NIZACARD 1000 (Ranolazine Extended-Release Tablets 1000 mg)

Ranolazine extended-release tablet is indicated for the treatment of chronic angina. Ranolazine extended-release tablet may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. Ranolazine extended-release tablet is an antianginal indicated for the treatment of chronic angina. ( 1 )

• 500 mg twice daily and increase to 1000 mg twice daily, based on clinical symptoms Dosing Information Initiate ranolazine extended-release tablet dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms
• Take ranolazine extended-release tablet with or without meals
• Swallow ranolazine extended-release tablet whole; do not crush, break, or chew
• The maximum recommended daily dose of ranolazine extended-release tablet is 1000 mg twice daily
• If a dose of ranolazine extended-release tablet is missed, take the prescribed dose at the next scheduled time; do not double the next dose
• Dose Adjustments in Specific Populations Dose adjustments may be needed when ranolazine extended-release tablet is taken in combination with certain other drugs [see Drug Interactions ]
• Limit the maximum dose of ranolazine extended-release tablet to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin
• Use of ranolazine extended-release tablet with strong CYP3A inhibitors is contraindicated [ see Contraindications , Drug Interactions ]
• Use of P-gp inhibitors, such as cyclosporine, may increase exposure to ranolazine extended-release tablet
• Titrate ranolazine extended-release tablet based on clinical response [see Drug Interactions ]

Ranolazine extended-release tablets are supplied as film-coated, oval-shaped, extended-release tablets in the following strengths: 500 mg tablets are light orange, with 588 on one side 1000 mg tablets are pale yellow, with 589 on one side Extended-release tablets: 500 mg, 1000 mg ( 3 )

• Safety and effectiveness have not been established
• Pediatric patients

Of the chronic angina patients treated with ranolazine in controlled studies, 496 (48%) were ≥65 years of age, and 114 (11%) were ≥75 years of age. No overall differences in efficacy were observed between older and younger patients. …

• Advise the patient to read the FDA-approved patient labeling (Patient Information)
• Inform patients that ranolazine will not abate an acute angina episode
• Strong CY3PA Inhibitors, CYP3A Inducers, Liver Cirrhosis Inform patients that ranolazine should not be used with drugs that are strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir) [(see Contraindications , Drug Interactions ]
• Inform patients that ranolazine should not be used with drugs that are inducers of CYP3A (e.g., rifampin, rifabutin, rifapentine, barbiturates, carbamazepine, phenytoin, St
• John's wort) [(see Contraindications , Drug Interactions ]. …

• Ranolazine is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions ] Taking inducers of CYP3A [see Drug Interactions ] With liver cirrhosis [see Use in Specific Populations ] Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) CYP3A inducers (e.g., rifampin, phenobarbital, St
• John's wort) Liver cirrhosis

Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit ranolazine to 500 mg twice daily. ( 7.1 ) P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased. Titrate ranolazine based on clinical response. ( 7.1 ) CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with ranolazine. ( 7.2 ) OCT2 substrates: Limit the dose of metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily. Doses of other OCT2 substrates may require adjusted doses. …

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 ) Renal failure: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL1000 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 Q …

Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2018 patients with chronic angina were treated with ranolazine in controlled clinical trials. …

8.1 Pregnancy Risk Summary There are no available data on ranolazine 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) (see Data). In the U.S. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. …

Hypotension, QT prolongation, bradycardia, myoclonic activity, severe tremor, unsteady gait/incoordination, dizziness, nausea, vomiting, dysphasia, and hallucinations have been seen in cases of oral overdose of ranolazine. In cases of extreme overdose of ranolazine fatal outcomes have been reported. In clinical studies, high intravenous exposure resulted in diplopia, paresthesia, confusion, and syncope. In addition to general supportive measures, continuous ECG monitoring may be warranted in the event of overdose. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.