Isosorbide 5-mononitrate: a review of a sustained-release formulation (Imdur) in stable angina pectoris

Abstract

Imdur (IMD) is a sustained-release isosorbide 5-mononitrate preparation for the treatment of chronic stable angina pectoris. Controlled medication release is achieved using the Durules principle of insoluble matrix embedding. Data from randomised double-blind trials show that IMD 60 mg once daily (the most widely studied dosage) has significant antianginal and anti-ischaemic effects compared with placebo after 2 weeks' treatment. Efficacy was generally observed approximately 1 to 12 hours after administration, indicating that once-daily administration in the morning will provide effective prophylaxis of symptoms throughout the day. Improvements from baseline are generally maintained during IMD repeated treatment. There was no evidence of classical tolerance to IMD 30 to 240 mg/day in a large well designed study. Although improvements from baseline were maintained over 6 weeks with IMD 30 or 60 mg/day, statistical significance versus placebo was eventually lost because of improved performance in the placebo group. IMD 120 or 240 mg/day were more effective than placebo after 6 weeks. Studies lasting up to 2 weeks found no evidence of tolerance to IMD 60 mg/day. In comparative trials lasting approximately 2 weeks, IMD 60 mg once daily was more effective than isosorbide dinitrate 30 mg 4 times daily and similar to or better than isosorbide dinitrate 20 mg 3 times daily. Preliminary data show that IMD 60 mg once daily has similar efficacy to diltiazem 60 mg 3 times daily and is at least as effective as certain other sustained-release isosorbide 5-mononitrate preparations. There is no evidence for rebound worsening of ischaemia 24 hours after IMD administration. Abrupt discontinuation during long term IMD treatment may exacerbate anginal symptoms. In general, IMD is well tolerated. The most frequently reported adverse event, headache, is usually mild to moderate, improves with long term therapy and rarely leads to treatment withdrawal. Patient compliance is better with once-daily administration of IMD than with twice-daily administration of conventional isosorbide 5-mononitrate.

Conclusions: In patients with chronic stable angina, IMD provides effective antianginal prophylaxis for up to 12 hours and does not seem to be associated with rebound phenomena at the end of the dosage interval. Improvements from baseline are maintained during repeated administration, although loss of statistically significant superiority over placebo was evident during 6 weeks' treatment with IMD < or =60 mg/day in 1 study. Further evaluation of comparative efficacy (particularly with respect to other sustained-release preparations) and long term effects would be beneficial. Nevertheless, the available data suggest that IMD is a useful and convenient agent for the treatment of patients with chronic stable angina pectoris.