What are the potential side effects of Acyclovir?

Acyclovir Side Effects

Acyclovir is generally well-tolerated, but can cause several side effects ranging from common gastrointestinal disturbances to rare but serious neurological and renal complications. 1

Common Side Effects

Gastrointestinal

• Nausea and vomiting: Occurs in 2.7% of patients on short-term treatment and 4.8% on long-term administration 1
• Diarrhea: Reported in 2.4-3.2% of patients on various treatment regimens 1
• Gastrointestinal distress 1

General

• Malaise: Reported in 11.5% of herpes zoster patients 1
• Headache 1
• Fever 1
• Pain 1
• Peripheral edema 1

Serious Side Effects

Renal

• Renal impairment: Most significant serious adverse effect, particularly with IV administration 1, 2
  • Occurs in up to 20% of patients after 4 days of IV therapy 3
  • Caused by crystalluria and obstructive nephropathy 3
  • Risk factors: dehydration, bolus injection, high doses, pre-existing renal dysfunction 1, 4
  • Manifests as elevated BUN, creatinine, hematuria, renal pain 1

Neurological

• Neurotoxicity: Usually occurs within 24-48 hours of therapy initiation 2
  • More common in elderly, those with renal impairment, or patients on nephrotoxic drugs 2
  • Symptoms include: confusion, hallucinations, agitation, seizures, tremors, ataxia, dysarthria, encephalopathy, decreased consciousness, delirium, psychosis, somnolence 1, 2
  • Particularly marked in older adults and patients with renal impairment 1
  • Reversible after therapy withdrawal 2

Other Serious Reactions

• Hypersensitivity reactions: Anaphylaxis, angioedema 1
• Hematologic: Anemia, leukopenia, thrombocytopenia, leukocytoclastic vasculitis 1
• Hepatic: Elevated liver function tests, hepatitis, jaundice 1
• Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme 1

Special Populations

Pregnancy

• Classified as Category B in FDA pregnancy rating 3
• Registry data on 596 infants exposed to acyclovir during first trimester showed birth defect rates similar to general population 3
• Not routinely recommended during pregnancy except for serious infections 3

Immunocompromised Patients

• May experience more severe side effects 3
• Higher doses often needed, increasing risk of adverse effects 3
• Risk of acyclovir-resistant strains with persistent lesions during treatment 3

Overdose Considerations

• Can lead to agitation, coma, seizures, lethargy 1
• Precipitation in renal tubules when solubility (2.5 mg/mL) is exceeded 1
• Hemodialysis may be beneficial in acute renal failure 1

Risk Mitigation

• Maintain adequate hydration to reduce risk of nephropathy 3
• Monitor renal function, especially with IV therapy 3
• Adjust dosage in patients with pre-existing renal impairment 4
• Discontinue immediately if neurological symptoms develop 2
• Consider hemodialysis for severe toxicity or overdose 1

Monitoring Recommendations

• Regular assessment of renal function during treatment
• Close observation for neurological symptoms, particularly in high-risk patients
• Prompt evaluation of any mental status changes during therapy 2

Acyclovir's safety profile is generally favorable compared to its antiviral benefits 5, but clinicians should remain vigilant for the development of serious adverse effects, particularly in high-risk populations.