RANOLAZINE
| RANOLAZINE (ra-no'la-zeen) Ranexa Classifications: antianginal agent; Therapeutic:antianginal; partial fatty acid oxidation (pfox) inhibitor Pregnancy Category: C |
Availability
500 mg extended release tablets
Action
Complete mechanism of action is unknown. Ranolazine is a partial fatty-acid oxidation inhibitor that shifts myocardial metabolism away from fatty acids to glucose. This shift in fuel source requires less oxygen for oxidation and results in decreased oxygen demand by the myocardium.
Therapeutic Effect
Ranolazine improves exercise tolerance and angina symptoms. It has no effect on heart rate or hemodynamic action of the heart.
Uses
Treatment of chronic stable angina in patients who are unresponsive or cannot tolerate other antianginal agents. Used in combination with amlodipine, beta-blockers, or nitrates.
Contraindications
Mild, moderate, or severe hepatic impairment; severe renal impairment, renal failure, hypokalemia, hypomagnesemia; preexisting QT prolongation, history of torsades de pointes, ventricular tachycardia, ventricular arrhythmias, significant bradycardia, acute MI, cardiac arrhythmia; concurrent use with QT prolongation drugs; grapefruit juice; concurrent use of potent or moderately potent CYP3A inhibitors; pregnancy (category C); lactation. Safety and efficacy in children have not been established.
Cautious Use
History of QT prolongation; older adult.
Route & Dosage
| Chronic Stable Angina Adult: PO 500–1000 mg b.i.d. |
Administration
Oral- Must be swallowed whole. Should not be crushed, broken, or chewed.
- Store at 15°–30° C (59°–86° F).
Adverse Effects (≥1%)
Body as a Whole: Peripheral edema. CNS: Dizziness, headache. CV: Palpitations. GI: Abdominal pain, constipation, dry mouth, nausea, vomiting. Respiratory: Dyspnea. Special Senses: Tinnitus, vertigo.Diagnostic Test Interference
Ranolazine is not known to interfere with any diagnostic laboratory test.
Interactions
Drug: Inhibitors of P-glycoprotein (e.g., ritonavir, cyclosporine) may increase ranolazine absorption. Ranolazine increases the plasma concentrations of digoxin and simvastatin. Inhibitors of CYP3A4 [e.g., diltiazem, grapefruit juice, hiv protease inhibitors, ketoconazole, macrolide antibiotics (especially ketoconazole), verapamil] can increase plasma levels and QTc elevation. Paroxetine, a CYP2D6 inhibitor, increases the plasma levels of ranolazine. class i or iii antiarrhythmics (e.g., quinidine, dofetilide, sotalol), thioridazine, and ziprasidone can cause additive increases in QTc elevation.Pharmacokinetics
Absorption: 73% of PO dose absorbed. Peak: 2–5 h. Distribution: 62% protein bound. Metabolism: Extensive hepatic metabolism. Elimination: 75% in urine; 25% in feces. Half-Life: 7 h.Nursing Implications
Assessment & Drug Effects
- Monitor ECG at baseline and periodically for prolongation of the QTc interval.
- Lab tests: Baseline and periodic LFTs.
- Monitor blood levels of digoxin with concurrent therapy.
- When coadministered with simvastatin, monitor for and report unexplained muscle weakness or pain.
Patient & Family Education
- Follow directions for taking the drug (see Administration).
- Do not drink grapefruit juice or eat grapefruit while taking this drug.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug