Dilatrate-SR Dosage

As noted above (see CLINICAL PHARMACOLOGY), multiple studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for organic nitrates including dilatrate®-SR must provide a daily nitrate-free interval to avoid the development of tolerance. To achieve the necessary nitrate-free interval with immediate-release oral ISDN, it appears that at least one of the daily interdose intervals must be at least 14 hours long. The necessary interdose interval for dilatrate®-SR has not been clearly identified, but it must be greater than 18 hours.

As noted under Clinical Pharmacology, only one trial has ever studied the use of extended-release isosorbide dinitrate for more than one dose. In that trial, 40 mg of dilatrate®-SR was administered twice daily in doses given 6 hours apart. After 4 weeks, dilatrate®-SR could not be distinguished from placebo.

Large controlled studies with other nitrates suggest that no dosing regimen with dilatrate®-SR should be expected to provide more than about 12 hours of continuous antianginal efficacy per day.

In clinical trials, immediate-release oral isosorbide dinitrate has been administered in a variety of regimens, with total daily doses ranging from 30 to 480 mg.

Do not exceed 160 mg (4 capsules) per day.