6 Nitroglycerin Interactions and How to Manage Them

The history of nitroglycerin is dynamite, literally. This heart medicine actually got its start as an explosive in the mid-1800s. In fact, it was only after dynamite factory workers reported feeling pain relief on the days that they worked that researchers determined nitroglycerin is an effective treatment for chest pain.

Fast forward to the present, and nitroglycerin (Nitrostat, NitroMist, others) is now commonly used to prevent or treat chest pain caused by coronary artery disease (plaque buildup in your blood vessels). It’s also occasionally used in hospitals to help manage high blood pressure. It works by relaxing your blood vessels and allowing blood to flow more freely.

If you have a history of heart disease or chest pain, this medication might be a part of your regular regimen. Some people use it as under-the-tongue tablets or an oral spray for emergencies. Others apply it regularly as a topical patch.

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Regardless of how you use it, nitroglycerin can be a life-saving medication. But it doesn’t mix well with all medications. Here, we’ll discuss six problematic nitroglycerin interactions to watch for.

1. Erectile dysfunction medications like Viagra

Medications such as Viagra (sildenafil) and Cialis (tadalafil) are go-to choices for erectile dysfunction (ED). But they’re not a good option if you also take nitroglycerin. 

Viagra and Cialis are phosphodiesterase-5 (PDE-5) inhibitors. They relax blood vessels in the penis, allowing for increased blood flow. This makes it easier to get and maintain an erection. But combining PDE-5 inhibitors with nitroglycerin can exaggerate the blood vessel relaxation effect, potentially leading to dangerously low blood pressure, fainting, or heart damage. A recent study also found that combining PDE-5 inhibitors with nitroglycerin was linked to worsening heart problems and even death. You should never take them together — even if you only have nitroglycerin on hand for emergencies.

So what to do if you’re taking nitroglycerin and need something for ED? Sometimes, losing weight or lowering cholesterol can be enough to relieve ED symptoms. It might also be worth looking at your current medications to see if any of them might be contributing to ED. Communication with your healthcare team is key, as they can check for all the possible reasons you might be having ED.

You also could try an alternative ED medication, such as Muse (alprostadil), Caverject (alprostadil), or TriMix (alprostadil, phentolamine, papaverine). These medications have to be injected or inserted into the penis, so they might not be the right choice for everyone.

Another option is to ask your care team if your chest pain could be managed without nitroglycerin. Beta blockers, calcium channel blockers, and Ranexa (ranolazine) treat chest pain and may be safe to take with your ED medication. Your provider can help you decide which approach is best for you.

2. Adempas

Other medications can relax your blood vessels too, such as Adempas (riociguat). Adempas is a soluble guanylate cyclase (sGC) stimulator; it’s used to lower high blood pressure in vessels that lead to the lungs (pulmonary hypertension). 

When combined with nitroglycerin, Adempas has the same additive blood pressure-lowering effects as PDE-5 inhibitors. This means Adempas shouldn’t be used at the same time as nitroglycerin. In clinical studies, people who took nitroglycerin 4 to 8 hours after Adempas experienced lower blood pressure. Some even fainted. To be safe, try to separate the two by a few days.

Not all sGC stimulators interact in the same way, though. Verquvo (vericiguat) is an sGC stimulator that’s used for heart failure. It doesn’t seem to have the same interaction with nitroglycerin as Adempas. One small study didn’t see any major changes in blood pressure when Verquvo and nitroglycerin were used together.

Keep in mind: PDE-5 inhibitors, such as Revatio (sildenafil), can also treat pulmonary hypertension. But they’re not good alternatives to Adempas because they interact with nitroglycerin too.

3. Blood pressure medications

All medications that lower blood pressure can potentially have additive effects with nitroglycerin.

Calcium channel blockers, such as diltiazem, and beta blockers, such as metoprolol, seem to be a particular concern. When nitroglycerin relaxes your blood vessels, your body tries to increase blood pressure again by increasing your heart rate. Beta blockers and certain calcium channel blockers don’t allow this to happen because they also slow your heart rate down. 

Why is this risky? Taking any of these medications with nitroglycerin can lower your blood pressure too much, which can increase your risk of orthostatic hypotension. This is when your blood pressure drops when you sit up in bed or go from sitting to standing. You might then feel suddenly dizzy, lightheaded, or faint. You can minimize this effect by changing positions more slowly.

You should monitor your blood pressure regularly after making any changes to your blood pressure medications. Let your healthcare team know if your blood pressure drops below 90/60 mmHg or if you’re regularly experiencing dizziness, weakness, or abnormal heartbeats. Your provider might need to adjust your blood pressure medication.

4. Anticholinergic medications

Anticholinergic medications tend to cause dry mouth as a side effect. They block your salivary glands from making saliva. Dry mouth can make it difficult for under-the-tongue nitroglycerin tablets to dissolve. Common anticholinergic medications include:

• Tricyclic antidepressants such as amitriptyline

• Overactive bladder medications such as oxybutynin 

• Allergy medications such as diphenhydramine (Benadryl)

• Motion sickness medications such as scopolamine (Transderm Scop)

The nitroglycerin oral spray is a better option for people with dry mouth. If you’re already taking the nitroglycerin tablet, taking a sip of water before placing it under your tongue can help. But, if your dry mouth is severe, you could talk to your healthcare team about switching your medication to one that doesn’t have anticholinergic properties. You could also try to increase salivation by chewing gum or using an over-the-counter (OTC) artificial saliva product.

5. Ergot derivatives

Ergot derivatives, such as Ergomar (ergotamine) and dihydroergotamine, are older migraine medications. They help headaches by blocking pain signals and narrowing blood vessels in the brain. But the narrowing of blood vessels can contribute to many side effects, including chest pain.

At the same time, oral nitroglycerin can increase levels of ergot derivatives in the body. It does this by increasing their absorption. This can lead to ergot side effects such as nausea, poor blood flow to the hands and feet, and more.

This interaction isn’t as much of a concern with topical nitroglycerin. But if you’re taking an oral version of nitroglycerin, then you should avoid ergot derivatives. The healthcare provider who manages your migraines can recommend a safer alternative for you. 

6. Alcohol

Some people drink alcohol to relax the mind after a busy or stressful day. But alcohol can also relax your blood vessels.

Alcohol can have an additive blood pressure-lowering effect when used with nitroglycerin. In particular, it can increase your risk of experiencing orthostatic hypotension. But alcohol seems to only have this effect for a short period of time; long-term alcohol use can actually increase blood pressure.

It’s best that you avoid alcohol with nitroglycerin. If having a drink is part of your regular routine, try to limit your alcohol intake to 2 drinks or less in a day for men or 1 drink or less in a day for women.

Do other nitrates have the same interactions as nitroglycerin?

Yes, for the most part. Other nitrates, such as isosorbide mononitrate (Monoket) and isosorbide dinitrate (Isordil), have almost all the same interaction concerns as nitroglycerin. But anticholinergics aren’t an issue with them, as dry mouth doesn’t interfere with how isosorbide is absorbed.

When to contact a healthcare professional about a nitroglycerin interaction

You should reach out to your healthcare team if you’re prescribed nitroglycerin and any of the following situations apply to you:

• You’ve been prescribed a PDE-5 inhibitor, Adempas, or ergot derivative.

• You’re frequently experiencing dizziness, lightheadedness, or low blood pressure.

• You’re not sure whether a prescription or OTC medication, herbal product, or supplement is OK to take with nitroglycerin.

• You’re experiencing severe dry mouth.

If you’re experiencing chest pain and you aren’t sure whether it’s safe to take nitroglycerin due to a potential interaction, you should call 911 or go to the nearest ER without delay.

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Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

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