What is the difference between Isosorbide Dinitrate (ISDN) and Isosorbide Mononitrate (ISMN)?

From the Guidelines

Isosorbide mononitrate is generally preferred over isosorbide dinitrate for most patients due to its simpler dosing schedule, fewer side effects, and more consistent blood levels. The key differences between isosorbide dinitrate and isosorbide mononitrate lie in their pharmacokinetics and dosing regimens. Isosorbide mononitrate is taken once or twice daily, typically at doses of 30-60mg for extended-release formulations or 20mg twice daily for immediate-release formulations 1. In contrast, isosorbide dinitrate often requires multiple daily doses, typically ranging from 5-40mg taken 2-3 times daily 1.

Pharmacological Differences

The primary pharmacological difference between the two medications is that isosorbide dinitrate is a prodrug that must be converted in the liver to isosorbide mononitrate, which is the active metabolite. This extra conversion step results in a more variable bioavailability for isosorbide dinitrate, approximately 25%, compared to nearly 100% for isosorbide mononitrate 1. Both medications work by releasing nitric oxide, which relaxes blood vessels to improve blood flow to the heart. However, isosorbide mononitrate produces more consistent blood levels and less tolerance development.

Side Effects and Tolerance

Side effects are similar for both medications and include headache, dizziness, and hypotension, though these tend to be less severe with isosorbide mononitrate. For patients with severe or unstable angina, isosorbide dinitrate may sometimes be preferred due to its faster onset of action in certain formulations. The duration of effect for isosorbide dinitrate is up to 8 hours, whether administered orally or in a slow-release formulation 1, while isosorbide mononitrate has a duration of effect ranging from 12 to 24 hours, depending on the formulation 1.

Clinical Considerations

In clinical practice, the choice between isosorbide dinitrate and isosorbide mononitrate should be based on individual patient needs, including the severity of angina, tolerance development, and side effect profiles. Given the more consistent pharmacokinetics and simpler dosing regimen of isosorbide mononitrate, it is generally the preferred option for most patients, unless specific clinical circumstances dictate the use of isosorbide dinitrate.

From the FDA Drug Label

Isosorbide mononitrate (ISMN), an organic nitrate and the major biologically active metabolite of isosorbide dinitrate (ISDN), is a vasodilator with effects on both arteries and veins. The chemical name for isosorbide mononitrate is 1,4:3,6-dianhydro-,D-glucitol 5-nitrate; The chemical name for isosorbide dinitrate is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate.

The main difference between isosorbide dinitrate and isosorbide mononitrate is:

• Chemical structure: Isosorbide mononitrate has one nitrate group, while isosorbide dinitrate has two nitrate groups.
• Metabolism: Isosorbide mononitrate is the major biologically active metabolite of isosorbide dinitrate 2. Key pharmacological differences are not explicitly stated in the provided drug labels. 3

From the Research

Difference between Isosorbide Dinitrate and Isosorbide Mononitrate

• Isosorbide dinitrate and isosorbide mononitrate are both nitrates used to treat angina pectoris, but they have some differences in terms of their pharmacokinetics and clinical effects 4, 5, 6.
• Isosorbide dinitrate is a prodrug that is converted to isosorbide mononitrate in the body, which is the active form of the drug 4.
• Isosorbide mononitrate has a more predictable pharmacokinetic profile and a longer duration of action compared to isosorbide dinitrate 5, 6.
• Studies have shown that once-daily administration of isosorbide mononitrate can prevent the development of tolerance, which is a common problem with nitrate therapy 4, 5, 6, 7.
• Isosorbide mononitrate has been shown to be effective in improving quality of life and reducing angina symptoms in patients with stable angina pectoris 5, 6, 7.
• However, one study found that isosorbide mononitrate had limited effects in patients with microvascular angina and was not well tolerated by many patients 8.

Clinical Effects

• Both isosorbide dinitrate and isosorbide mononitrate have been shown to be effective in reducing angina symptoms and improving exercise tolerance in patients with stable angina pectoris 4, 5, 6, 7.
• Isosorbide mononitrate has been shown to have a rapid onset of action and a long duration of action, making it a convenient option for once-daily administration 5, 6.
• However, the clinical effects of isosorbide mononitrate may be limited in certain patient populations, such as those with microvascular angina 8.

Tolerance and Dosage

• Tolerance to nitrates is a common problem that can limit their effectiveness, but once-daily administration of isosorbide mononitrate can help prevent tolerance 4, 5, 6, 7.
• The optimal dosage of isosorbide mononitrate is not well established, but studies have used doses ranging from 30-100mg once daily 5, 6, 7.
• The dosage of isosorbide dinitrate is typically higher than that of isosorbide mononitrate, and it is often administered multiple times a day 4.