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What's the Safest Drug for Erectile Dysfunction?

Kristin Hall, FNP

Medically reviewed by Kristin Hall, FNP

Written by Our Editorial Team

Last updated 2/1/2022

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

Although ED is often associated with older men, men of all ages experience ED. In fact, findings from large-scale studies suggest that as many as 40 percent of all men will deal with some level of erectile dysfunction by the age of 40 -- a number that increases with age.

Luckily, erectile dysfunction is a treatable issue. In fact, numerous medications are available for ED, including well-known options such as sildenafil (the active ingredient in Viagra®) to tadalafil (Cialis®) and newer, second-generation ED treatments such as avanafil (Stendra®).

Safety is an essential factor to consider before using any type of medication, and treatments for ED are no exception. 

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.

We’ve also answered some common questions regarding which ED medication is the safest for you to use, with a focus on factors such as potential side effects and general safety. 

Erectile Dysfunction Drugs: An Overview

Erectile dysfunction medication has been around since the late 1990s, when the FDA approved Viagra as the first pill for treating ED. Currently, there are four different medications available to treat ED that have received FDA approval. They are:

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

  • Tadalafil. The active ingredient in Cialis®, tadalafil is a long-lasting ED drug that offers relief from erectile dysfunction for up to 36 hours per dose -- a duration of action that’s earned it the nickname of the “weekend pill.”Tadalafil is available as 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, meaning it remains active in the body for longer. It’s sold as Levitra and is also 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, starts working in as little as 15 minutes and is less likely to cause some side effects. Currently, avanafil is only available as Stendra® and is not sold as a generic medication. 

Currently, all ED medications approved by the FDA are prescription drugs, meaning you’ll need to talk to your healthcare provider and receive a valid prescription before you can purchase and use them. 

We offer several FDA-approved ED medications online, following a consultation with a licensed healthcare provider who will determine if a prescription is appropriate.

How Do ED Medications Work?

All four of the medications listed above belong to a class of drugs called PDE5 inhibitors, which work by inhibiting the effects of the enzyme phosphodiesterase-5 (PDE5). PDE5 is found inside the smooth muscle cells of your blood vessels and is responsible for regulating blood flow.

Erections are all about blood flow. When you’re aroused, nerve signals trigger the flow of blood to the corpora cavernosa -- a pair of sponge-like areas of erectile tissue inside your penis.

As blood flows in to the corpora cavernosa, your penis expands and becomes firmer, leading to an erection that’s hard enough for penetrative sex. To trap blood inside your penis, a membrane called the tunica albuginea contracts, helping to maintain the erection during sex.

Erectile dysfunction can 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 interest in sexual stimulation.

By blocking the effects of PDE5, ED medications like sildenafil, tadalafil, vardenafil and avanafil dilate the blood vessels that supply your penis, improving blood flow and making it easier to get and maintain an erection.

However, these medications don’t treat the psychological side of ED, meaning they won’t cause you to feel more sexually stimulated or cause erections without arousal. 

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Which ED Medication is the Safest?

Whether they’re sold as brand name drugs or in generic form, sildenafil, tadalafil, vardenafil and avanafil are all safe for most men to use.

All medications, including these medications for erectile dysfunction, undergo extensive clinical testing to check that they’re safe before they’re approved by the FDA. 

This testing process involves multiple phases of clinical trials, each involving anywhere from 20 to several thousand participants. The FDA reviews the findings from these tests to check that drugs aren’t just effective, but also that they’re safe for the public to use.

All four of the oral ED medications have passed this process, meaning the FDA has determined that they’re safe and effective for their intended use -- in this case, treating erectile dysfunction.

However, like all medications, ED drugs like sildenafil, tadalafil, vardenafil and avanafil do have the potential to cause side effects. 

Most of the side effects associated with erectile dysfunction drugs are mild and temporary. The most common side effects of these medications include:

  • Headaches 

  • Muscle aches 

  • Nasal congestion 

  • Dizziness 

  • Facial flushing 

  • Indigestion/heartburn 

  • Nausea 

  • Visual disturbances 

  • Slightly reduced blood pressure

The rate of side effects can vary from one ED medication to another, but most issues only affect a small percentage of users.

For example, headache -- the most common side effect of most ED medication -- was reported by 21 percent of men who used sildenafil in clinical trials at a 50mg 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 produce certain side effects than other ED medications. 

For example, in trials of avanafil, only 6.9 percent of men reported developing headaches while using the medication at a typical starting dosage of 100mg. Other side effects only occurred in a small percentage of users, even at the maximum 200mg dosage. 

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

Although uncommon, ED medications can cause more serious side effects, including temporary vision loss, sudden decrease or loss of hearing and priapism -- a painful, persistent erection that 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 four FDA-approved medications as directed without major issues, with few reporting more than mild, transient adverse effects.

Erectile Dysfunction Drug Interactions

While ED drugs are safe for most men, there are certain medications that shouldn’t be used with them. These include several medications 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, second-generation ED drugs such as avanafil (Stendra). 

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

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

Other medications that can interact with ED medications include alpha-blockers used to manage hypertension (high blood pressure) and other anti-hypertensive medications.

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 before discussing any treatment for erectile dysfunction.

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Which Conditions Can Affect 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 (high blood pressure), hypotension (low blood pressure) or a heart valve issue.

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

These conditions may increase your risk of experiencing 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, such as leukemia or multiple myeloma

  • Eye disorders, such as retinitis pigmentosa

  • Previous cases of priapism (long-lasting, painful erections)

  • Liver or kidney problems

  • Stomach ulcers or a history of 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 experienced in the past. 

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. 

Are Over-the-Counter ED Drugs Safe?

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

Some of these products, such as Rhino pills and other “herbal” products, are perceived as safer than prescription drugs, since they’re sold over the counter in gas stations and other stores with no need for a visit to the doctor.

The reality is that these over-the-counter products are almost always significantly less safe than FDA-approved prescription drugs used as treatments for erectile dysfunction. 

Over the years, the FDA has investigated many of these products and found that they often use unlabeled, hazardous ingredients. Some contain the same ingredients as prescription erectile dysfunction pills in either unusually low or dangerously high amounts. 

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

Because they’re not held to the same standards as real medications, these over-the-counter ED pills may cause side effects, interactions and other issues even in healthy individuals. 

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

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So, What’s the Safest Drug for Erectile Dysfunction?

All four of the ED medications approved by the FDA -- sildenafil (the active ingredient in Viagra), tadalafil (Cialis), vardenafil (Levitra) and avanafil (Stendra) -- are safe for most men to use.

However, just like other medications, ED medications do have the potential to cause side effects and drug interactions in certain situations. 

As the newest ED medication, avanafil (Stendra) has a more selective effect on blood flow than older erectile dysfunction drugs, meaning it may be worth considering if you’re concerned about side effects. 

We offer several FDA-approved ED medications online, following a consultation with a licensed healthcare provider who will determine if a prescription is appropriate.

You can also learn more about using medication to treat ED in our guide to what to expect from common erectile dysfunction medications

13 Sources

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.

  1. Definition & Facts for Erectile Dysfunction. (2017, July). Retrieved from https://www.niddk.nih.gov/health-information/urologic-diseases/erectile-dysfunction/definition-facts
  2. Lakin, M. & Wood, H. (2018, June). Erectile Dysfunction. Retrieved from http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/erectile-dysfunction/
  3. VIAGRA® (sildenafil citrate) tablets, for oral use. (2014, March). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/20895s039s042lbl.pdf
  4. CIALIS (tadalafil) tablets, for oral use. (2011, October). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf
  5. LEVITRA (vardenafil hydrochloride) tablets, for oral use. (2014, April). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021400s017lbl.pdf
  6. Hellstrom, W.J., et al. (2015, August). Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study. Journal of Urology. 194 (2), 485-92. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25591992/
  7. STENDRA™ (avanafil) tablets, for oral use. (2012, April). Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202276s000lbl.pdf
  8. Dhaliwal, A. & Gupta, M. (2021, June 25). PDE5 Inhibitors. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK549843/
  9. Erection Ejaculation: How It Occurs. (2020, November 27). Retrieved from https://my.clevelandclinic.org/health/articles/10036-erection-ejaculation-how-it-occurs
  10. Symptoms & Causes of Erectile Dysfunction. (2017, July). Retrieved from https://www.niddk.nih.gov/health-information/urologic-diseases/erectile-dysfunction/symptoms-causes
  11. Step 3: Clinical Research. (2018, January 4). Retrieved from https://www.fda.gov/patients/drug-development-process/step-3-clinical-research
  12. Step 4: FDA Drug Review. (2018, January 4). Retrieved from https://www.fda.gov/patients/drug-development-process/step-4-fda-drug-review
  13. Tainted Sexual Enhancement Products. (2021, December 8). Retrieved from https://www.fda.gov/drugs/medication-health-fraud/tainted-sexual-enhancement-products

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.