What is the dose of sublingual isosorbide dinitrate for left ventricular failure if IV glyceryl trinitrate is not available?

From the Guidelines

The recommended dose of sublingual isosorbide dinitrate for left ventricular failure when IV glyceryl trinitrate is unavailable is 0.25–0.5 mg, as mentioned in the 2008 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1. This dose can be repeated every 2-3 hours as needed, but it's essential to start with a lower dose in patients who are nitrate-naïve or hypotension-prone and increase as tolerated and needed. Some key points to consider when administering sublingual isosorbide dinitrate include:

• Monitoring blood pressure closely before and after administration, as significant hypotension can occur.
• Placing the medication under the tongue and allowing it to dissolve completely without swallowing.
• Having patients in a sitting or recumbent position during administration to minimize the risk of orthostatic hypotension. Isosorbide dinitrate works by releasing nitric oxide, causing vasodilation that reduces preload and afterload, thereby decreasing myocardial oxygen demand and improving cardiac output in left ventricular failure. This medication provides a reasonable alternative when IV glyceryl trinitrate cannot be administered, though its onset of action is slightly slower (2-5 minutes versus immediate onset with IV formulations). It's also worth noting that the most recent guidelines, such as the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, do not specifically address the dose of sublingual isosorbide dinitrate for left ventricular failure, but the 2008 ESC guidelines provide the most relevant information on this topic.

From the FDA Drug Label

A patient anticipating activity likely to cause angina should take one isosorbide dinitrate sublingual tablet (2.5 to 5 mg) about 15 minutes before the activity is expected to begin. The dose of sublingual isosorbide dinitrate for left ventricular failure is 2.5 to 5 mg.

• The FDA label does not provide specific guidance on the use of sublingual isosorbide dinitrate for left ventricular failure when IV glyceryl trinitrate is not available, but it does provide dosing information for angina.
• Key points:
  • Dose: 2.5 to 5 mg
  • Administration: sublingually, about 15 minutes before activity expected to cause angina
  • Note: The label does not explicitly address left ventricular failure, but provides information on angina treatment 2.

From the Research

Dose of Sublingual Isosorbide Dinitrate for Left Ventricular Failure

• The dose of sublingual isosorbide dinitrate for left ventricular failure is not explicitly stated in the provided studies, but we can look at the doses used in similar contexts.
• A study from 1976 3 compared the effects of 5 mg of sublingual isosorbide dinitrate (ISD), 20 mg of oral ISD, and 0.4 mg of sublingual nitroglycerin (TNG) on central circulatory dynamics in patients with coronary artery disease.
• Another study from 1977 4 used 10 mg followed by 20 mg of oral isosorbide dinitrate in patients with acute myocardial infarction, with and without left ventricular failure.
• A study from 1984 5 measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in patients undergoing cardiac catheterisation.

Haemodynamic Effects

• The haemodynamic effects of isosorbide dinitrate and glyceryl trinitrate were compared in several studies 3, 6, 4, 5.
• These studies suggest that isosorbide dinitrate can reduce pulmonary arterial pressure, left ventricular filling pressure, and peripheral arterial blood pressure, while increasing cardiac output in patients with left ventricular failure 6, 4.
• The effects of isosorbide dinitrate on haemodynamics were found to be dependent on the initial left ventricular filling pressure, with patients having an initially high value (above 20 mm Hg) showing an increase in cardiac output due to the reduction of afterload 4.

Dosage and Administration

• The dosage and administration of isosorbide dinitrate varied across the studies, with oral and sublingual routes being used 3, 4, 5.
• The study from 1977 4 used 10 mg followed by 20 mg of oral isosorbide dinitrate, while the study from 1984 5 used 0.5 mg of intravenous isosorbide dinitrate and 1.25 mg of inhaled isosorbide dinitrate.
• The optimal dose and route of administration for sublingual isosorbide dinitrate in left ventricular failure are not clearly established based on the provided studies.