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Acyklovir


Dose & administration
Acyclovir is dosed 20mg/kg/dose IV at intervals depending on gestational age.  Specifically, Sampson et al (PMID: 24346595) recommend dosing intervals to be 12 hours (q12h) in infants < 30 weeks PMA; 8 hours (q8h) in infants 30 to <36 weeks PMA; and 6 hours (q6h) in infants 36-41 weeks PMA.  Administer over one hour in order to prevent adverse effects. 

For congenital HSV infections, treatment course depends on type of infection.  SEM disease is treated for 14 days.  Disseminated and CNS infections require a minimum of 21 days of therapy.  Asymptomatic infants born to mothers with active genital lesions may require 10 days of treatment. 

Oral acyclovir may be used for suppressive therapy following completion of full IV course.  This dose is 300mg/m2 PO three times daily.

Indications
Acyclovir is most commonly used in the neonatal population as treatment for congenital herpes simplex infections.  It may also be used for chronic suppression of HSV or for treatment of herpes zoster infection.

Contraindications and special considerations (incl incompatibilities)
The risk of nephrotoxicity is increased when acyclovir is administered in conjunction with other nephrotoxic drugs.

Acyclovir’s incompatibilities include: dopamine, dobutamine, epinephrine, fat emulsions, aztreonam, caffeine, caspofungin, cefepime, meropenem, piperacillin/tazobactam, and parenteral nutrition solutions.

Adverse effects
The most common adverse effects are neutropenia and renal dysfunction secondary to crystalluria.  Ensuring adequate hydration during therapy can prevent crystalluria and subsequent renal dysfunction.  Frequent  monitoring of CBCs can detect neutropenia.  With a pH of 10, acyclovir can cause phlebitis and may be very damaging to tissue if extravasation occurs. One might consider using a dedicated PICC-line for acyclovir administration.

Pharmacological  aspects
Acyclovir works by inhibiting viral DNA synthesis.  Its primary route of elimination is renal.  Postmenstrual age has been determined to be the variable with the most significant influence on clearance of acyclovir.

References

  • Oral acyclovir suppression and neurodevelopment after neonatal herpes.  NEJM. 2011;365:1284-92.  PMID 21991950.
  • Population pharmacokinetics of intravenous acyclovir in preterm and term infants.  Pediatr Infect Dis J. 2014;33:42-9.  PMID 24346595.
  • Guidance on management of asymptomatic neonates born to women with active genital herpes lesions.  Pediatrics.  2013;131:e635-e646.  PMID 23359576.
  • The use of antiviral drugs during the neonatal period.  Clin Perinatol.  2012;39:69-81.  PMID 22341538.

Document version history
Created 2016/6/26 / Amy Holmes

 

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