Erectile dysfunction (ED) affects millions of men worldwide and continues to be one of the most common sexual health concerns in 2025. Fortunately, oral medications remain highly effective and widely accessible. Four drugs dominate the field: Viagra (sildenafil), Cialis (tadalafil), Levitra (vardenafil), and Stendra (avanafil).
Although all belong to the same class, known as PDE5 inhibitors, they differ in how quickly they work, how long their effects last, and how men tolerate them. Understanding these differences is essential for choosing the right option with your doctor.
What are PDE5 inhibitors and how they work
PDE5 inhibitors target a specific enzyme, phosphodiesterase type 5, found in penile tissue. Normally, this enzyme breaks down cyclic GMP, a chemical messenger that relaxes smooth muscles and widens blood vessels. By blocking PDE5, these medications allow cyclic GMP to accumulate, making it easier for blood to flow into the penis during sexual stimulation.
The key point is that PDE5 inhibitors do not trigger an erection automatically. Sexual arousal must still be present. What the drugs do is restore the natural erectile response that may have been weakened by age, medical conditions, or psychological stress.
Extensive research published by the FDA and summarized in the American Urological Association (AUA) Erectile Dysfunction Guideline confirms that PDE5 inhibitors are effective in the majority of men, though individual response varies.
Some men respond better to one drug than another, which is why comparing them is so valuable.
Drug comparisons
Viagra (sildenafil): pros and cons
Viagra was the first oral treatment for erectile dysfunction and remains one of the most commonly prescribed. Approved in 1998, it has built the longest safety record of any ED drug. Viagra typically takes effect within 30 to 60 minutes, with results lasting about 4 to 6 hours.
One of its strengths is reliability: it works well for most men with mild to moderate ED. Generics are widely available, which makes sildenafil one of the most affordable choices.
Advantages
- More than two decades of real-world data confirming safety and effectiveness.
- Affordable generics available worldwide.
- A proven starting option for men new to ED treatment.
Drawbacks
- Works best on an empty stomach; high-fat meals can slow absorption.
- Shorter duration compared to newer drugs.
- Side effects may include flushing, headache, or nasal congestion.
Doctors often recommend Viagra as a first-line option because of its strong research base. It is particularly suitable for men who want a dependable medication for occasional use.
Cialis (tadalafil): long-lasting effect
Cialis offers a very different experience. Unlike Viagra, which requires careful timing, Cialis is known for its long duration — up to 36 hours. This extended window has earned it the nickname “the weekend pill.” Its onset is slower, usually 60 to 120 minutes, but the trade-off is flexibility: sexual activity does not need to be planned around a short timeframe.
Another unique aspect of Cialis is that it can be taken in a daily low dose, providing continuous readiness. This option appeals to men in long-term relationships who want spontaneity rather than planning.
Advantages
- Longest duration of action of any PDE5 inhibitor.
- Daily dosing option for men with frequent sexual activity.
- Additional benefit for urinary symptoms of benign prostatic hyperplasia (BPH).
Drawbacks
- Slower onset than sildenafil or avanafil.
- Can cause back pain or muscle aches in some users.
- Cost remains higher than sildenafil, although generics are available.
Cialis is often chosen by men who value flexibility and want ED treatment that supports a more natural sex life. It also appeals to those with both erectile dysfunction and urinary problems, offering two benefits in one medication.
Other PDE5 inhibitors
Levitra (vardenafil): unique properties
Levitra, with the active ingredient vardenafil, was introduced as a close alternative to Viagra. It works in a very similar way, with an onset of 30 to 60 minutes and a duration of about 6 to 8 hours. For many men, Levitra offers a balance between Viagra’s shorter action and Cialis’s much longer effect.
One of Levitra’s distinct advantages is its potency at lower doses. Clinical trials have shown that even small amounts can achieve strong results, which may be beneficial for men who are sensitive to medication. Another useful feature is the orally disintegrating form (Staxyn), which dissolves on the tongue without water. This makes it discreet and convenient, particularly in social situations.
However, Levitra is not as widely prescribed today, partly because its patents expired later than Viagra’s, which delayed the arrival of affordable generics. Some men also report side effects such as flushing, nasal congestion, and occasional dizziness. Still, for men who do not respond well to sildenafil, vardenafil remains a valuable alternative.
Stendra (avanafil): the new generation
Stendra, also known as avanafil, is the newest PDE5 inhibitor on the market. Approved in 2012, it was designed to provide rapid onset and fewer side effects. Stendra can work in as little as 15 to 30 minutes, making it the fastest-acting drug in this class. Its duration is shorter than Cialis but similar to Viagra and Levitra, lasting 4 to 6 hours.
A key advantage of avanafil is its improved selectivity for the PDE5 enzyme, which may reduce side effects such as headaches or flushing. While not entirely side-effect free, studies published in PubMed suggest that Stendra is often better tolerated than earlier drugs, particularly for men who experienced unpleasant reactions with sildenafil or tadalafil.
Cost, however, remains a consideration. Stendra is newer, and while generic versions are starting to appear in some regions, it is often more expensive than Viagra or Cialis. Despite this, its rapid action and favorable side-effect profile make it appealing for men seeking convenience and tolerability.
For patients exploring newer options, discussions with doctors about avanafil often overlap with conversations about generics. Many providers now guide men toward broader choices, including generic medications for erectile dysfunction, which can significantly reduce cost while maintaining safety and efficacy.
Comparison Table: Viagra, Cialis, Levitra, Stendra
| Drug | Onset of Action | Duration | Typical Dosage | Common Side Effects |
| Viagra (sildenafil) | 30–60 minutes | 4–6 hours | 25–100 mg as needed | Headache, flushing, nasal congestion |
| Cialis (tadalafil) | 60–120 minutes | Up to 36 hours | 2.5–20 mg (daily or as needed) | Back pain, muscle aches, flushing |
| Levitra (vardenafil) | 30–60 minutes | 6–8 hours | 5–20 mg as needed | Flushing, nasal congestion, dizziness |
| Stendra (avanafil) | 15–30 minutes | 4–6 hours | 50–200 mg as needed | Headache, flushing, nasal congestion |
This comparison makes it clear that each drug has strengths: Viagra is reliable and affordable, Cialis offers long duration, Levitra is effective at lower doses, and Stendra provides the fastest onset with fewer side effects. The choice often depends on lifestyle, medical conditions, and personal preference.
Side effects and safety considerations
Although PDE5 inhibitors are generally safe, they are not risk-free. All four drugs – Viagra, Cialis, Levitra, and Stendra share similar side effects because they work through the same biochemical pathway. The most common include headache, flushing, nasal congestion, indigestion, and dizziness. These symptoms are usually mild and temporary.
Cialis, due to its longer duration, is more likely to cause back pain and muscle aches. Viagra and Levitra can sometimes cause visual disturbances, such as a blue-tinged vision or sensitivity to light. Stendra is often reported to have a lower rate of these visual side effects, likely because of its greater selectivity for the PDE5 enzyme.
Rare but serious risks include sudden vision or hearing loss, priapism (an erection lasting longer than 4 hours), and dangerous interactions with medications containing nitrates. For this reason, men with certain cardiovascular conditions must be evaluated carefully before starting treatment.
According to the FDA and the Cleveland Clinic, combining PDE5 inhibitors with nitrates or recreational “poppers” can cause a severe drop in blood pressure. Men with unstable heart disease, severe liver disease, or very low blood pressure are typically advised against using these drugs.
Choosing the right ED drug with your doctor
Selecting the right ED medication is not about finding the “best” pill overall, but about finding the one that best fits your health, lifestyle, and relationship needs. Some men value speed and spontaneity, making Stendra attractive. Others prefer the long coverage of Cialis. Viagra remains a reliable starting option, while Levitra may help men who did not respond well to sildenafil.
Doctors usually consider
- Medical history: including heart disease, diabetes, or prostate issues.
- Other medications: to avoid dangerous drug interactions.
- Lifestyle preferences: whether spontaneity or predictability is more important.
- Side effect tolerance: since some men may experience bothersome reactions with one drug but not another.
Personalized medicine is increasingly important in 2025. Online telehealth platforms now allow men to consult discreetly with licensed providers, review their health history, and receive prescriptions for ED drugs safely. This approach helps avoid counterfeit medications and ensures that dosing and follow-up are handled properly.
F.A.Q
Which erectile dysfunction drug works the fastest?
Stendra (avanafil) typically works within 15–30 minutes, faster than Viagra, Cialis, or Levitra. This makes it a good choice for men who want spontaneity.
Which erectile dysfunction medication lasts the longest?
Cialis (tadalafil) lasts up to 36 hours, far longer than the other PDE5 inhibitors. Many men prefer it for its flexibility and daily dosing option.
Are generic erectile dysfunction medications as effective as brand-name drugs?
Yes. FDA-approved generics of sildenafil, tadalafil, and vardenafil are equally effective and often much cheaper. For men looking to save money, generic ED medications can be a safe and reliable option.
Can I take erectile dysfunction drugs if I have heart disease?
Many men with stable heart conditions can take PDE5 inhibitors, but it is essential to consult a doctor first. They should never be combined with nitrates.
What if one erectile dysfunction medication doesn’t work for me?
It is common for men to respond better to one drug than another. If Viagra does not provide the desired effect, your doctor may suggest trying Levitra, Cialis, or Stendra.
References
- Comparative Efficacy and Safety of Sildenafil, Tadalafil … – PMC 2025
- StatPearls – PDE5 Inhibitors NCBI Bookshelf
- Efficacy and safety of oral phosphodiesterase 5 inhibitors – PubMed 2021
- A comparison of the available phosphodiesterase-5 – PMC 2015
- Phosphodiesterase-5 (PDE5) Inhibitors In the Management of … – PMC