage in renal impairment

Caution is advised when administering Zovirax I.V. to patients with impaired renal function. Adequate hydration should be maintained.

Dosage adjustment for patients with renal impairment is based on creatinine clearance, in units of ml/min for adults and adolescents and in units of ml/min/1.73m² for infants and children less than 13 years of age. The following adjustments in dosage are suggested:

Dosage adjustments in adults and adolescents

Dosage adjustments in infants and children

Overdosage of intravenenous aciclovir has resulted in elevations of serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with overdosage.

Patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of aciclovir from the blood and may, therefore, be considered an option in the management of overdose of this drug.

Shelf life: 60 months.

Store below 25°C.

Type I glass vials closed with butyl or bromobutyl rubber stoppers secured by aluminium collars.

17 ml-nominal capacity of vial containing 250 mg aciclovir.

25 ml-nominal capacity of vial containing 500 mg aciclovir.

Reconstitution

Zovirax I.V. should be reconstituted using the following volumes of either Water for Injections BP or Sodium Chloride Intravenous Injection BP (0.9% w/v) to provide a solution containing 25 mg aciclovir per ml:

From the calculated dose, determine the appropriate number and strength of vials to be used. To reconstitute each vial add the recommended volume of infusion fluid and shake gently until the contents of the vial have dissolved completely.

Administration

The required dose of Zovirax I.V. should be administered by slow intravenous infusion over a one-hour period.

After reconstitution Zovirax I.V. may be administered by a controlled-rate infusion pump.

Alternatively, the reconstituted solution may be further diluted to give an aciclovir concentration of not greater than 5 mg/ml (0.5% w/v) for administration by infusion:

Add the required volume of reconstituted solution to the chosen infusion solution, as recommended below, and shake well to ensure adequate mixing occurs.

For children and neonates, where it is advisable to keep the volume of infusion fluid to a minimum, it is recommended that dilution is on the basis of 4 ml reconstituted solution (100 mg aciclovir) added to 20 ml of infusion fluid.

For adults, it is recommended that infusion bags containing 100 ml of infusion fluid are used, even when this would give an aciclovir concentration substantially below 0.5% w/v. Thus one 100 ml infusion bag may be used for any dose between 250 mg and 500 mg aciclovir (10 and 20 ml of reconstituted solution) but a second bag must be used for doses between 500 mg and 1000 mg.

When diluted in accordance with the recommended schedules, Zovirax I.V. is known to be compatible with the following infusion fluids and stable for up to 12 hours at room temperature (15°C to 25°C):

Sodium Chloride Intravenous Infusion BP (0.45% and 0.9% w/v)

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP

Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion BP

Compound Sodium Lactate Intravenous Infusion BP (Hartmann’s Solution).

Zovirax I.V. when diluted in accordance with the above schedule will give an aciclovir concentration not greater than 0.5% w/v.

Since no antimicrobial preservative is included, reconstitution and dilution must be carried out under full aseptic conditions, immediately before use, and any unused solution discarded.

Should any visible turbidity or crystallisation appear in the solution before or during infusion, the preparation should be discarded.