Acyclovir (Injection)
Indications
Acyclovir 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
Pharmacology
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.
Dosage
- 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
Administration
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.
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)
Interaction
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.
Contraindications
Acyclovir IV Injection is contraindicated in patients known to be hypersensitive to Acyclovir or Valacyclovir.
Side Effects
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 & Lactation
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.
Precautions & Warnings
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.
Use in Special Populations
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:
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.
Overdose Effects
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.
Therapeutic Class
Herpes simplex & Varicella-zoster virus infections
Duration of Treatment
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.
Reconstitution
Each 250 mg vial of Acyclovir 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 Acyclovir per ml.
Each 500 mg vial of Acyclovir 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 Acyclovir per ml.
Each 500 mg vial of Acyclovir 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 Acyclovir per ml.
Storage Conditions
Store at 15°C to 25°C. Protected from light and moisture. Keep the medicine out of the reach of children.
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