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What Is the Safest ED Medication?

Safety is an essential factor to consider before using any type of medication, and treatments for ED are no exception. Luckily, erectile dysfunction is a treatable issue with a number of well-known options such as sildenafil (the active ingredient in Viagra®), tadalafil (Cialis®) and newer, second-generation ED treatments such as avanafil (Stendra®).

All of the FDA-approved ED medications on the market right now are safe for most men to use on a regular basis. However, there are some side effects and drug interactions that you should be aware of if you’re considering using any type of medication for ED. These side effect rates can differ from one medication to another, meaning one may be a more effective option for you than its alternatives.

Below, we’ve explained how ED medications work, their potential side effects, drug interactions and other key safety data that you should be aware of before using medication to treat ED, and how to determine the right and safe option for yourself. 

Erectile Dysfunction Drugs: An Overview

Erectile dysfunction is a common form of sexual dysfunction that affects an estimated 30 to 50 million men in the United States alone. 

Studies estimate that as many as 40 percent of all men will deal with some level of erectile dysfunction by the age of 40 — and that rate only increases with age. But certain treatments can help manage the condition’s key symptoms.

Erectile dysfunction medication has been around since the late 1990s, when the FDA approved Viagra as the first pill for treating ED (here is a guide on where to buy Viagra).

Currently, there are four FDA-approved oral medications for ED:

  • Sildenafil. The active ingredient in Viagra, sildenafil, is the most well-known medication for erectile dysfunction. It’s designed for use at least one hour before sex and works for about four hours per dose. Sildenafil is available as the brand-name Viagra and as a generic version. It’s a popular choice that works well for most men affected by ED.

  • Tadalafil. The active ingredient in Cialis®, tadalafil, is an ED drug that offers relief for up to 36 hours per dose. This long duration of action has earned it the nickname, the “weekend pill.” Tadalafil is available as the brand-name Cialis and as a generic medication. It can be used as needed before sexual activity or taken daily at a reduced dosage to provide ongoing ED relief.

  • Vardenafil. The active ingredient in Levitra®, vardenafil, works similarly to sildenafil but has a slightly longer half-life. This means it remains active in the body for longer. It’s only available as a generic medication.

  • Avanafil. The active ingredient in Stendra®, avanafil, is a second-generation medication for ED. It’s more selective in its effects than older ED drugs and starts working in as little as 15 minutes. It’s also less likely to cause some side effects. Currently, it’s only available as the brand-name medication, with no generic option available for sale.

Other ED medications exist besides these oral ones. Alprostadil (Caverject®) is an FDA-approved medication for ED that can be injected or used inside the urethra. Compounded medications like BiMix, TriMix, and QuadMix can also be used for ED and are given by injection or in the urethra—but know that compounded medications are not FDA-approved.

How Do ED Medications Work?

All four of the oral medications listed above belong to a class of drugs called PDE5 inhibitors. These medications work by inhibiting the effects of the enzyme phosphodiesterase type 5 (PDE5). This enzyme breaks down a signaling molecule called cyclic guanosine monophosphate (cGMP), which plays a key role in relaxing smooth muscles and regulating blood flow to the erectile tissue of the penis.

When cGMP is active, it triggers the release of nitric oxide, which causes blood vessels to widen. This allows blood to flow into the penis, expanding the corpora cavernosa and leading to a firmer, fuller erection.

By breaking down cGMP, PDE5 stops the signal that allows blood vessels to relax, limiting blood flow and making erections harder to achieve.

PDE5 inhibitors work by blocking this enzyme, allowing cGMP levels to rise. As a result, blood vessels in the penis can dilate more fully, making it easier to get and maintain an erection.

The other treatment options for ED work through a variety of processes, including dilating the blood vessels, stimulating the nerves of the penis, and pulling more blood into the penis with negative pressure.

However, these options don’t treat the psychological side of ED, meaning they won’t help you to feel more sexually stimulated or increase your libido. 

And, after all, erectile dysfunction can certainly have physical and psychological causes. Physical causes include heart and blood vessel disease, diabetes, atherosclerosis (clogged arteries), and damage to the penis or surrounding tissue, which can affect nerve function and blood flow.

Psychological causes may include depression, feelings of guilt, sexual performance anxiety, and stress. Although these don’t physically reduce blood flow, they can affect a person’s comfort in sexual situations and response to stimulation.  

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What Is the Safest ED Medication?

There is no single safest ED drug. Viagra (sildenafil), Cialis (tadalafil), Levitra (vardenafil), Stendra (avanafil), and Caverject (alprostadil) are all FDA-approved for the treatment of erectile dysfunction and are safe for most men to use.

These medications for erectile dysfunction underwent extensive clinical testing to check that they’re safe and effective before the FDA approved them. 

This testing process involves multiple phases of clinical trials and thousands of participants. The FDA reviews the findings from these studies to ensure the drugs aren’t just effective, but also safe for patients to use.

All FDA-approved ED medications have passed this process, meaning the FDA has determined that each is safe and effective for its intended use — in this case, treating erectile dysfunction.

The safest medication for you depends on your health history, needs, and other factors. You can work with a healthcare provider to determine which medication is best and least likely to cause side effects for you.

Are Over-the-Counter ED Drugs Safe?

If you’ve searched for information about treating erectile dysfunction, you may have come across certain products marketed as over-the-counter alternatives to prescription ED medications.

These products include Rhino pills and other supplements that are sold in gas stations and other stores with no need for a visit to the doctor. The reality is that these products are almost always significantly less safe than FDA-approved prescription drugs for treating erectile dysfunction. 

Over the years, the FDA has investigated many of these products and found that they often include unlabeled, hazardous ingredients. Some contain the same ingredients as prescription erectile dysfunction pills in either unusually low or dangerously high amounts. Because these “ED pills” are not held to the same standards as regulated medications,  they may be more likely to cause side effects, interactions, and other issues—even if you’re otherwise healthy. 

The FDA maintains a list of tainted sexual enhancement products that includes recent products found to contain unlabeled and/or dangerous ingredients.

Our guide to over-the-counter ED “medications” goes into more detail about these products and why they’re best avoided for your sexual health.

ED Medication Side Effects

If you’re wondering which ED medication is the safest when it comes to side effects, you should know that all FDA-approved options for ED are fairly comparable.

As is true for nearly all prescriptions, medications like sildenafil, tadalafil, vardenafil, and avanafil have the potential to cause side effects. While these effects may be mild or nonexistent for some users, other folks may see more intense effects.

That said, most of the side effects associated with oral erectile dysfunction drugs are mild and temporary.

The most common side effects of these oral medications include:

  • Headaches 

  • Back pain 

  • Nasal congestion 

  • Dizziness 

  • Facial flushing 

  • Indigestion/heartburn 

  • Nausea (upset stomach)

  • Visual disturbances 

Side effects of other ED medications differ.

How Common Are Side Effects?

The rate of side effects can vary from one ED medication to another, but most issues affect a small portion of users and subside quickly.

For example, headache—the most common side effect of many oral ED medications—was reported by 21 percent of men who used sildenafil citrate in clinical trials at a 50 milligram (mg) dosage. In clinical trials of tadalafil and vardenafil, headaches were reported by 11 and 15 percent of men, respectively.

For most men who use ED medications, these side effects aren’t serious. Our guides to the side effects of Viagra, Cialis, and Levitra discuss these issues in more detail. 

As a newer, more selective medication for ED, avanafil (Stendra) is less likely to cause certain side effects than other ED medications. 

Trials of avanafil found that only 6.9 percent of men reported headaches while using the typical starting dosage of 100 mg. Other side effects only occurred in a small number of users, even at the maximum 200 mg dosage. 

Do ED Medications Have Serious Side Effects?

If you’re worried about side effects from ED medications, you may prefer avanafil to older drugs such as sildenafil or tadalafil. 

Although uncommon, ED medications can cause certain serious side effects, including temporary vision loss, sudden decrease or loss of hearing, and priapism — a painful, persistent erection that lasts more than four hours and requires medical attention. 

If you develop any serious or concerning side effects after taking ED medication, it’s best to talk to your healthcare provider. In the event of an emergency, seek urgent medical attention. 

Overall, side effects — both mild and serious — are rare with ED medication. The vast majority of men with ED are able to safely use all FDA-approved medications as directed without experiencing major issues.

Erectile Dysfunction Drug Interactions

While oral ED drugs are safe for most men, there are certain medications that shouldn’t be used in conjunction. These include several drugs prescribed for angina (chest pain caused by low blood flow to the heart), heart failure, high blood pressure, and other conditions.

Interactions can potentially happen with all ED medications, including newer oral ED medications, such as avanafil (Stendra). 

In particular, oral ED medications can interact with nitrates and nitroglycerin used to treat angina and cardiovascular disease, among other heart conditions, such as congestive heart failure (CHF).

When taken with nitrate drugs, prescription medications for ED can trigger a dangerous drop in blood pressure that may cause dizziness, fainting, or life-threatening events such as a heart attack or stroke. 

Other medications that can interact with oral ED medicine include alpha blockers used to manage hypertension (high blood pressure). For this reason, these should only be combined with proper medical advice.

To use ED drugs safely, make sure to tell your healthcare provider about all medications, herbal supplements, and/or other substances you currently use or have recently used.

Warnings to Consider Before Taking ED Medication

It’s important to take caution with ED medication if you have any type of cardiovascular health condition, such as heart disease, congestive heart failure, an irregular heartbeat, hypertension, hypotension (low blood pressure), or a heart valve issue.

It’s also important to use caution before using ED medication if you’ve ever suffered a heart attack, stroke, or have undergone heart surgery within the last six months.

These conditions may increase your risk of having side effects or safety issues from some ED medications. To keep yourself safe, make sure to inform your healthcare provider about any of these medical issues before using any medication for ED. 

Other conditions that may affect ED medication include:

  • Injuries to or deformations of the penis

  • Blood cell disorders, such as sickle cell anemia

  • ​​Blood or bone marrow cancers

  • Eye disorders, such as retinitis pigmentosa

  • Previous cases of priapism

  • Liver or kidney problems

  • Stomach ulcers

  • Bleeding problems

The best way to keep yourself safe while using ED medication is to tell your healthcare provider about your full health history, including any current medical conditions and issues that you have had in the past. 

You may also wish to get medical advice on what lifestyle changes might be helpful in restoring erectile function. 

They’ll be able to assess your risk of issues from ED medication and recommend a treatment plan that’s both safe and effective for you.

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A Final Word on the Safest Medication for Erectile Dysfunction

The safest ED medication is the one your healthcare provider recommends.

Here’s what we know:

  • All of the ED medications approved by the FDA are safe for most men to use. Medications like sildenafil, tadalafil, vardenafil, and avanafil have been rigorously tested by the FDA. They are much safer than any unregulated over-the-counter supplements said to enhance sexual function.

  • Like other medications, ED medications do have the potential to cause side effects. These side effects may include headaches, back pain, nausea, and dizziness. Or, you may not experience any side effects at all.

  • ED medications can cause drug interactions and may not be safe for some users. If you have cardiovascular issues or you’re recovering from a heart attack, you may not be a good candidate for ED medications. You may also not be able to take ED medications if you’re taking drugs for chest pain, blood pressure, or other cardiovascular issues.

Hims offers access to several FDA-approved ED medications online, which you can access following a consultation with a licensed healthcare professional.

Get advice today to explore your options.

Related Drug Comparisons

Cialis vs. Viagra Levitra vs. Viagra
Revatio vs. Sildenafil Sildenafil vs. Tadalafil
Sildenafil vs. Vardenafil Sildenafil vs. Cialis
Sildenafil vs. Viagra Viagra vs. Flomax
  1. CIALIS (tadalafil) tablets, for oral use. (2011). https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf
  2. Dhaliwal A, et al. (2021). PDE5 Inhibitors. https://www.ncbi.nlm.nih.gov/books/NBK549843/
  3. Food and Drug Administration. (2018). Step 3: Clinical Research. https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
  4. Food and Drug Administration. (2018). Step 4: FDA Drug Review. https://www.fda.gov/patients/drug-development-process/step-4-fda-drug-review
  5. Food and Drug Administration. (2021). Tainted Sexual Enhancement Products. https://www.fda.gov/drugs/medication-health-fraud/tainted-sexual-enhancement-products
  6. Hellstrom W, et al. (2015). Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study. https://pubmed.ncbi.nlm.nih.gov/25591992/
  7. Leslie S, et al. (2024). Erectile Dysfunction. https://www.ncbi.nlm.nih.gov/books/NBK562253/
  8. LEVITRA (vardenafil hydrochloride) tablets, for oral use. (2014). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021400s017lbl.pdf
  9. National Institute of Diabetes and Digestive and Kidney Diseases. (2024). Definition & Facts for Erectile Dysfunction. https://www.niddk.nih.gov/health-information/urologic-diseases/erectile-dysfunction/definition-facts
  10. National Institute of Diabetes and Digestive and Kidney Diseases. (2024). Symptoms & Causes of Erectile Dysfunction. https://www.niddk.nih.gov/health-information/urologic-diseases/erectile-dysfunction/symptoms-causes
  11. STENDRA™ (avanafil) tablets, for oral use. (2012). https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202276s000lbl.pdf
  12. VIAGRA® (sildenafil citrate) tablets, for oral use. (2014). https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/20895s039s042lbl.pdf
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Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at blog@forhims.com!

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.