Isosorbide Mononitrate (Lexi-Drugs)

Pronunciation

(eye soe SOR bide mon oh NYE trate)

Brand Names: Canada

APO-ISMN; Imdur; ISMN [DSC]; PMS-ISMN; PRO-ISMN-60

Pharmacologic Category

Antianginal AgentVasodilator

Dosing: Adult

Angina pectoris: Oral: 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. Recommended twice daily dosage regimens incorporate this interval. Short periods of nitrate withdrawal may help minimize tolerance.

Immediate release: 20 mg twice daily with the 2 doses given 7 hours apart (eg, 8 AM and 3 PM) to decrease tolerance development; patients with small stature may initiate therapy with 5 mg twice daily and titrate to at least 10 mg twice daily in first 2 to 3 days of therapy.

Extended release: Initial: 30 to 60 mg once daily in the morning; may titrate after several days to 120 mg once daily; rarely, 240 mg once daily may be required

Heart failure with reduced ejection fraction (off-label use): Note: As additional therapy for persistent NYHA class III or IV heart failure with reduced ejection fraction (HFrEF) despite optimal medical therapies or for patients who cannot tolerate an ACE inhibitor, angiotensin II receptor blocker (ARB), or angiotensin II-neprilysin inhibitor (ARNI). Although ACCF/AHA guidelines recommend isosorbide dinitrate with hydralazine, some experts substitute isosorbide mononitrate for isosorbide dinitrate to reduce pill burden and improve adherence (ACC/AHA/HFSA [Yancy 2017]; ACCF/AHA [Yancy 2013]; Colucci 2018; Gottlieb 2018).

Oral: Extended release: Initial: 30 to 60 mg once daily in combination with hydralazine 3 or 4 times daily; titrate dose every 2 to 4 weeks; maximum dose: 120 mg/day (Gottlieb 2018). Note: May also consider use of the fixed-dose combination of isosorbide dinitrate/hydralazine instead of separate components (ACC/AHA/HFSA [Yancy 2017]; ACCF/AHA [Yancy 2013]).

Dosing: Geriatric

Refer to adult dosing; initiate with lowest recommended dose.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Hemodialysis: Supplemental dose is not necessary. Dose after dialysis (Aronoff 2007)

Continuous ambulatory peritoneal dialysis: Supplemental dose is not necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Use: Labeled Indications

Angina pectoris: Treatment (immediate-release only) and prevention of angina pectoris caused by coronary artery disease. Note: The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

Use: Off-Label: Adult

  Heart failure with reduced ejection fraction (HFrEF)Level of Evidence [C]

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for the management of heart failureisosorbide dinitrate (in combination with hydralazine) is effective and recommended as additional therapy to optimal guideline directed medical therapy for self-identified African-American patients with persistent NYHA class III or IV HFrEF or for patients who do not tolerate an ACE inhibitor or an angiotensin II receptor blocker (ARB). Some experts recommend isosorbide dinitrate (in combination with hydralazine) in addition to optimal guideline-directed medical therapy for black and nonblack patients with persistent NYHA class III or IV HFrEF, particularly for those with low output states or hypertension, or for patients who do not tolerate an ACE inhibitor, ARB, or angiotensin II-neprilysin inhibitor (ARNI). In order to improve compliance, it may be reasonable to replace isosorbide dinitrate with isosorbide mononitrate (in combination with hydralazine) Ref.

Clinical Practice Guidelines

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

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); administer extended release tablet once daily in the morning upon rising with a half-glassful of fluid. Do not chew or crush extended release tablets; may be divided in half. Due to insoluble matrix embedding, extended release tablets that are scored may be split (Gunasekara 1999).

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber angina, severe dizziness, passing out, bradycardia, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
Contraindications

Hypersensitivity to isosorbide mononitrate, other nitrates or nitrites, or any component of the formulation; concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, or vardenafil) or riociguat.

Canadian labeling: Additional contraindications (not in US labeling): Acute circulatory failure associated with marked hypotension (shock and states of collapse); postural hypotension; myocardial insufficiency due to obstruction (eg, in the presence of aortic or mitral stenosis or of constrictive pericarditis); increased intracranial pressure; severe anemia.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hypotension/bradycardia: Severe hypotension can occur; paradoxical bradycardia and increased angina pectoris can accompany hypotension. Orthostatic hypotension can also occur; ethanol can accentuate this. Severe hypotension, particularly with upright posture, may occur with even small doses.

• 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) (Rangel-Castilla 2008).

Disease-related concerns:

• Cardiovascular disease: Not recommended for use in patients with acute myocardial infarction (MI) or heart failure (has not been studied). Use with caution in volume depletion and moderate hypotension, and with extreme caution with inferior wall MI and suspected right ventricular infarctions. The Canadian labeling contraindicates use in acute circulatory failure associated with marked hypotension, postural hypotension, and myocardial insufficiency due to obstruction (eg, in the presence of aortic or mitral stenosis or of constrictive pericarditis).

• Hypertrophic cardiomyopathy (HCM): Avoid use in patients with HCM with outflow tract obstruction; nitrates may reduce preload, exacerbating obstruction and cause hypotension or syncope and/or worsening of heart failure (Gersh 2011).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• 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).

Dosage forms related issues:

• Extended-release tablets: Empty matrix “ghosts” (tablets) may pass in patients via colostomy or in the stool; this is of no concern.

Other warnings/precautions:

• Appropriate use: Extended-release: Not intended for the immediate relief of acute attacks of angina pectoris.

• 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.

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.

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. Nitric oxide donors, such as isosorbide, have been evaluated for pre-eclampsia and cervical ripening; isosorbide mononitrate use in these conditions is not currently recommended (Kalidindi 2012; Ramirez 2011).

Breast-Feeding Considerations

It is not known if isosorbide mononitrate is excreted in breast milk. The manufacturer recommends that caution be exercised when administering isosorbide mononitrate to nursing women.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%: Central nervous system: Headache (≤57%), dizziness (≤11%)

1% to 10%:

Cardiovascular: Abnormal heart sounds (≤5%), atrial arrhythmia (≤5%), atrial fibrillation (≤5%), bradycardia (≤5%), bundle branch block (≤5%), cardiac arrhythmia (≤5%), cardiac failure (≤5%), chest pain (≤5%), ECG abnormality (Q wave: ≤5%), edema (≤5%), exacerbation of angina pectoris (≤5%), extrasystoles (≤5%), flushing (≤5%), heart murmur (≤5%), hypertension (≤5%), hypotension (≤5%), intermittent claudication (≤5%), myocardial infarction (≤5%), palpitations (≤5%), tachycardia (≤5%), varicose veins (≤5%), ventricular tachycardia (≤5%), cardiovascular toxicity (2%)

Central nervous system: Anxiety (≤5%), confusion (≤5%), depression (≤5%), drowsiness (≤5%), fatigue (≤5%), hypoesthesia (≤5%), insomnia (≤5%), lack of concentration (≤5%), malaise (≤5%), migraine (≤5%), myasthenia (≤5%), nervousness (≤5%), neuritis (≤5%), nightmares (≤5%), paresis (≤5%), paresthesia (≤5%), rigors (≤5%), vertigo (≤5%), pain (4%), emotional lability (2%)

Dermatologic: Abnormal hair texture (≤5%), acne vulgaris (≤5%), diaphoresis (≤5%), leg ulcer (≤5%), pruritus (≤5%), skin rash (≤5%)

Endocrine & metabolic: Decreased libido (≤5%), hot flash (≤5%), hyperuricemia (≤5%), hypokalemia (≤5%)

Gastrointestinal: Abdominal pain (≤5%), constipation (≤5%), diarrhea (≤5%), dyspepsia (≤5%), flatulence (≤5%), gastric ulcer (≤5%), gastric ulcer with hemorrhage (≤5%), gastritis (≤5%), glossitis (≤5%), hemorrhoids (≤5%), loose stools (≤5%), melena (≤5%), nausea (≤5%), vomiting (≤5%), xerostomia (≤5%)

Genitourinary: Atrophic vaginitis (≤5%), impotence (≤5%), mastalgia (≤5%), urinary tract infection (≤5%)

Hematologic & oncologic: Hypochromic anemia (≤5%), nonthrombocytopenic purpura (≤5%), thrombocytopenia (≤5%)

Hepatic: Increased serum alanine aminotransferase (≤5%), increased serum aspartate aminotransferase (≤5%)

Hypersensitivity: Hypersensitivity reaction (2%)

Infection: Bacterial infection (≤5%), candidiasis (≤5%), viral infection (≤5%)

Neuromuscular & skeletal: Arthralgia (≤5%), asthenia (≤5%), back pain (≤5%), musculoskeletal pain (≤5%), myalgia (≤5%), myositis (≤5%), shoulder stiffness (frozen shoulder: ≤5%), tendon disease (≤5%), torticollis (≤5%), tremor (≤5%)

Ophthalmic: Blepharoptosis (≤5%), conjunctivitis (≤5%), photophobia (≤5%), visual disturbance (≤5%)

Otic: Otalgia (≤5%), perforated tympanic membrane (≤5%), tinnitus (≤5%)

Renal: Nephrolithiasis (≤5%), polyuria (≤5%)

Respiratory: Bronchitis (≤5%), bronchospasm (≤5%), cough (≤5%), dyspnea (≤5%), flu-like symptoms (≤5%), increased bronchial secretions (≤5%), nasal congestion (≤5%), pharyngitis (≤5%), pneumonia (≤5%), pulmonary infiltrates (≤5%), rales (≤5%), rhinitis (≤5%), sinusitis (≤5%), upper respiratory infection (1% to 4%), increased cough (2%)

Miscellaneous: Fever (≤5%), nodule (≤5%)

<1%, postmarketing, and/or case reports: Acute myocardial infarction, amblyopia, anorexia, asthma, bitter taste, cerebrovascular accident, increased thirst, muscle cramps, neck pain, pallor, prostatic disease, restlessness, syncope, weight loss

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions 

Alcohol (Ethyl): May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased.Risk C: Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Risk D: Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Vasodilators (Organic Nitrates). Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Vasodilators (Organic Nitrates). Risk X: Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Risk D: Consider therapy modification

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

Rilmenidine: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy

Riociguat: Vasodilators (Organic Nitrates) may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination

Rosiglitazone: Vasodilators (Organic Nitrates) may enhance the adverse/toxic effect of Rosiglitazone. Specifically, a greater risk of ischemia and other adverse effects has been associated with this combination in some pooled analyses. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

St John’s Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Monitoring Parameters

Blood pressure, heart rate

Advanced Practitioners 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.

Nursing Physical Assessment/Monitoring

Tolerance to nitrates will develop and proper timing of doses is needed to minimize tolerance. Monitor for hypotension and GI disturbance when beginning therapy, when dose is adjusted, and at regular intervals during therapy. Teach patient importance of maintaining dosing schedule.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 10 mg, 20 mg

Tablet Extended Release 24 Hour, Oral:

Generic: 30 mg, 60 mg, 120 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Imdur: 60 mg

Generic: 60 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • C01DA14
Generic Available (US)

Yes

Pricing: US

Tablet, 24-hour (Isosorbide Mononitrate ER Oral)

30 mg (per each): $0.52 – $3.35

60 mg (per each): $0.54 – $4.28

120 mg (per each): $0.73 – $8.80

Tablets (Isosorbide Mononitrate Oral)

10 mg (per each): $0.51 – $0.85

20 mg (per each): $0.41 – $0.89

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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 to 45 minutes (Thadani 1987)

Duration: Immediate release: ≥6 hours (Thadani 1987); Extended release: ≥12 to 24 hours (Anderson 2007)

Absorption: Rapid and complete

Distribution: Vd: ~0.6 L/kg

Protein binding: <5%

Metabolism: Hepatic

Bioavailability: ~100%

Half-life elimination: 5 to 6 hours (Thadani 1987)

Time to peak, plasma: 30 to 60 minutes

Excretion: Predominantly urine (2% as unchanged drug); feces (1%)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Imdur; ISMN

FDA Approval Date
December 30, 1991
References

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi:10.1111/jgs.13702.[PubMed 26446832]

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.[PubMed 17692738]

Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Philadelphia, PA: American College of Physicians; 2007.

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.[PubMed 9935041]

Colucci WS. Use of beta blockers in heart failure with reduced ejection fraction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 7, 2018.

Flaherty JT, “Hemodynamic Attenuation and the Nitrate Dose-Free Interval: Alternative Dosing Strategies for Transdermal Nitroglycerin,” Am J Cardiol, 1985, 56(17):321-71.[PubMed 3895880]

Fihn SD, Gardin JM, Abrams J, et al, “2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons,” Circulation, 2012, 126(25):3097-137.[PubMed 23166211]

Gersh BJ, Maron BJ, Bonow RO, et al, “2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 124(24):e783-831.[PubMed 22068434]

Gottlieb SS. Pharmacologic therapy of heart failure with reduced ejection fraction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 7, 2018.

Gunasekara NS, Noble S, Isosorbide 5-Mononitrate – a review of a sustained-release formulation (Imdur) in stable angina pectoris. Drugs. 1999;57(2):261-277.[PubMed 10188765]

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.[PubMed 11738322]

Imdur (isosorbide mononitrate) [product monograph]. Oakville, Ontario, Canada: MDA Inc; August 2018.

Isosorbide mononitrate tablets [prescribing information]. Parsippany, NJ: Actavis Pharma Inc.; January 2015.

Isosorbide mononitrate extended-release tablets [prescribing information]. Pennington, NJ: Zydus Pharmaceuticals USA Inc.; May 2015.

Kalidindi M, Velauthar L, Khan K, et al, “The Role of Nitrates in the Prevention of Preeclampsia: An Update,” Curr Opin Obstet Gynecol, 2012, 24(6):361-7.[PubMed 23108288]

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.[PubMed 20956226]

Parker JO, “Eccentric Dosing With Isosorbide-5-Mononitrate in Angina Pectoris,” Am J Cardiol, 1993, 72(12):871-6.[PubMed 8213541]

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.[PubMed 3574424]

Ramirez MM, “Labor Induction: A Review of Current Methods,” Obstet Gynecol Clin North Am, 2011, 38(2):215-25.[PubMed 21575797]

Rangel-Castilla L, Gopinath S, Robertson CS. Management of intracranial hypertension. [published correction appears in Neurol Clin. 2008;26(3):xvii]. Neurol Clin. 2008;26(2):521-41, x.[PubMed 18514825]

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.[PubMed 3595067]

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.[PubMed 11547718]

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.2013;62(16):e147-239. doi: 10.1016/j.jacc.2013.05.019.[PubMed 23747642]

Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776-803. doi: 10.1016/j.jacc.2017.04.025.[PubMed 28461007]

Brand Names: International

AngiFix (BD); Angifree SR (LK); Angirest (EG); Angisor (BD); Angistad (PH); Angitrate (ZA); Apo-ISMN (HK); Cardismo (ID); Cardisorb (HU); Cardoxx (HR); Cincordil (BR); Conpin (DE); Corangin (CH, NZ); Corangin SR (TW); Coronur (ES); Coronur Retard (ES); Coxine (TW); Coxine SR (TW); Danlixin (CN); Duride (AU, NZ, TW); Effox (EG, PL); Elan (IT); Elantan (AE, AT, CR, CZ, DE, DO, EC, GT, HN, ID, IE, JO, KR, LU, MX, MY, NI, PA, PE, PH, PK, SG, SV, VE); Elantan LA (MY); Elantan Long (CZ, DE, LT, MY, PH, SG); Elonton SR (KR); Imdex (HK, TH); Imdex CR (MY, SG); Imdur (AE, BF, BH, BJ, CI, CN, CY, DK, EE, EG, ET, GB, GH, GM, GN, HK, ID, IE, KE, KW, LK, LR, LU, LV, MA, ML, MR, MT, MU, MW, NE, NG, PH, PT, SA, SC, SD, SE, SG, SL, SN, TN, TR, TZ, UG, VN, ZM, ZW); Imdur 60 (MX, TW); Imdur Durules (AU, KR); Imtrate (NZ); Ismexin (FI); ISMN (AT, DE); ISMN AL (HU); ISMN Genericon (HR); ISMN Pharmavit (HU); Ismo (AE, LU, SA); ISMO (CL, DK, GB, IE, IS, IT, NL, SE); Ismo 20 (BB, BM, BS, BZ, GY, IN, JM, MY, NZ, PR, SR, TH, TT, TW, ZA); Ismo-20 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Ismodin (PH); Ismox (FI); Isobid (KR); Isocard (HR); Isolan (AR); Isomel (IE); Isomon (GR); Isomonat (AT, CZ); Isomonit (AU, DE, IE, LU, PL); Isomonit Retard (VN); Isonate (PH); Isopen-20 (TH); Isorat (TR); Isosorbide (CY, HR); Isospan SR (HU); Isotril ER (KR); MNI (PY); Monicor (FR, LK); Monis (CO); Monis-XR (PH); Monit (BD); Monit 20 (IN); Mono Corax (DE); Mono Corax Retard (DE); Mono Mack (CY, HU, LU, MX); Mono-Mack (CZ); Mono-Sanorania (DE); Monobide (EC); Monocinque (LB); Monocinque Retard (LB); Monoclair (DE); Monocord 40 (IL); Monocord 50 SR (IL); Monodur Durules (AU); Monoket (IT, NO, PY, SE, UY); Monoket OD (SE); Monoket Retard (AT, IT); Monolong (DE); Mononit (PE, PL); Monopront (FI); Monorem (TR); Monosan (RU, UA); Monosorb (TH); Monosorbitrate (IN); Monosordil (GR); Monotab (SK); Monotrate (IN); Monotrate OD (LK); Montra (PH); Nitramin (GR); Olicard (BG, HR, HU, RO, UA); Pentacard (BE, ID); Rangin (HU); Solotrate (TH); Solotrate SR (LK); Sorbimon (HU); Sorbinate SR (TH); Sormon (IE); Trangina XL (MT); Unicard (BD); Uniket (ES); Vasotrate (IN, PH); Vasotrate-60 OD (PH); Vasotrate-OD (SG); Vasotrol (VN); Xismox XL (GB)

Isosorbide Mononitrate (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(eye soe SOR bide mon oh NYE trate)

Brand Names: Canada

Imdur

What is this drug used for?
  • It is used to prevent chest pain.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to isosorbide mononitrate or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Avanafil, riociguat, sildenafil, tadalafil, or vardenafil.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this drug affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Have your blood pressure checked often. Talk with your doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Talk with your doctor before you drink alcohol.
  • If you are taking this drug for chest pain, it will not treat chest pain as it happens. This drug is only used to prevent or lower the number of chest pain attacks.
  • If you have been taking this drug for a long time without a break, it may not work as well. This is known as tolerance. Be sure to have a “nitrate-free” period of time each day. Talk with your doctor if this drug stops working well. Do not take more than ordered.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Extended-release tablets:
  • You may see something that looks like the tablet in your stool. This is normal and not a cause for concern. If you have questions, talk with your doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Chest pain or pressure lasting more than 15 minutes. Get emergency medical care right away.
  • Very bad dizziness or passing out.
  • Fast or slow heartbeat.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • You may have headaches when you start taking this drug. Most of the time it gets better with time. Do not change how you use this drug to avoid these headaches. Talk with your doctor for ways to lessen this side effect.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Extended-release tablets:
  • If you are taking this drug once a day, take it in the morning when you get up unless your doctor tells you otherwise.
  • Swallow whole. Do not chew, break, or crush.
  • Some products may be broken in half. Talk with the doctor.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.