What is the recommended dosage and management of Isosorbide dinitrate (isosorbide dinitrate) for angina pectoris?

Isosorbide Dinitrate Dosage and Management for Angina Pectoris

For angina pectoris, isosorbide dinitrate should be initiated at 5-20 mg orally 2-3 times daily, with maintenance dosing of 10-40 mg 2-3 times daily, ensuring a daily nitrate-free interval of at least 14 hours to prevent tolerance. 1

Dosing Recommendations

• Initial dosing: 5-20 mg orally two to three times daily 1
• Maintenance therapy: 10-40 mg orally two to three times daily 1
• Maximum duration of anti-anginal effect is approximately 8 hours after a single dose, with total daily anti-anginal efficacy limited to about 12 hours 1
• A nitrate-free interval of at least 14 hours daily is essential to minimize tolerance development 1, 2

Administration Schedule

• Optimal dosing regimen provides doses with a nitrate-free interval (e.g., morning, early afternoon, and early evening) 1
• Example regimen: 8 AM, 2 PM, and 6 PM dosing to maintain efficacy while minimizing tolerance 3
• Effects of second and later doses are typically smaller and shorter-lasting than the first dose of the day 1
• Anti-anginal activity begins approximately 1 hour after oral dosing 1

Pharmacodynamics and Duration

• Isosorbide dinitrate has anti-anginal effects lasting up to 8 hours after a single dose 1
• Effects begin approximately 1 hour after administration 1
• In clinical studies, significant anti-anginal effectiveness totaled about 6 hours in a 24-hour period 1
• Controlled trials have shown statistically significant anti-anginal efficacy for only 2 hours after multiple-dose oral administration 1

Mechanism of Action

• Promotes vasodilation of veins, arteries, and arterioles through nitric oxide release 4
• Reduces right and left ventricular preload through peripheral vasodilation 4
• Decreases afterload through arterial vasodilation 4
• Reduces cardiac work and myocardial oxygen requirements 4

Tolerance Management

• Tolerance to hemodynamic effects typically develops after 24 hours of continuous therapy 2
• Providing a nitrate-free interval of at least 14 hours daily helps minimize tolerance 1
• Avoid continuous 24-hour plasma levels which result in refractory tolerance 1
• Lower doses and intermittent dosing help prevent tolerance development 2

Side Effects and Precautions

• Common side effects include headache (most frequent), dizziness, and hypotension 4
• Hypotension may result in reflex tachycardia and potential worsening of myocardial ischemia 4
• Contraindicated when used with phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of profound hypotension 2
• Sildenafil should not be used within 24 hours of nitrate administration 2
• Tadalafil should not be used within 48 hours of nitrate administration 2

Special Populations

• Use with caution in patients with right ventricular infarction, as they depend on adequate RV preload to maintain cardiac output 4
• Exercise caution in patients with inferior wall MI with RV involvement due to risk of profound hypotension 4
• African American patients with heart failure may benefit from combination therapy with hydralazine and isosorbide dinitrate 2
• For African American patients with heart failure, fixed-dose combination starts at 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily 2

Clinical Pearls

• Titrate to the minimum effective dose that produces the desired clinical effect 1
• Higher doses may be required in some patients who don't respond to standard dosing 5
• Isosorbide dinitrate is more effective when administered as part of a regimen that includes a daily nitrate-free interval 1
• Monitor for hypotension, especially when initiating therapy or increasing doses 4