Isordil

Isordil (isosorbide mononitrate/dinitrate) is a cornerstone prophylactic and therapeutic agent in the management of angina pectoris. As a potent vasodilator primarily affecting venous capacitance vessels, it effectively reduces cardiac preload and myocardial oxygen demand, thereby preventing ischemic episodes. Its well-established pharmacokinetic profile and predictable efficacy make it a first-line option for patients requiring long-term antianginal therapy. This detailed monograph provides a comprehensive overview for healthcare professionals to ensure optimal patient outcomes.

Features

• Active Pharmaceutical Ingredient: Isosorbide Mononitrate or Isosorbide Dinitrate
• Pharmacologic Class: Organic Nitrate Vasodilator
• Available Formulations: Sublingual tablets, chewable tablets, oral tablets, and extended-release capsules
• Mechanism of Action: Bioconversion to nitric oxide, activating guanylyl cyclase, increasing cyclic GMP, leading to venous and arterial vasodilation
• Primary Indication: Prophylaxis and treatment of angina pectoris attacks
• Standard Dosing Schedules: Multiple daily dosing or once-daily for some extended-release formulations

Benefits

• Proven Reduction in Anginal Frequency and Severity: Significantly decreases the number of angina attacks and sublingual nitroglycerin consumption.
• Enhanced Exercise Tolerance: Allows patients to engage in physical activity for longer durations before the onset of anginal symptoms by reducing cardiac workload.
• Rapid Onset of Action (Sublingual/Chewable Forms): Provides prompt symptomatic relief during acute anginal episodes, typically within 2-5 minutes.
• Flexible Dosing Regimens: Availability of multiple formulations allows for tailored treatment plans based on individual patient needs and severity of condition.
• Long-Term Cardiovascular Management: Effective for chronic prophylaxis, helping to maintain stable coronary artery disease and improve quality of life.
• Well-Characterized Safety Profile: Decades of clinical use have established a clear understanding of its effects, interactions, and management of adverse events.

Common use

Isordil is primarily indicated for the prevention and treatment of angina pectoris due to coronary artery disease. Its use is central to the long-term management of chronic stable angina, where it serves to prevent predictable ischemic episodes, such as those triggered by exertion or stress. The sublingual and chewable formulations are employed for the acute resolution of an ongoing anginal attack. Furthermore, it may be used as part of a combination therapy regimen with other antianginal agents like beta-blockers or calcium channel blockers when monotherapy provides insufficient symptomatic control. Its role is prophylactic and therapeutic, not for the immediate treatment of acute coronary syndromes like myocardial infarction.

Dosage and direction

Dosage is highly individualized based on the specific formulation, patient response, and the presence of hemodynamic tolerance.

• Isosorbide Dinitrate (acute attack): Sublingual tablet, 2.5 to 5 mg at the onset of an attack. May be repeated every 5 to 10 minutes for a maximum of 3 doses in a 15-30 minute period. If pain persists, emergency medical attention is required.
• Isosorbide Dinitrate (prophylaxis): Oral tablets, typically 5 to 40 mg administered two to three times daily. A key dosing strategy involves providing a daily 10-12 hour nitrate-free interval (e.g., last dose at 6 PM, first dose at 7 AM) to prevent tolerance.
• Isosorbide Mononitrate (prophylaxis): Standard tablets are given twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to maintain a daily nitrate-low period. Extended-release formulations are typically administered once daily in the morning.
• Administration: Sublingual tablets must be placed under the tongue and allowed to dissolve completely without swallowing. Chewable tablets should be chewed thoroughly and not swallowed whole. Oral tablets should be swallowed whole with a half glass of water, with or without food, but consistency is key.

The dose must be carefully titrated starting from the lowest possible dose to achieve the desired therapeutic effect while minimizing side effects like headache and hypotension.

Precautions

• Tolerance Development: Continuous, around-the-clock dosing leads to rapid tolerance and loss of clinical effect. A dosing schedule that incorporates a nitrate-free interval is mandatory for long-term efficacy.
• Hypotension: Severe hypotension, particularly orthostatic hypotension, may occur, especially shortly after dose initiation or following a dose increase. Patients should be cautioned to rise slowly from a sitting or lying position.
• Paradoxical Bradycardia and Angina: Excessive hypotension may provoke a reflex tachycardia and, in rare cases, worsened angina pectoris.
• Hypertrophic Cardiomyopathy (HOCM): Nitrates may exacerbate outflow tract obstruction in patients with HOCM and are generally contraindicated.
• Headache: A very common, dose-related side effect that usually diminishes with continued therapy. Abruptly stopping treatment can lead to rebound angina.
• Use in Specific Populations: Use with extreme caution in patients with hypovolemia, inferior wall MI with right ventricular involvement, or increased intracranial pressure (e.g., after head trauma or cerebral hemorrhage).

Contraindications

• Known hypersensitivity to isosorbide mononitrate, isosorbide dinitrate, other nitrates, or any component of the formulation.
• Concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or soluble guanylate cyclase (sGC) stimulators (e.g., riociguat). This combination can cause profound, life-threatening hypotension.
• History of increased intracranial pressure, severe anemia, or closed-angle glaucoma.
• Cardiogenic shock or marked hypotension (systolic BP < 90 mmHg).
• Circulatory failure and constrictive pericarditis.

Possible side effect

The majority of adverse reactions are dose-dependent and linked to its vasodilatory properties.

• Very Common (>10%): Headache (often pulsating and persistent), dizziness, lightheadedness, orthostatic hypotension.
• Common (1-10%): Flushing, reflex tachycardia, nausea, vomiting, weakness, syncope (fainting).
• Uncommon (0.1-1%): Dermatitis, rash, exfoliative dermatitis.
• Rare (<0.1%): Methemoglobinemia (more common with overdose), severe hypotension leading to shock, blurred vision, dry mouth.

Drug interaction

• PDE-5 Inhibitors (Sildenafil, Tadalafil, Vardenafil): Absolute Contraindication. Risk of severe hypotension, syncope, myocardial infarction, or stroke.
• Other Vasodilators (e.g., Alpha-blockers, CCBs, other nitrates): Additive hypotensive effects. Requires careful hemodynamic monitoring.
• Antihypertensive Agents: Enhanced blood-pressure-lowering effect. Dosage of the antihypertensive may need adjustment.
• Alcohol: Potentiates vasodilation and orthostatic hypotension.
• Dihydroergotamine: Isordil may decrease the vasoconstrictive effect of dihydroergotamine.
• Sympathomimetics (e.g., Epinephrine, Norepinephrine): May partially counteract the antianginal and hypotensive effects of Isordil.

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered.
• However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should never take a double dose to make up for the missed one.
• It is critical to maintain the prescribed nitrate-free interval. Taking a dose too close to the next one disrupts this interval and can accelerate the development of tolerance.

Overdose

Nitrate overdose is characterized by severe, life-threatening hypotension and its sequelae.

• Signs/Symptoms: Vertigo, syncope, persistent throbbing headache, palpitations, visual disturbances, nausea/vomiting, diaphoresis (cold sweat), cyanosis with methemoglobinemia, syncope, seizures, coma. Death can occur from circulatory collapse.
• Management: Immediate medical attention is required. Primary treatment is to place the patient in a supine position with legs elevated to promote venous return. Administer IV fluids for volume expansion. If hypotension persists, alpha-adrenergic agonists (e.g., phenylephrine) may be considered. Avoid epinephrine. Methemoglobinemia exceeding 30% should be treated with methylene blue (1-2 mg/kg IV over 5 minutes). Supportive care is essential.

Storage

• Store at room temperature (20°-25°C or 68°-77°F), protected from light, moisture, and heat.
• Keep in the original container with the cap tightly closed. Sublingual tablets are particularly susceptible to degradation by moisture and must be kept in their original glass container.
• Do not store in the bathroom or kitchen.
• Keep all medications out of the reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain. Dispose of unused medication through a official medicine take-back program.

Disclaimer

This information is intended for educational purposes and for use by qualified healthcare professionals only. It is a summary and does not contain all possible information about this product. It does not constitute medical advice and must not be used for diagnosis or treatment of any medical condition. The prescriber must rely on their own professional knowledge, clinical experience, and a complete evaluation of the individual patient to determine the correct diagnosis, appropriate drug, dose, and therapy. Always inform your healthcare provider of all medical conditions and all medications you are taking, including prescription, over-the-counter, vitamins, and herbal products.

Reviews

• “Isordil remains a foundational therapy in our cardiology practice. Its predictable hemodynamic effects and flexible dosing make it indispensable for managing chronic stable angina. The challenge of tolerance is well-managed with asymmetric dosing.” – Cardiologist, 15 years experience
• “From a clinical pharmacy perspective, patient education is paramount with this drug. Ensuring they understand the dosing schedule, the reason for the ‘drug-free’ window, and the critical interaction with ED medications dramatically improves safety and efficacy.” – Clinical Pharmacist, Hospital Setting
• “As a patient, it took a week for the initial headaches to subside, but the freedom from constant fear of an angina attack has been life-changing. I can now garden and walk my dog without pain.” – Patient with CAD for 8 years
• “The sublingual formulation’s rapid action is highly effective for aborting acute attacks. It’s a reliable tool that our patients can carry with them for immediate relief, providing significant peace of mind.” – General Practitioner