Can acyclovir cause side effects in elderly patients with impaired renal function?

Acyclovir Causes Significant Side Effects in Elderly Patients, Especially with Renal Impairment

Yes, acyclovir causes serious side effects in elderly patients, particularly neurotoxicity, and this risk is dramatically increased in those with impaired renal function—dose adjustment based on creatinine clearance is mandatory, not optional. 1, 2

Why Elderly Patients Are at High Risk

Elderly patients have higher plasma acyclovir concentrations compared to younger adults, primarily due to age-related decline in renal function. 1 Even when serum creatinine appears normal, significant renal impairment may be present because creatinine is a byproduct of muscle mass breakdown, which decreases with age. 3

• Acyclovir is primarily renally cleared, with renal clearance representing 42% of total plasma clearance 4
• The half-life and total body clearance of acyclovir are dependent on renal function 1
• In patients with end-stage renal disease (ESRD), the average acyclovir half-life increases from 2.5-3.3 hours to approximately 14 hours 4

Neurotoxicity: The Most Serious Side Effect

Acyclovir-induced neurotoxicity is the most clinically significant adverse effect in elderly patients with renal impairment, characterized by confusion, altered consciousness, hallucinations, agitation, dysarthria, seizures, and myoclonus. 5, 6

Clinical Presentation

• Symptoms typically begin within 3.1 days (range 0.2-28 days) after starting acyclovir 5
• The most characteristic symptoms include confusion, altered level of consciousness, hallucinations, agitation, and dysarthria 5
• Seizures and myoclonus may also occur 6
• In 83.3% of reported neurotoxicity cases, renal impairment was documented, with 57.1% having end-stage renal disease 5

Mechanism

Neurotoxicity results from accumulation of acyclovir and its metabolite 9-carboxymethoxymethylguanine (CMMG) 6. This occurs predominantly in older patients with impaired renal function. 6

Other Side Effects

Beyond neurotoxicity, acyclovir can cause:

• Renal impairment: Crystalluria and obstructive nephropathy can occur, typically manifesting after 4 days of intravenous therapy and affecting up to 20% of patients 3
• Rare adverse events include hepatitis, bone marrow failure, and encephalopathy 3

Critical Dosing Requirements

The administered dose was higher than renal adjustment recommendations in 59.7% of reported neurotoxicity cases—this is a preventable error. 5

Mandatory Dose Adjustments

• Dosage reduction is required in geriatric patients with underlying renal impairment 1
• For patients with creatinine clearance <50 mL/min/1.73m², dose reduction is recommended 1
• Guidelines for acyclovir dosage based on creatinine clearance are located in the package insert 1
• Even when acyclovir is properly adjusted based on manufacturer recommendations, it can still cause neurotoxicity in patients with ESRD 7

Consensus Expert Recommendations

Expert geriatric clinical pharmacists reached consensus that specific dose reduction or interval extension is required for acyclovir in elderly patients with renal impairment. 3

Management of Acyclovir Toxicity

If neurotoxicity occurs, discontinue acyclovir immediately and consider emergent hemodialysis for severe cases. 2, 8

Recovery Timeline

• Mean recovery time is 9.8 days (range 0.2-180 days) 5
• 74.4% of patients recover within ≤7 days 5
• 15.9% recover between 8-15 days 5
• 9.8% require >15 days for recovery 5

Hemodialysis Considerations

• Hemodialysis removes approximately one-third of acyclovir during a 4-hour session 4
• During hemodialysis, the acyclovir half-life decreases to approximately 4 hours 4
• Critically, peritoneal dialysis has little effect on reversing toxic effects of acyclovir 6
• In severe cases of neurotoxicity with ESRD, hemodialysis should be utilized to promote rapid excretion and recovery 8

Common Pitfalls to Avoid

The most critical error is failing to adjust acyclovir dose based on renal function in elderly patients. 2, 8 This occurs in nearly 60% of neurotoxicity cases. 5

• Do not rely on serum creatinine alone to assess renal function in elderly patients—calculate creatinine clearance using Cockcroft-Gault formula 3
• Do not assume normal renal function based on "normal" serum creatinine in elderly patients with decreased muscle mass 3
• Do not overlook acyclovir neurotoxicity in the differential diagnosis of altered mental status in elderly patients recently started on acyclovir 2
• The primary challenge is differentiating acyclovir-induced neurotoxicity from viral encephalitis 6
• Monitor patients carefully for adverse reactions, and further reduce dose or discontinue if side effects occur 1

Monitoring Requirements

• Maintain adequate hydration to reduce risk of crystalluria and nephropathy 3
• Monitor renal function during therapy 3
• Observe patients closely for neurological symptoms, particularly confusion, hallucinations, and altered consciousness 2, 5
• Consider measuring serum CMMG concentration if neurotoxicity is suspected 6