What are the side effects of ACYCLOVIR?

Side Effects of Acyclovir

Acyclovir is generally well-tolerated, but the most clinically significant adverse effects are neurotoxicity (particularly in patients with renal impairment) and renal dysfunction from drug precipitation in renal tubules. 1

Common Side Effects (Short-Term Use)

The most frequently reported adverse events during clinical trials include:

• Nausea and/or vomiting (2.7% in genital herpes treatment trials) 1
• Diarrhea (3.2% in chickenpox trials, 2.4% in long-term administration) 1
• Headache (reported in long-term use) 1
• Malaise (11.5% in herpes zoster treatment) 1

These gastrointestinal symptoms are also frequently seen with placebo, suggesting they may not always be drug-related. 1, 2

Serious Adverse Effects

Neurotoxicity (Most Critical)

Neurological side effects are the most concerning complication, occurring primarily in elderly patients and those with renal impairment. 3

The characteristic neurological symptoms include:

• Confusion and altered level of consciousness (most common presentation) 1, 3
• Hallucinations (visual and auditory) 1, 3, 4
• Agitation and aggressive behavior 1, 3
• Seizures 1, 2
• Tremors and myoclonus 1, 5, 4
• Ataxia and dysarthria 1, 5, 3
• Encephalopathy, delirium, and coma 1, 2
• Lethargy and somnolence 1

Critical timing: Neurotoxic symptoms typically develop within 3.1 days (range 0.2-28 days) after starting therapy, with most cases occurring within 24-48 hours. 3, 6 Recovery time averages 9.8 days, with 74.4% of patients recovering within 7 days after drug discontinuation. 3

Key risk factors for neurotoxicity:

• Renal impairment (documented in 83.3% of neurotoxicity cases, with 57.1% having end-stage renal disease) 3
• Elderly patients (mean age 59.5 years in neurotoxicity cases) 3, 6
• Inappropriate dosing (59.7% of neurotoxicity cases received doses higher than recommended for renal function) 3
• Polypharmacy and multiple comorbidities 6

Renal Toxicity

• Renal failure from acyclovir precipitation in renal tubules when drug solubility (2.5 mg/mL) is exceeded 1
• Elevated BUN and serum creatinine 1
• Hematuria and renal pain (may be associated with renal failure) 1

This occurs most commonly following bolus injections, inappropriately high doses, or inadequate fluid/electrolyte monitoring. 1

Hematologic Effects

• Neutropenia (observed in 46% of infants on long-term oral acyclovir, though generally self-limited) 7
• Anemia, leukopenia, and thrombocytopenia 1
• Leukocytoclastic vasculitis 1

Severe Dermatologic Reactions

• Stevens-Johnson syndrome 1
• Toxic epidermal necrolysis 1
• Erythema multiforme 1
• Photosensitive rash, pruritus, urticaria 1

Other Serious Reactions

• Anaphylaxis and angioedema 1
• Hepatitis, elevated liver function tests, hyperbilirubinemia, and jaundice 1
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (reported with high-dose valacyclovir 8 g/day, but not at standard HSV treatment doses) 8

Special Population Considerations

Pregnancy

• FDA Category B: Animal studies show no teratogenic effects, but adequate human studies are lacking. 8
• Pregnancy registry data (596 first-trimester exposures) showed birth defect rates approximating the general population with no consistent pattern of abnormalities. 8
• IV acyclovir is indicated for life-threatening maternal HSV infections (disseminated infection, encephalitis, pneumonitis, hepatitis). 8
• Not recommended for routine use in pregnant women for recurrent disease or suppressive therapy, except in life-threatening situations. 8

Infants and Neonates

• Safety not established in neonates and young children. 2
• Neutropenia monitoring recommended during long-term therapy. 7
• Dose adjustment required based on renal function. 7

Critical Management Pitfalls to Avoid

The most common and dangerous error is failure to adjust dosing for renal impairment. 7, 5, 3

• Always calculate creatinine clearance before prescribing, as acyclovir is primarily renally excreted. 7
• Monitor renal function at treatment initiation and once or twice weekly during high-dose IV therapy. 8
• Ensure adequate hydration to prevent renal precipitation. 1
• Recognize neurotoxicity early: Any patient developing confusion, altered mental status, or neurological symptoms during acyclovir therapy should be immediately evaluated for drug toxicity. 5, 6
• Treatment of neurotoxicity: Discontinue acyclovir immediately; consider hemodialysis for severe cases or those with renal failure (removes approximately 45% of total body drug in 3 hours). 3, 6, 4

Overdose

Overdoses up to 100 capsules (20 g) have been reported, with symptoms including agitation, coma, seizures, and lethargy. 1 Hemodialysis may benefit patients with acute renal failure and anuria until renal function is restored. 1