ADMINISTRATION ROUTES:
PO, NG, IV, Topical
ALTERNATIVE NAMES:
Zovirax, Acyclovir, Aciclovir
ICU INDICATIONS:
- Herpes Simplex encephalitis
- Prophylaxis in an allogeneic bone marrow transplant patient (at risk of CMV)
- Varicella Pneumonia
- Uncomplicated Herpes Simplex or Varicella Zoster infection in an immunocompromised patient
- Treatment of Shingles
PRESENTATION AND ADMINISTRATION:
PO / NG:
Acyclovir is available in 200 mg, 400 mg and 800 mg tablets. 200 mg dispersible tablets are also available.
IV:
Acyclovir sodium for IV administration comes in a vial containing 250 mg in 10 mL. 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: 25 mg/mL solution via a controlled rate infusion pump over at least one hour (preferred method if administering via a central line)
OR: dilute 25 mg/mL solution to make a solution of 5 mg/mL using a compatible IV fluid (eg dilute 5 mL into 25 mL 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
Topical:
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 TDS for 10 days
Give as infusion over 1 hour
Herpes Simplex Infections in Immunocompromised Patients
Adults and Adolescents (12 years of age and older):
5 mg/kg IV TDS for 7 days
Give as infusion over 1 hour
Varicella Zoster Infections including Varicella Pneumonia
Adults and Adolescents (12 years of age and older):
10 mg/kg IV TDS for 7 days
Give as infusion over 1 hour
OR (for uncomplicated Shingles in the non-immunocompromised patient):
800 mg five times daily for 10 days
Note: 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 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) | DOSE |
|---|---|
| <10 | 2.5 - 5 mg/kg OD |
| 10-25 | 5 - 10 mg/kg BD |
| >25-50 | 5 - 10 mg/kg BD |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | Dose as for GFR < 10 ml/min |
| HD | Dose as for GFR < 10 ml/min |
| CVVHDF | Dose as for GFR 10 - 25 ml/min |
DOSAGE IN PAEDIATRICS:
Herpes Simplex Encephalitis
Paediatrics (3 months to 12 years of age):
20 mg/kg IV TDS for 10 days
Give as infusion over 1 hour
Herpes Simplex Infections in Immunocompromised patients
Paediatrics (under 12 years of age):
20 mg/kg IV TDS for 7 days
Give as infusion over 1 hour
Varicella Zoster Infections including Varicella Pneumonia
Paediatrics (under 12 years of age):
20 mg/kg IV TDS for 7 days
Give as infusion over 1 hour
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/haemolytic uraemic 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 IN ICU:
Co-administration with other nephrotoxic drugs increases the risk of renal toxicity
ADVERSE REACTIONS:
General:
Anaphylaxis, fever, pain, peripheral oedema.
Cardiovascular:
Hypotension.
Gastrointestinal:
Diarrhoea, gastrointestinal distress, nausea.
Neurological:
Aggressive behaviour,agitation, ataxia, coma, confusion, delirium, dizziness, hallucinations, obtundation, paraesthesia, psychosis, seizure, somnolence.
These symptoms may be marked, particularly in older adults.
Haematologic and Lymphatic:
Disseminated intravascular coagulation, haemolysis, leukopaenia, lymphadenopathy.
Hepatobiliary Tract and Pancreas:
Elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice.
Musculoskeletal:
Myalgia.
Dermatological:
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