Zovirax

Aciclovir.

Dispersible tab: Dispersible Tablets containing either 200 mg or 800 mg aciclovir.
Oral susp: Oral suspensions containing 200 mg aciclovir per 5 ml.
Powd for inj: ZOVIRAX 250 mg: The sodium ion content is approximately 26 mg per vial.
Excipients/Inactive Ingredients: Dispersible tab: Aluminium Magnesium Silicate; Anhydrous Ethanol; Microcrystalline Cellulose; Magnesium Stearate; Purified Water; Polyethylene Glycol 8000; Povidone K30; White colour concentrate Y-1-7000; Sodium Starch Glycolate.
Oral susp: Methyl Parahydroxybenzoate; Banana flavour 5708023; Glycerol Ph. Eur.; 70% Sorbitol Solution; Dispersible Cellulose; Vanillin; Propyl Parahydroxybenzoate; Purified water.
Powd for inj: Sodium hydroxide; Nitrogen; Water for injection.

Pharmacotherapeutic group: Direct acting antivirals, Nucleosides and nucleotides excl. reverse transcriptase inhibitors. ATC code: J05AB01.
Pharmacology: Pharmacodynamics: Mechanism of Action: Aciclovir 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, varicella zoster virus (VZV), Epstein Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, aciclovir 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 aciclovir for HSV-1, HSV-2, VZV, EBV and CMV is highly selective. The enzyme thymidine kinase (TK) of normal, non-infected cells does not use aciclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV and EBV converts aciclovir to aciclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Aciclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Pharmacodynamic Effects: Prolonged or repeated courses of aciclovir in severely immune-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued aciclovir treatment.
Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK however, strains with altered viral TK or DNA polymerase have also been reported. In vitro exposure of HSV isolates to aciclovir can also lead to the emergence of less sensitive strains. The relationship between the in vitro determined sensitivity of HSV isolates and clinical response to aciclovir therapy is not clear.
All patients should be cautioned to ensure they avoid the potential of virus transmission, particularly when active lesions are present.
Clinical Studies: Oral susp/Powd for inj: There is no information on the effect of ZOVIRAX oral formulations & infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir 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.
Pharmacokinetics: Absorption: Dispersible tab: Aciclovir is only partially absorbed from the gut. Mean steady state peak plasma concentrations (C_ssmax) following doses of 200 mg administered four-hourly were 3.1 micromolar (0.7 micrograms/mL) and equivalent trough plasma levels (C_ssmin) were 1.8 micromolar (0.4 micrograms/mL). Corresponding C_ssmax levels following doses of 400 mg and 800 mg administered four-hourly were 5.3 micromolar (1.2 micrograms/mL) and 8 micromolar (1.8 micrograms/mL) respectively, and equivalent C_ssmin levels were 2.7 micromolar (0.6 micrograms/mL) and 4 micromolar (0.9 micrograms/mL).
In adults, mean steady state peak plasma concentrations (C_ssmax) following a one-hour infusion of 2.5 mg/kg, 5 mg/kg and 10 mg/kg and 15 mg/kg were 22.7 micromolar (5.1 micrograms/mL), 43.6 micromolar (9.8 micrograms/mL), 92 micromolar (20.7 micrograms/mL) and 105 micromolar (23.6 micrograms/mL) respectively. The corresponding through levels (C_ssmin) 7 hours later were 2.2 micromolar (0.5 micrograms/mL), 3.1 miromolar (0.7 micrograms/mL), 10.2 micromolar (2.3 micrograms/mL) and 8.8 micromolar (2.0 micrograms/mL), respectively. In children over 1 year of age similar mean peak (C_ssmax) and through (C_ssmin) levels were observed when a dose of 250 mg/m² was substituted for 5 mg/kg and a dose of 500 mg/m² was substituted for 10 mg/kg. In neonates (0 to 3 months of age) treated with doses of 10 mg/kg administered by infusion over a one-hour period every 8 hours the C_ssmax was found to be 61.2 micromolar (13.8 micrograms/mL) and the C_ssmin to be 10.1 micromolar (2.3 micrograms/mL). A separate group of neonates treated with 15 mg/kg every 8 hours showed approximate dose proportional increases, with a C_max of 83.5 micromolar (18.8 micrograms/mL) and C_min of 14.1 micromolar (3.2 micrograms/mL).
Oral susp: Aciclovir is only partially absorbed from the gut. The average oral bioavailability varies between 10 and 20%. Under fasting conditions, mean peak concentrations (C_max) of 0.4 microgram/ml are achieved at approximately 1.6 hours after a 200 mg dose administered as oral suspension or capsule. Mean peak plasma concentrations (C_ssmax) increase to 0.7 microgram/ml (3.1 micromoles) at steady state following doses of 200 mg administered every four hours. A less than proportional increase is observed for C_ssmax levels following doses of 400 mg and 800 mg administered four-hourly, with values reaching 1.2 and 1.8 microgram/ml (5.3 and 8 micromoles), respectively.
Powd for inj: Not Applicable.
Distribution: The mean volume of distribution of 26 L indicates that aciclovir is distributed within total body water. Apparent values after oral administration (Vd/F) ranged from 2.3 to 17.8 L/kg. As plasma protein binding is relatively low (9 to 33%), drug interactions involving binding site displacement are not anticipated. Cerebrospinal fluid levels are approximately 50% of corresponding plasma levels at steady-state.
Metabolism: Aciclovir is predominantly excreted unchanged by the kidney. The only known urinary metabolite is 9-[(carboxymethoxy)methyl] guanine, and accounts for 10-15% of the dose excreted in the urine.
Elimination: In neonates (0 to 3 months of age) treated with doses of 10 mg/kg administered by infusion over a one-hour period every 8 hours the terminal plasma half-life was 3.8 hours.
Dispersible tab: In adults the terminal plasma half life of aciclovir after administration of intravenous aciclovir is about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of aciclovir is substantially greater than creatinine clearance, indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of the drug. 9-carboxymethoxy-methylguanine is the only significant metabolite of aciclovir and accounts for approximately 10 to 15% of the dose excreted in the urine. When aciclovir is given one hour after 1 gram of probenecid the terminal half life and the area under the plasma concentration time curve is extended by 18% and 40% respectively.
Oral susp/Powd for inj: Mean systemic exposure (AUC_0-∞) to aciclovir ranges between 1.9 and 2.2 microgram*h/mL after a 200 mg dose. In adults the terminal plasma half-life after oral administration has been shown to vary between 2.8 and 4.1 hours. Renal clearance of aciclovir (CLr=14.3 L/h) is substantially greater than creatinine clearance, indicating that tubular secretion, in addition to glomerular filtration, contributes to the renal elimination of the drug. The half-life and total clearance of aciclovir are dependent on renal function. Therefore, dosage adjustment is recommended for renally impaired patients.
Special Patient Populations: In patients with chronic renal failure the mean terminal half-life was found to be 19.5 hours. The mean aciclovir half-life during haemodialysis was 5.7 hours. Plasma aciclovir levels dropped approximately 60% during dialysis.
In the elderly total body clearance falls with increasing age, associated with decreases in creatinine clearance, although there is little change in the terminal plasma half-life.
Dispersible tab/Oral susp: Studies have shown no apparent changes in the pharmacokinetic behaviour of aciclovir or zidovudine when both are administered simultaneously to HIV infected patients.
Toxicology: Non-Clinical Information/Preclinical Safety Data: The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir is unlikely to pose a genetic risk to man.
Aciclovir was not carcinogenic in long-term studies in the rat and the mouse.
Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of aciclovir greatly in excess of those employed therapeutically. Two-generation studies in mice did not reveal any effect of orally administered aciclovir on fertility.
Systemic administration of aciclovir in intentionally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice. In a non-standard test in rats, foetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

Dispersible tab/Oral susp: Zovirax Dispersible Tablets/Oral Suspension is indicated for the treatment of Herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes.
Zovirax Dispersible Tablets/Oral Suspension is indicated for the suppression (prevention of recurrences) of recurrent Herpes simplex infections in immunocompetent patients.
Zovirax Dispersible Tablets/Oral Suspension is indicated for the prophylaxis of Herpes simplex infections in immunocompromised patients.
Zovirax Dispersible Tablets/Oral Suspension is indicated for the treatment of Varicella infections (chickenpox) and Herpes zoster (shingles). Studies have shown that early treatment of shingles with ZOVIRAX has a beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain).
Powd for inj: ZOVIRAX i.v. for infusion is indicated for the treatment of herpes simplex infections.
ZOVIRAX i.v. for infusion is indicated for the prophylaxis of herpes simplex infections in immune-compromised patients.
ZOVIRAX i.v. for infusion is indicated in the treatment of varicella zoster infections.
ZOVIRAX i.v. for infusion is indicated for the treatment of herpes simplex infections in the neonate.

Dispersible tab/Oral susp: Adults: Treatment of herpes simplex: For treatment of herpes simplex infections, 200 mg ZOVIRAX should be taken five times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for five days but in severe initial infections may have to be extended.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
Dosing should begin as early as possible after the start of an infection; for recurrent episodes this should preferably be during the prodromal period or when lesions first appear.
Suppression of herpes simplex: For suppression of Herpes simplex infections in immune-competent patients, 200 mg ZOVIRAX should be taken four times daily at approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of 400 mg ZOVIRAX taken twice daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg ZOVIRAX taken thrice daily at approximately eight-hourly intervals or even twice daily at approximately twelve-hourly intervals, may prove effective.
Some patients may experience breakthrough infections on total daily doses of 800 mg ZOVIRAX.
Therapy should be interrupted periodically at intervals of six to twelve months in order to observe possible changes in the natural history of the disease.
Prophylaxis of herpes simplex: For prophylaxis of herpes simplex infections in immune-compromised patients, 200 mg ZOVIRAX should be taken four times daily at approximately six-hourly intervals.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
Treatment of varicella and herpes zoster: For treatment of varicella and herpes zoster infections, 800 mg ZOVIRAX should be taken five times daily at approximately four-hourly intervals, omitting the night time dose. Treatment should continue for seven days.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing.
Dosing should begin as early as possible after the start of an infection. Treatment yields better results if initiated as soon as possible after onset of the rash.
Oral susp: Treatment of chickenpox in immunocompetent patients should begin within 24 hours after onset of the rash.
Infants and children: For treatment of herpes simplex infections, and for prophylaxis of herpes simplex infections in the immune-compromised, children aged two years and over should be given adult dosages and infants and children below the age of two years should be given half the adult dose.
For treatment of varicella infections in children: 6 years and over: 800 mg ZOVIRAX four times daily. 
2 - <6 years: 400 mg ZOVIRAX four times daily.
Under 2 years: 200 mg ZOVIRAX four times daily.
Dosing may be more accurately calculated as 20 mg ZOVIRAX/kg body weight (not to exceed 800 mg) four times daily. Treatment should continue for five days.
No specific data are available on the suppression of herpes simplex infections or the treatment of Herpes zoster infections in immune-competent children.
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal impairment as follows).
Adequate hydration of elderly patients taking high oral doses of ZOVIRAX should be maintained.
Renal impairment: Caution is advised when administering ZOVIRAX oral formulations to patients with impaired renal function. Adequate hydration should be maintained.
In the treatment and prophylaxis of herpes simplex infections in patients with impaired renal function, the recommended oral doses will not lead to accumulation of aciclovir above levels that have been established safe by intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 mL/minute) an adjustment of dosage to 200 mg twice daily at approximately twelve-hourly intervals is recommended.
In the treatment of varicella and herpes zoster infections, it is recommended to adjust the dosage to 800 mg twice daily, at approximately twelve-hourly intervals, for patients with severe renal impairment (creatinine clearance less than 10 mL/minute) and to 800 mg three times daily, at intervals of approximately eight hours, for patients with moderate renal impairment (creatinine clearance in the range 10 to 25 mL/minute).
Powd for inj: To be given as intravenous infusion over 1 hour.
A course of treatment with ZOVIRAX IV. For infusion 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 IV for infusion is determined by the duration of the period at risk.
Adults: Treatment of herpes simplex: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with herpes simplex (except herpes encephalitis) should be given aciclovir IV for infusion in doses of 5 mg/kg body weight every eight hours if renal function is not impaired.
Patients with herpes encephalitis should be given aciclovir IV for infusion in doses of 10 mg/kg body weight every eight hours provided renal function is not impaired.
Prophylaxis of herpes simplex in immune-compromised patients: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Refer to adult dosing recommendations for the treatment of herpes simplex with ZOVIRAX IV for infusion.
Treatment of varicella and herpes zoster: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with varicella zoster infections should be given aciclovir IV for infusion in doses of 5 mg/kg body weight every eight hours if renal function is not impaired.
Immune-compromised patients with varicella zoster infections should be given aciclovir IV for infusion in doses of 10 mg/kg body weight every eight hours provided renal function is not impaired.
Infants and children: The dose of ZOVIRAX IV for infusion for infants and children aged between 3 months and 12 years is calculated on the basis of body weight.
Treatment of herpes simplex: Infants and children 3 months of age or older with herpes simplex infections should be given aciclovir 20 mg/kg body weight IV every eight hours for 21 days for herpes encephalitis, or for 14 days for disease limited to skin and mucous membrane if renal function is not impaired.
Children with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Renal impairment as follows).
Prophylaxis of herpes simplex in immune-compromised patients: Refer to infant and children dosing recommendations for the treatment of herpes simplex with aciclovir IV for infusion.
Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment, see Table 2.
Treatment of varicella and herpes zoster: Infants and children with varicella zoster infections should be given aciclovir 20 mg/kg body weight IV every eight hours if renal function is not impaired.
Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Table 2, Dosage adjustments in neonates, infants and children).
Neonates: Treatment of herpes simplex: The dosage of ZOVIRAX IV for infusion in neonates is calculated on the basis of body weight.
The recommended regimen for treatment for known or suspected neonatal herpes is aciclovir 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. Patients with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Renal impairment as follows).
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal impairment as follows).
Adequate hydration should be maintained.
Renal Impairment: Caution is advised when administering ZOVIRAX IV 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/1.73 m² for infants and children less than 13 years of age.
The following adjustments in dosage are suggested: (See Tables 1 and 2).

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Symptoms & signs: Overdosage of intravenous 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 intravenous overdosage.
Dispersible tab/Oral susp: Aciclovir is only partly absorbed in the gastrointestinal tract. Patients have ingested overdoses of up to 20 g aciclovir on a single occasion, usually without toxic effects.
Accidental, repeated overdoses of oral aciclovir over several days have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).
Treatment: Patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of aciclovir from the blood and may therefore be considered a management option in the event of symptomatic overdose.

ZOVIRAX is contraindicated in patients known to be hypersensitive to acyclovir or valaciclovir.

Dispersible tab/Oral susp: Hydration status: Care should be taken to maintain adequate hydration in patients receiving high oral doses of aciclovir.
Powd for inj: In patients receiving ZOVIRAX IV for infusion 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 for infusion has a pH of approximately 11.0 and should not be administered by mouth.
Effects on Ability to Drive and Use Machines: There have been no studies to investigate the effect of aciclovir on driving performance or the ability to operate machinery.
Dispersible tab/Oral susp: The clinical status of the patient and the adverse event profile of ZOVIRAX should be borne in mind when considering the patient's ability to drive or operate machinery.
Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.
Powd for inj: ZOVIRAX IV for infusion is generally used in an in-patient hospital population and information on ability to drive and operate machinery is not usually relevant.
In patients receiving ZOVIRAX IV for infusion 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 for infusion has a pH of approximately 11.0 and should not be administered by mouth.
Use in patients with renal impairment and in elderly patients: Aciclovir is eliminated by renal clearance, therefore the dose must be reduced in patients with renal impairment (see Dosage & Administration). 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 Adverse Reactions).

Pregnancy: A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of ZOVIRAX. The registry findings have not shown an increase in the number of birth defects amongst ZOVIRAX exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.
The use of aciclovir should be considered only when the potential benefits outweigh the possibility of unknown risks.
Lactation: Following oral administration of 200 mg aciclovir five times a day, aciclovir 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 aciclovir dosages of up to 0.3 mg/kg/day. Caution is therefore advised if ZOVIRAX is to be administered to a nursing woman.

The frequency categories associated with the adverse events as follows 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 ≥1/1000 and <1/100, rare ≥1/10,000 and <1/1000, very rare <1/10,000.
Dispersible tab/Oral susp: Blood and lymphatic system disorders: Very rare: Anaemia, leukopenia, thrombocytopenia.
Immune system disorders: Rare: Anaphylaxis.
Psychiatric and nervous system disorders: Common: Headache, dizziness. Very rare: Agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment, or with other predisposing factors (see Precautions).
Respiratory, thoracic and mediastinal disorders: Rare: Dyspnoea.
Gastrointestinal disorders: Common: Nausea, vomiting, diarrhoea, abdominal pains.
Hepatobiliary disorders: Rare: Reversible rises in bilirubin and liver-related enzymes. Very rare: Hepatitis, jaundice.
Skin and subcutaneous tissue disorders: Common: Pruritus, rashes (including photosensitivity). Uncommon: Urticaria. Accelerated diffuse hair loss. Rare: Angioedema.
Accelerated diffuse hair loss has been associated with a wide variety of disease processes and medicines, the relationship of the event to aciclovir therapy is uncertain.
Renal and urinary disorders: Rare: Increases in blood urea and creatinine. Very rare: Acute renal failure, renal pain.
Renal pain may be associated with renal failure.
General disorders and administration site conditions: Common: Fatigue, fever.
Powd for inj: Blood and lymphatic system disorders: Uncommon: Decreases in haematological indices (anaemia, thrombocytopenia, leukopenia).
Immune system disorders: Very rare: Anaphylaxis.
Psychiatric and nervous system disorders: Very rare: Headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors (see Precautions).
Vascular disorders: Common: Phlebitis.
Respiratory, thoracic and mediastinal disorders: Very rare: Dyspnoea.
Gastrointestinal disorders: Common: Nausea, vomiting. Very rare: Diarrhoea, abdominal pain.
Hepatobiliary disorders: Common: Reversible increases in liver-related enzymes. Very rare: Reversible increases in bilirubin, jaundice, hepatitis.
Skin and subcutaneous tissue disorders: Common: Pruritus, urticaria, rashes (including photosensitivity). Very rare: Angioedema.
Renal and urinary disorders: Common: Increases in blood urea and creatinine. Very rare: Renal impairment, acute renal failure, renal pain.
Rapid increases in blood urea and creatinine levels are believed to be related to the peak plasma levels and the state of hydration of the patient. To avoid this effect, when administered intravenously the drug should not be given as an intravenous bolus injection but by infusion over a one-hour period.
Adequate hydration should be maintained. Renal impairment usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of the drug. Progression to acute renal failure, however, can occur in exceptional cases.
Renal pain may be associated with renal failure.
General disorders and administration site conditions: Very rare: Fatigue, fever, local inflammatory reactions.
Severe local inflammatory reactions sometimes leading to breakdown of the skin have occurred when ZOVIRAX IV for infusion has been inadvertently infused into extracellular tissues.

No clinically significant interactions have been identified.
Aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase aciclovir plasma concentrations. Probenecid and cimetidine increase the AUC of aciclovir by this mechanism, and reduce aciclovir renal clearance. Similarly increases in plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients have been shown when the drugs are coadministered. However no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.
Powd for inj: In patients receiving intravenous ZOVIRAX, caution is required during concurrent administration with drugs which compete with aciclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites.
Care is also required (with monitoring for changes in renal function) if administering intravenous ZOVIRAX with drugs which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Incompatibilities: Dispersible tab: None known.
Oral susp: There are no special requirements for use on handling of this product.
Powd for inj: The reconstituted concentrate and diluted solution for infusion must not be mixed with other medicinal products except those mentioned in Use and Handling.
Instructions for Use/Handling: Dispersible tab: ZOVIRAX Dispersible Tablets may be swallowed whole or with a little water, or dispersed in a minimum of 50 ml of water.
Oral susp: For administration of 100 mg dose, the measuring device provided may be used, or alternatively a graduated syringe.
Powd for inj: Reconstitution: The required dose of ZOVIRAX IV for infusion should be administered by slow IV infusion over a one-hour period.
ZOVIRAX IV for infusion should be reconstituted using the following volumes of either Water for Injections or Sodium Chloride Injection (0.9% w/v) to provide a solution containing 25 mg ZOVIRAX per mL: (See Table 3.)

Click on icon to see table/diagram/image

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.
After reconstitution ZOVIRAX IV for infusion may be administered by a controlled-rate infusion pump.
Alternatively, the reconstituted solution may be further diluted to give a ZOVIRAX 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 as follows, 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 ZOVIRAX) 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 a ZOVIRAX 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 ZOVIRAX (10 and 20 mL of reconstituted solution) but a second bag must be used for doses between 500 and 1000 mg.
When diluted in accordance with the recommended schedules, ZOVIRAX IV for infusion is known to be compatible with the following infusion fluids and stable for up to 12 hours at room temperature (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 IV for infusion when diluted in accordance with the previously mentioned schedule will give a ZOVIRAX concentration not greater than 0.5% w/v.
When reconstituted as directed, ZOVIRAX IV for infusion has a pH of approximately 11.
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.

Store below 30°C.
Dispersible tab: Keep dry. Protect from light.

Antivirals

J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

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