Guidelines for Ranolazine Use in ESRD Patients on Hemodialysis
Dosing Recommendations
For patients with ESRD on hemodialysis, ranolazine should be started at a lower dose of 500 mg once daily, with cautious titration based on clinical response and tolerability, and should not exceed 500 mg twice daily. 1, 2
- Ranolazine pharmacokinetics show significant variability in hemodialysis patients, with hemodialysis removing approximately 52-69% of the drug during a session 1
- The elimination half-life of ranolazine is prolonged in patients with renal impairment, with AUC increasing up to 2-fold with advancing degrees of renal dysfunction 3
- Doses greater than 500 mg twice daily should be avoided in patients with creatinine clearance less than 30 ml/minute due to risk of adverse effects 2
Administration Timing
- Administer ranolazine after hemodialysis on dialysis days to prevent premature removal of the drug 1
- The extended-release formulation allows for twice-daily dosing with maintained efficacy and should be used in ESRD patients 3
Monitoring Recommendations
- Closely monitor for neurologic adverse effects, which may include dysarthria, dysmetria, hallucinations, tremors, and difficulty with word finding 2
- Monitor QTc interval regularly, as ranolazine prolongs the QTc interval in a dose-related manner 4
- Assess for drug-drug interactions, particularly with CYP3A inhibitors which can increase ranolazine exposure 3, 5
Clinical Considerations
- Ranolazine is indicated for chronic stable angina and can be used in combination with amlodipine, beta-blockers, or nitrates 4
- The antianginal effect of ranolazine does not depend on changes in heart rate or blood pressure, making it potentially useful in ESRD patients with hemodynamic instability 4, 3
- In the MERLIN-TIMI trial, ranolazine was associated with reduced recurrent ischemia in patients with prior chronic angina 4
Contraindications and Precautions
- Avoid concomitant use with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) which can significantly increase ranolazine exposure 3
- Use with caution in elderly ESRD patients who may be at higher risk for adverse effects 2
- Avoid use in patients with pre-existing QT prolongation or those taking other QT-prolonging medications 4, 3
Common Pitfalls and Caveats
- Failure to adjust ranolazine dosing in ESRD patients is a common medication error that can lead to serious adverse effects 6
- Neurologic adverse effects may be mistaken for stroke symptoms or other neurologic conditions in elderly patients with renal impairment 2
- The evidence supporting specific dosing guidelines for ranolazine in ESRD patients on hemodialysis is limited, with most recommendations based on small pharmacokinetic studies and case reports 1, 2