DOSAGE AND ADMINISTRATION
As noted above (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.
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