Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
Post Marketing Experience
Metabolism and Nutrition Disorders
- Cases of hypoglycemia have been reported in diabetic patients on antidiabetic medication.
WARNINGS AND PRECAUTIONS
- Renal Impairment: Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] < 30 mL/min) while taking RANEXA. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue RANEXA and treat appropriately
- Laboratory Abnormalities: …More marked and progressive increases in serum creatinine, associated with increases in BUN or potassium, indicating acute renal failure, have been reported after initiation of RANEXA in patients with severe renal impairment
USE IN SPECIFIC POPULATIONS
Use in Patients with Renal Impairment
- A pharmacokinetic study of RANEXA in subjects with severe renal impairment (CrCL <30 mL/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving RANEXA 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 (5.2)]. Monitor renal function periodically in patients with moderate to severe renal impairment. Discontinue RANEXA if acute renal failure develops. …
- With liver cirrhosis [see Use in Specific Populations (8.6)]
5 WARNINGS AND PRECAUTIONS
5.1 QT Interval Prolongation
- However, there is little experience with high doses (> 1000 mg twice daily.....
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
paragraph 5 and 6 changed
6.2 Postmarketing Experience
new section added
7 DRUG INTERACTIONS
7.2 Drugs Metabolized by CYP3A
- ......to include information on dosing with simvastatin
8 USE IN SPECIFIC POPULATIONS
8.6 Use in Patients with Hepatic Impairment
- Ranexa is contraindicated in patients with liver cirrhosis.....
8.7 Use in Patients with Renal Impairment
- Compared to patients with no renal impairment.....
17 PATIENT COUNSELING INFORMATION
- to inform their physician if they are receiving drugs that are moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin)
- to inform their physician if they are receiving P-gp inhibitors (e.g., cyclosporine)
- that Ranexa should not be used in patients with liver cirrhosis
Effects of Ranolazine on Other Drugs
- Drugs Metabolized by CYP2D6: Ranexa 750 mg twice daily increased the plasma concentrations of a single dose of immediate-release metoprolol (100 mg), a CYP2D6 substrate, by 1.8-fold. The exposure to other CYP2D6 substrates, such as tricyclic antidepressants and antipsychotics, may be increased during co-administration with Ranexa, and lower doses of these drugs may be required.