Nitrostat Drug Interactions: What to Avoid and What to Tell Your Doctor

Nitrostat (nitroglycerin sublingual tablets) is a powerful vasodilator — and that power comes with serious interaction risks. Certain drugs, when combined with Nitrostat, can cause catastrophic drops in blood pressure. Others reduce its effectiveness. Knowing what to avoid can be life-saving.

Always tell every provider you see about all medications, supplements, and recreational drugs you use — including those prescribed by other specialists. Drug interactions with nitroglycerin can be life-threatening.

CONTRAINDICATED: PDE-5 Inhibitors (Absolutely Do Not Combine)

This is the most critical drug interaction with Nitrostat. PDE-5 inhibitors, commonly prescribed for erectile dysfunction and pulmonary hypertension, are absolutely contraindicated with all forms of nitroglycerin.

Sildenafil (Viagra, Revatio): Contraindicated. Do not take Nitrostat within 24 hours of sildenafil.

Tadalafil (Cialis, Adcirca): Contraindicated. Do not take Nitrostat within 48 hours of tadalafil. (Tadalafil stays in the body longer than other PDE-5 inhibitors.)

Vardenafil (Levitra, Staxyn): Contraindicated. Do not take Nitrostat within 24 hours of vardenafil.

Avanafil (Stendra): Contraindicated. Do not take Nitrostat within 24 hours of avanafil.

Why? PDE-5 inhibitors increase levels of cGMP — the same chemical messenger that nitroglycerin amplifies. Combining them creates an additive vasodilation effect that can cause sudden, severe hypotension (dangerously low blood pressure), syncope (fainting), heart attack, or death.

If you have angina and erectile dysfunction, talk with your cardiologist about safe management of both conditions — do not try to manage this on your own.

CONTRAINDICATED: Riociguat (Adempas)

Riociguat (Adempas) is a soluble guanylate cyclase (sGC) stimulator used for pulmonary arterial hypertension. Like PDE-5 inhibitors, it amplifies the cGMP pathway. Combining riociguat with any nitrate, including Nitrostat, is contraindicated due to the risk of severe hypotension.

AVOID: Ergot Alkaloids

Ergot alkaloids — medications derived from ergot fungus used to treat migraines — interact with nitroglycerin in two problematic ways: nitroglycerin can increase ergotamine levels (increasing the risk of ergot toxicity, including serious arterial spasm), while ergot alkaloids can reduce nitroglycerin's antianginal effectiveness. Avoid combining.

Ergotamine (Cafergot, Ergomar)

Dihydroergotamine (DHE-45, Migranal)

Methylergonovine (used postpartum)

USE CAUTION: Blood Pressure Medications

Nitrostat lowers blood pressure. When combined with other antihypertensive medications, the cumulative effect can be more pronounced than intended:

Beta-blockers (metoprolol, atenolol, carvedilol)

Calcium channel blockers (amlodipine, diltiazem, verapamil)

ACE inhibitors and ARBs (lisinopril, losartan, etc.)

Alpha-blockers (doxazosin, tamsulosin — often used for prostate conditions)

This combination isn't necessarily contraindicated — many patients with angina are on blood pressure medications — but you should be aware of the additive hypotension risk and always sit or lie down when taking Nitrostat.

USE CAUTION: Alcohol

Alcohol is a vasodilator in its own right. Drinking alcohol while using Nitrostat can significantly increase the blood pressure-lowering effect, raising the risk of severe dizziness, lightheadedness, and falls. Avoid alcohol use around the time you take Nitrostat.

REDUCED EFFECTIVENESS: Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) such as amitriptyline, desipramine, and doxepin cause dry mouth as a side effect, which reduces saliva production. Since Nitrostat depends on dissolution in saliva to be absorbed sublingually, dry mouth can significantly slow or reduce absorption — meaning the drug may not work as well or as quickly. If you have dry mouth, drinking a small amount of water before taking Nitrostat can help.

What to Tell Every Doctor You See

Tell all your providers that you use nitroglycerin — including dentists, urologists, ophthalmologists, and any telehealth providers. The interaction with PDE-5 inhibitors is so dangerous that it must be disclosed in every clinical encounter. For complete side effect information, see: Nitrostat Side Effects: What to Expect and When to Call Your Doctor. If you need help finding Nitrostat near you, visit medfinder.com.