Ranexa (Ranolazine) in ESRD on Hemodialysis
Ranolazine is contraindicated in patients with severe renal impairment (CrCl <30 mL/min) and should not be used in ESRD patients on hemodialysis due to significant safety concerns including acute renal failure and lack of pharmacokinetic data in dialysis populations. 1
Critical Safety Data
The FDA label provides definitive evidence against use in this population 1:
- A pharmacokinetic study in severe renal impairment (CrCl <30 mL/min) was terminated early when 2 of 4 subjects developed acute renal failure after receiving ranolazine 500 mg twice daily for 5 days followed by 1000 mg twice daily 1
- One subject required hemodialysis, while two others showed increases in creatinine, BUN, and potassium during the 500 mg lead-in phase 1
- The pharmacokinetics of ranolazine has not been assessed in patients on dialysis 1
Pharmacokinetic Concerns
Several factors make ranolazine particularly problematic in ESRD-HD patients:
- Ranolazine is approximately 62% protein-bound, making hemodialysis unlikely to be effective in clearing the drug 1
- Drug exposure (Cmax) increases 40-50% in patients with any degree of renal impairment compared to those with normal renal function 1
- Only ~5% of ranolazine is excreted unchanged renally, with extensive hepatic metabolism via CYP3A and CYP2D6 2
- The drug exhibits saturable elimination kinetics, with oral clearance decreasing from 45 L/h at 500 mg twice daily to 33 L/h at 1000 mg twice daily 2
Clinical Implications
If ranolazine is absolutely necessary (which should be rare), the FDA label mandates: 1
- Monitor renal function periodically in patients with moderate to severe renal impairment
- Discontinue ranolazine immediately if acute renal failure develops
- Recognize that standard hemodialysis will not effectively remove accumulated drug due to high protein binding
Alternative Management
For chronic angina in ESRD-HD patients, consider 1:
- Beta-blockers (with appropriate renal dosing adjustments) 3
- Calcium channel blockers like amlodipine or diltiazem (though diltiazem increases ranolazine exposure 1.5-fold if ranolazine were used) 2
- Long-acting nitrates
- Careful medication reconciliation to identify drug-drug interactions that are particularly problematic in ESRD 4
Key Pitfalls to Avoid
- Do not assume that hemodialysis will "rescue" a patient from ranolazine toxicity - the drug is not dialyzable 1
- Do not extrapolate dosing from less severe renal impairment - the study was stopped due to safety concerns specifically in severe impairment 1
- Be aware that ESRD patients commonly experience adverse drug reactions due to altered pharmacokinetics and multiple comorbidities 4
- Remember that drug removal during hemodialysis is substantially lower than often assumed for most medications 5