ED Medications Compared: Viagra, Cialis, Levitra, and Stendra

Four oral PDE5 inhibitors are FDA-approved in the United States for treating erectile dysfunction. Sildenafil came first in 1998 and changed the conversation around male sexual health overnight. Three others followed. The choice between them is not arbitrary – they differ meaningfully in onset, duration, food interactions, and side effects, even though they all work through the same mechanism. The right ED medications for any given man depend on lifestyle, other health conditions, and personal preference more than on raw potency. All four are prescription-only, and the descriptions below are general education, not a recommendation to start, stop, or dose any drug on your own. Which drug (if any) is appropriate, and at what strength, is a decision for you and a licensed clinician.

A Critical Safety Warning First: Nitrates

Before anything else: never take any PDE5 inhibitor together with a nitrate medication. Nitrates include nitroglycerin (tablets, sprays, patches, or ointment for chest pain), isosorbide dinitrate and isosorbide mononitrate, and recreational “poppers” (amyl or butyl nitrite). Combining a nitrate with a PDE5 inhibitor can cause a profound, sudden, potentially life-threatening drop in blood pressure. Per MedlinePlus, a clinician will tell you not to take sildenafil (or any drug in this class) if you use nitrates in any form. If you take a nitrate for angina, PDE5 inhibitors are off the table – tell your doctor so you can discuss other options. This warning applies to every product discussed on this page.

How PDE5 Inhibitors Work

All four drugs block phosphodiesterase type 5, the enzyme that breaks down cyclic GMP in penile smooth muscle. By slowing that breakdown, they amplify the natural nitric-oxide-driven erection signal triggered by sexual stimulation. They do not cause spontaneous erections – sexual arousal is still required for them to work. The AUA Erectile Dysfunction Guideline lists FDA-approved oral PDE5 inhibitors as a first-line option that should be offered to men with ED who do not have a contraindication, within a shared decision-making conversation about all reasonable treatments.

Beyond the absolute nitrate contraindication, concurrent use with alpha-blockers (often prescribed for blood pressure or an enlarged prostate) requires caution and usually dose separation because of additive blood-pressure lowering. Men with severe or unstable cardiovascular disease, a recent heart attack or stroke, uncontrolled blood pressure, or unstable arrhythmia should be evaluated – and cleared – by their clinician before starting therapy. Sexual activity itself is a form of exertion, which is part of why a cardiovascular check matters.

ED Can Be an Early Sign of Heart Disease

This point is easy to overlook but genuinely important. The same blood-vessel problems that cause heart disease can show up first in the smaller penile arteries, so new-onset erectile dysfunction is often an early marker of underlying cardiovascular disease. The AUA guideline notes that ED can be as strong a predictor of future cardiac events as smoking or a family history of heart attack. Treating the erection with a pill without looking at the bigger picture can mean missing a warning sign. A new ED diagnosis is a good reason to see a clinician for a cardiovascular and metabolic evaluation – blood pressure, cholesterol, blood sugar, and lifestyle – not just a prescription.

Sildenafil (Viagra)

Sildenafil typically begins working in about 30 to 60 minutes and lasts roughly 4 to 6 hours. Prescribers select an on-demand dose from available tablet strengths (commonly 25, 50, or 100 mg) based on response and tolerability – these strengths are reference information, not a dosing instruction. A high-fat meal substantially delays and reduces absorption, so many urologists suggest taking it on an empty stomach or with a light meal. Generic sildenafil has been available in the US since 2017 and now often costs only a few dollars to around $30 per dose with pharmacy discount pricing, dramatically less than the brand. The FDA label describes a response rate of roughly 70% across studied populations.

Common side effects include headache, facial flushing, nasal congestion, indigestion, and visual changes (often a temporary bluish tint, from mild cross-reactivity with PDE6 in the retina). The visual effect is generally mild and transient.

Tadalafil (Cialis)

Tadalafil is the long-acting agent of the class. It begins working in about 30 minutes and can last up to 36 hours, which is why it is sometimes called “the weekend pill.” It is used in two ways: on-demand or as a low daily dose. Daily dosing maintains steady-state PDE5 inhibition and allows for spontaneous, unscheduled activity. Tadalafil is also FDA-approved for benign prostatic hyperplasia, making it a logical choice for men who have both ED and lower urinary tract symptoms. Which strategy and strength fit you is a prescriber decision.

Food does not meaningfully affect tadalafil absorption. Generic tadalafil has been available since around 2018 and is typically inexpensive per on-demand dose, with the low daily strength commonly running a modest monthly cost with discount pricing. The side-effect profile is similar to sildenafil but with more back pain and muscle aches and fewer visual side effects, since tadalafil has weaker PDE6 cross-reactivity.

Vardenafil (Levitra, Staxyn)

Vardenafil works much like sildenafil – onset in about 30 minutes and a duration of roughly 4 to 6 hours. It has been sold as a film-coated tablet (Levitra) and as an orally disintegrating tablet (Staxyn) that dissolves without water. Pharmacologically, vardenafil is fairly selective for PDE5, which some clinicians associate with a slightly lower rate of visual side effects.

Vardenafil has fallen out of commercial favor in the US; brand-name Levitra has been discontinued, though generic vardenafil generally remains available. Pricing is broadly similar to sildenafil. Vardenafil can prolong the QT interval at higher doses and should be used cautiously by men taking certain antiarrhythmic drugs – another reason dosing belongs with a prescriber who knows your full medication list.

Avanafil (Stendra)

Avanafil is the newest of the four, FDA-approved in 2012. Its main advantage is rapid onset – clinical trials showed effective erections as early as about 15 minutes after dosing. Duration is shorter, around 4 to 6 hours. It is available in several tablet strengths, again selected by the prescriber.

Avanafil’s selectivity profile is favorable in some respects: lower PDE6 cross-reactivity (fewer visual effects) and less PDE11 inhibition (less muscle aching), and side effects in trials were generally mild. The main downside is cost – avanafil is still brand-name only in the US, so out-of-pocket costs are typically much higher than the generics, and insurance coverage varies considerably.

At-a-Glance Comparison

These figures are general reference ranges from FDA labeling and drug references; individual response varies, and none of this substitutes for your clinician’s advice.

Side Effects Across the Class

All four drugs share a similar side-effect profile: headache, flushing, nasal congestion, indigestion, and back pain. Rare but serious adverse events include sudden hearing loss, non-arteritic anterior ischemic optic neuropathy (NAION), and priapism (a prolonged, painful erection). Anyone with an erection lasting more than about four hours, or sudden vision or hearing loss after taking a PDE5 inhibitor, should stop the drug and seek immediate medical care. For more on emergency erectile complications, see our priapism guide.

Who Each Drug Tends to Suit

For many men without a strong preference, generic sildenafil or generic tadalafil are rational starting points on cost and effectiveness – but the starting choice is your clinician’s call. Men who want spontaneity and are active several times a week often prefer daily tadalafil. Men whose schedule allows planned use may favor on-demand sildenafil. Tadalafil is a natural choice when BPH coexists. Avanafil is reasonable when rapid onset matters and cost is not a barrier, or when other PDE5 inhibitors caused intolerable side effects. For men who do not respond to oral therapy, second-line options include intracavernosal injections, vacuum devices, or a penile implant; shockwave therapy remains investigational and is not FDA-approved for ED.

Cost, Insurance, and Buying Safely

Many commercial plans cover generic sildenafil and tadalafil, sometimes with prior authorization and a monthly quantity limit; brand-name and avanafil coverage is patchier. Some Medicare Part D plans cover the generics. Without insurance, pharmacy discount programs can bring the generics to a very low per-dose cost at certain pharmacies. Telehealth platforms bundle a prescription and shipping for a monthly fee; the convenience comes at a premium versus filling a generic locally. For a broader view of paying for care, see our healthcare costs guide and our medical conditions guide.

Whatever route you choose, buy only from a licensed US pharmacy with a valid prescription. The FDA has repeatedly warned that ED products sold by unverified online sellers – and “herbal” or “natural” male-enhancement supplements that promise Viagra-like effects – are frequently counterfeit or secretly spiked with unlisted prescription drug ingredients, including hidden PDE5 inhibitors that can be dangerous for someone on nitrates or with heart disease. The price difference is not worth the risk.

Frequently Asked Questions

Which ED drug has the fewest side effects?

In head-to-head analyses, avanafil and tadalafil tend to show slightly lower rates of headache and visual disturbance than sildenafil, with vardenafil in between. Individual response varies widely; the best-tolerated drug is the one a given patient does best on, which is worth discussing with a prescriber.

Can these be taken every day?

Low-dose tadalafil is FDA-approved for daily use. Sildenafil, vardenafil, and avanafil are designed for on-demand use. Any daily-dosing decision should be made and monitored by your clinician, not self-directed.

Does alcohol interfere with ED medication?

Modest alcohol (one to two drinks) does not meaningfully change how these drugs perform. Heavy drinking lowers libido, worsens erection quality, and can amplify headache and flushing, and combining heavy drinking with these drugs is not advised.

Are online ED prescriptions safe?

Telehealth platforms that use US-licensed clinicians and US-licensed pharmacies are generally legitimate. Foreign or no-prescription websites selling sildenafil or “herbal” products have been repeatedly flagged by the FDA for counterfeiting and adulteration. Stick with verified, licensed sources.

Should I see a doctor if I only need it occasionally?

Yes. Because these drugs are prescription-only, interact dangerously with nitrates, and because ED can signal underlying heart or metabolic disease, even occasional use should start with a clinician evaluation.

The Bottom Line

Four FDA-approved oral medications cover the spectrum of needs: rapid onset, long duration, daily flexibility, and low cost. Most men respond to one of the generics – sildenafil or tadalafil – and most do well at moderate, prescriber-set doses. Switching agents when one is poorly tolerated is reasonable; abandoning oral therapy after a single failed trial usually is not. But the safest, most effective path starts with a conversation with a primary care physician or urologist, who can screen for heart disease, review your other medications for nitrate and alpha-blocker interactions, and match the right molecule to the right patient.

Sources

• American Urological Association – Erectile Dysfunction Guideline (2018): first-line PDE5 inhibitors, contraindications, and ED as a cardiovascular risk marker
• MedlinePlus (U.S. National Library of Medicine) – drug pages for sildenafil, tadalafil, vardenafil, and avanafil, including the nitrate warning
• FDA prescribing information / DailyMed labels for Viagra, Cialis, Levitra/Staxyn, and Stendra
• FDA consumer safety warnings on counterfeit and tainted ED products and “male enhancement” supplements