Acyclovir side effect

 Q: 44 years old male with End-Stage Renal Failure (ESRD) on chronic peritoneal dialysis is admitted to ICU with Herpes pneumonia and started on acyclovir. Patient progressively developed agitation, delirium and went into coma. Patients on peritoneal dialysis have higher risk of acyclovir toxicity?

A) True

B) False

Answer: A

When it comes to Acyclovir two considerations are very important. First, acyclovir itself can cause Acute Kidney Injury (AKI) by precipitating relatively insoluble acyclovir crystals in the renal tubules. This risk is high with intravenous (IV) route and can be eliminated by reducing the dose and prior high hydration with urine output around 75-100 cc/hr. This can be challenging in cardiac or renal patients, not on dialysis yet. 

When it comes to patients already on dialysis, peritoneal dialysis is not very effective in the removal of acyclovir. This is due to the fact that the drug is not highly bound to plasma protein. It quickly penetrates tissue and fluid including cerebrospinal fluid (CSF). A nephrologist and a pharmacist should be consulted to avoid this dreaded complication.

#pharmacology

References:

1. Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy 2009; 29:562. 

2. Patel J, Hayes B, Bauler L, Mastenbrook J. Neurologic Acyclovir Toxicity in the Absence of Kidney Injury. J Emerg Med 2019; 57:e35. 

3. Gentry JL 3rd, Peterson C. Death Delusions and Myoclonus: Acyclovir Toxicity. Am J Med 2015; 128:692. 

4. Davenport A, Goel S, Mackenzie JC. Neurotoxicity of acyclovir in patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1992; 20:647. 

5. Stathoulopoulou F, Almond MK, Dhillon S, Raftery MJ. Clinical pharmacokinetics of oral acyclovir in patients on continuous ambulatory peritoneal dialysis. Nephron 1996; 74:337.