Ranocor ER Tablet (Extended Release)

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.

Absorption: C_max: 2-5 h
Half-life: 6-22 h
Distribution: Over the concentration range of 0.25 to 10 µg/ml, Ranolazine is approximately 62% bound to human plasma proteins.
Metabolism and Excretion: Ranolazine is metabolized mainly by CYP3A and, to a lesser extent, by CYP2D6. Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces. Following a single oral dose of Ranolazine solution, approximately 75% of the dose is excreted in urine and 25% in feces.

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.

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

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

CYP 3A Inducers: Do not use Ranocor ER with inducers.

P-gp Inhibitors (e.g., Cyclosporin): May need to lower the Ranocor ER 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 Ranocor ER.

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

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.

Ranocor ER 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 Ranocor ER 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 Ranocor ER Is co-admlnistered. Caution should be exercised when co-adminlstering Ranocor ER with P-gp inhibitors such as ritonavir or cydosporine.

High oral doses of Ranocor ER 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. Since Ranocor ER is about 62% bound to plasma proteins, hemodialysis is unlikely to be effective in clearing Ranocor ER.

Other Anti-anginal & Anti-ischaemic drugs

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.