What are the potential side effects of acyclovir and what monitoring is required?

Acyclovir Side Effects and Monitoring

The most important side effect of acyclovir is renal impairment secondary to crystalluria and obstructive nephropathy, which can affect up to 20% of patients after 4 days of intravenous therapy, requiring regular monitoring of renal function and adequate hydration during treatment. 1

Common Side Effects

Oral Acyclovir

• Gastrointestinal effects:
  • Nausea/vomiting (2.7% with short-term use, 4.8% with long-term use)
  • Diarrhea (2.4-3.2%)
  • Gastrointestinal distress 2
• General symptoms:
  • Malaise (11.5% in herpes zoster treatment)
  • Headache
  • Peripheral edema 2

Intravenous Acyclovir

• Renal effects:
  • Crystalluria and obstructive nephropathy (up to 20% after 4 days)
  • Elevated BUN and serum creatinine
  • Reversible nephropathy 1, 2
• Infusion-related:
  • Phlebitis (moderate tendency)
  • Local inflammation at injection site 1, 3

Rare but Serious Side Effects

• Neurological:
  • Encephalopathy
  • Confusion, hallucinations, seizures, tremors
  • Agitation, decreased consciousness
  • Symptoms may be more pronounced in elderly or renally impaired patients 2
• Hematologic:
  • Thrombocytopenia
  • Leukopenia
  • Anemia 2
• Hepatic:
  • Elevated liver enzymes
  • Hepatitis
  • Jaundice 2
• Dermatologic:
  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis
  • Erythema multiforme 2

Monitoring Requirements

For All Patients

• Baseline assessment:
  • Renal function (BUN, creatinine)
  • Liver function tests
  • Complete blood count 1, 2

For Intravenous Therapy

• Renal function monitoring:
  • Daily monitoring of BUN and creatinine for first 4-7 days
  • More frequent monitoring in high-risk patients (elderly, pre-existing renal disease)
  • Monitor for signs of crystalluria (hematuria, flank pain) 1, 2
• Hydration status:
  • Maintain adequate hydration to reduce risk of crystalluria
  • Consider IV fluids if oral intake inadequate 1
• Infusion site:
  • Regular inspection for signs of phlebitis or inflammation 1

For Oral Therapy

• Renal function:
  • Periodic monitoring, especially in long-term use
  • More frequent in high-risk patients 2
• Clinical response:
  • Re-examination 3-7 days after treatment initiation 4

Dose Adjustments for Renal Impairment

Intravenous Acyclovir

• Dose must be reduced based on creatinine clearance
• For HSV encephalitis treatment (10 mg/kg every 8 hours):

  Creatinine Clearance (mL/min)	Dose Adjustment
  >25	Standard dose
  10-25	Standard dose every 12 hours
  0-10	Standard dose every 24 hours
  Hemodialysis	Dose after dialysis 4, 5

Oral Acyclovir

• Adjust based on creatinine clearance:

  Creatinine Clearance (mL/min)	Dose 800 mg Adjustment
  >25	800 mg 5 times daily
  10-25	800 mg every 8 hours
  0-10	800 mg every 12 hours

Management of Acyclovir Toxicity

• For crystalluria/nephropathy:
  • Increase hydration
  • Consider temporary discontinuation if severe
  • Monitor urine output 1, 2
• For neurotoxicity:
  • Discontinue or reduce dose
  • Consider hemodialysis in severe cases (more effective than peritoneal dialysis) 5
• For overdose:
  • Hemodialysis is effective for drug removal
  • Supportive care for neurological symptoms 2

Special Considerations

• Elderly patients: Higher risk of neurological side effects and renal impairment; consider lower doses 2
• Immunocompromised patients: May require longer treatment duration and closer monitoring 4
• Pregnancy: Generally considered safe based on established safety profile 4
• Patients on CAPD: Acyclovir removal is negligible with peritoneal dialysis; hemodialysis is preferred if toxicity occurs 5

Clinical Pitfalls to Avoid

1. Failing to adjust dose in renal impairment - can lead to neurotoxicity and worsening renal function
2. Inadequate hydration - increases risk of crystalluria and nephropathy
3. Rapid IV bolus administration - increases risk of crystalluria; administer as slow infusion
4. Overlooking early signs of nephrotoxicity - monitor renal function regularly, especially after day 4 of IV therapy
5. Ignoring neurological symptoms - may indicate neurotoxicity, especially in renally impaired patients