Pharm 101: Aciclovir

Class

Antiviral agent

Pharmacodynamics

• Guanosine derivative with activity against HSV-1 and HSV-2, and VZV (10x less potent)
• In vitro activity against EBV, CMV and HHV-6 is present but weaker
• Inhibits viral DNA synthesis
  • Selectively activated in virus cells by virus-specific thymidine kinase (three phosphorylation steps for activation)
  • Irreversibly binds to viral DNA polymerase
  • Incorporation into viral DNA with termination

Pharmacokinetics

• Absorption unaffected by food
• Low bioavailability 15-20%
• Widely distributed
• CSF concentrations 20-50% of serum values
• Half-life 2-3 hours in normal renal function (5x daily dosing oral)
• Renal clearance, mostly excreted unchanged in urine

Clinical uses

• HSV encephalitis
• Serious HSV or VZV infections
• Immunocompromised patients with VZV
• Topical administration for primary HSV infection (genital herpes)

Adverse effects

• GI upset: nausea, vomiting, diarrhoea
• Headache
• IV infusion is associated with reversible renal toxicity or neurological effects (tremor, delirium, seizures)

Precautions/contraindications

• Concurrent administration of nephrotoxic agents may enhanced potential for nephrotoxicity

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 866