Simplovir IV Infusion

Simplovir intravenous infusion is indicated for the treatment of-

• Acute clinical manifestations of Herpes simplex virus in immunocompromised patients
• Severe primary or non-primary genital herpes in immune competent patients
• Varicella zoster virus infection in immunocompromised patients
• Herpes zoster (shingles) in immune competent patients who show very severe acute local or systemic manifestations of the disease
• Herpes simplex encephalitis

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.

• 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 probenecid with Simplovir has been shown to increase the mean Simplovir 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 Simplovir very significantly.

Acyclovir IV Injection is contraindicated in patients known to be hypersensitive to Acyclovir or Valacyclovir.

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 Simplovir 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.

Simplovir IV injection is intended for intravenous infusion only and should not be used through any other route. Reconstituted Simplovir IV Infusion has a pH of approximately 11.0 and should not be administered by mouth. Simplovir 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. Simplovir 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 Simplovir. As Simplovir 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 Simplovir 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 Simplovir 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 Simplovir 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: Simplovir 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.

Overdosage of intravenous Simplovir 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 Simplovir from the blood and may, therefore, be considered an option in the management of overdose of Simplovir.

Herpes simplex & Varicella-zoster virus infections

It is recommended that Simplovir 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.

Each 250 mg vial of Simplovir IV Injection should be reconstituted by the addition of 10 ml of either Water for Injection or Sodium Chloride Intravenous Infusion (0.9% w/v). This provides a solution containing 25 mg Simplovir per ml.

Each 500 mg vial of Simplovir IV Injection should be reconstituted by the addition of 10 ml of either Water for Injection or Sodium Chloride Intravenous Infusion (0.9% w/v). This provides a solution containing 50 mg Simplovir per ml.

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