Acyclovir

Acyclovir

ADMINISTRATION ROUTES: IV, PO, NG and TOP

ALTERNATIVE NAMES: Zovirax, Acyclovir, Aciclovir

ICU INDICATIONS:

  1. Herpes Simplex encephalitis
  2. Prophylaxis in an allogeneic bone marrow transplant patient (at risk of CMV)
  3. Varicella Pneumonia
  4. Uncomplicated Herpes Simplex or Varicella Zoster infection in an immunocompromised patient.
  5. Treatment of Shingles

PRESENTATION AND ADMINISTRATION:

  • PO / NG: Acyclovir is available in 200mg, 400mg and 800mg tablets; 200mg dispersible tablets are also available.
  • IV: Acyclovir sodium for IV administration comes in a vial containing 250mg in 10ml. It is a clear, colourless to pale yellow solution. Do not refrigerate. Stable in compatible IV fluid for 24 hours at room temperature. Do not use solution if it appears cloudy or visible crystals are present. Acyclovir solution is highly alkaline. It should not be administered by mouth. Administer as:
    • EITHER: 25mg/ml solution via a controlled rate infusion pump over at least one hour (preferred method if administering via a central line)
    • OR: dilute 25mg/ml solution to make a solution of 5mg/ml using a compatible IV fluid (eg dilute 5ml into 25ml total) and then administer by controlled infusion over at least one hour (preferred method if administering via a peripheral line)
    • Compatible with the following IV fluids: Saline, Hartmann’s, Glucose and Sodium Chloride
  • TOP: Each gram of Zovirax cream 5% contains 50 mg acyclovir in an aqueous cream base. It is supplied in 2 g tubes.

DOSAGE:

  • Herpes Simplex Encephalitis: Adults and Adolescents (12 years of age and older): 10 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 10 days.
  • Herpes Simplex Infections in Immunocompromised Patients: Adults and Adolescents (12 years of age and older): 5 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 7 days.
  • Varicella Zoster Infections including Varicella Pneumonia:
    • Adults and Adolescents (12 years of age and older): 10 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 7 days.
    • OR (for uncomplicated Shingles in the non-immunocompromised patient): 800 mg five times daily for 10 days (There are no data on treatment initiated more than 72 hours after onset of the zoster rash.)
    • NOTE: IV therapy is indicated in the immunocompromised and in patients with Varicella pneumonia
  • Cold sores (in the non-immunocompromised): Acyclovir cream should be applied 5 times per day for 4 days. Therapy should be initiated as early as possible following onset of signs and symptoms. Data indicating efficacy are poor and use in the critically ill has not been studied.

NOTE: Obese patients should be dosed at the recommended adult dose using ideal body weight.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    • <10          2.5-5mg/kg every 24 hours
    • -25           5-10mg/kg every 12 hours
    • >25-50     5-10mg/kg every 12 hours
  • Dose in renal replacement therapy
    • CAPD Dose as for GFR <10ml/min
    • HD Dose as for GFR <10ml/min
    • CVVHDF Dose as for GFR 10-25ml/min

DOSAGE IN PAEDIATRICS:

  • Herpes Simplex Encephalitis: Paediatrics (3 months to 12 years of age): 20 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 10 days.
  • Herpes Simplex Infections in Immunocompromised patients: Paediatrics (under 12 years of age): 10 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 7 days.
  • Varicella Zoster Infections including Varicella Pneumonia: Paediatrics (under 12 years of age): 20 mg/kg IV infused at a constant rate over 1 hour, every 8 hours for 7 days.

CLINICAL PHARMACOLOGY:

  • Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).

CONTRAINDICATIONS:

  • Hypersensitivity to acyclovir or valacyclovir

WARNINGS

  • Acyclovir for injection is intended for IV infusion only, and should not be administered topically, intramuscularly, orally, subcutaneously, or into the eye.
  • IV infusions must be given over a period of at least 1 hour to reduce the risk of renal tubular damage. Renal failure, in some cases resulting in death, has been observed with acyclovir therapy.
  • Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy.

PRECAUTIONS

  • General: Precipitation of acyclovir crystals in renal tubules can occur if the drug is administered by bolus injection. Ensuing renal tubular damage can produce acute renal failure.
  • Abnormal renal function (decreased creatinine clearance) can occur as a result of acyclovir administration and depends on the state of the patient’s hydration, other treatments, and the rate of drug administration. Concomitant use of other nephrotoxic drugs, pre-existing renal disease, and dehydration make further renal impairment with acyclovir more likely.
  • Approximately 1% of patients receiving IV acyclovir have manifested encephalopathic changes characterised by either lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, or coma.
  • Laboratory Tests: No tests are required in addition to routine ICU blood tests.
  • Drug/Laboratory Test Interactions: None reported

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Co-administration with other nephrotoxic drugs increases the risk of renal toxicity

ADVERSE REACTIONS

  • Body as a Whole: Anaphylaxis, fever, pain, peripheral oedema.
  • Cardiovascular System: Hypotension.
  • Digestive System: Diarrhoea, gastrointestinal distress, nausea.
  • Nervous System: Aggressive behavior, agitation, ataxia, coma, confusion, delirium, dizziness, hallucinations, obtundation, paresthesia, psychosis, seizure, somnolence. These symptoms may be marked, particularly in older adults
  • Haematologic and Lymphatic: Disseminated intravascular coagulation, haemolysis, leukopenia, lymphadenopathy.
  • Hepatobiliary Tract and Pancreas: Elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice.
  • Musculoskeletal: Myalgia.
  • Skin: Alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. Severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of acyclovir into extravascular tissues.
  • Special Senses: Visual abnormalities.
  • Urogenital: Renal failure, elevated blood urea nitrogen, elevated creatinine.

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