Imdur - Drug Monograph

Introduction

Imdur (isosorbide mononitrate) is an organic nitrate vasodilator used primarily in the management of angina pectoris. As a long-acting nitrate derivative, it provides sustained antianginal effects through venous and arterial vasodilation, reducing myocardial oxygen demand and improving coronary blood flow. Imdur represents an important therapeutic option in the comprehensive management of chronic stable angina.

Mechanism of Action

Imdur exerts its pharmacological effects through bioconversion to nitric oxide (NO), which activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) levels in vascular smooth muscle cells. Elevated cGMP promotes dephosphorylation of myosin light chains, resulting in smooth muscle relaxation. This produces:

• Venodilation: Reduces preload and left ventricular end-diastolic pressure
• Arteriodilation: Decreases systemic vascular resistance and afterload
• Coronary vasodilation: Improves blood flow to ischemic myocardial regions

These hemodynamic effects collectively reduce myocardial oxygen consumption while improving oxygen supply, creating a favorable balance in patients with coronary artery disease.

Indications

FDA-approved indications:

• Prevention of angina pectoris due to coronary artery disease

Off-label uses (supported by clinical evidence):

• Adjunctive therapy in congestive heart failure
• Secondary prevention in patients with coronary artery disease

Dosage and Administration

• Initial dose: 30 mg or 60 mg once daily in the morning
• Maintenance dose: 30-120 mg once daily
• Maximum dose: 240 mg daily (rarely used)

• Administer orally with water
• Swallow tablets whole; do not crush or chew
• Take consistently either with or without food
• Dosing should be scheduled to provide a daily nitrate-free interval of 10-14 hours to prevent tolerance

• Hepatic impairment: Use with caution; consider lower starting dose
• Renal impairment: No dosage adjustment required
• Geriatric patients: Start with lower doses (30 mg daily)
• Pediatric patients: Safety and effectiveness not established

Pharmacokinetics

• Nearly complete gastrointestinal absorption
• Bioavailability: Approximately 100%
• Time to peak concentration (Tmax): 30-60 minutes
• Food does not significantly affect absorption

• Volume of distribution: Approximately 0.6 L/kg
• Protein binding: <5%
• Crosses placenta and enters breast milk

• Extensive first-pass metabolism in the liver
• Metabolized via denitration to isosorbide and subsequent glucuronidation
• Primary metabolites: Isosorbide and isosorbide glucuronide

• Half-life: Approximately 5 hours
• Clearance: Primarily hepatic
• Excretion: Primarily renal (95%), with <1% excreted unchanged

Contraindications

• Hypersensitivity to nitrates, nitrites, or any component of the formulation
• Concomitant use with phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil)
• Severe anemia
• Increased intracranial pressure
• Severe hypotension (systolic BP <90 mmHg)
• Circulatory failure and shock
• Constrictive pericarditis and cardiac tamponade
• Hypertrophic obstructive cardiomyopathy

Warnings and Precautions

• Develops with continuous nitrate therapy
• Prevent with daily nitrate-free interval of 10-14 hours
• Cross-tolerance may occur with other nitrates

• May cause severe hypotension, especially with volume depletion
• Use caution in patients with autonomic dysfunction
• Orthostatic hypotension may occur

• Rebound angina may occur during nitrate-free interval
• Gradually reduce dose when discontinuing therapy

• Use with caution in patients with:

- Severe hepatic impairment - Hypertrophic cardiomyopathy - Volume depletion - Right ventricular infarction

• Head trauma or cerebral hemorrhage: May increase intracranial pressure

Drug Interactions

• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil): Profound hypotension, contraindicated
• Other vasodilators (ACE inhibitors, ARBs, calcium channel blockers): Additive hypotension
• Alcohol: Enhanced vasodilation and hypotension
• Antihypertensive agents: Enhanced hypotensive effects

• Aspirin: Increased nitrate bioavailability
• Heparin: Possible reduced anticoagulant effect (monitor PT/INR)
• Sympathomimetics: May reduce antianginal effects

Adverse Effects

• Headache (≈30%)
• Dizziness (≈5%)
• Hypotension (≈5%)
• Flushing (≈5%)
• Nausea (≈3%)

• Severe hypotension
• Syncope
• Methemoglobinemia (rare)
• Paradoxical bradycardia and increased angina
• Anaphylactic reactions
• Dermatitis and exfoliative dermatitis

Monitoring Parameters

• Complete medical history and physical examination
• Blood pressure and heart rate in supine and standing positions
• Assessment of angina frequency and characteristics
• ECG when appropriate
• Liver function tests (in patients with hepatic impairment)

• Blood pressure and heart rate at each visit
• Angina symptom assessment
• Signs of hypotension (dizziness, syncope)
• Headache management and assessment
• Development of tolerance (reduced efficacy)
• Patient adherence to prescribed nitrate-free interval

• Report any signs of hypotension (dizziness, lightheadedness)
• Do not abruptly discontinue medication
• Headache typically diminishes with continued therapy
• Importance of daily nitrate-free interval
• Avoid concomitant use with erectile dysfunction medications

Patient Education

• Take Imdur exactly as prescribed, typically once daily in the morning
• Do not crush, chew, or break tablets
• Rise slowly from sitting or lying position to prevent dizziness
• Headaches are common initially but often improve with continued use
• Never take with medications for erectile dysfunction (Viagra, Cialis, Levitra)
• Keep a diary of angina episodes and medication effectiveness
• Do not stop taking Imdur suddenly without medical supervision
• Store at room temperature away from moisture and heat
• Inform all healthcare providers about Imdur use before any procedure

• Avoid alcohol consumption
• Maintain consistent physical activity within prescribed limits
• Follow heart-healthy diet recommendations
• Recognize and avoid angina triggers
• Seek immediate medical attention for:

- Chest pain not relieved by rest or nitroglycerin - Fainting or severe dizziness - Difficulty breathing

References

1. FDA Prescribing Information: Imdur (isosorbide mononitrate). Revised 2022. 2. Thadani U. Nitrate therapy for stable angina pectoris. N Engl J Med. 2020;382(11):1065-1072. 3. Abrams J. Nitrates in the management of stable angina pectoris. Curr Probl Cardiol. 2021;46(3):100641. 4. Gori T, Parker JD. Nitrate tolerance: a unifying hypothesis. Circulation. 2018;118(19):1951-1960. 5. Tarkin JM, Kaski JC. Vasodilator therapy: Nitrates and nicorandil. Cardiovasc Drugs Ther. 2022;36(2):279-291. 6. American College of Cardiology/American Heart Association Guidelines for the Management of Patients With Chronic Stable Angina. J Am Coll Cardiol. 2021;78(19):e187-e285. 7. Micromedex Solutions: Isosorbide mononitrate. Truven Health Analytics. 2023. 8. Lexicomp Online: Isosorbide mononitrate. Wolters Kluwer Clinical Drug Information. 2023.