What is the use of Isosorbide dinitrate (ISDN)?

From the Guidelines

Isosorbide dinitrate is recommended for African Americans with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite concomitant use of ACEi (or ARB), beta blockers, and MRA, with a typical oral dosage of 20-40 mg taken 2-3 times daily. The medication works by relaxing blood vessels, allowing more oxygen-rich blood to flow to the heart muscle, and is often used in combination with hydralazine 1. When starting treatment, lower doses are recommended to minimize side effects like headaches and dizziness. Patients should take this medication regularly as prescribed, not just when experiencing symptoms. It's essential to maintain a nitrate-free interval of 10-14 hours daily to prevent tolerance development. Common side effects include headache, dizziness, and lightheadedness, especially when starting therapy. Patients should avoid taking phosphodiesterase inhibitors (like sildenafil) while using isosorbide dinitrate due to the risk of dangerous blood pressure drops 1.

Some key points to consider when prescribing isosorbide dinitrate include:

• The combination of hydralazine and isosorbide dinitrate is appropriate for African Americans with HFrEF who remain symptomatic despite concomitant use of ACEi (or ARB), beta blockers, and MRA 1
• The initial dose of the fixed-dose combination should be 1 tablet containing 37.5 mg of hydralazine hydrochloride and 20 mg of isosorbide dinitrate 3 times daily, with the dose increased to 2 tablets 3 times daily for a total daily dose of 225 mg of hydralazine hydrochloride and 120 mg of isosorbide dinitrate as needed and tolerated 1
• Isosorbide dinitrate can also be used to treat angina, with a typical oral dosage ranging from 5-40 mg taken 2-3 times daily, and sublingual tablets (2.5-5 mg) can be placed under the tongue for rapid relief of acute angina attacks 1
• Patients should be carefully instructed about how to use short-acting nitroglycerin and should have a ‘nitrate free’ interval each day to preserve the therapeutic effects 1

Overall, isosorbide dinitrate is a valuable medication for the treatment of HFrEF and angina, and its use should be guided by the most recent and highest quality evidence, with careful consideration of the patient's individual needs and medical history 1.

From the FDA Drug Label

Isosorbide dinitrate tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

• Indication: Isosorbide dinitrate is used for the prevention of angina pectoris due to coronary artery disease.
• Use in acute angina: It is not recommended for aborting an acute anginal episode due to its slow onset of action 2.

From the Research

Mechanism of Action

• Isosorbide dinitrate primarily causes arterial and venous vasodilation effects, which increases coronary artery blood supply, and decreases cardiac preload and afterload by enhancing nitric oxide (NO) levels 3.
• The drug works by releasing nitric oxide, leading to the relaxation of smooth muscle cells in blood vessels, resulting in vasodilation 4.

Dosage and Efficacy

• Higher than recommended dosage of sublingual isosorbide dinitrate might establish better efficacy for angina pectoris in rare patients 3.
• A study found that patients who did not respond to low doses of isosorbide dinitrate (40 mg/day) may respond to high doses (480 mg/day) and tolerate them, with a significant reduction in the weekly rate of angina attacks 5.
• Isosorbide-5-mononitrate, a metabolite of isosorbide dinitrate, has been shown to have therapeutic benefits in patients with angina pectoris, with significant reductions in the frequency of anginal attacks and consumption of sub-lingual nitrates 6.

Tolerance and Side Effects

• Some patients may develop tolerance to isosorbide dinitrate, requiring increasing doses to achieve the same therapeutic effect 3, 5.
• Common side effects of isosorbide dinitrate include headache, which may improve gradually with continued treatment 6, 7.
• A high proportion of patients with microvascular angina may show intolerance to isosorbide-5-mononitrate, with significant side effects leading to discontinuation of treatment 7.

Clinical Use

• Isosorbide dinitrate is commonly used in the treatment of angina pectoris, particularly in patients with stable effort angina, variant angina, and unstable angina 4.
• The drug may be used in combination with other anti-anginal agents, such as beta-blockers, calcium channel blockers, and antithrombotic agents, to achieve optimal therapeutic effects 4.