see also:

• viruses
• Herpes simplex virus (HSV)
• varicella-zoster virus (chickenpox/shingles)
• herpes zoster (shingles)
• meningitis

• aciclovir is an antiviral agent which is active against Herpes simplex virus (HSV) types I and II and varicella-zoster virus (chickenpox/shingles)).
• in infected cells, HSV or VZV coded thymidine kinases facilitate the conversion of aciclovir to the active aciclovir monophosphate which then acts as an inhibitor of, and substrate for, the herpes specified DNA polymerase, preventing further viral DNA synthesis.
• plasma half-life is ~3hrs
• 60-90% of aciclovir is excreted unchanged in urine where it is insoluble
• adjust dose in renal impaired patients
• probenecid increases the half life by ~18%
• high doses are cytotoxic in animal studies
• crosses the placenta readily and is excreted in breast milk
• category B3 for pregnant women
• use in lactating women if benefits outweigh risks

• headache is most common reported adverse effect
• nausea, vomiting, diarrhea, abdominal pain, and constipation
• fatigue, dizziness, dry mouth, and rash
• allergic reaction
• rarely (usually with high doses):
  • nephrotoxicity (see warning below)
  • neurotoxicity - usually with high doses - confusion, hallucinations, agitation, tremors, ataxia, or coma
  • thrombotic thrombocytopenic purpura (TTP) which can be fatal, mostly in immunocompromised patients on high doses.

• probably safer to use famciclovir instead when oral dosing is needed (see below)

• herpes zoster within 72hrs of onset of rash (800mg tabs x 35)
• herpes zoster ophthalmicus (800mg tabs x 35)
• mod-severe primary genital herpes within 1st 72hrs (200mg tabs x 25 x 2)
• episodic Rx of recurrent genital herpes after PCR proof (200mg tabs x 90)
• HIV patients with CD4 counts < 150 million/L (800mg tabs x 120)

• pregnant women with varicella within 72hrs of onset of rash
• immunocompromised patients with varicella irrespective of duration of rash
  • NB. infants aged < 28 days are regarded as immunocompromised by paediatricians
  • ATG - varicella in HIV patients
• normal patients with severe chickenpox (eg. pneumonitis, encephalitis or hepatitis) irrespective of duration of rash
• primary or recurrent genital herpes
• severe primary or recurrent herpes on any part of skin or mucosa:
  • 400mg 5/day for 7 days or normal dose regime iv
  • NB. sun protection is important in preventing recurrences
• suppressive Rx for severe disabling, recurrent herpetic episodes (eg. frequent episodes assoc. with erythema multiforme, or for immunocompromised patients with chronic lesions):
  • 400mg bd for up to 6 months

• most patients are given a 5-7 day iv course, then oral course for total of 10 days

• varicella zoster infection in immunocompromised patients
• severe chickenpox pneumonitis, encephalitis, etc.
• herpes simplex encephalitis (10 day iv course)
• adult dose: 10mg/kg 8hrly iv
• paediatric dose: 250mg/m2 body surface area 8hrly iv

• severe shingles in immunocompetent patient
• HSV infection
• adult dose: 10mg/kg 8hrly iv
• paediatric dose: 500mg/m2 body surface area 8hrly iv

• reduce iv dosing frequency as follows:
  • creatinine clearance 25-50ml/min: 12hrly dosing
  • creatinine clearance 10-25ml/min: 24hrly dosing
  • creatinine clearance <10ml/min or anuric: 24hrly dosing and after dialysis, and halve dose

• probably safer and more efficacious to use famciclovir instead when oral dosing is needed
• primary genital herpes:
  • 200mg 5/day (every 4 waking hours) for 10 days
• recurrent genital herpes:
  • suppressive Rx: 200mg tds for up to 6 months
  • intermittent Rx: 200mg 5/day (every 4 waking hours) for 10 days
• acute herpes zoster (shingles) within 72hrs of rash or acute herpes zoster ophthalmicus:
  • 800mg 5/day (every 4 waking hours) for 10 days
• advanced, symptomatic HIV patients with CD4 counts < 150 million/L:
  • 800mg qid

• 5% cream (eg. Stoxil) are very useful for Mx of cold sores if started early and applied frequently (5/day for 4 days)
• avoid topical antivirals to the eye for HSV keratitis without ophthalmology consult as they are cytotoxic to the cornea.

• famciclovir
  • compared to aciclovir has greater oral bioavailability (approx. 77% vs. 12-20%) and thus allows bd dosing instead of 3-5x a day giving better compliance, while its active metabolite (penciclovir triphosphate) lasts longer in herpes-infected cells (7hrs) than aciclovir triphosphate (<1 hour) and there is evidence of greater efficacy for zoster and can allow single dose for some cases of HSV
  • unlike aciclovir and valaciclovir, it does NOT cause crystalline nephropathy but high doses can still be nephrotoxic
  • not available IV
  • usual adult dose in herpes zoster (shingles): 250mg tds for 10 days (use 500mg dose for immunocompromised)
  • usual adult dose in severe primary HSV: 500mg bd for 7 days
  • usual adult dose in severe recurrent HSV: 1500mg as a single dose
  • PBS: https://www.pbs.gov.au/pbs/search?term=famciclovir - zoster or genital HSV; oral HSV in AIDS;
• valaciclovir
  • pro-drug which is converted to aciclovir but which has greater oral bioavailability (approx. 50% vs. 12-20%) and thus allows bd dosing instead of 3-5x a day giving better compliance and there is evidence of greater efficacy for zoster
  • probably safer to use famciclovir instead
  • not available IV
  • usual adult dose in herpes zoster (shingles) or primary HSV: 1g tds for 10 days
  • usual adult dose in severe primary HSV: 1g bd for 7 days
  • usual adult dose in severe recurrent HSV: 2g bd for 1 day
  • usual adult suppressive dose in severe recurrent HSV: 500mg daily for up to 6 months
  • PBS authority: https://www.pbs.gov.au/medicine/item/5480K-8064K-8133C-8134D - zoster or genital HSV; oral HSV in AIDS;