Diazoxide Use in ESRD Patients
Diazoxide (Proglycem) can be used in ESRD patients, but requires dose reduction due to its prolonged plasma half-life in patients with impaired renal function. 1
Pharmacokinetics in Renal Failure
- Diazoxide protein binding is reduced in renal failure, which correlates with reduced albumin concentration 2
- The renal clearance of diazoxide and its metabolites is impaired in ESRD, affecting drug elimination 2
- The prolonged plasma half-life in renal impairment necessitates dose adjustment to prevent accumulation 1
Dosing Recommendations
- A reduced dosage should be considered for ESRD patients due to impaired drug clearance 1
- Close clinical supervision is required when initiating treatment, with careful monitoring of blood glucose and clinical response until the patient's condition stabilizes 1
- Regular monitoring of urine glucose and ketones is necessary during prolonged treatment, especially under stress conditions 1
Monitoring Requirements
- Blood glucose should be monitored at periodic intervals until stabilized 1
- Monitor serum electrolyte levels in ESRD patients 1
- Consider monitoring:
- Blood urea nitrogen (BUN) and creatinine clearance
- Hematocrit, platelet count, total and differential leukocyte counts
- Serum aspartate aminotransferase (AST)
- Serum uric acid level 1
Clinical Applications in ESRD
- Diazoxide has been successfully used to manage spontaneous hypoglycemia in ESRD patients 3
- Spontaneous hypoglycemia in ESRD can occur due to decreased renal gluconeogenesis and impaired renal insulin clearance 3
- Diazoxide works by binding ATP-sensitive K channels in pancreatic beta cells, inhibiting insulin release 3
Potential Concerns and Precautions
- Hyperuricemia risk is increased in patients with renal insufficiency, requiring monitoring of serum uric acid levels 1
- Drug interactions may be more significant in ESRD patients due to altered pharmacokinetics 4
- Diazoxide may displace other protein-bound substances (like bilirubin or coumarin derivatives), potentially requiring dose adjustments of concomitant medications 1
- Patients with ESRD are at higher risk of adverse drug reactions due to altered pharmacological responses 4
Practice Recommendations
- Start with a reduced dose compared to patients with normal renal function 1
- Implement more frequent monitoring of blood glucose, electrolytes, and other laboratory parameters 1
- Be vigilant for signs of drug accumulation or adverse effects 4
- Consider the potential for drug-drug interactions, which are common in ESRD patients on multiple medications 4
Unlike medications such as metformin that should be avoided in severe renal impairment, diazoxide can be used in ESRD with appropriate dose adjustments and monitoring 3, 1.