Acyclovir-Vaxcel is indicated:
1. For the treatment of Herpes simplex infections in immunocompromised patients
and severe initial genital herpes in the non-immunocompromised.
2. For the prophylaxis of Herpes simplex infections in immune-compromised
patients.
3. For the treatment of Varicella zoster infections.
4. For the treatment of herpes encephalitis.
5. For the treatment of Herpes simplex infections in the neonate and infant up to 3
months of age.
 

A course of treatment with Acyclovir intravenous infusion 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. 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 Acyclovir intravenous infusion 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 Acyclovir intravenous infusion in doses of 5mg/kg body weight every 8 hours provided renal function is not impaired.

Immunocompromised patients with Varicella zoster infections or patients with herpes encephalitis should be given Acyclovir intravenous infusion in doses of 10 mg/kg body weight every 8 hours provided renal function is not impaired.

In obese patients dosed with intravenous acyclovir based on their actual body weight,
higher plasma concentrations may be obtained. 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 Acyclovir intravenous infusion 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 Acyclovir intravenous infusion 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, Acyclovir intravenous infusion should be given in doses of 500 mg per square meter body surface area every 8 hours if renal function is not impaired.

The dosage of Acyclovir intravenous infusion 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 arovir 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.

Dosage in the elderly:
The possibility of renal impairment in the elderly must be considered and the dosage
should be adjusted accordingl. Adequate hydration should be maintained.

Dosage in impairment:
Caution is advised when administering Acyclovir intravenous infusion 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

ROUTE OF ADMINISTRATION:
Reconstitution:
Acyclovir-Vaxcel should be reconstituted using the 10ml volumes of either Water for Injection, Sodium Chloride Intravenous Injection BP (0.9%w/v) to provide a solution containing 25mg/ml acyclovir.
For 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 Acyclovir-Vaxcel should be administered by slow intravenous infusion over one-hour period.
Alternatively, the reconstituted solution may be further diluted to give an acyclovir concentration of not greater than 5mg/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 fluid to a minimum, it is

recommended that dilution is on the basis of 4ml reconstituted solution (100mg acyclovir) added to 20ml of infusion fluid.
For adults, it is recommended that infusion bags containing 100ml of infusion fluid are used, even when this would give an acyclovir concentration substantially below 0.5%w/v. Thus one 100ml infusion bag may be used for any dose between 250mg and 500mg acyclovir (10 and 20ml of reconstituted solution) but a second bag must be used for doses between 500mg and 1000mg.
When diluted in accordance with the recommended schedules, Acyclovir-Vaxcel is known to be compatible with the following infusion fluids and stable for up to 48 hours below 25°C, beyond that unused solution should be discarded: -
• Water for Injection
• Sodium Chloride Intravenous Infusion BP (0.9% w/v)
• Sodium Chloride (0.45% w/v) and Glucose (4% w/v) Intravenous Infusion
BP
• Compound Sodium Lactate Intravenous Infusion BP (Hartmann’s
Solution)
Acyclovir-Vaxcel when diluted in accordance with the above schedule will give an
acyclovir 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 crystallization appear in the solution before or during
infusion, the preparation should be discarded.
Reconstituted or diluted solutions SHOULD NOT BE REFRIGERATED.
 

Adequate hydration should be maintained in patients given iv or high oral doses of acyclovir.
Intravenous doses should be given by infusion over one hour to avoid precipitation of acyclovir in the kidney; rapid or bolus injection should be avoided.
The risk of renal impairment is increased by the use of other nephrotoxic drugs. Care is required if administering iv acyclovir with other nephrotoxic drugs.
 

Use in patients with renal impairment and in elderly patients:
Acyclovir is eliminated by renal clearance; therefore the dose must be reduced in patients with renal impairment. 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.
Prolonged or repeated courses of acyclovir in severely immunocompromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued acyclovir treatment In patients receiving Vaxcel Acyclovir 250mg Injection 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 Vaxcel Acyclovir 250mg Injection has a pH of approximately 11.0 and should not be administered by mouth.
 

Acyclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism or affect renal physiology may increase acyclovir plasma concentrations. Probenecid and cimetidine increase the AUC of acyclovir by this mechanism, and reduce acyclovir renal clearance. However, no dosage adjustment is necessary because of the wide therapeutic index of acyclovir.

In patients receiving intravenous acyclovir, caution is required during concurrent administration with drugs which compete with acyclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites.

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 drugs are co-administered.

If lithium is administered concurrently with high dose acyclovir IV, the lithium serum concentration should be closely monitored because of the risk of lithium toxicity.

Care is also required (with monitoring for changes in renal function) if administering intravenous acyclovir which affect other aspects of renal physiology (e.g. cyclosporine, tacrolimus).
 

Fertility:
There is no information on the effect of acyclovir on human female fertility.

Pregnancy:
Caution should be exercised by balancing the potential benefits of treatment against
any possible hazard.

Breast-feeding:
Following oral administration of 200 mg five times a day, acyclovir has been detected in human 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 body weight/day. Caution is therefore advised if acyclovir is to be administered to a nursing woman.
 

Acyclovir IV for infusion is generally used in an inpatient hospital population and information on ability to drive and operate machinery is not usually relevant. There have been no studies to investigate the effect of acyclovir on driving performance or the ability to operate machinery.
 

The frequency categories associated with the adverse events below are estimates. For most events, suitable data for estimating incidence were not available. In addition,
adverse events may vary in their incidence depending on the indication.
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.
 

To report any side effect(s):
- Kingdom of Saudi Arabia
- National Pharmacovigilance Center (NPC)
o SFDA call center: 19999
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa/
 

Symptoms and Signs:
Overdosage of intravenous acyclovir 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.

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

Pharmacotherapeutic group: Direct acting antivirals, Nucleosides and nucleotides excl. reverse transcriptase inhibitors
ATC code: J05AB01.
 

Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including Herpes simplex virus types 1 and 2 and Varicella zoster virus (VZV), Epstein Barr virus (EBV) and Cytomegalovirus (CMV). In cell culture acyclovir has the greatest antiviral activity against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV.

The inhibitory activity of acyclovir for HSV-1, HSV-2, VZV and EBV 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 and EBV 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.
 

Pharmacotherapeutic group: Direct acting antivirals, Nucleosides and nucleotides excl. reverse transcriptase inhibitors
ATC code: J05AB01.
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including Herpes simplex virus types 1 and 2 and Varicella zoster virus (VZV), Epstein Barr virus (EBV) and Cytomegalovirus (CMV). In cell culture acyclovir has the greatest antiviral activity against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV.

The inhibitory activity of acyclovir for HSV-1, HSV-2, VZV and EBV 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 and EBV 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.
 

NA

Not applicable.
 

None known.
 

Store below 30oC. After reconstitution, store below 25°C for 48 hours.
Do not refrigerate. Protect from light.
 

Available in one vial & 10 vials of sterile powder for intravenous infusion per box.
 

Since no antimicrobial preservative is included, reconstitution and dilution must be carried out under full aseptic conditions, immediately before use. Acyclovir-Vaxcel should be reconstituted using the 10ml volumes of either Water for Injection, or Sodium Chloride Intravenous Injection BP (0.9%w/v) to provide a solution containing 25mg/ml acyclovir (see ROUTE OF ADMINISTRATION).