ACICLOVIR

  • Important to know PD of acyclovir.
  • Zidovudine, amphotericin and the azoles are small print, and the key points have been summarized below.
Structure/Class
  1. DNA polymerase inhibitor
Pharmacodynamics
  1. It is a prodrug that requires activation by viral thymidine kinase before become active.
    • It then functions by inhibiting viral DNA polymerase, preventing replication of viral DNA.
    • Spectrum of activity as follows: HSV-1, HSV-2 and VZV. No in vivo activity against EBV/CMV and HHV-6.
    • Therefore, indications as follows:
      1. Herpes simplex encephalitis
      2. Neonatal HSV
      3. Serious HSV/VZV infections, especially in the immunocompromised
  2. Resistance is due to reduction in viral thymidine kinase or the alteration of DNA polymerase binding site. If there is a reduction in the viral thymidine kinase, then the virus will have cross resistance to valacyclovir, ganciclovir and famciclovir.
Absorption/administration
  1. PO or IV. Bioavailability is very low.
Distribution
  1. Readily distributes into most tissues and body fluids, with CSF concentrations approximately 20-50%.
Metabolism
  1. Not metabolized – it is excreted unchanged in the urine.

 
Excretion
  1. T ½ of 2.5 hours, which is prolonged in renal failure.
Adverse events  
Dosing/administration  
Toxicology  
Withdrawal syndrome  
Special notes