Nitroglycerindosage

As noted above (CLINICAL PHARMACOLOGY), careful studies with other formulations of nitroglycerin have shown that maintenance of continuous 24-hour plasma levels of nitroglycerin result in tolerance (i.e. loss of clinical response). Every dosing regimen for Nitroglycerin Extended-Release Capsules should provide a daily nitrate-free interval avoid the development of this tolerance. The minimum necessary length of such an interval has not been defined, but studies with other nitroglycerin formulations have shown that 10-12 hours is sufficient. Large controlled studies with other formulations of nitroglycerin show that no dosing regimen with Nitroglycerin Extended-Release should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day. The pharmacokinetics of Nitroglycerin Capsules and the clinical effects of multiple-dose regimens, have not been well studied. In clinical trials, the initial regimen of nitroglycerin has been 2.5 to 6.5 mg three to four times a day, with subsequent upward dose adjustment guided by symptoms and side effects. In one trial, 5 of the 18 subjects were titrated up to a dose of 26 mg four times a day.