Differences Between Isosorbide Dinitrate and Isosorbide Mononitrate
Isosorbide mononitrate (ISMN) is superior to isosorbide dinitrate (ISDN) due to its 100% bioavailability, longer half-life of 4-5 hours, and once-daily dosing convenience, making it more effective for angina management with better patient compliance. 1, 2
Pharmacokinetic Differences
Isosorbide Dinitrate (ISDN)
- Undergoes extensive first-pass metabolism in the liver
- Shorter half-life of 40-90 minutes 1
- Metabolized to two active metabolites: isosorbide-2-mononitrate and isosorbide-5-mononitrate
- Requires multiple daily doses (typically 2-3 times daily)
- Bioavailability is significantly reduced due to first-pass metabolism
Isosorbide Mononitrate (ISMN)
- No first-pass metabolism
- 100% bioavailable after oral dosing 1, 2
- Longer half-life of 4-5 hours 1, 2
- Can be administered once daily (in extended-release formulations)
- Primary active metabolite of ISDN 2
Clinical Efficacy
- ISMN is more cost-effective, requiring doses 1.5-2 times lower than ISDN for equivalent antianginal effects 3
- Extended-release ISMN provides effective antianginal prophylaxis for up to 12 hours after administration 4
- Once-daily ISMN has been shown to be more effective than ISDN 30 mg four times daily in comparative trials 4
- ISMN produces fewer signs of myocardial ischemia compared to ISDN in patients with stable angina 5
Tolerance Development
Both medications require a nitrate-free interval to prevent tolerance:
- A nitrate-free period of at least 10 hours is recommended for both drugs 1, 6
- Extended-release formulations of ISMN are designed to provide appropriate plasma concentration profiles that help minimize tolerance 1
- For transdermal nitroglycerin, patches should be removed during part of the day or at night 1
Side Effects
Both medications share similar side effect profiles:
Practical Considerations
Dosing Convenience
- ISMN extended-release formulations allow for once-daily dosing, improving patient compliance 4, 5
- ISDN typically requires multiple daily doses, which can reduce adherence
Clinical Application Algorithm
- First-line option: Extended-release ISMN once daily (typically 30-60 mg) for patients requiring nitrate therapy
- Alternative option: ISDN if ISMN is unavailable or not tolerated
- For acute angina attacks: Short-acting sublingual nitroglycerin remains the preferred option for immediate relief
Important Caveats
- Both medications require a nitrate-free interval to prevent tolerance development
- Neither should be used concurrently with phosphodiesterase-5 inhibitors due to risk of severe hypotension
- Abrupt discontinuation during long-term nitrate therapy may exacerbate anginal symptoms 4
- Headache is the most common side effect but typically improves with continued therapy 4, 7
In summary, ISMN offers significant advantages over ISDN in terms of pharmacokinetics, dosing convenience, and patient compliance, making it generally the preferred option for long-term nitrate therapy in cardiovascular conditions.