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Pronunciation
(eye soe SOR bide mon oh NYE trate)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Prevention of angina pectoris
Pregnancy Risk Factor
B/C (manufacturer dependent)
Pregnancy Considerations
Teratogenic effects were not observed in animal reproduction studies. Adverse events in the offspring were observed with use later in pregnancy at doses that were also maternally toxic.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to isosorbide mononitrate or any component of the formulation; hypersensitivity to organic nitrates; concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, or vardenafil)
Warnings/Precautions
Concerns related to adverse effects:
• Hypotension/bradycardia: Severe hypotension can occur; paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur; ethanol can accentuate this. Use with caution in volume depletion and moderate hypotension, and with extreme caution with inferior wall MI and suspected right ventricular infarctions.
• Intracranial pressure increased: Nitrates may precipitate or aggravate increased intracranial pressure and subsequently may worsen clinical outcomes in patients with neurologic injury (eg, intracranial hemorrhage, traumatic brain injury).
Disease-related concerns:
• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Avoid use in patients with HCM; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (Gibbons, 2003).
Concurrent drug therapy issues:
• PDE-5 inhibitors: Avoid concurrent use with PDE-5 inhibitors (eg, sildenafil, tadalafil, vardenafil). When nitrate administration becomes medically necessary, may administer nitrates only if 24 hours have elapsed after use of sildenafil or vardenafil (48 hours after tadalafil use) (O'Connor, 2010).
Other warnings/precautions:
• Tolerance: Appropriate dosing intervals are needed to minimize tolerance development. Tolerance can only be overcome by short periods of nitrate absence from the body. Dose escalation does not overcome this effect.
Adverse Reactions
>10%: Central nervous system: Headache (13% to 35%)
1% to 10%:
Cardiovascular: Angina (≤2%), flushing (≤2%)
Central nervous system: Dizziness (≤4%), fatigue (≤4%), pain (≤4%), emotional lability (≤2%)
Dermatologic: Pruritus (≤2%), rash (≤2%)
Gastrointestinal: Nausea (≤3%), abdominal pain (≤2%), diarrhea (≤2%)
Respiratory: Upper respiratory infection (≤4%), cough increased (≤2%)
Miscellaneous: Allergic reaction (≤2%)
<1% (Limited to important or life-threatening): Amblyopia, anorexia, anxiety, apoplexy, arrhythmia, asthma, back pain, bradycardia, concentration impaired, depression, diaphoresis, dyspepsia, dyspnea, edema, hyper-/hypotension, insomnia, methemoglobinemia (rare; overdose), MI, muscle cramps, neck pain, nervousness, nightmares, pallor, palpitation, paresthesia, postural hypotension, prostatic disorder, restlessness, sinusitis, susurrus aurium, tachycardia, taste disturbance, thirst, tremor, vertigo, vomiting, xerostomia
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Rosiglitazone: Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of myocardial ischemia was reported for users of this combination in a meta-analysis. Management: Consider alternatives to this combination when possible. Rosiglitazone prescribing information states that the combination of rosiglitazone and a nitrate is not recommended. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Caution with ethanol (may increase risk of hypotension).
Storage
Tablets should be stored in a tight container at room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Nitroglycerin and other nitrates form free radical nitric oxide. In smooth muscle, nitric oxide activates guanylate cyclase which increases guanosine 3'5' monophosphate (cGMP) leading to dephosphorylation of myosin light chains and smooth muscle relaxation. Produces a vasodilator effect on the peripheral veins and arteries with more prominent effects on the veins. Primarily reduces cardiac oxygen demand by decreasing preload (left ventricular end-diastolic pressure); may modestly reduce afterload; dilates coronary arteries and improves collateral flow to ischemic regions.
Pharmacodynamics/Kinetics
Onset of action: 30-60 minutes
Duration: Immediate release: ≥6 hours (Thadani, 1987); Extended release: ≥12-24 hours (Anderson, 2007)
Absorption: Nearly complete and low intersubject variability in its pharmacokinetic parameters and plasma concentrations
Distribution: Vd: ~0.6 L/kg
Protein binding: <5%
Metabolism: Hepatic
Bioavailability: ~100%
Half-life elimination: Mononitrate: ~5-6 hours
Excretion: Predominantly urine (2% as unchanged drug); feces (1% of dose)
Dosage
Oral:
Adults:
Regular release tablet: Initial: 5-20 mg twice daily with the 2 doses given 7 hours apart (eg, 8 AM and 3 PM) to decrease tolerance development; patients initiating therapy with 5 mg twice daily (eg, small stature) should be titrated up to 10 mg twice daily in first 2-3 days.
Extended release tablet: Initial: 30-60 mg given once daily in the morning; titrate upward as needed, giving at least 3 days between increases; maximum daily single dose: 240 mg
Elderly: Start with lowest recommended adult dose.
Dosing adjustment in renal impairment: Dose adjustment not necessary
Hemodialysis: Dose supplementation is not necessary.
Peritoneal dialysis: Dose supplementation is not necessary.
Dosing adjustment in hepatic impairment: Dose adjustment not necessary
Note: 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 of nitrate withdrawal may help minimize tolerance. Recommended twice daily dosage regimens incorporate this interval. Administer sustained release tablet once daily in the morning.
Administration: Oral
Do not administer around-the-clock. Immediate release tablet should be scheduled twice daily with doses 7 hours apart (8 AM and 3 PM); extended release tablet may be administered once daily in the morning upon rising with a half-glassful of fluid and should not be chewed or crushed.
Monitoring Parameters
Monitor for orthostasis, increased hypotension
Patient Education
Take at same time(s) each day. Do not crush or chew extended release tablets; swallow whole with water. Avoid excess alcohol intake; combination may cause severe hypotension. May cause dizziness, headache, and flushed feeling. Report severe headache, persistent dizziness, loss of consciousness, or any rash. If chest pain occurs, seek emergency medical help at once.
Geriatric Considerations
The first dose of nitrates (sublingual, chewable, oral) should be taken in a physician's office to observe for maximal cardiovascular dynamic effects and adverse effects (eg, orthostatic blood pressure drop, headache). The use of nitrates for angina may occasionally promote reflux esophagitis. This may require dose adjustments or changing therapeutic agents to correct this adverse effect.
Anesthesia and Critical Care Concerns/Other Considerations
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.
Cardiovascular Considerations
Nitrates improve the balance between myocardial oxygen supply and demand, primarily by decreasing oxygen demand. Nitrates decrease myocardial oxygen demand by reducing preload via dilation of peripheral veins. Nitrates improve myocardial oxygen supply by dilating epicardial coronary arteries and collateral vessels, leaving resistance vessels alone. Nitrates are unlikely to induce a coronary steal syndrome. Nitrates improve exercise tolerance in stable angina patients. An adequate nitroglycerin-free period must be provided with all nitrate products to prevent nitrate tolerance from developing. Caution should be observed if administering nitrates to individuals who are volume depleted or are experiencing a right ventricular infarction. Additionally, nitrates should not be given concomitantly to an individual who has received a phosphodiesterase-5 (PDE-5) enzyme inhibitor. When nitrate administration becomes medically necessary, may administer nitrates only if 24 hours have elapsed after use of sildenafil or vardenafil (48 hours after tadalafil use) (O'Connor, 2010).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness; may rarely cause drowsiness, agitation, anxiety, confusion, nervousness, or insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess patient closely for previous hypersensitivity. Use caution in presence of volume depletion, hypotension, right ventricular infarction, and hypertrophic cardiomyopathy. Tolerance to nitrates will develop and proper timing of doses is needed to minimize tolerance. Monitor for hypotension and GI disturbance when beginning therapy, adjusting dosage, and at regular intervals during therapy. Teach patient importance of maintaining dosing schedule.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 10 mg, 20 mg
Ismo®: 20 mg [scored]
Monoket®: 10 mg, 20 mg [scored]
Tablet, extended release, oral: 30 mg, 60 mg, 120 mg
Imdur®: 30 mg, 60 mg [scored]
Imdur®: 120 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Imdur)
30 mg (30): $91.17
60 mg (30): $95.30
Tablet, 24-hour (Isosorbide Mononitrate CR)
30 mg (30): $20.99
60 mg (30): $19.99
120 mg (50): $33.99
Tablets (Isosorbide Mononitrate)
10 mg (60): $25.99
20 mg (60): $19.99
Tablets (Monoket)
10 mg (60): $101.99
20 mg (60): $171.99
References
Anderson JL, Adams CD, Antman EM, et al, “ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration With the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine,” J Am Coll Cardiol, 2007, 50(7):e1-e157.
Cheitlin MD, Hutter AM Jr, Brindis RG, et al, “ACC/AHA Expert Consensus Document. Use of Sildenafil (Viagra) in Patients With Cardiovascular Disease. American College of Cardiology/American Heart Association,” J Am Coll Cardiol, 1999, 33(1):273-82.
Flaherty JT, “Hemodynamic Attenuation and the Nitrate Dose-Free Interval: Alternative Dosing Strategies for Transdermal Nitroglycerin,” Am J Cardiol, 1985, 56(17):321-71.
Fraker TD, Fihn SD, Gibbons RJ, et al, “2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to Develop the Focused Update of the 2002 Guidelines for the Management of Patients With Chronic Stable Angina,” Circulation, 2007, 116(23):2762-72.
Gibbons RJ, Abrams J, Chatterjee K, et al, “ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina),” Circulation, 2003, 107(1):149-58.
Hunt SA, Baker DW, Chin MH, et al, “ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure),” J Am Coll Cardiol, 2001, 38(7):2101-13.
O'Connor RE, Brady W, Brooks SC, et al, "Part 10: Acute Coronary Syndromes: 2010 American Heart Association Care Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care," Circulation, 2010, 122(18 Suppl 3):787-817.
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.
Thadani U, Prasad R, Hamilton SF, et al, “Isosorbide-5-Mononitrate in Angina Pectoris: Plasma Concentrations and Duration of Effects After Acute Therapy,” Clin Pharmacol Ther, 1987, 42(1):58-65.
Villaneuva C, Minana J, Ortiz J, et al, “Endoscopic Litigation Compared With Combined Treatment With Nadolol and Isosorbide Mononitrate to Prevent Recurrent Variceal Bleeding,” N Engl J Med, 2001, 345(9):647-55.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
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