What are the contraindications to acyclovir?

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Last updated: September 12, 2025View editorial policy

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Contraindications to Acyclovir

Acyclovir is contraindicated in patients who develop hypersensitivity to acyclovir or valacyclovir. 1

Primary Contraindications

  • Hypersensitivity reactions: The only absolute contraindication to acyclovir is a history of hypersensitivity to acyclovir or its prodrug valacyclovir 1

Relative Contraindications and Special Considerations

Renal Impairment

  • Pre-existing renal dysfunction: Requires dose adjustment as acyclovir is primarily excreted via the kidneys through glomerular filtration and tubular secretion 2
  • Risk of nephropathy: Acyclovir can cause renal impairment through crystalluria and obstructive nephropathy, which typically manifests after 4 days of intravenous therapy and can affect up to 20% of patients 2
  • End-stage renal disease: Patients with end-stage renal disease are at particularly high risk for neurotoxicity 3

Neurological Considerations

  • Neurotoxicity risk: Patients with renal impairment are at increased risk for acyclovir-induced neurotoxicity, which can present as confusion, altered level of consciousness, hallucinations, agitation, and dysarthria 3, 4
  • Advanced age: Elderly patients have increased susceptibility to neurotoxic effects, especially when combined with renal impairment 3

Monitoring and Management Recommendations

For Patients with Renal Impairment

  • Monitor renal function at initiation of treatment and once or twice weekly during treatment 2
  • Maintain adequate hydration to reduce risk of nephropathy 2
  • Adjust dosage based on creatinine clearance 5

For IV Administration

  • Avoid rapid bolus administration, which increases risk of crystalluria 6
  • Monitor for signs of infusion site inflammation 6

Clinical Pearls and Pitfalls

  • Common pitfall: Failure to adjust dosing in patients with renal impairment, which can lead to serious neurotoxicity 4
  • Important consideration: Even with appropriate dosing, acyclovir can accumulate in patients with renal dysfunction, requiring careful monitoring 3
  • Duration of treatment: For HSV encephalitis, treatment should continue for 14-21 days, with consideration of repeat CSF testing to confirm viral clearance 2
  • Empiric use caution: Unnecessary or prolonged empiric use of acyclovir should be avoided when alternative diagnoses become apparent 7

By carefully considering these contraindications and special precautions, clinicians can maximize the therapeutic benefits of acyclovir while minimizing potential adverse effects.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases.

Journal of clinical pharmacy and therapeutics, 2021

Research

Altered mental status from acyclovir.

The Journal of emergency medicine, 2011

Research

Acyclovir. Pharmacology and clinical experience.

Archives of internal medicine, 1984

Research

A retrospective review of empiric acyclovir prescribing practices for suspected viral central nervous system infections: A single-centre study.

Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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