Ranolin XR

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.

CYP 3A Inhibitors: Do not use Ranolazine with strong CYP 3A inhibitors. With moderate CYP 3A inhibitors (e.g., diltiazem, verapamil, erythromycin) limit maximum dose of ranolazine to 500 mg twice daily.

CYP 3A Inducers: Do not use Ranolazine with 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 reduced doses of these drugs when used with ranolazine.

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

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.

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.

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

Renal Impairment:

• Mild to moderate (CrCl 30-80 mL/min): Dose titration needed
• Severe (CrCl <30 mL/min): Contraindicated

Hepatic Impairment:

• Mild: Dose titration needed
• Moderate to severe: Contraindicated

Other Anti-anginal & Anti-ischaemic drugs

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

Management: Symptomatic and supportive treatment.

Store Ranolazine tablets at 25°C with excursion permitted to 15° to 30°C. Protect from light and moisture.