Ranolazine has anti-ischemlc and antlanginal 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 (I_Na). 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 I_Kr which prolongs the ventricular action potential.

Ranolazine is indicated for the treatment of chronic angina. Ranolazine may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. It has been shown to decrease angina episodes in patients with coronary artery disease on maximal doses of amlodipine. Because Ranolazine prolongs the QT interval, it should be reserved for patients who have not achieved an adequate response with other antianginal drugs.The effect on angina rate or exercise tolerance appeared to be smaller in women than men.

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. If a dose of Ranolazine is missed, take the prescribed dose at the next scheduled time; do not double the next dose.

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.

Cardiac Disorders: bradycardia, palpitations

Ear and Labyrinth Disorders: tinnitus, vertigo

Gastrointestinal Disorders: abdominal pain, dry mouth, vomiting

General Disorders and Administrative Site Adverse Events: peripheral edema

Respiratory, Thoracic, and Mediastinal Disorders: dyspnea

Vascular Disorders: hypotension, orthostatic hypotension

Overdose Effects

Symptoms: Dizziness, nausea, vomiting, diplopia, lethargy, syncope, severe tremor, incoordination, dysplasia, hallucination.

Management: Symptomatic and supportive treatment.

Ranolazine blocks QTc 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-admlnistered. Caution should be exercised when co-adminlstering ranolazine with P-gp inhibitors such as ritonavir or cydosporine.

Use in Special Populations

Pediatric use: Safety and effectiveness in pediatric patients have not been established.

Pregnancy & Lactation

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.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.