Ranolazine approved for angina treatment

The drug is indicated for patients who have not responded to other agents for angina.

A new antiangina treatment will be distributed to pharmacies at the end of March.

Ranolazine (Ranexa, CV Therapeutics) has antianginal and antiischemic effects that do not depend on reductions in heart rate or blood pressure, according to prescribing information. Although the exact mechanism of action is unknown, ranolazine has been shown to selectively inhibit the late sodium current.

The FDA officially approved ranolazine in late January, for the treatment of chronic angina. Louis G. Lange, MD, chairman and CEO of CV Therapeutics, said it was the first treatment for chronic angina approved in over 10 years.

“As a cardiologist I know Ranexa has the potential to make a profound impact on patients’ lives,” Lange said during a conference call.

According to the approved indication, ranolazine 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 in men.

“Women display chest pain differently than men, but it’s clear that Ranexa works in women. I am not aware of any other agent that has shown any degree of efficacy,” Lange said.

Ranolazine is an oral agent that should be initiated at 500 mg twice daily and titrated to 1,000 mg twice daily if needed.

Clinical trials

Ranolazine was evaluated in two clinical trials: ERICA (Efficacy of Ranolazine in Chronic Angina), which enrolled 565 patients, and CARISA (Combination Assessment of Ranolazine in Stable Angina), which enrolled 823 patients.

ERICA researchers randomized patients to an initial dose of 500 mg twice daily or placebo for one week followed by 1,000 mg twice daily or placebo for six weeks. During the 1,000-mg dose period, patients were concomitantly treated with 10 mg of amlodipine four times a day, and 45% of the population received long-acting nitrates.

At the 1,000-mg dose, ranolazine was associated with a mean of 3.3 angina attacks a week compared to 4.3 on placebo (P=.028).

Patients in CARISA were randomized to 12 weeks of treatment with twice-daily ranolazine at 750 mg, 1,000 mg, or placebo. All patients received daily doses of atenolol 50 mg, amlodipine 5 mg or diltiazem CD 180 mg.

In this trial, patients treated with ranolazine went 24 seconds longer on the treadmill, by Bruce protocol, 12 hours after dosing than patients in the placebo group.

Ranolazine is contraindicated for patients with pre-existing QT prolongation or hepatic impairment. It is also contraindicated for patients already assigned QT prolonging drugs or potent and moderately potent CYP3A inhibitors. – by Jeremy Moore