Concurrent Use of Isosorbide Mononitrate and Nitroglycerin Patch
Yes, you can use isosorbide mononitrate together with a nitroglycerin transdermal patch, but you must structure the dosing to provide a nitrate-free interval of at least 10-14 hours daily to prevent tolerance, and you must carefully monitor for additive hypotensive effects. 1, 2
Rationale for Combined Nitrate Therapy
- The American Heart Association guidelines support using long-acting nitrates like isosorbide mononitrate for angina relief, particularly when β-blockers are contraindicated or for combination therapy with β-blockers for synergistic anti-ischemic effects. 1
- Both medications work through the same mechanism—promoting nitric oxide release to cause vasodilation of veins, arteries, and arterioles, reducing preload and afterload while decreasing myocardial oxygen requirements. 2
- The combination provides extended anti-anginal coverage when properly timed, but requires strategic dosing to avoid continuous 24-hour nitrate exposure. 1, 2
Critical Dosing Strategy to Prevent Tolerance
You must provide a nitrate-free interval of at least 10-14 hours daily to maintain efficacy and prevent tolerance development. 1, 2, 3
Recommended Dosing Schedule:
- Apply the nitroglycerin patch in the morning and remove it 12 hours later (typically at bedtime), providing a 12-hour patch-free interval overnight. 4
- Dose isosorbide mononitrate once daily in the morning (20-60 mg) OR twice daily with morning and early afternoon dosing (e.g., 8 AM and 2 PM), ensuring the second dose is at least 6-8 hours before bedtime. 1, 5, 6
- This schedule ensures a nitrate-free period during nighttime hours when most patients experience fewer angina attacks, while optimizing nitrate sensitivity during daytime. 4
Why This Matters:
- Tolerance to hemodynamic effects typically develops after 24 hours of continuous nitrate therapy, resulting in complete loss of anti-ischemic effects. 2, 6, 7
- Without a nitrate-free interval, you will experience progressive loss of therapeutic benefit from both medications within 24-48 hours. 3, 7
- The nitrate-free interval restores nitrate sensitivity and maintains long-term efficacy. 6, 8
Critical Safety Monitoring
Monitor blood pressure closely, especially during the first week of combined therapy, as additive hypotensive effects can cause reflex tachycardia and paradoxically worsen myocardial ischemia. 2
Specific Blood Pressure Parameters:
- Avoid systolic BP <90 mmHg or >30 mmHg below baseline. 3
- In previously normotensive patients, do not allow systolic BP to drop below 110 mmHg. 3
- In hypertensive patients, do not reduce mean arterial pressure by >25%. 3
High-Risk Situations Requiring Extreme Caution:
- Right ventricular infarction or inferior wall MI with RV involvement—these patients depend on adequate RV preload and can experience profound hypotension with nitrate therapy. 2, 3
- Patients taking phosphodiesterase inhibitors—sildenafil must not be used within 24 hours of nitrate administration, and tadalafil must not be used within 48 hours, due to risk of life-threatening hypotension. 2, 5
Management of Common Side Effects
- Headaches are the most frequent side effect and typically diminish after several days of continued use. 2, 9
- Hypotension can be managed by dose adjustment, leg elevation, rapid fluid administration, or atropine if severe. 2, 3
- Dizziness related to blood pressure changes is common and may require dose reduction. 2
Alternative Approach if Tolerance Develops
If you develop tolerance despite proper dosing intervals, consider:
- Reducing to single daily dosing of isosorbide mononitrate (40-60 mg once daily in the morning) while continuing intermittent patch use. 5, 6
- Combining nitrates with a different class of antianginal agent (β-blocker or calcium channel blocker) rather than using two nitrate preparations. 1, 8
- Switching to twice-daily isosorbide mononitrate alone (morning and early afternoon) without the patch, which provides adequate coverage for most patients. 5, 8