Usage
- This combination is prescribed for the prevention and long-term management of angina pectoris (chest pain) due to coronary artery disease. It helps to prevent heart attacks and strokes in patients with a history of these conditions or unstable angina. It may also be used to reduce the risk of recurrent stroke in patients with a history of ischemic stroke or transient ischemic attack. Aspirin is used to decrease the risk of blood clots and Isosorbide Mononitrate increases blood flow to the heart.
- Pharmacological Classification: Antiplatelet (Aspirin) and Vasodilator/Nitrate (Isosorbide Mononitrate).
- Mechanism of Action: Aspirin inhibits cyclooxygenase, reducing thromboxane A2 production and platelet aggregation. Isosorbide Mononitrate is metabolized to nitric oxide, a potent vasodilator, relaxing vascular smooth muscle and increasing blood flow to the heart.
Alternate Names
- Isosorbide-5-Mononitrate + Aspirin is sometimes used.
- Brand Names: Numerous brand names exist depending on the manufacturer and region. Examples from sources include Aspitrate, Aspitrate G, Imdur (for Isosorbide Mononitrate), Monoket (for Isosorbide Mononitrate), APO-ISOSORBIDE MONONITRATE.
How It Works
- Pharmacodynamics: Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) enzyme, leading to reduced thromboxane A2 synthesis, inhibiting platelet activation and aggregation. Isosorbide Mononitrate dilates coronary arteries and reduces preload and afterload, decreasing myocardial oxygen demand.
- Pharmacokinetics:
- Aspirin: Absorbed rapidly in the stomach and small intestine. Metabolized to salicylic acid in the liver and other tissues. Excreted primarily by the kidneys.
- Isosorbide Mononitrate: Absorbed well from the gastrointestinal tract. Metabolized in the liver. Excreted primarily in urine as metabolites.
- Mode of Action: Aspirin inhibits COX-1 enzyme, responsible for thromboxane A2 production and platelet activation. Isosorbide Mononitrate activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) leading to vasodilation.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Aspirin through COX-1 inhibition reduces thromboxane A2. Isosorbide Mononitrate acts by increasing nitric oxide, which activates guanylate cyclase.
- Elimination Pathways: Both drugs are predominantly eliminated by the kidneys. Aspirin is first metabolized to salicylic acid in the liver.
Dosage
Standard Dosage
Adults:
- Aspirin: Usually 75mg to 325mg orally once daily, depending on indication. For angina prevention, lower doses (75-150mg) are generally recommended.
- Isosorbide Mononitrate:
- Immediate Release: 5-10mg orally twice daily initially (doses 7 hours apart); can be increased to 20 mg twice daily.
- Extended Release: 30-60mg orally once daily in the morning; may be increased up to 120mg (or even 240mg in rare cases) once daily.
Children:
- Use of this combination in children is not routinely recommended, and any use should be carefully considered and supervised by a physician.
Special Cases:
- Elderly Patients: Initiate at the lower end of the dosing range. Close monitoring for side effects is essential.
- Patients with Renal Impairment: Aspirin dosage may need to be reduced. Isosorbide Mononitrate dosage adjustments are typically not necessary but caution is advised.
- Patients with Hepatic Dysfunction: Dosage adjustments may be needed for both drugs. Close monitoring is required.
- Patients with Comorbid Conditions: Dosage adjustments and careful monitoring are required, particularly for patients with hypotension, anemia, hyperthyroidism, glaucoma, active peptic ulcer disease, asthma, or bleeding disorders.
Clinical Use Cases
- Use in intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is generally not indicated for this specific combination, except for aspirin in acute coronary syndromes.
Dosage Adjustments
- Based on patient’s response and tolerance, as well as renal and hepatic function.
Side Effects
Common Side Effects
- Headache (especially with nitrates), dizziness, lightheadedness, nausea, flushing, stomach upset.
Rare but Serious Side Effects
- Bleeding (aspirin), severe hypotension, allergic reactions, signs of gastrointestinal bleeding (aspirin).
Long-Term Effects
- Gastrointestinal issues (aspirin) if high doses are taken chronically. Nitrate tolerance may develop with continuous use.
Adverse Drug Reactions (ADR)
- Severe bleeding, anaphylaxis, angioedema, Reye’s syndrome (aspirin in children).
Contraindications
- Hypersensitivity to aspirin or nitrates, active bleeding, severe asthma, Reye’s syndrome (aspirin in children), severe anemia, hypotension, hypovolemia, concurrent use of PDE-5 inhibitors (e.g., sildenafil, tadalafil) or riociguat.
Drug Interactions
- PDE-5 inhibitors, riociguat, alcohol (enhanced hypotensive effects), anticoagulants/antiplatelets (increased bleeding risk with aspirin), NSAIDs (reduced antiplatelet effect of aspirin, increased risk of GI bleeding), antihypertensives (additive hypotensive effects), methotrexate.
Pregnancy and Breastfeeding
- Pregnancy: Aspirin should be avoided, especially in the third trimester. Isosorbide Mononitrate should be used with caution only if clearly needed.
- Breastfeeding: Aspirin is excreted in breast milk and should be used with caution. It is unknown if isosorbide mononitrate is excreted in breast milk; caution is advised.
Drug Profile Summary
- Mechanism of Action: Aspirin inhibits COX-1, reducing platelet aggregation. Isosorbide Mononitrate dilates blood vessels, reducing myocardial oxygen demand.
- Side Effects: Headache, dizziness, lightheadedness, nausea, flushing, stomach upset, bleeding.
- Contraindications: Hypersensitivity, active bleeding, asthma, Reye’s syndrome, concurrent use of PDE-5 inhibitors.
- Drug Interactions: PDE-5 inhibitors, alcohol, anticoagulants, NSAIDs, antihypertensives.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: See Dosage section above.
- Monitoring Parameters: Blood pressure, heart rate, signs of bleeding, renal and hepatic function in specific populations.
Popular Combinations
- Often used with other antianginal medications like beta-blockers and calcium channel blockers.
Precautions
- Assess for allergies, bleeding disorders, asthma, renal/hepatic impairment.
- Avoid alcohol.
- Caution in pregnancy and breastfeeding.
- Monitor blood pressure and for signs of bleeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aspirin + Isosorbide Mononitrate?
A: Please see the detailed Dosage section above, as it varies based on the formulation of isosorbide mononitrate (immediate release vs. extended release) and patient-specific factors.
Q2: Can patients crush or chew extended-release isosorbide mononitrate?
A: No, extended-release tablets should be swallowed whole. Crushing or chewing can alter the release profile and potentially lead to adverse effects.
Q3: What are the key drug interactions to be aware of with this combination?
A: Co-administration with PDE-5 inhibitors (e.g., sildenafil, tadalafil) or riociguat is contraindicated due to the risk of severe hypotension. Concurrent use with anticoagulants and antiplatelets increases bleeding risk. Alcohol can potentiate the hypotensive effects of both drugs.
Q4: How should nitrate tolerance be managed?
A: Ensure a nitrate-free interval (typically 10-12 hours or overnight) by appropriate dosing scheduling. This helps maintain the drug’s effectiveness.
Q5: Can this combination be used in patients with asthma?
A: Aspirin can exacerbate asthma symptoms and should be used cautiously or avoided in patients with aspirin-sensitive asthma.
Q6: What are the symptoms of an overdose?
A: Aspirin overdose: Tinnitus, hyperventilation, fever, confusion, seizures, coma. Isosorbide Mononitrate overdose: Severe hypotension, reflex tachycardia, dizziness, headache, syncope.
Q7: Is this combination safe during pregnancy?
A: Aspirin is generally avoided, especially in the third trimester. Isosorbide Mononitrate should be used with caution only if the benefits clearly outweigh potential risks to the fetus. Consult with a specialist.
Q8: Are there any dietary restrictions with this medication?
A: Avoiding excessive alcohol consumption is important due to the increased risk of hypotension. No specific dietary restrictions are typically necessary, but patients should be advised to take isosorbide mononitrate on an empty stomach for optimal absorption.
Q9: What should be done if a dose is missed?
A: If a dose of either medication is missed, advise patients to take it as soon as they remember. If it is close to the time for the next dose, they should skip the missed dose and continue with their regular schedule. Doubling up on doses should be avoided.
