What are the considerations for using Phenytoin (an antiepileptic medication) in a patient with Chronic Kidney Disease (CKD)?

From the Guidelines

Phenytoin dosing in chronic kidney disease (CKD) patients should be approached with caution, considering altered drug metabolism and protein binding, and maintenance doses should be reduced by 25-50% depending on the severity of kidney dysfunction, as evidenced by general principles of drug dosing in CKD patients 1.

Key Considerations

• Altered drug metabolism and protein binding in CKD patients affect phenytoin levels, making it essential to monitor free phenytoin levels rather than total levels 1.
• Target free phenytoin levels of 1-2 mg/L, equivalent to total levels of 10-20 mg/L in patients with normal kidney function, to avoid toxicity.
• Check levels more frequently in CKD patients, initially after 5-7 days of therapy and then every 1-3 months or with any change in clinical status.
• Be vigilant for signs of toxicity, including nystagmus, ataxia, and confusion, which may occur at lower total phenytoin levels in CKD.

Alternative Options

• Consider alternative antiseizure medications with less protein binding and renal clearance issues, such as levetiracetam or lamotrigine, for patients with advanced CKD or those on dialysis 1.

General Principles

• The selection and dosing of drugs in patients with CKD require multiple and dynamic assessments, understanding the phases of CKD, and the likelihood of CKD progression 1.
• Factors such as mode of drug excretion, potential for nephrotoxicity, and effect of CKD on drug metabolites should be taken into account when selecting a treatment regimen 1.

From the Research

Phenytoin Use in CKD Patients

• Phenytoin is an antiepileptic drug that requires careful consideration in patients with chronic kidney disease (CKD) due to its pharmacokinetic properties 2.
• The protein binding of phenytoin can be reduced significantly by renal failure, causing difficulties in the interpretation of total serum concentrations 2.
• CKD patients may require adjusted dosing of phenytoin to avoid toxicity, as the clearance of drugs eliminated primarily by renal filtration is decreased by renal disease 3.
• Continuous venovenous hemofiltration (CVVH) can remove a substantial amount of phenytoin, approximately 30% of the total daily dose, and patients may require higher than expected empiric doses 4.

Monitoring and Dosing Considerations

• Phenytoin concentrations should be closely monitored in critically ill patients receiving CVVH to avoid subtherapeutic or supratherapeutic levels 4.
• The use of antiepileptic drugs in patients with renal or hepatic disease is complex and requires great familiarity with the pharmacokinetics of these agents 2.
• Closer follow-up of patients and more frequent monitoring of serum concentrations are required to optimize clinical outcomes in CKD patients taking phenytoin 2.

Clinical Implications

• CKD patients with seizures may require multiple antiepileptic drugs, including phenytoin, valproic acid, and levetiracetam, to control seizures 5.
• Renal replacement therapy, such as hemodialysis, may be necessary to manage CKD patients with uncontrolled hypertension and uremia, which can lead to complications like posterior reversible encephalopathy syndrome (PRES) 5.
• Successful renal transplantation can be a viable option for CKD patients with PRES, allowing for better management of seizures and other complications associated with uremia and uncontrolled hypertension 5.