Zovirax Injection

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 7/15/2022

Drug Summary

What Is Zovirax Injection?

Zovirax (acyclovir sodium) for Injection is an antiviral that is used for treating infections caused by the herpes virus.

What Are Side Effects of Zovirax Injection?

Common side effects of Zovirax Injection include nausea, vomiting, diarrhea, loss of appetite, headache, muscle pain, numbness or tingling, loss of coordination, drowsiness, lightheadedness, or swelling in your hands or feet.

Dosage for Zovirax Injection

Zovirax is given as an IV injection as directed by your doctor. It is usually given for at least once every 8 hours for 5 to 10 days.

What Drugs, Substances, or Supplements Interact with Zovirax Injection?

Zovirax may interact with tizanidine, probenecid, or drugs affecting the kidneys (e.g., amphotericin B, cisplatin, and aminoglycosides such as gentamicin). Tell your doctor all medications you use. Zovirax will not prevent the spread of genital herpes. Avoid sexual intercourse or use a latex condom to prevent spreading the virus to others.

Zovirax Injection During Pregnancy and Breastfeeding

Zovirax should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Zovirax is excreted in breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Zovirax (acyclovir sodium) for Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Drug Description


ZOVIRAX is the brand name for acyclovir, a synthetic nucleoside analog active against herpesviruses. Acyclovir sodium for injection is a sterile lyophilized powder for intravenous administration only. Each 500-mg vial contains 500 mg of acyclovir and 49 mg of sodium, and each 1,000-mg vial contains 1,000 mg acyclovir and 98 mg of sodium. Reconstitution of the 500-mg or 1,000-mg vials with 10 mL or 20 mL, respectively, of Sterile Water for Injection, USP results in a solution containing 50 mg/mL of acyclovir. The pH of the reconstituted solution is approximately 11. Further dilution in any appropriate intravenous solution must be performed before infusion (see DOSAGE AND ADMINISTRATION: Method of Preparation and Administration).

Acyclovir sodium is a white, crystalline powder with the molecular formula C8H10N5NaO3 and a molecular weight of 247.19. The maximum solubility in water at 25°C exceeds 100 mg/mL. At physiologic pH, acyclovir sodium exists as the un-ionized form with a molecular weight of 225 and a maximum solubility in water at 37°C of 2.5 mg/mL. The pka's of acyclovir are 2.27 and 9.25.

The chemical name of acyclovir sodium is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one monosodium salt; it has the following structural formula:

ZOVIRAX®  (acyclovir sodium) Structural Formula Illustration


Mechanism of Antiviral Action: Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).

The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.

Antiviral Activities: The quantitative relationship between the in vitro susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC50 of 1.35 mcg/mL.

Drug Resistance: Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection. While most of the acyclovir-resistant mutants isolated thus far from such patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults. The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.

Indications & Dosage


  1. Herpes simplex infections in immunocompromised patients:
    • ZOVIRAX IV is indicated for the treatment of herpes simplex infections.
    • ZOVIRAX IV is indicated for the prophylaxis of herpes simplex infections in patients.
  2. ZOVIRAX IV is indicated in the treatment of varicella zoster infections in immuno-compromised patients:
  3. ZOVIRAX IV is indicated for treatment of herpes simplex infections in the neonate.
  4. ZOVIRAX IV is indicated for the treatment of herpes simplex encephalitis.
  5. ZOVIRAX IV is indicated for the prevention of reactivation of cytomegalovirus infection in seropositive patients following bone marrow transplantation.


The required dose of ZOVIRAX IV should be administered by slow intravenous infusion over a one hour period. A course of treatment with ZOVIRAX IV usually lasts 5 days, but this may be adjusted according to the patient's condition and response to therapy. Treatment for herpes encephalitis and neonatal herpes simplex infections usually lasts 10 days. The duration of prophylactic administration of ZOVIRAX IV is determined by the duration of the period at risk.

Dosge in Adults

Immune Status Dosage
Herpes simplex infection (except herpes encephalitis) Immuno compromised 5 mg/kg every 8 hours
Varicella zoster infection Immuno compromised (normal renal function) 10 mg/kg every 8 hours
Herpes simplex encephalitis Normal or immuno-
(normal renal function)
10 mg/kg every 8 hours

Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.

Dosage in Children

The dose of ZOVIRAX IV for children aged between 3 months and 12 years is calculated on the basis of body surface area.

Immune Status Dosage
Herpes simplex infection (except herpes encephalitis) Immuno compromised 250 mg/m2 every 8 hours
Varicella zoster infection Immuno compromised (normal renal function) 500 mg/m2 every 8 hours
Herpes simplex encephalitis Normal
(normal renal function)
500 mg/m2 every 8 hours

Children with impaired renal function require an appropriately modified dose and/or dose interval, according to the degree of impairment as indicated under ‘Dosage in Renal Impairment’.

Dosage in Neonates

The dosage of ZOVIRAX IV in neonates is calculated on the basis of bodymass. Neonates with herpes simplex infections should be given ZOVIRAX IV in doses of 10 mg/kg every 8 hours.

Dosage in the Elderly

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

Adequate hydration should be maintained.

Dosage For The Prevention Of Cytomegalovirus Reactivation Following Bone Marrow Transplantation


500 mg/m2 ZOVIRAX IV should be given intravenously 3 times daily at approximately 8 hour intervals. The duration of treatment recommended in bone marrow transplant recipients is from 5 days before, up to 30 days after transplant.


Limited data suggest that for the prevention of cytomegalovirus reactivation in children over 2 years of age, who have undergone bone marrow transplantation, the adult dose may be given.

Dosage In Renal Impairment For Adult And Paediatric Patients

Caution is advised when administering ZOVIRAX IV to patients with impaired renal function. The following adjustments in dosage are suggested

Creatinine Clearance
Percentage of recommended dose (%) Dosing interval (hours)
> 50 100 % 8
25-50 100 % 12
10-25 100 % 24
0-10 50% 24

Guidelines For Acyclovir Administration In Neonates With Renal Impairment

Creatinine clearance of 20-50 ml/min/1,73 m2 or serum creatinine 70-100 μmol/l: a dose of 10 mg/kg/12 hours. Creatinine clearance of 10-25 ml/min/1,73 m2 or serum creatinine 110-130 μmol/l with decreasing urine output: a dose of 10 mg/kg/24 hours. Renal failure with creatinine clearance of < 10 ml/min/1,73 m2 or serum creatinine > 130 μmol/l or urine output < 1 ml/kg/hour and peritoneal dialysis: a dose of 5 mg/kg/24 hours.


ZOVIRAX IV should be reconstituted using the following volumes of either Water for Injections BP or Sodium Chloride Intravenous Infusion BP (0,9 % m/v) to provide a solution containing 25 mg acyclovir per ml.

Volume of fluid for reconstitution
250 mg vial 10 ml

From the calculated dose, determine the appropriate number and strength of vials to be used. Reconstitute each vial by adding the recommended volume of infusion fluid and shaking gently until contents of the vial have dissolved completely.


After reconstitution, ZOVIRAX IV may be administered intravenously over a one hour period by a controlled-rate infusion pump. Alternatively, the reconstituted solution may be further diluted to give an acyclovir concentration of not greater than 5 mg/ml (0,5 % m/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 acyclovir) 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 acyclovir concentration substantially below 0,5 % m/v. Thus, one 100 ml infusion bag may be used for any dose between 250 mg and 500 mg acyclovir (10 and 20 ml of reconstituted solution) but a second bag must be used for doses between 500 and 1 000 mg. When diluted in accordance with the recommended schedules, ZOVIRAX IV 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 % m/v)
  • Sodium Chloride (0,18 % m/v) and Glucose (4 % m/v) Intravenous Infusion BP
  • Sodium Chloride (0,45 % m/v) and Glucose (2,5 % m/v) Intravenous Infusion BP
  • Compound Sodium Lactate Intravenous Infusion BP (Hartmann’s Solution).

ZOVIRAX IV when diluted in accordance with the above schedule, will give an acyclovir concentration not greater than 0,5 % m/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. Reconstituted or diluted solutions should not be refrigerated.

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



Vial containing a white to off-white powder.


Carton containing 5 clear, colourless glass vials.

Storage Instructions

Store below 25 °C.

Keep out of reach of children.

Use immediately after reconstitution and discard any excess.

Reconstituted or diluted solution should not be refrigerated.

GlaxoSmithKline South Africa (Pty) Ltd, 39 Hawkins Avenue, Epping Industria 1, 7460. Revised: Mar 2012

Side Effects


Adverse Effects Derived from Clinical Trials

The adverse reactions listed have been observed in controlled and uncontrolled clinical trials in approximately 700 patients who received ZOVIRAX at ~5 mg/kg (250 mg/m2) 3times daily and approximately 300 patients who received 10 mg/kg (500 mg/m2) 3 times daily.

The following convention has been used for the classification of undesirable effects in terms of frequency: Very common ≥ 1/10, common ≥ 1/100 and < 1/10, uncommon ≥ 1/1 000 and < 1/100, rare ≥ 1/10 000 and < 1/1 000, very rare < 1/10 000.

Blood and Lymphatic System Disorders

Uncommon: decreases in haematological indices (anaemia, thrombocytopenia, leucopenia).

Vascular Disorders

Common: phlebitis.

Gastrointestinal Disorders

Common: nausea, vomiting.

Hepatobiliary Disorders

Common: reversible increases in liver-related enzymes.

Skin and Subcutaneous Tissue Disorders

Common: rashes (including photosensitivity), urticaria, pruritus, fevers.

Renal and Urinary Disorders

Common: increases in blood urea and creatinine levels. Rapid increases in blood urea and creatinine levels are believed to be related to peak plasma levels and the state of hydration of the patient. To avoid this effect, ZOVIRAX should not be given as an intravenous bolus injection, but by slow infusion over a one hour period.

Adverse Effects Derived from Post-Marketing Data

The following events have been identified during post-approval use of ZOVIRAX from spontaneous reports. As these are reported from a population of unknown size, precise estimates of frequency cannot be made.

Immune system disorders: Anaphylaxis.

Psychiatric and nervous system disorders: Headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.

The above events are generally reversible and usually reported in patients with renal impairment, or with other predisposing factors (see WARNINGS AND SPECIAL PRECAUTIONS).

Respiratory, thoracic and mediastinal disorders: Dyspnoea.

Gastrointestinal disorders: Diarrhoea, abdominal pain.

Hepatobiliary disorders: Reversible increases in bilirubin, hepatitis, jaundice.

Skin and subcutaneous tissue disorders: Angioedema, accelerated diffuse hair loss. The relationship of accelerated diffuse hair loss to ZOVIRAX therapy is uncertain.

Renal and urinary disorders: Renal impairment, acute renal failure.

Adequate hydration of the patient should be maintained. Renal impairment usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of ZOVIRAX. Progression to acute renal failure, may occur.

General disorders and administration site conditions: Fatigue, fever, local inflammatory reactions.

Severe local inflammatory reactions sometimes leading to ulceration have occurred when ZOVIRAX IV has been inadvertently infused into extravascular tissues.

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of acyclovir cream. Because they arereported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination oftheir seriousness, frequency of reporting, or potential causal connection to acyclovir cream.

General: Angioedema, anaphylaxis.

Skin: Contact dermatitis, eczema.

Drug Interactions


No clinically significant interactions have been identified. Acyclovir as contained in ZOVIRAX IV is eliminated primarily unchanged in the urine via active renal tubular secretion. Any medicines administered concurrently that compete with this mechanism may increase acyclovir plasma concentrations. Probenecid and cimetidine increases the AUC of acyclovir by this mechanism, and reduces acyclovir renal clearance.

In patients receiving intravenous ZOVIRAX, caution is required during concurrent administration with medicines which compete with acyclovir for elimination, because of the potential for increased plasma levels of one or both medicines or their metabolites.Clinical experience has identified no interactions resulting from topical or systemic administration of other drugs concomitantly with ZOVIRAX Cream. Due tominimal systemic absorption of ZOVIRAX Cream, systemic drug interactions are unlikely.

Increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the medicines are co-administered.
Care is also required (with monitoring for changes in renal function) if administering intravenous ZOVIRAX with medicines which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Warnings & Precautions


Included as part of the PRECAUTIONS section.


Safety of ZOVIRAX treatment in pregnancy and lactation has not been established (see Pregnancy and Lactation).

Use In Patients With Renal Impairment And In Elderly Patients

Acyclovir, as contained in ZOVIRAX IV, is eliminated by renal clearance, therefore the dose must be reduced in patients with renal impairment (see Dosage And Directions For Use).

Elderly patients are likely to have reduced renal function and therefore the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see SIDE EFFECTS).

The dose of ZOVIRAX IV must be adjusted in patients with impaired renal function in order to avoid accumulation of acyclovir in the body (see Dosage in Renal Impairment).

In patients receiving ZOVIRAX IV at higher doses (e.g. for herpes encephalitis), specific care regarding renal function should be taken, particularly when patients are dehydrated or have any renal impairment.
Reconstituted ZOVIRAX IV has a pH of approximately 11,0 and should not be administered by mouth.

Pregnancy and Lactation

Safety in pregnancy has not been established (see WARNINGS and SPECIAL PRECAUTIONS).


Following oral administration of 200 mg five times a day, acyclovir has been detected in breast milk at concentrations ranging from 0,6 to 4,1 times the corresponding plasma levels. These levels would potentially expose nursing infants to acyclovir dosages of up to 0,3 mg/kg/day. Lactating women on ZOVIRAX treatment should not breastfeed.


There is no information on the effect of ZOVIRAX IV on human female fertility. In a study of 20 male patients with normal sperm count, oral acyclovir administered at doses of up to 1 g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

Overdose & Contraindications


Known Symptoms Of Overdosage And Particulars Of Its Treatment

Overdosage of intravenous ZOVIRAX has resulted in elevations in 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. Haemodialysis significantly enhances the removal of acyclovir from the blood and may, therefore, be considered an option in the management of overdose of ZOVIRAX. Treatment is symptomatic and supportive


ZOVIRAX IV is contra-indicated in patients known to be previously hypersensitive to acyclovir or valaciclovir.

Clinical Pharmacology


Pharmacological Action

Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV). In cell culture, acyclovir has the greatest anti-viral activity against HSV-1, followed (in decreasing order of potency) by HSV-2 and VZV. The inhibitory activity of acyclovir for HSV-1, HSV-2 and VZV is highly selective. The enzyme thymidine kinase (TK) of normal, uninfected cells does not use acyclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV converts acyclovir to acyclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.

Medication Guide


No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

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