t head trauma or intracranial bleeding) because it's vasodilatory effects on the meningeal blood vessels can exacerbate these conditions.
Nitrate hypersensitivity
Isosorbide dinitrate is absolutely contraindicated in patients who have known nitrate hypersensitivity.
Closed-angle glaucoma
Isosorbide dinitrate is contraindicated in patients with closed-angle glaucoma due to the risk of drug-induced increased intraocular pressure.
Anemia
Isosorbide dinitrate is contraindicated in patients with severe anemia because the drug causes oxidation of hemoglobin to methemoglobin, which could exacerbate this condition.
Hepatic disease
Because isosorbide dinitrate plasma concentrations increase in patients with cirrhosis, isosorbide dinitrate should be used cautiously in patients with hepatic disease as metabolism of the drug can be impaired; accumulation of isosorbide dinitrate can result in an increased risk of methemoglobinemia.
GI disease
Extended-release isosorbide dinitrate products should be avoided in patients with GI disease such as hypermotility or malabsorption syndromes. This dosage form may not dissolve and may be excreted intact in these conditions.
Abrupt discontinuation
When isosorbide dinitrate is to be discontinued following long-term or high-dose administration, avoid abrupt discontinuation to avoid potential for rebound angina.
Pregnancy
Isosorbide dinitrate (ISDN) is classified as FDA pregnancy risk category C. Animal studies have shown no hazard at doses approximating usual human dosage. At oral doses 35 and 150 times the daily Maximum Recommended Human Dose (MRHD), isosorbide dinitrate has been shown to cause a dose related increase in embryotoxicity (increase in mummified pups) in rabbits. Human data are limited. Limited case reports exist of the successful use of nitrates for cardiac ischemia during pregnancy when necessary; these reports do not indicate the possibility of adverse effects resulting from the use of nitrates during pregnancy. Safety in pregnancy however, has not been established. For chronic anti-anginal therapy, other drugs (e.g., cardioselective beta-blockers) may also be considered. In making the decision to administer ISDN during pregnancy, the potential risks to the fetus must be weighed against the potential benefits to the mother.
Breast-feeding
It is not known whether isosorbide dinitrate or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isosorbide dinitrate is administered to a woman who is breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Children
The safety and effectiveness of isosorbide dinitrate in children have not been established.
ADVERSE REACTIONS
Severe
bradycardia / Rapid / Incidence not known
cyanosis / Early / Incidence not known
methemoglobinemia / Early / Incidence not known
Moderate
hypotension / Rapid / 5.0-10.0
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
tolerance / Delayed / Incidence not known
Mild
headache / Early / 3.0-40.0
dizziness / Early / 1.0-30.1
nausea / Early / 2.0-4.0
vomiti |
