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What is Ranexa?
Ranexa (ranolazine extended-release tablets) is the first new pharmaceutical approach to the treatment of chronic angina in the United States in over 20 years.13 Ranexa has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure.1
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What is the indication for Ranexa?1
Ranexa is indicated for the treatment of chronic angina. Because Ranexa prolongs the QT interval, it should be reserved for patients who have not achieved an adequate response with other antianginal drugs. Ranexa should be used in combination with amlodipine, beta-blockers, or nitrates. The effect on angina rate or exercise tolerance appeared to be smaller in women than men.
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What are the electrocardiographic effects of Ranexa?1
Dose and plasma concentration-related increases in the QTc interval, reductions in T wave amplitude and, in some cases, notched T waves, have been observed in patients treated with ranolazine. These effects are believed to be caused by ranolazine and not by its metabolites. The relationship between the change in QTc and ranolazine plasma concentrations is linear with a slope of about 2.6 msec/1000 ng/mL ranolazine. The variable blood levels attained after a given dose of ranolazine give a wide range of effects on QTc. At Tmax following repeat dosing at 1000 mg b.i.d., the mean change in QTc is about 6 msec but in the 5% of the population with the highest plasma concentrations, the prolongation of QTc is at least 15 msec. In subjects with mild or moderate hepatic impairment, the relationship between plasma level of ranolazine and QTc is much steeper. Congestive heart failure, diabetes, renal impairment, and gender did not alter the slope of the QTc-concentration relationship of ranolazine. Ranolazine has been shown to prolong the QTc interval in a dose-related manner. While the clinical significance of the QTc prolongation in the case of ranolazine is unknown, other drugs with this potential have been associated with torsades de pointes-type arrhythmias and sudden death.
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What is the mechanism of action of Ranexa?1
The
mechanism of action of ranolazine has not been determined. Ranolazine has antianginal and
anti-ischemic effects that do not depend upon
reductions in heart rate or blood pressure. It does not affect the rate-pressure
product, a measure of myocardial work, at maximal exercise. Ranolazine at therapeutic levels can
inhibit the late INa. 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 IKr, which prolongs the ventricular action potential.
Minimal changes in mean heart rate (< 2 bpm) and systolic blood pressure
(< 3 mm Hg) were observed in patients with chronic angina treated with Ranexa in controlled studies. However, in six patients with severe renal insufficiency taking Ranexa 500 mg twice daily, mean diastolic blood pressure increased 10 to 15 mm Hg. Ranexa should be generally avoided in patients with severe renal impairment. If Ranexa is started in these patients, blood pressure should be monitored regularly.
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What are the main pharmacokinetic parameters for Ranexa?1
The apparent terminal half-life of ranolazine is 7 hours and peak plasma concentrations occur in 2 to 5 hours. Steady state is generally achieved within 3 days of b.i.d. dosing with Ranexa. Ranolazine is metabolized mainly by CYP3A and to a lesser extent by CYP2D6. Ranolazine plasma levels appeared to increase approximately 50% in patients with varying degrees of renal insufficiency, and were also increased in subjects with mild and moderate liver impairment. No significant effect on Ranexa pharmacokinetics for age, gender, congestive heart failure (NYHA Class I to IV), and diabetes mellitus have been reported. Caution should be exercised when coadministering Ranexa and P-gp inhibitors such as ritonavir or cyclosporine. Read more about potential drug interactions with Ranexa.
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Can Ranexa be taken to relieve an acute angina episode?1
No, Ranexa will not abate an acute angina episode.
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