Virux

Acyclovir exerts its antiviral e­ects on Herpes simplex virus and Varicella zoster virus by interfering with DNA synthesis and inhibiting viral replication. In cells infected with Herpes virus, the antiviral activity of Acyclovir appears to depend principally on the intracellular conversion of the drug to Acyclovir Triphosphate. Acyclovir is converted to Acyclovir Monophosphate principally via virus coded thymidine kinase, the monophosphate is phosphorylated to diphosphate via cellular guanylate kinase and then via other cellular enzymes to the Triphosphate, which is the pharmacologically active form of the drug.

Co-administration of probenecid with Acyclovir has been shown to increase the mean Acyclovir half-life and the area under the concentration time curve. Urinary excretion and renal clearance correspondingly reduced. In patients over 60 years of age concurrent use of diuretics increases plasma levels of Acyclovir very significantly.

Some infrequent adverse reactions are lethargy, obtundation, tremors, confusion, hallucinations, agitation, somnolence, psychosis, convulsions and coma, phlebitis, nausea, vomiting, reversible increases in liver-related enzymes, pruritus, urticaria, rashes, increases in blood urea and creatinine. Local inflammatory reactions may occur if Acyclovir IV Infusion is inadvertently infused into extracellular tissues.

Pregnancy category B. There have been no adequate and well controlled studies concerning the safety of Acyclovir in pregnant women. It should not be used during pregnancy unless the benefits to the patient clearly outweigh the potential risks to the fetus. Acyclovir should only be administered to nursing mothers if the benefits to the mother outweigh the potential risks to the baby. There is no experience of the effect of Acyclovir on human fertility.

Acyclovir IV injection is intended for intravenous infusion only and should not be used through any other route. Reconstituted Acyclovir IV Infusion has a pH of approximately 11.0 and should not be administered by mouth. Acyclovir IV injection as infusion must be given over a period of at least one hour in order to avoid renal tubular damage. It should not be administered as a bolus injection. Acyclovir IV infusion must be accompanied by adequate hydration. Since maximum urine concentration occurs within the first few hours following infusion, particular attention should be given to establish sufficient urine ‑ow during that period. Concomitant use of other nephrotoxic drugs, pre-existing renal disease and dehydration increase the risk of further renal impairment by Acyclovir. As Acyclovir has been associated with reversible encephalopathic changes, it should be used with caution in patients with neurological abnormalities, significant hypoxia or serious renal, hepatic or electrolyte abnormalities.

Pediatric use: The dose of Acyclovir IV injection in children aged 1-12 years should be calculated on the basis of body surface area. Children in this age group with Herpes simplex infections (except Herpes simplex encephalitis) or Varicella zoster infections should be given Acyclovir IV Infusion in doses of 250 mg/m² (equivalent to 5 mg/kg in adults). Immunocompromised children in this age group with Varicella zoster virus infection or with Herpes simplex encephalitis should be given Acyclovir IV Infusion in doses of 500 mg/m² (equivalent to 10 mg/kg in adults). Children with impaired renal function require an appropriately modified dose, according to the degree of impairment.

Geriatric use: No data are available on this age group. However, as creatinine clearance is often low in the elderly, special attention should be given to dosage reduction.

In patients with renal impairment: Acyclovir should be administered with caution since the drug is excreted through the kidneys. The following modifications in dosage are suggested:

• CrCl: 25-50 ml/min: 5 or 10 mg/kg every 12 hours
• CrCl: 10-25 ml/min: 5 or 10 mg/kg every 24 hours
• CrCl: 0-10 ml/min: 2.5 or 5 mg/kg every 24 hours and after dialysis.

Herpes simplex & Varicella-zoster virus infections

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 over dosage. Adequate hydration is essential to reduce the possibility of crystal formation in the urine. Hemodialysis significantly enhances the removal of Acyclovir from the blood and may, therefore, be considered an option in the management of overdose of Acyclovir.

Store at 15°C to 25°C. Protected from light and moisture. Keep the medicine out of the reach of children.