Ranolazine
Ranolazine Prescribing Information
Ranolazine extended-release tablets are indicated for the treatment of chronic angina.
Ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.
- 500 mg twice daily and increase to 1000 mg twice daily, based on clinical symptoms ()
2.1 Dosing InformationInitiate Ranolazine extended-release tablets dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take Ranolazine extended-release tablets with or without meals. Swallow Ranolazine extended-release tablets whole; do not crush, break, or chew.
The maximum recommended daily dose of Ranolazine extended-release tablets is 1000 mg twice daily.
If a dose of Ranolazine extended-release tablets is missed, take the prescribed dose at the next scheduled time; do not double the next dose.
Ranolazine extended-release tablets are in the following strengths:
- Peach, oblong shaped, film-coated, extended release tablet debossed with“423”on one side and “SG” on the other side.
- Pale yellow, oblong shaped, film-coated, extended release tablet debossed with“424”on one side and “SG” on the other side.
There are no available data on Ranolazine extended-release tablets use in pregnant women to inform any drug-associated risks. Studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (MRHD)
Data)
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. In rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the AUC for the MRHD) that caused maternal weight loss. No adverse fetal effects were observed in either species exposed (AUC) to ranolazine at exposures (AUC) equal to the MRHD.
Ranolazine extended-release tablets are contraindicated in patients:
- Taking strong inhibitors of CYP3A[see]
7.1 Effects of Other Drugs on RanolazineStrong CYP3A InhibitorsDo not use Ranolazine extended-release tablets with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir
[see Contraindications (4), Clinical Pharmacology (12.3)].Moderate CYP3A InhibitorsLimit the dose of Ranolazine extended-release tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products
[see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].P-gp InhibitorsConcomitant use of Ranolazine extended-release tablets and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations. Titrate Ranolazine extended-release tablets based on clinical response in patients concomitantly treated with predominant P-gp inhibitors such as cyclosporine
[see Dosage and Administration (2.2)].CYP3A InducersDo not use Ranolazine extended-release tablets with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s wort
[see Contraindications (4), Clinical Pharmacology (12.3)]. - Taking inducers of CYP3A[see]
7.1 Effects of Other Drugs on RanolazineStrong CYP3A InhibitorsDo not use Ranolazine extended-release tablets with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir
[see Contraindications (4), Clinical Pharmacology (12.3)].Moderate CYP3A InhibitorsLimit the dose of Ranolazine extended-release tablets to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products
[see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].P-gp InhibitorsConcomitant use of Ranolazine extended-release tablets and P-gp inhibitors, such as cyclosporine, may result in increases in ranolazine concentrations. Titrate Ranolazine extended-release tablets based on clinical response in patients concomitantly treated with predominant P-gp inhibitors such as cyclosporine
[see Dosage and Administration (2.2)].CYP3A InducersDo not use Ranolazine extended-release tablets with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s wort
[see Contraindications (4), Clinical Pharmacology (12.3)]. - With liver cirrhosis[see]
8.6 Use in Patients with Hepatic ImpairmentRanolazine extended-release tablets are contraindicated in patients with liver cirrhosis. In a study of cirrhotic patients, the Cmaxof 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 (12.2)].
- QT interval prolongation: Can occur with ranolazine. Little data available on high doses, long exposure, use with QT interval- prolonging drugs, potassium channel variants causing prolonged QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation ()
5.1 QT Interval ProlongationRanolazine blocks IKrand prolongs the QTc interval in a dose-related manner.
Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death
[see Clinical Studies (14.2)]. However, there is little experience with high doses (>1000 mg twice daily) or exposure, other QT-prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. - Renal failure: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60 mL/min). If acute renal failure develops, discontinue Ranolazine extended-release tablets. ()
5.2 Renal FailureAcute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] <30 mL/min) while taking Ranolazine extended-release tablets. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue Ranolazine extended-release tablets and treat appropriately
[see Use in Specific Populations (8.7)].Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.