Intravenous acyclovir is used in the following situations:

• To treat severe symptoms of herpes simplex virus infection in immunocompromised patients
• To treat severe primary or non-primary genital herpes in immunocompetent patients
• To treat varicella-zoster virus infection in immunocompromised patients
• To treat shingles (herpes zoster) in immunocompetent patients with severe local or systemic symptoms
• To treat herpes simplex encephalitis

Acyclovir works against Herpes simplex virus and Varicella zoster virus by interfering with DNA synthesis and stopping viral replication. In cells infected with herpes virus, its antiviral effect mainly depends on the conversion of Acyclovir into its active form, Acyclovir Triphosphate. The drug is first converted into Acyclovir Monophosphate by a virus-coded enzyme called thymidine kinase. The monophosphate is then converted to Acyclovir Diphosphate by a cellular enzyme called guanylate kinase, and finally to Acyclovir Triphosphate by other cellular enzymes. This triphosphate form is the pharmacologically active form that stops the virus from multiplying.

• Herpes simplex infection: For normal or immunocompromised immune status: 5 mg/kg every 8 hours
• Very severe Herpes zoster infection (shingles): For normal immune status: 5 mg/kg every 8 hours
• Varicella zoster infection: For immunocompromised immune status: 10 mg/kg every 8
• hours Herpes simplex encephalitis: For normal or immunocompromised immune status: 10 mg/kg every 8 hours

Each dose should be administered by slow intravenous infusion over a one-hour period.

It is recommended that Acyclovir IV Injection for Intravenous Infusion should be administered for five to seven days in the treatment of most infections and for at least ten days in the treatment of Herpes simplex encephalitis. Acyclovir IV Injection after reconstitution may be injected directly into a vein over one hour by a controlled-rate infusion pump or be further diluted for administration by infusion. For intravenous infusion each vial of Acyclovir IV Injection should be reconstituted and then, wholly or in part according to the dosage required, added to and mixed with at least 50 mL-100 ml infusion solution. A maximum of 250 mg & 500 mg of Acyclovir may be added to 50 ml & 100 ml infusion solution respectively. After addition of Acyclovir IV Injection to an infusion solution the mixture should be shaken to ensure thorough mixing. Acyclovir IV Injection when diluted in accordance with the above schedule will give an Acyclovir concentration not greater than 0.5% w/v.

Acyclovir IV Injection is known to be compatible with the following infusion fluids and stable for up to 12 hours at room temperature (below 25°C) when diluted to a concentration not greater than 0.5% w/v Acyclovir.

• 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
• Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion Compound Sodium Lactate Intravenous Infusion BP (Hartmann's Solution)

Acyclovir IV Injection for Intravenous Infusion contains no preservative. Reconstitution and dilution should therefore
be carried out immediately before use and any unused solution should be discarded. The solution should not be
refrigerated.

Co-administration of Acyclovir with probenecid can increase the average half-life of Acyclovir and raise the total exposure (area under the concentration-time curve). At the same time, urinary excretion and renal clearance of Acyclovir are reduced. In patients over 60 years old, concurrent use of diuretics can significantly increase plasma levels of Acyclovir.

Acyclovir IV Injection should not be used in patients who are known to be hypersensitive to Acyclovir or Valacyclovir.

Some less common adverse effects of Acyclovir IV Injection include lethargy, drowsiness, tremors, confusion, hallucinations, agitation, somnolence, psychosis, convulsions, and coma. Other possible reactions are phlebitis, nausea, vomiting, reversible increases in liver enzymes, itching, hives, rashes, and increased blood urea and creatinine. Local irritation or inflammation may occur if Acyclovir IV Injection is accidentally infused into surrounding tissues.

Acyclovir IV Injection is classified as pregnancy category B. There are no well-controlled studies that fully establish its safety in pregnant women. It should only be used during pregnancy if the benefits to the mother clearly outweigh the potential risks to the fetus. Nursing mothers should take Acyclovir IV Injection only if the benefits to the mother outweigh any possible risks to the baby. There is no available data on the effects of Acyclovir on human fertility.

Acyclovir IV Injection is meant strictly for intravenous infusion and should not be administered via any other route. Reconstituted Acyclovir IV Infusion has a pH of approximately 11.0 and must not be taken orally. The infusion should be given over at least one hour to prevent renal tubular damage and should never be administered as a bolus injection. Adequate hydration must accompany the infusion. Since the highest urine concentration occurs within the first few hours after infusion, it is important to maintain sufficient urine flow during this time. Concomitant use of nephrotoxic drugs, pre-existing kidney disease, and dehydration increase the risk of renal complications. Because Acyclovir may cause reversible encephalopathic changes, caution is advised in patients with neurological disorders, significant hypoxia, or severe renal, hepatic, or electrolyte abnormalities.

Pediatric use: The dose of Acyclovir IV Injection for children aged 1–12 years should be calculated based on body surface area. Children in this age group with Herpes simplex infections (excluding Herpes simplex encephalitis) or Varicella zoster infections should receive Acyclovir IV Infusion at 250 mg/m² (equivalent to 5 mg/kg in adults). Immunocompromised children with Varicella zoster virus infection or Herpes simplex encephalitis should receive 500 mg/m² (equivalent to 10 mg/kg in adults). Children with impaired renal function require dose adjustment according to the severity of kidney impairment.

Geriatric use: There is limited data on elderly patients. Since creatinine clearance is often reduced in this population, careful attention should be given to dose adjustments.

Patients with renal impairment: Acyclovir should be used cautiously as it is primarily excreted by the kidneys. Suggested dose modifications are:

• 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

Overdose of Acyclovir IV Injection may lead to elevated serum creatinine, increased blood urea nitrogen, and potentially renal failure. Neurological effects such as confusion, hallucinations, agitation, seizures, and coma have also been reported with overdose. Adequate hydration is essential to reduce the risk of crystal formation in the urine. Hemodialysis effectively increases the removal of Acyclovir from the bloodstream and can be considered as a treatment option in cases of overdose.

Herpes simplex & Varicella-zoster virus infections

Store Acyclovir IV Injection at a temperature between 15°C and 25°C. Keep it protected from light and moisture. Ensure the medicine is out of reach of children.