Why Nitroglycerin Drug Interactions Matter

Nitroglycerin lowers blood pressure by relaxing blood vessels. This means any other medication or substance that also lowers blood pressure can create a dangerous additive effect. Some interactions are life-threatening, while others simply require monitoring.

Before starting Nitroglycerin, it's essential to give your doctor a complete list of everything you take — including prescription drugs, over-the-counter medications, supplements, and alcohol use. If you're new to this medication, read our overview of what Nitroglycerin is and how it's used.

Contraindicated Interactions (Never Combine)

These interactions are so dangerous that Nitroglycerin must never be used with these medications:

PDE5 Inhibitors — CONTRAINDICATED

This is the most critical Nitroglycerin interaction. PDE5 inhibitors include:

• Sildenafil (Viagra, Revatio)
• Tadalafil (Cialis, Adcirca)
• Vardenafil (Levitra, Staxyn)
• Avanafil (Stendra)

Why it's dangerous: Both Nitroglycerin and PDE5 inhibitors work on the same cGMP pathway that controls blood vessel relaxation. Nitroglycerin increases cGMP while PDE5 inhibitors block its breakdown. Together, they cause extreme, potentially fatal drops in blood pressure. For more on the science, see our article on how Nitroglycerin works.

Timing matters:

• Do not take Nitroglycerin within 24 hours of sildenafil or vardenafil
• Do not take Nitroglycerin within 48 hours of tadalafil (it has a longer half-life)
• If you're in the ER with chest pain and have recently taken a PDE5 inhibitor, tell the medical team immediately

Riociguat (Adempas) — CONTRAINDICATED

Riociguat, used for pulmonary hypertension, also works through the cGMP pathway. Like PDE5 inhibitors, combining it with Nitroglycerin can cause severe hypotension. This combination is absolutely prohibited.

Major Drug Interactions (Use With Extreme Caution)

Other Blood Pressure Medications

Nitroglycerin combined with other antihypertensives can cause additive blood pressure lowering. While these combinations are sometimes used together under medical supervision, they require careful monitoring:

• ACE inhibitors (lisinopril, enalapril, ramipril)
• ARBs (losartan, valsartan)
• Calcium channel blockers (amlodipine, diltiazem, verapamil)
• Beta-blockers (metoprolol, atenolol, carvedilol)
• Diuretics (furosemide, hydrochlorothiazide)

If you take any of these with Nitroglycerin, monitor for signs of low blood pressure: dizziness, lightheadedness, fainting, or blurred vision.

Alcohol

Alcohol is a vasodilator — it widens blood vessels on its own. Combined with Nitroglycerin, even moderate alcohol consumption can cause:

• Severe dizziness
• Fainting
• Dangerous drops in blood pressure
• Rapid heartbeat

Recommendation: Avoid alcohol while using Nitroglycerin, or at minimum discuss safe limits with your doctor. Even small amounts can amplify Nitroglycerin's blood pressure-lowering effects.

Ergot Alkaloids

Medications containing ergotamine (used for migraines) can have antagonistic effects on coronary arteries when combined with Nitroglycerin. These include:

• Ergotamine (Cafergot)
• Dihydroergotamine (Migranal)

The interaction can reduce the effectiveness of both medications on coronary blood flow.

Alteplase (tPA)

Sublingual Nitroglycerin may reduce the thrombolytic (clot-busting) effect of alteplase. This is primarily a concern in hospital settings during treatment of heart attacks or strokes.

Heparin

Nitroglycerin may reduce heparin's anticoagulant effect. Patients receiving both medications (typically in hospital settings) may need heparin dose adjustments and closer monitoring of coagulation tests.

Moderate Drug Interactions

These interactions are manageable but require awareness:

Tricyclic Antidepressants

TCAs like amitriptyline, nortriptyline, and imipramine can cause orthostatic hypotension on their own. Adding Nitroglycerin increases this risk. Stand up slowly and watch for dizziness.

Phosphodiesterase Inhibitors for Pulmonary Hypertension

Beyond the PDE5 inhibitors used for erectile dysfunction, similar drugs are used for pulmonary arterial hypertension (PAH). Sildenafil (marketed as Revatio for PAH) and tadalafil (marketed as Adcirca for PAH) carry the same contraindication with Nitroglycerin regardless of the indication they're prescribed for.

Other Nitrates

Taking multiple nitrate medications (e.g., Nitroglycerin patches plus isosorbide mononitrate) increases the risk of excessive blood pressure lowering and tolerance. Your doctor will manage your nitrate regimen carefully if multiple forms are needed.

Food and Supplement Interactions

Alcohol (Repeated for Emphasis)

This interaction is significant enough to mention again. Alcohol with Nitroglycerin is a dangerous combination that many patients underestimate. Avoid alcohol or discuss strict limits with your doctor.

Grapefruit

While grapefruit is not a major concern with Nitroglycerin specifically (unlike many cardiac medications), it can affect other medications you may be taking alongside Nitroglycerin. Mention grapefruit consumption to your doctor.

What to Tell Your Doctor and Pharmacist

Before starting Nitroglycerin, make sure your healthcare providers know about:

1. All prescription medications — especially blood pressure drugs, PDE5 inhibitors, and blood thinners
2. Over-the-counter medications — including cold medicines, decongestants, and pain relievers
3. Supplements and herbal products — some can affect blood pressure
4. Alcohol use — be honest about frequency and quantity
5. Recreational drugs — particularly those that affect blood pressure or heart rate
6. Any planned procedures — Nitroglycerin can interact with anesthetic agents

Signs of a Dangerous Interaction

Seek emergency medical care if you experience:

• Severe dizziness or fainting
• Blood pressure below 90/60 mmHg with symptoms
• Rapid or irregular heartbeat
• Chest pain that worsens despite taking Nitroglycerin
• Blue discoloration of lips or fingernails
• Confusion or altered consciousness

Managing Your Medications Safely

Living with multiple medications is common for heart patients. Here are tips for staying safe:

• Use one pharmacy for all prescriptions — pharmacists check for interactions automatically
• Keep an updated medication list in your wallet or phone
• Don't start or stop medications without telling your doctor
• Ask your pharmacist about interactions every time you add a new medication
• Wear a medical alert bracelet if you take Nitroglycerin regularly, so emergency responders know

For more on using Nitroglycerin safely, learn about common side effects and when to call your doctor. If you're having trouble finding Nitroglycerin at your pharmacy, check our guide on how to check pharmacy availability or search on MedFinder.