|Drug Name:||Isosorbide Dinitrate|
|Manufacturer:||West-ward Pharmaceutical Corp.|
Methemoglobinemia: Nitrate ions liberated during metabolism of ISDN can oxidize hemoglobin into methemoglobin.
Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moieties of ISDN are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of ISDN should be required before any of these patients manifests clinically significant (?10%) methemoglobinemia.
In patients with normal reductase function, significant production of methemoglobin should require even larger doses of ISDN.
In one study in which 36 patients received 2 to 4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 4.8 to 6.9 mg of bioavailable ISDN per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates.
None of the affected patients had been thought to be unusually susceptible.Methemoglobin levels are available from most clinical laboratories.
The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2.Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.
Isosorbide dinitrate tablets are indicated for the prevention of angina pectoris due to coronary artery disease.The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.
Allergic reactions to organic nitrates are extremely rare, but they do occur.The isosorbide dinitrate tablet is contraindicated in patients who are allergic to ISDN or any of its other ingredients.
Amplification of the vasodilatory effects of ISDN by sildenafil can result in severe hypotension.
The time course and dose dependence of this interaction have not been studied.
Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.The benefits of immediate-release oral ISDN in patients with acute myocardial infarction or congestive heart failure have not been established.
If one elects to use ISDN in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.Because the effects of oral ISDN are so difficult to terminate rapidly, this formulation is not recommended in these settings.