Ranolazine

Use in Patients with Renal Impairment A pharmacokinetic study of ranolazine extended-release tablets in subjects with severe renal impairment (CrCL <30 mL/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other).

Increases in creatinine, BUN, and potassium were observed in 3 subjects during the 500 mg lead-in phase. One subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see Warnings and Precautions ]. Monitor renal function periodically in patients with moderate to severe renal impairment.

Discontinue ranolazine extended-release tablets if acute renal failure develops. In a separate study, C max was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment.

The pharmacokinetics of ranolazine has not been assessed in patients on dialysis.

Use in Patients with Hepatic Impairment Ranolazine extended-release tablets are contraindicated in patients with liver cirrhosis. In a study of cirrhotic patients, the C max of ranolazine was increased 30% in cirrhotic patients with mild (Child- Pugh Class A) hepatic impairment, but increased 80% in cirrhotic patients with moderate (Child-Pugh Class B) hepatic impairment compared to patients without hepatic impairment.

This increase was not enough to account for the 3-fold increase in QT prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see Clinical Pharmacology ] .