Angina:
Indications for: RANEXA
Chronic angina; may be used with beta-blockers, nitrates, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, anti-platelet and lipid-lowering therapies.
Clinical Trials:
Chronic Stable Angina
The CARISA (Combination Assessment of Ranolazine In Stable Angina) study involved 823 chronic angina patients who were randomly assigned to receive 12 weeks of treatment with twice-daily Ranexa 750 mg, 1000 mg, or placebo, and were also continued on daily doses of atenolol 50 mg, amlodipine 5 mg, or diltiazem CD 180 mg; sublingual nitrates were used as needed.
In this trial, statistically significant (P <0.05) increases in modified Bruce treadmill exercise duration and time to angina were observed for each Ranexa dose versus placebo, at both trough (12 hours after dosing) and peak (4 hours after dosing) plasma levels, with minimal effects on blood pressure and heart rate. Results showed no increase in effect on exercise at the 1000 mg dose vs the 750 mg dose during the treadmill exercise.
Ranexa has been evaluated in patients with chronic angina who remained symptomatic despite treatment with the maximum dose of an antianginal agent. In the ERICA (Efficacy of Ranolazine In Chronic Angina) trial, 565 patients were randomly assigned to receive an initial dose of Ranexa 500 mg twice daily or placebo for 1 week, followed by 6 weeks of treatment with Ranexa 1000 mg twice daily or placebo, in addition to concomitant treatment with amlodipine 10 mg once daily. Moreover, 45% of the study population also received long-acting nitrates. Sublingual nitrates were used as needed to treat angina episodes. Statistically significant decreases in angina attack frequency (P =0.028) and nitroglycerin use (P =0.014) were seen with Ranexa compared to placebo. These treatment effects appeared consistent across age and use of long-acting nitrates.
Lack of Benefit in Acute Coronary Syndrome
In a large (n=6560) placebo-controlled trial (MERLIN-TIMI 36) in patients with acute coronary syndrome, there was no benefit shown on outcome measures. However, the study is somewhat reassuring regarding proarrhythmic risks, as ventricular arrhythmias were less common on ranolazine, and there was no difference between Ranexa and placebo in the risk of all-cause mortality (relative risk ranolazine:placebo 0.99; upper 95% confidence limit of 1.22).
Adult Dosage:
Swallow whole. Initially 500mg twice daily, may increase to max 1g twice daily. Concomitant moderate CYP3A inhibitors (eg, diltiazem, verapamil, erythromycin, fluconazole, grapefruit-containing products): max 500mg twice daily. Concomitant P-gp inhibitors (eg, cyclosporine): titrate ranolazine dose based on response. Concomitant simvastatin: limit simvastatin to 20mg once daily. Concomitant metformin: give max metformin 1.7g/day if taking ranolazine 1g twice daily.
Children Dosage:
Not established.
RANEXA Contraindications:
Liver cirrhosis. Concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir) or CYP3A inducers (eg, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort).
RANEXA Warnings/Precautions:
Not for acute angina episodes or for treating diabetes. History of or congenital long QT syndrome. Monitor renal function after initiation and periodically in moderate to severe renal impairment. Discontinue if acute renal failure develops. Elderly. Pregnancy. Nursing mothers.
RANEXA Classification:
Antianginal.
RANEXA Interactions:
See Contraindications. Potentiates metformin; monitor glucose levels. May potentiate drugs metabolized by CYP3A (eg, simvastatin, lovastatin, cyclosporine, tacrolimus, sirolimus), P-gp transporters (eg, digoxin), CYP2D6 (eg, antipsychotics, tricyclic antidepressants); adjust doses of these drugs. May be potentiated by P-gp inhibitors (eg, cyclosporine). Caution with drugs that cause QT prolongation (eg, Class IA, Class III antiarrhythmics, thioridazine, ziprasidone).
Adverse Reactions:
Dizziness, headache, constipation, nausea; QT prolongation.
Drug Elimination:
Following a single oral dose of ranolazine solution, ~75% of the dose is excreted in urine and 25% in feces. Half-life: range 6–22 hours.
Generic Drug Availability:
YES
How Supplied:
Tabs—60
