RANOLAZINE GRNL,EC-ORAL
Clinical Criteria Summary
FDA Approved Indication
- Treatment of chronic stable angina
Exclusion Criteria
- Clinically significant hepatic impairment
- Receiving strong CYP 3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir)
- Receiving strong CYP 3A4 inducers (rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John’s wort)
Inclusion Criteria
- Anginal episodes averaging 3 or more times per week despite maximal or maximally tolerated anti-anginal drug therapy (defined as treatment with a beta-blocker, long-acting dihydropyridine calcium channel blocker, and a long-acting nitrate)
- Active VA healthcare provider involvement in monitoring and management of ranolazine therapy, with re-assessment of therapeutic effectiveness and tolerability within 12 weeks after initiation
Precautions & Drug Interactions
- QT-interval prolongation: Dose-dependent increase (mean QTc increase of 6 ms at 1000 mg twice daily); use with caution in patients with pre-existing QT interval prolongation (Normal QTc <440 ms) due to lack of safety data
- Drug-drug interactions: Ranolazine is a CYP 3A4 and P-glycoprotein inhibitor/substrate, and lesser extent CYP 2D6 substrate; carefully review medications prior to initiation; dose adjustment or avoidance may be recommended; use with caution alongside other QT-prolonging drugs (Class Ia [quinidine] or Class III [amiodarone, dofetilide, sotalol] antiarrhythmics, erythromycin, certain antipsychotic agents) due to limited safety data
Dosage & Administration
- Initiate therapy at 500 mg twice daily; maximum dose 1000 mg twice daily (dose escalation not consistently shown to improve symptoms; adverse events are dose-related)
- Maximum recommended dose limited to 500 mg twice daily with concurrent moderate CYP3A inhibitors (diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit-containing products)
- Down-titration may be needed when used concurrently with P-glycoprotein inhibitors (e.g., cyclosporine)
Issues for Consideration
- Reserve for patients who have not received an adequate response with other antianginal drugs; use in combination with beta-blockers, nitrates, and dihydropyridine calcium channel blockers
- Not shown to be pro-arrhythmic in a high-risk ACS population
- Increases simvastatin drug levels by 2-fold; monitor and counsel for potential adverse events despite manufacturer/FDA not recommending dosing adjustment
Renewal Criteria
- Therapeutic effectiveness and tolerability must be assessed within the first 12 weeks of therapy
- Documented improvement in anginal symptoms and/or reduction in sublingual nitroglycerin consumption while receiving ranolazine
- Patient is not experiencing treatment-limiting adverse effects