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Pronunciation |
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(eye
soe SOR bide mon oh NYE
trate) |

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U.S. Brand
Names |
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Imdur™; Ismo®;
Monoket® |

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Generic
Available |
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No |

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Synonyms |
|
ISMN |

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Pharmacological Index |
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Vasodilator |

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

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Pregnancy Risk
Factor |
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C |

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Contraindications |
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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 |

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Warnings/Precautions |
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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. |

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Adverse
Reactions |
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>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®). |

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Overdosage/Toxicology |
|
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.
|

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

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

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Mechanism of
Action |
|
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. |

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Pharmacodynamics/Kinetics |
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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)
|

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Usual Dosage |
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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. |

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

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Monitoring
Parameters |
|
Monitor for orthostasis |

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Cardiovascular
Considerations |
|
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. |

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Mental Health: Effects
on Mental Status |
|
May cause dizziness; may rarely cause drowsiness, agitation, anxiety,
confusion, nervousness, or insomnia |

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Mental Health:
Effects on Psychiatric
Treatment |
|
None reported |

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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |

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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |

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Patient
Information |
|
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. |

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

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Dosage Forms |
|
Tablet (Ismo®, Monoket®): 10 mg,
20 mg
Tablet, extended release (Imdur™): 30 mg, 60 mg, 120
mg |

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References |
|
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. |

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