Yes

Vasodilator

Prevention and treatment of angina pectoris; for congestive heart failure; to relieve pain, dysphagia, and spasm in esophageal spasm with GE reflux

C

Hypersensitivity to isosorbide dinitrate or any component; hypersensitivity to organic nitrates; concurrent use with sildenafil; angle-closure glaucoma (intraocular pressure may be increased); head trauma or cerebral hemorrhage (increase intracranial pressure); severe anemia

Severe hypotension can occur. Use with caution in volume depletion, hypotension, and right ventricular infarctions. Paradoxical bradycardia and increased angina pectoris can accompany hypotension. Postural hypotension can also occur. Tolerance does develop to nitrates and appropriate dosing is needed to minimize this. Safety and efficacy have not been established in pediatric patients. Nitrate may aggravate angina caused by hypertrophic cardiomyopathy. Avoid concurrent use with sildenafil.

Incidence of reactions are not reported.

Central nervous system: Headache (most common), lightheadedness (related to blood pressure changes), syncope (uncommon), dizziness, restlessness

Gastrointestinal: Nausea, vomiting, bowel incontinence, xerostomia

Genitourinary: Urinary incontinence

Hematologic: Methemoglobinemia (rare, overdose)

Neuromuscular & skeletal: Weakness

Ocular: Blurred vision

Miscellaneous: Cold sweat

The incidence of hypotension and adverse cardiovascular events may be increased when used in combination with sildenafil (Viagra®).

Symptoms of overdose which are most common include hypotension, throbbing headache, tachycardia, and flushing. Methemoglobinemia may occur with massive doses; hypotension may aggravate symptoms of cardiac ischemia or cerebrovascular disease and may even cause seizures (rare).

Treatment consists of placing patient in recumbent position and administering fluids; alpha-adrenergic vasopressors may be required; treat methemoglobinemia with oxygen and methylene blue at a dose of 1-2 mg/kg I.V. slowly.

Sildenafil: Significant reduction of systolic and diastolic blood pressure with concurrent use. Do not give sildenafil within 24 hours of a nitrate preparation.

Stimulation of intracellular cyclic-GMP results in vascular smooth muscle relaxation of both arterial and venous vasculature. Increased venous pooling decreases left ventricular pressure (preload) and arterial dilatation decreases arterial resistance (afterload). Therefore, this reduces cardiac oxygen demand by decreasing left ventricular pressure and systemic vascular resistance by dilating arteries. Additionally, coronary artery dilation improves collateral flow to ischemic regions; esophageal smooth muscle is relaxed via the same mechanism.

Onset of action:

Sublingual tablet: 2-10 minutes

Chewable tablet: 3 minutes

Oral tablet: 45-60 minutes

Sustained release tablet: 30 minutes

Duration:

Sublingual tablet: 1-2 hours

Chewable tablet: 0.5-2 hours

Oral tablet: 4-6 hours

Sustained release tablet: 6-12 hours

Metabolism: Extensive in the liver to conjugated metabolites, including isosorbide 5-mononitrate (active) and 2-mononitrate (active)

Half-life: Parent drug: 1-4 hours; Metabolite (5-mononitrate): 4 hours

Elimination: In urine and feces

Adults (elderly should be given lowest recommended daily doses initially and titrate upward): Oral:

Congestive heart failure:

Initial dose: 10 mg 3 times/day

Target dose: 40 mg 3 times/day

Maximum dose: 80 mg 3 times/day

Sublingual: 2.5-10 mg every 4-6 hours

Chew: 5-10 mg every 2-3 hours

Tolerance to nitrate effects develops with chronic exposure

Dose escalation does not overcome this effect. Tolerance can only be overcome by short periods of nitrate absence from the body. Short periods (14 hours) or nitrate withdrawal help minimize tolerance.

Hemodialysis: During hemodialysis, administer dose postdialysis or administer supplemental 10-20 mg dose

Peritoneal dialysis: Supplemental dose is not necessary

Monitor for orthostasis

cholesterol (S)

Concomitant use of sildenafil (Viagra®) may precipitate acute hypotension, myocardial infarction, or death. Nitrates used in right ventricular infarction may induce acute hypotension. Nitrate use in severe pericardial effusion may reduce cardiac filling pressure and precipitate cardiac tamponade. In the management of heart failure, the combination of isosorbide dinitrate and hydralazine confers beneficial effects on disease progression and cardiac outcomes.

May cause dizziness

None reported

No information available to require special precautions

No effects or complications reported

Take as directed, at the same time each day. Do not chew or swallow sublingual tablets; allow them to dissolve under your tongue. Do not change brands without consulting prescriber. Do not discontinue abruptly. Keep medication in original container, tightly closed. Avoid alcohol; combination may cause severe hypotension. Take medication while sitting down and use caution when changing position (rise from sitting or lying position slowly). May cause dizziness; use caution when driving or engaging in hazardous activities until response to drug is known. If chest pain is unresolved in 15 minutes, seek emergency medical help at once. Report acute headache, rapid heartbeat, unusual restlessness or dizziness, muscular weakness, or blurring vision. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

8- to 12-hour nitrate-free interval is needed each day to prevent tolerance

Capsule, sustained release: 40 mg

Tablet:

Chewable: 5 mg, 10 mg

Oral: 5 mg, 10 mg, 20 mg, 30 mg, 40 mg

Sublingual: 2.5 mg, 5 mg, 10 mg

Sustained release: 40 mg

Aderka D, Garfinkel D, Bograd H, et al, "Isosorbide Dinitrate-Induced Hemolysis in G-6-PD-Deficient Subjects," Acta Haematol, 1983, 69(1):63-4.

Flaherty JT, "Hemodynamic Attenuation and the Nitrate-Free Interval: Alternative Dosing Strategies for Transdermal Nitroglycerin," Am J Cardiol, 1985, 56(17):321-71.

Nakashima E, Rigod JF, Lin ET, et al, "Pharmacokinetics of Nitroglycerin and Its Dinitrate Metabolites Over a Thirty-Fold Range of Oral Doses," Clin Pharmacol Ther, 1990, 47(5):592-8.

Parker JO, "Eccentric Dosing With Isosorbide-5-Mononitrate in Angina Pectoris," Am J Cardiol, 1993, 72(12):871-6.

Parker JO, Fanell B, Lahey KA, et al, "Effect of Intervals Between Doses on the Development to Tolerance to Isosorbide Dinitrate," N Engl J Med, 1987, 316(23):1440-4.

Rosenthal R, "Visual Hallucinations and Suicidal Ideation Attributed to Isosorbide Dinitrate," Psychosomatics, 1987, 28(10):555-6.

Silfvast T, Kinnunen A, and Varpula T, "Laryngeal Oedema After Isosorbide Dinitrate Spray and Sublingual Nifedipine," BMJ, 1995, 311(6999):232.