No

Vasodilator

Long-acting metabolite of the vasodilator isosorbide dinitrate used for the prophylactic treatment of angina pectoris

C

Hypersensitivity to isosorbide 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. Orthostatic hypotension can also occur. Alcohol can accentuate this. Tolerance does develop to nitrates and appropriate dosing is needed to minimize this (drug-free interval). Safety and efficacy have not been established in pediatric patients. Nitrates may aggravate angina caused by hypertrophic cardiomyopathy. Avoid concurrent use with sildenafil.

>10%: Central nervous system: Headache (19% to 38%)

1% to 10%:

Central nervous system: Dizziness (3% to 5%)

Gastrointestinal: Nausea/vomiting (2% to 4%)

<1% (Limited to important or life-threatening symptoms): Angina pectoris, arrhythmias, atrial fibrillation, hypotension, palpitations, postural hypotension, premature ventricular contractions, supraventricular tachycardia, syncope, pruritus, rash, abdominal pain, diarrhea, dyspepsia, tenesmus, tooth disorder, vomiting, dysuria, impotence, urinary frequency, asthenia, blurred vision, cold sweat, diplopia, edema, malaise, neck stiffness, rigors, agitation, anxiety, confusion, dyscoordination, hypoesthesia, nightmares, bronchitis, pneumonia, upper respiratory tract infection, arthralgia, methemoglobinemia (rare, overdose)

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.

Tablets should be stored in a tight container at room temperature of 15°C to 30°C (59°F to 86°F)

Prevailing mechanism of action for nitroglycerin (and other nitrates) is systemic venodilation, decreasing preload as measured by pulmonary capillary wedge pressure and left ventricular end diastolic volume and pressure; the average reduction in left ventricular end diastolic volume is 25% at rest, with a corresponding increase in ejection fractions of 50% to 60%. This effect improves congestive symptoms in heart failure and improves the myocardial perfusion gradient in patients with coronary artery disease.

Onset of effect: Oral: 30-60 minutes

Absorption: Oral: Nearly complete and low intersubject variability in its pharmacokinetic parameters and plasma concentrations

Metabolism: Metabolite of isosorbide dinitrate

Half-life: Mononitrate: ~4 hours (8 times that of dinitrate)

Geriatrics (start with lowest recommended dose) and Adults: Oral:

Extended release tablet (Imdur™): Initial: 30-60 mg given in morning as a single dose; titrate upward as needed, giving at least 3 days between increases; maximum daily single dose: 240 mg

Dosing adjustment in renal impairment: Not necessary for elderly or patients with altered renal or hepatic function.

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 (10-12 hours) of nitrate withdrawal help minimize tolerance. General recommendations are to take the last dose of short-acting agents no later than 7 PM; administer 2 times/day rather than 4 times/day. Administer sustained release tablet (Imdur™) once daily in the morning.

Alcohol: Has been found to exhibit additive effects of this variety

Monitor for orthostasis

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.

May cause dizziness; may rarely cause drowsiness, agitation, anxiety, confusion, nervousness, or insomnia

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 crush extended release capsules; swallow with 8 oz of water. 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.

Do not crush; 8- to 12-hour nitrate-free interval is needed each day to prevent tolerance

Tablet (Ismo®, Monoket®): 10 mg, 20 mg

Tablet, extended release (Imdur™): 30 mg, 60 mg, 120 mg

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

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.