From the FDA Drug Label
The recommended starting dose of isosorbide mononitrate extended-release tablets, USP is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required.
- Maximum dose: The maximum dose of isosorbide mononitrate is 240 mg once daily 1.
- Dose escalation: Attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed 1.
From the Research
The maximum recommended dose of isosorbide mononitrate is 120 mg per day, as supported by the most recent and highest quality study 2.
Key Considerations
- For immediate-release formulations, this dose is typically divided into two or three doses, while extended-release formulations are usually given once daily.
- The usual starting dose is lower, often 20 mg for immediate-release or 30-60 mg for extended-release, with gradual titration to higher doses based on patient response and tolerance.
- It's essential to maintain a nitrate-free interval of at least 10-14 hours daily when using immediate-release formulations to prevent tolerance development, as noted in 3 and 4.
- Extended-release formulations are designed to provide this nitrate-free interval automatically.
Mechanism and Efficacy
- Isosorbide mononitrate works by releasing nitric oxide, causing vasodilation particularly in the venous system, which reduces cardiac preload and myocardial oxygen demand.
- This makes it effective for preventing angina attacks, though it's not typically used for acute angina relief due to its slower onset of action compared to sublingual nitroglycerin.
Safety and Side Effects
- Common side effects include headache, dizziness, and hypotension, which may limit dose escalation in some patients.
- The risk of rebound phenomenon during nitrate withdrawal is a concern, as discussed in 5, but can be lessened by concomitant anti-anginal drugs or avoiding any abrupt decline in blood nitrate concentrations.
Clinical Evidence
- Studies such as 6, 3, and 4 provide insight into the use of nitrates, including isosorbide mononitrate, for angina prevention and the importance of avoiding tolerance.
- The efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris have been demonstrated in clinical trials, such as 2.