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Drug interactions to monitor when prescribing erectile dysfunction medications


The prevalence of erectile dysfunction (ED) increases with age, making it common for those affected to have other comorbidities or treatment regimens. Many of the medications used in the treatment of ED have interactions with other medications, so it is crucial to carefully examine patient profiles to optimize therapy and ensure safety.

Common Causes of ED

The most common cause of ED is when blood flow to the penis is reduced. This can be caused by a multitude of reasons, but we most often see this issue arise commonly in patients who suffer from hypertension and atherosclerosis. The antihypertensive drugs designed to lower blood pressure in those patients can also contribute to reducing blood flow to the penis.

ED can also be associated with diabetes, obesity, smoking, and excessive alcohol consumption. Stress, anxiety, and depression can also psychologically affect a man’s ability to get an erection.

Treating ED

Phosphodiesterase type 5 (PDE-5) inhibitors are considered the first line and the mainstay treatment for ED. When sexually stimulated, nitric oxide is released locally, which increases cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation, which permits more blood flow into the penis, allowing for an erection. PDE-5 is a natural enzyme that degrades cGMP and shuts off the erection mechanism when sexual stimulation ends.

By inhibiting PDE-5, drugs such as sildenafil (Viagra; Pfizer), tadalafil (Cialis; Eli Lilly and Co.), vardenafil (Levitra; Bayer Pharmaceuticals), and avanafil (Stendra; Metuchen Pharmaceuticals) work to temporarily maintain an erection.

Drug Interactions

PDE-5 inhibitors have very important interactions that must be kept in mind at all times. It is contraindicated to use these meds with nitrates [e.g., nitroglycerin (Nitrostat; Pfizer)], isosorbide mononitrate (Imdur; TopRidge Pharma), isosorbide dinitrate (Isordil; Bausch), or riociguat (Adempas; Bayer).

Doing so can result in severe hypotension, potentially leading to fainting, heart attack, or stroke. Patients who take nitrate-containing products for angina or other cardiac-related problems must avoid using PDE-5 inhibitors. If a patient experiences angina and needs nitroglycerin, it cannot be used until 24 hours after sildenafil or vardenafil, 12 hours after avanafil, and 48 hours after tadalafil.

In general, sexual activity can put a strain on the heart, so it ends up being an even more dangerous situation for those with cardiac issues if they take PDE-5 inhibitors. Additionally, PDE-5 inhibitors also need to be used in caution with other drugs that can cause hypotension, such as antihypertensives and alpha blockers, because they potentiate the hypotensive effects when used together.

Other than these interactions, PDE-5 inhibitors should also be avoided with moderate to strong CYP450 3A4 inhibitors, because these drugs can increase the levels of PDE-5 inhibitors in the body. The reverse is also true for the opposite; CYP450 3A4 inducers could decrease drug levels.

Alternative to PDE-5 Inhibitors

Another drug used to treat ED is alprostadil (injection: Edex; Endo Pharmaceuticals) or (pellets: Muse; Mylan), which is Prostaglandin E1. It acts as a vasodilator, allowing increased blood to flow into the penis. The delivery method of this drug is more invasive because it needs to either be injected directly into the penis or inserted as a pellet into the urethra. Though it’s not often used, it is recommended in patients where PDE-5 inhibitor drugs are contraindicated.

Alprostadil, because it has more of a local effect than a systemic one, does not have many drug-drug interactions. You would still exercise caution while taking other drugs with hypotensive effects, including the PDE-5 inhibitors. Use of alprostadil is contraindicated in certain conditions that predispose patients to priapism, such as leukemia, multiple myeloma, and sickle cell anemia.

OTC Medications

It should also be kept in mind that patients may sometimes resort to OTC medicines to self-treat their ED rather than going to a medical professional. There are many natural products that have become popularized for their supposed positive effects.

At the time of writing this article, the most common mainstream ones include ashwagandha, yohimbe, and L-arginine. None of these have sufficient evidence at this time proving efficacy toward treating ED, but because patients may still take them, it is important to know about potential interactions.

Studies have shown ashwagandha to have sedative and GABAnergic properties, causing additive effects with anticonvulsants, barbiturates, and benzodiazepines. Yohimbe should be avoided if patients are on any monoamine oxidase inhibitors, such as phenelzine (Nardil; Kyowa Kirin) and tranylcypromine (Parnate; Concordia).

Finally, L-arginine may have potential interactions with anticoagulant and antiplatelet drugs, increasing the risk of bleeding. It can also potentially lower blood pressure and should be used in caution with other drugs with hypotensive effects. Many of these natural products do not have enough safety and efficacy studies to properly and safely recommend their use for ED treatment.

The Takeaway

ED is a growing problem in our aging populations. When treating these patients, it is essential to identify and rectify potential drug interactions.

About the Author

Steven P. Mathew, PharmD, is a pharmacist with Community Care Rx, a full-service, long-term care pharmacy with offices in Hempstead, NY, and Totowa, NJ.


Sooriyamoorthy T, Leslie SW. Erectile Dysfunction. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from https://www.ncbi.nlm.nih.gov/books/NBK562253/

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