Isordil (isosorbide mononitrate/dinitrate) is a cornerstone prescription medication in the management of angina pectoris, a condition characterized by chest pain due to heart disease. It belongs to the class of drugs known as organic nitrates, which work by systematically dilating blood vessels. This action reduces the heart’s workload and oxygen demand, while simultaneously improving blood flow and oxygen supply to the heart muscle. By effectively preventing and treating angina attacks, Isordil helps patients achieve greater functional capacity and an improved quality of life, allowing for increased physical activity with reduced discomfort.

Features

• Active Pharmaceutical Ingredient: Isosorbide Mononitrate or Isosorbide Dinitrate
• Drug Class: Organic nitrate vasodilator
• Available Formulations: Sublingual tablets, chewable tablets, oral tablets, and extended-release capsules
• Mechanism of Action: Venous and arterial vasodilation via nitric oxide release
• Primary Indication: Prophylaxis and treatment of angina pectoris attacks
• Onset of Action: Sublingual/chewable forms act within 2-5 minutes; oral tablets for prophylaxis
• Duration of Effect: Varies by formulation (short-acting: 2-6 hours; extended-release: up to 12 hours)

Benefits

• Proven Angina Prevention: Significantly reduces the frequency and severity of anticipated angina attacks, allowing for predictable daily planning.
• Rapid Symptom Relief: Sublingual and chewable formulations provide fast-acting relief from acute angina pain, often within minutes of administration.
• Improved Exercise Tolerance: By reducing cardiac preload and afterload, it decreases myocardial oxygen consumption, enabling patients to engage in physical activity with less chest pain.
• Enhanced Quality of Life: Effective angina management reduces the anxiety associated with unpredictable pain episodes, supporting better mental well-being and daily functioning.
• Complementary to Other Therapies: Works synergistically with beta-blockers and calcium channel blockers in a comprehensive anti-anginal regimen.
• Multiple Administration Options: Various formulations allow for tailored treatment plans based on individual patient needs and patterns of angina.

Common use

Isordil is primarily prescribed for the management of coronary artery disease (CAD) manifesting as angina pectoris. Its uses are specifically categorized:

• Prophylactic Treatment: Used on a scheduled basis to prevent angina attacks from occurring. This is the most common use for standard oral tablets and extended-release formulations. Patients with predictable, effort-induced angina (stable angina) take it to allow for physical exertion without pain.
• Acute Treatment: Sublingual or chewable tablets are used to abort an ongoing angina attack, providing rapid relief of chest pain, pressure, or tightness.
• Variant (Prinzmetal’s) Angina: Can be used to prevent coronary artery spasm, which is the underlying cause of this type of angina.
• Chronic Heart Failure (Adjuvant Therapy): While not a first-line treatment, it may be used in combination with other heart failure medications to reduce cardiac workload in certain patients.

It is not intended for the treatment of acute myocardial infarction (heart attack) or for use as a primary antihypertensive.

Dosage and direction

Dosage is highly individualized based on the formulation, severity of angina, and patient response. Always adhere to the specific prescription provided by a physician.

General Guidance:

• Sitting Down: Administer doses while sitting or lying down to minimize the risk of orthostatic hypotension (dizziness upon standing).
• Nitrate-Free Interval: To prevent tolerance (a reduced effect over time), a daily nitrate-low period of 10-14 hours is typically recommended. This often means dosing schedules are arranged so that the last dose of the day is taken in the late afternoon, ensuring overnight coverage is not provided by the nitrate. This does not apply to PRN (as-needed) sublingual use for acute attacks.

Specific Formulations:

• Isosorbide Dinitrate Sublingual Tablets (acute relief): Place tablet under the tongue or in the buccal pouch at the first sign of an angina attack. Dose is usually 2.5 to 5 mg. Do not swallow. May repeat every 5 minutes for a maximum of 3 doses in 15 minutes. If pain persists after 3 doses, seek emergency medical attention.
• Isosorbide Dinitrate Oral Tablets (prophylaxis): Typical starting dose is 5 to 20 mg, taken two or three times daily. The dosing schedule must provide a daily nitrate-free interval.
• Isosorbide Mononitrate Immediate-Release Tablets (prophylaxis): Usually 20 mg taken twice daily, with doses 7 hours apart (e.g., 8 am and 3 pm) to ensure a nitrate-free interval.
• Isosorbide Mononitrate Extended-Release Tablets/Capsules (prophylaxis): Typical dose is 30, 60, or 120 mg taken once daily in the morning. This formulation is designed for once-daily dosing and should not be chewed or crushed.

Precautions

• Hypotension: Isordil can cause severe hypotension, especially shortly after dose initiation or following a dose increase. Symptoms include dizziness, lightheadedness, and fainting. Rise slowly from a sitting or lying position.
• Tolerance: Continuous, around-the-clock exposure leads to tolerance, rendering the drug ineffective. The prescribed nitrate-free interval is critical to maintain efficacy. Do not deviate from the scheduled dosing times.
• Headache: Nitrate-induced headaches are very common, particularly when starting therapy. These often diminish with continued use. Do not stop taking the medication; consult a doctor for pain management options.
• Hypertrophic Cardiomyopathy (HOCM): Use with extreme caution or avoid in patients with HOCM, as nitrates can exacerbate outflow obstruction.
• Hypovolemia: Patients who are dehydrated or have low blood volume are at increased risk of severe hypotension.
• Renal/Hepatic Impairment: Use with caution; while not extensively metabolized, impaired function can alter drug handling. Dose adjustment may be necessary.
• Pregnancy and Lactation: Use only if clearly needed and the potential benefit justifies the potential risk to the fetus. Nitrates are excreted in breast milk; caution is advised.

Contraindications

Isordil is contraindicated and must not be used in patients with:

• Known hypersensitivity to isosorbide mononitrate, isosorbide dinitrate, other nitrates, or any ingredient in the formulation.
• Concurrent use of phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or soluble guanylate cyclase (sGC) stimulators (e.g., riociguat). Concomitant use can cause profound, life-threatening hypotension.
• Severe anemia.
• Increased intracranial pressure (e.g., following head trauma or cerebral hemorrhage).
• Cardiac tamponade or constrictive pericarditis.
• Circulatory failure or states of shock.

Possible side effect

Side effects are dose-related. Common side effects often subside with continued therapy.

• Very Common (>10%): Headache (often throbbing), dizziness, lightheadedness.
• Common (1-10%): Orthostatic hypotension, reflex tachycardia (fast heart rate), flushing, nausea, vomiting.
• Uncommon (0.1-1%): Dermatitis, rash, pruritus (itching), weakness, restlessness.
• Rare (<0.1%): Syncope (fainting), severe hypotension, methemoglobinemia (a blood disorder that reduces oxygen delivery, more common with overdose), exfoliative dermatitis.
• Paradoxical Effects: In rare cases, nitrates may precipitate angina pectoris, particularly in patients with HOCM.

Drug interaction

Isordil has significant interactions that require careful management:

• PDE-5 Inhibitors (e.g., Sildenafil, Tadalafil, Vardenafil): CONTRAINDICATED. Concomitant use can cause severe, potentially fatal hypotension. A minimum separation of 24 hours for short-acting nitrates and 48 hours for long-acting nitrates from PDE-5 inhibitor dosing is required, but avoidance is strongly preferred.
• sGC Stimulators (e.g., Riociguat): CONTRAINDICATED. Risk of catastrophic hypotension.
• Other Vasodilators (e.g., other nitrates, alpha-blockers, ACE inhibitors, ARBs): Additive hypotensive effects. Blood pressure must be monitored closely.
• Phosphodiesterase Inhibitors (e.g., Theophylline, Milrinone): May potentiate vasodilatory effects.
• Calcium Channel Blockers and Beta-Blockers: Additive hemodynamic effects; used together intentionally in angina management but requires monitoring for excessive bradycardia or hypotension.
• Alcohol: Potentiates vasodilation and hypotensive effects. Avoid or limit consumption.
• Dihydroergotamine: Nitrates may increase its bioavailability and ergotism potential.
• Antihypertensives: Additive blood pressure-lowering effect.

Missed dose

• For scheduled (prophylactic) doses: If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose. Do not double the dose to “catch up,” as this will increase the risk of severe side effects like hypotension and headache.
• Crucially: Do not take a missed dose if remembering it would disrupt your prescribed daily nitrate-free interval. Protecting this interval is more important than making up a single dose.
• For PRN (as-needed) sublingual doses: This is only taken during an attack. There is no concept of a “missed dose.”

Overdose

Nitrate overdose is a medical emergency characterized by severe, life-threatening hypotension and its consequences.

• Signs and Symptoms: Profound dizziness, fainting, blurred vision, nausea/vomiting, a feeling of extreme warmth, diaphoresis (sweating), syncope, seizures, signs of inadequate perfusion (paleness, cold/clammy skin), dyspnea (shortness of breath), tachycardia followed by bradycardia, heart palpitations, and methemoglobinemia (presenting as cyanosis - bluish skin - chocolate-brown colored blood, shortness of breath, fatigue, and confusion).
• Action: Seek emergency medical attention immediately. Do not induce vomiting.
• Treatment: Management is primarily supportive. The patient should be placed in a supine position with legs elevated to promote venous return. Administration of intravenous fluids and alpha-adrenergic agonists (e.g., phenylephrine) may be necessary to support blood pressure. Methylene blue is the specific antidote for methemoglobinemia. Hemodialysis is not effective.

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F). Avoid excessive heat and moisture (do not store in bathrooms).
• Protect from light. Keep tablets in their original light-resistant container.
• Sublingual tablets are highly sensitive to air and moisture. Keep the bottle tightly closed immediately after use. Do not put them in pill organizers that are not airtight.
• Keep all medications out of the reach of children and pets.
• Do not use after the expiration date printed on the packaging.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any errors or omissions or for any outcomes related to the use of this information. Drug information may change. Always refer to the official prescribing information provided with your medication.

Reviews

• Cardiologist, 15 years experience: “Isordil remains a fundamental tool in our anti-anginal arsenal. Its dual role for both prophylaxis and acute relief is invaluable. The key to success is patient education on proper dosing schedules to avoid tolerance and managing the initial headaches, which often leads to non-adherence.”
• Clinical Pharmacist: “The drug interaction with PDE-5 inhibitors is one of the most critical counseling points. We reinforce this repeatedly with every male patient receiving a nitrate prescription. Its efficacy is well-established, but its safety profile demands respect and vigilance.”
• Patient A, 68: “The sublingual tablets are a lifesaver. Knowing I have something that can stop the pain in minutes gives me peace of mind to still go for walks with my wife. The daily pills did cause headaches for the first week, but they went away.”
• Patient B, 72: “It took some time to get the dosing schedule right with my doctor. Forgetting the ‘off’ period made the pills stop working. Now that we have a routine, my angina is much better controlled, and I have far fewer episodes.”