What is the recommended dose of Ranolazine (anti-anginal medication) for patients with Impaired renal function undergoing dialysis?

Ranolazine Dosing in Dialysis Patients

For patients on dialysis, ranolazine should be initiated at 500 mg orally twice daily, with a maximum dose of 500 mg twice daily, and administered after dialysis sessions. 1

Pharmacology and Considerations in Renal Impairment

• Ranolazine is an antianginal medication that inhibits the late inward sodium current, reducing intracellular sodium and calcium overload that accompany myocardial ischemia 1
• Unlike other antianginals, ranolazine has minimal effects on heart rate and blood pressure, making it hemodynamically neutral 1
• Ranolazine is primarily metabolized by the liver, but renal impairment can lead to drug accumulation and increased risk of adverse effects 2, 3
• The drug prolongs QTc interval in a dose-related manner, which requires careful monitoring in patients with renal dysfunction 1

Dosing Recommendations Based on Renal Function

• For patients with normal renal function, the standard recommended initial dose is 500 mg orally twice daily, which can be uptitrated to a maximum of 1000 mg orally twice daily 1
• For patients on dialysis:
  • Initial dose: 500 mg orally twice daily 2
  • Maximum dose: 500 mg orally twice daily (do not increase to 1000 mg twice daily) 2, 3
  • Administration timing: After dialysis sessions to prevent premature removal of the drug 3

Rationale for Dose Adjustment

• Case reports have documented serious neurologic adverse effects in elderly patients with renal impairment receiving standard doses of ranolazine 2
• Higher doses in patients with renal impairment have been associated with:
  • Neurologic adverse effects including dysarthria, dysmetria, hallucinations, tremors, and difficulty with word finding 2
  • Bradycardia, hyperkalemia, and worsening renal function (BRASH syndrome variant) 3
  • Potential drug interactions with other medications that are affected by renal impairment 4

Monitoring Recommendations

• Monitor for QTc prolongation, especially when initiating therapy 1
• Assess renal function regularly during treatment 2, 3
• Monitor for neurologic adverse effects including dizziness, headache, and more severe manifestations 2
• Watch for signs of bradycardia and electrolyte abnormalities, particularly hyperkalemia 3

Common Adverse Effects

• Most common adverse effects include constipation, nausea, dizziness, and headache 1, 5
• More serious adverse effects that may be more common in renal impairment include:
  • QTc prolongation (though this rarely leads to clinical consequences) 1
  • Neurologic symptoms 2
  • Bradycardia and conduction abnormalities 3

Clinical Pitfalls to Avoid

• Avoid doses greater than 500 mg twice daily in patients with creatinine clearance less than 30 ml/minute 2
• Be cautious with concomitant use of other medications that may interact with ranolazine in patients with renal impairment, particularly P-glycoprotein inhibitors 4
• Do not administer immediately before dialysis sessions, as this may reduce drug efficacy 3
• Consider alternative antianginal agents in patients with severe renal dysfunction who cannot tolerate even reduced doses of ranolazine 2, 3