Sildenafil Must Never Be Taken with Isosorbide
Sildenafil is absolutely contraindicated with isosorbide or any nitrate medication due to the risk of potentially fatal hypotension. 1, 2, 3
Mechanism of Dangerous Interaction
The combination of these medications creates a dangerous synergistic effect:
- Sildenafil (a PDE5 inhibitor) blocks the breakdown of cGMP in blood vessels
- Isosorbide (a nitrate) increases cGMP production through the nitric oxide pathway
- Together, they cause excessive vasodilation, leading to severe and potentially life-threatening drops in blood pressure 1, 4
FDA Labeling and Guideline Recommendations
Both medications carry explicit contraindications against combined use:
- Sildenafil's FDA label states: "Never take sildenafil tablets with any nitrate medicines" and specifically lists isosorbide mononitrate or dinitrate as contraindicated 2
- Isosorbide's FDA label directly states: "Do not use Isordil Titradose in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil" 3
- Multiple medical societies including the American Urological Association, American College of Cardiology, and American Heart Association all emphasize this absolute contraindication 1
Clinical Evidence of Danger
Research has demonstrated that this combination causes dramatic blood pressure reductions:
- Clinical studies show that when sildenafil is combined with nitrates like isosorbide mononitrate, it produces standing mean maximum reductions in systolic/diastolic BP of -52/-29 mm Hg compared to -25/-15 mm Hg with nitrates alone 4
- This severe hypotension can lead to syncope, myocardial ischemia, stroke, and even death 5
Time Separation Is Not Sufficient
Even taking these medications at different times remains dangerous:
- Patients must wait at least 24 hours after taking sildenafil before using any nitrate medication 1
- For longer-acting PDE5 inhibitors like tadalafil, the waiting period extends to 48 hours 1
Emergency Situations
If a patient on sildenafil experiences a cardiac emergency:
- They must inform medical personnel about recent PDE5 inhibitor use
- Alternative treatments to nitrates must be considered 1
Alternative Options
For patients with both erectile dysfunction and angina requiring nitrates:
- Consultation with a cardiologist to assess whether nitrate therapy can be safely discontinued
- Exploration of alternative treatments for either condition 1
This contraindication is one of the strongest and most consistent in cardiovascular pharmacology, with no exceptions or situations where combined use would be considered safe.