The Food and Drug Administration has approved a revised indication and several label additions for the angina drug ranolazine, including a statement that the drug reduced hemoglobin A1c in people with diabetes.
The indication is still for “the treatment of chronic angina, but “the second-line restriction on the use of ranolazine to treat patients with chronic angina has been removed,” according to an announcement issued by the FDA.
Previously, the indication was for treatment of chronic angina, but with the added statement that it should be reserved for patients who have not had an adequate response with other antianginal drugs, because ranolazine increases the QT interval.
The additional statement has been removed from the revised label, with the information about the QT interval prolongation now in the warnings and precaution section.
Also added to the label is a statement that cites the significantly lower rate of arrhythmias in patients with coronary heart disease who were treated with ranolazine in the MERLIN-TIMI 36 trial, compared with those on placebo, CV Therapeutics Inc. noted in its announcement of the approval.
The indications section of the revised label also says that the drug can be used with β-blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.
CV Therapeutics markets ranolazine in extended-release tablet form as Ranexa, which was approved in January 2006.
Ranolazine has antianginal and anti-ischemic effects, but its exact mechanism of action is not known, according to the label.
In a statement, the company said that data from the MERLIN-TIMI 36 trial were submitted to the FDA in September 2007, as part of its supplemental application. The revised label includes the statement that in the study—which compared ranolazine to placebo in more than 6,000 patients with acute coronary syndrome—no benefit was seen on outcome measures, but that the study was “somewhat reassuring regarding proarrhythmic risks, as ventricular arrhythmias were less common on ranolazine.”
The incidence of arrhythmias (ventricular tachycardia, bradycardia, supraventricular tachycardia, and new atrial fibrillation) was 80% among those treated with ranolazine, compared with 87% of those on placebo, a significant difference, according to the label. However, the label also states that the difference in arrhythmias did not result in lower mortality, or reductions in arrhythmia hospitalizations or arrhythmia symptoms.
The label notes that there were no proarrhythmic effects seen on 7-day Holter recordings in 3,162 patients with acute coronary syndrome who were treated with ranolazine.
The revised label also includes the statement that ranolazine “produces small reductions in [hemoglobin A1c] in patients with diabetes, the clinical significance of which is unknown,” and that the drug “should not be considered a treatment for diabetes.”