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acyclovir (ACV, Zovirax, Sitavig)

Tradename: Zovirax, Sitavig. Indications: - *treatment of susceptible viral infections a) Herpes simplex type 1 & 2 infections b) Varicella zoster infections c) Epstein-Barr virus d) mucocutaneous infections e) *neonatal infections [7] - empiric treatment of meningoencephalitis Dosage: 1) 5-10 mg/kg IV every 8 hours, each dose over 1 hour. 2) 1st episode genital herpes: 400 mg PO TID x 7-10 days. 3) Recurrent genital herpes: a) 400 mg PO TID x 5 days b) 800 mg PO TID x 2 days [6] 4) Herpes prophylaxis: 400 mg PO BID. 5) Herpes simplex encephalitis: -> 10 mg/kg IV every 8 hours for 10 days. 6) Herpes Zoster: 800 mg PO 5 times/day for 7-10 days. 7) Varicella: 20 mg/kg up to 800 mg PO QID for 5 days. 8) Mucocutaneous Herpes in an immunocompromised host: a) 5 mg/kg IV every 8 hours b) 400 mg PO TID c) duration of therapy 7 days 9) Varicella or Herpes zoster in an immunocompromised host: - 10 m/kg IV every 8 hours for 7 days 10) Herpes simplex (cold sore) - 5% ointment 6 times/day for 7 days - buccal tablet, same side of mouth once per episode [8] Tabs: 200 & 800 mg. Suspension: 200 mg/5 mL. Buccal tablet: Sitavig [8] Topical agent: 5% ointment 6 times/day for 7 days. Tubes: 3 & 15 g. Dosage adjustment in renal failure: Adjustment of oral dose in renal failure creatinine clearance adjusted dose dosing interval > 50 mL/min 100% every 8 hours 25-50 mL/min 100% every 12 hours 11-15 mL/min 100% every 24 hours > 10 mL/min 50% every 24 hours Adjustment of IV dose in renal failure creatinine clearance adjusted dose [9] > 50 mL/min 10 mg/kg q8h 25-50 mL/min full dose q12 hours 11-25 mL/min full dose q24 hours 0-10 mL/min half dose q24 hours * intravenous normal saline to maintain urine output > 75 mL/hour if rise in serum creatinine [10] Pharmacokinetics: 1) oral bioavailability is 15-30% 2) food does not appear to affect absorption 3) peak serum levels a) 1.5-2 hours after oral dose b) 1 hours after IV administration 4) widely distributed to tissues 5) cerebrospinal fluid levels are about 50% of serum levels 6) protein binding 9-33% 7) metabolized by the liver [3] 8) eliminated by kidney (primary mechanism) [1,3] 9) elimination 1/2life 2-3 hours 10) 60% eliminated by hemodialysis 11) dose adjustment in renal failure Adverse effects: 1) common (> 10%) - headache - inflammation at site of injection 2) less common (1-10%) - lethargy, dizziness, seizures, delirium, nausea/vomiting, rash, tremor, nephrotoxicity 3) uncommon (< 1%) - mental depression, insomnia, anorexia, LFT elevation, sore throat, lethargy, diaphoresis 4) other - phlebitis [2] - nephrotoxicity: - 10-20% when given IV [4] - starts 1-2 days after IV administration - oliguria is uncommon - acyclovir crystals may deposit in the distal tubules* - recovery is the rule after discontinuation - neurotoxity [11] (in order of frequency) - disorientation - diminished level of consciousness - hallucinations - agitation - dysarthria - seizures/myoclonus - coma - tremor - ataxia - aphasia - delirium * intravenous normal saline to maintain urine output > 75 mL/hour if rise in serum creatinine [10] Drug interactions: 1) probenecid increases oral bioavailability & 1/2life of acyclovir 2) zidovudine results in an increase in drowsiness & lethargy Laboratory: 1) specimen: a) serum, plasma (heparin), CSF b) stable at -12 degrees C for 7 days 2) methods: HPLC, RIA, MB 3) laboratory tests a) acyclovir in CSF b) acyclovir in serum/plasma Mechanism of action: 1) viral thymidine kinase & cellular enzymes convert acyclovir to its active form 2) acyclovir triphosphate is a competitive inhibitor of viral DNA polymerase 3) Herpes zoster is 8-10 times less sensitive to acyclovir than Herpes simplex 4) Herpes virus resistance develops as the virus loses thymidine kinase activity

Interactions

drug interactions

General

antiviral agent

Properties

MISC-INFO: elimination route KIDNEY LIVER 1/2life 2-3 HOURS protein-binding 9-33% elimination by hemodialysis + pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  6. Journal Watch 22(9):69, 2002 Wald A et al, Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis 34:944, 2002 PMID: 11880960
  7. Deprecated Reference
  8. Prescriber's Letter 21(9): 2014 Treatment of Cold Sores Detail-Document#: 300905 (subscription needed) http://www.prescribersletter.com
  9. acyclovir (Rx) Medscape https://reference.medscape.com/drug/zovirax-acyclovir-342601
  10. NEJM Knowledge+ Complex Medical Care
  11. Brandariz-Nunez D, Correas-Sanahuja M, Maya-Gallego S, et al. Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases. Journal of Clinical Pharmacy and Therapeutics. 2021;46(4):918-926. PMID: 34146428

Component-of

acyclovir/cortisol (Lipsovir, Xerese) acyclovir/lidocaine