Ranolazine has anti-ischemic and anti-anginal effects that do not depend upon reductions in heart rate or blood pressure. The exact mechanism of action of Ranolazine is unknown. Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (INa). However, the relationship of this inhibition to angina symptoms is uncertain. The QT prolongation effect of Ranolazine on the surface electrocardiogram is the result of inhibition of IKr which prolongs the ventricular action potential

Ranolazine is indicated for the treatment of chronic angina.

Initiate Ranolazine dosing at 500 mg twice daily and increase to 1000 mg twice daily, if needed, based on clinical symptoms. Take Ranolazine with or without meals. Swallow Ranolazine tablets whole; do not crush, break or chew. The maximum recommended daily dose of Ranolazine is 1000 mg twice daily.

Ranolazine is contraindicated in patients: • With pre-existing QT prolongation • With hepatic impairment • Taking QT prolonging drugs • Taking potent and moderately potent CYP3A inhibitors such as Ketoconazole, Itraconazole, Clarithromycin, Nefazodone, Nelfinavir, Ritonavir, Indinavir, and Saquinavir, including Diltiazem.

Ranolazine blocks IKr and 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. Co-administration of Ranolazine with Digoxin increases the plasma concentrations of Digoxin by approximately 1.5-fold and the dose of Digoxin may have to be reduced accordingly. The dose of other P-gp substrates may have to be reduced as well when Ranolazine is co-administered. Caution should be exercised when co-adminlstering Ranolazine with P-gp inhibitors such as Ritonavir or Cyclosporine.

Cardiac Disorders: bradycardia, palpitations; Ear and Labyrinth Disorders: tinnitus, vertigo; Gastrointestinal Disorders: abdominal pain, dry mouth, vomiting; General Disorders: peripheral edema; Respiratory, Thoracic and Mediastinal Disorders: dyspnea; Vascular Disorders: hypotension, orthostatic hypotension.

Pregnancy: Pregnancy Category C. There are no adequate studies assessing the effect of Ranolazine on the developing fetus. There are no adequate well-controlled studies in pregnant women. Ranolazine should be used during pregnancy only when the potential benefit to the patient justifies the potential risk to the fetus. Lactation: lt is not known whether Ranolazine is excreted in human milk. Because of the potentiality for serious adverse reactions from Ranolazine in nursing infants, a decision should be made whether to discontinue nursing or to discontinue Ranolazine, taking into account the importance of the drug to the mother.

• CYP3A Inhibitors: Do not use Ranolazine with strong CYP3A inhibitors. With moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin) limit maximum dose of ranolazine to 500 mg twice daily. • CYP3A Inducers: Do not use Ranolazine with CYP3A inducers. • P-gp Inhibitors (e.g., Cyclosporin): May need to lower the Ranolazine dose based on clinical dose. • Drugs transported by P-gp or metabolized by CYP2D6 (eg., Digoxin, TCA): May need to reduce dose of these drugs when used with Ranolazine.

High oral doses of Ranolazine produce dose-related increases in dizziness, nausea, and vomiting. High intravenous exposure also produces diplopia, paresthesia, confusion, and syncope. In addition to general supportive measures, continuous ECG monitoring may be warranted in the event of overdose. Severe tremor, unsteady gait/incoordination, dysphasia, and hallucinations have been reported in cases of overdose with Ranolazine. Since, Ranolazine is about 62% bound to plasma proteins, hemodialysis is unlikely to be effective in clearing Ranolazine.

Store in a cool (below 30°C) and dry place, protect from light and moisture. Keep out of the reach of children.

Ranovent ER Tablet: Each box contains 3 x 10 tablets in Alu-PVC blister pack.