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

Common Causes of ED

The most common cause of erectile dysfunction is reduced blood flow to the penis. This can be caused by a multitude of reasons, but most often we see this problem occurring in patients who suffer from hypertension and atherosclerosis. Antihypertensive drugs designed to lower blood pressure in these patients may also help reduce blood flow to the penis.

Erectile dysfunction 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 have an erection.

Treat erectile dysfunction

Phosphodiesterase type 5 (PDE-5) inhibitors are considered the first line and basic treatment for erectile dysfunction. When sexually stimulated, nitric oxide is released locally, which increases cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation, which allows greater blood flow to the penis, allowing an erection. PDE-5 is a natural enzyme that degrades cGMP and stops 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.

Drugs interactions

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

This can lead to severe low blood pressure, which can lead to fainting, heart attack, or stroke. Patients taking nitrate-containing products for angina or other heart problems should avoid using PDE-5 inhibitors. If a patient has angina and needs nitroglycerin, it can only be used 24 hours after sildenafil or vardenafil, 12 hours after avanafil and 48 hours after tadalafil.

In general, sexual activity can put pressure on the heart, which ends up being an even more dangerous situation for people with heart problems if they are taking PDE-5 inhibitors. Additionally, PDE-5 inhibitors should also be used with caution with other drugs that can cause hypotension, such as antihypertensives and alpha-blockers, because they potentiate hypotensive effects when used together.

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

Alternative to PDE-5 inhibitors

Another drug used to treat erectile dysfunction is alprostadil (injection: Edex; Endo Pharmaceuticals) or (pellets: Muse; Mylan), which is prostaglandin E1. It acts as a vasodilator, allowing increased blood flow to the penis. The method of administration of this drug is more invasive as it must either be injected directly into the penis or inserted as a lozenge into the urethra. Although not often used, it is recommended for patients in whom PDE-5 inhibitor drugs are contraindicated.

Alprostadil, because it has a more local than systemic effect, does not have many drug interactions. You should always exercise caution when taking other drugs with blood pressure lowering effects, including PDE-5 inhibitors. The use of alprostadil is contraindicated in certain conditions that predispose patients to priapism, such as leukemia, multiple myeloma, and sickle cell disease.

Over-the-counter medications

It should also be kept in mind that patients may sometimes resort to over-the-counter medications to treat erectile dysfunction on their own rather than consulting a medical professional. There are many natural products that have become popular for their supposed positive effects.

At the time of writing, the most common are ashwagandha, yohimbe, and L-arginine. None of these currently have enough evidence proving their effectiveness in treating erectile dysfunction, but since patients can still take them, it is important to be aware of 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 taking monoamine oxidase inhibitors, such as phenelzine (Nardil; Kyowa Kirin) and tranylcypromine (Parnate; Concordia).

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

Takeaway meals

Erectile dysfunction 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 at Community Care Rx, a full-service long-term care pharmacy with offices in Hempstead, NY, and Totowa, NJ.


Sooriyamoorthy T, Leslie SW. Dyserection. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 January. Available at