Medications like sildenafil, tadalafil, and vardenafil can help keep an erection. They work by relaxing certain muscles and boosting blood flow to the penis.
But each one has its own timing, benefits, and possible side effects. Some work fast but wear off quickly. Others last longer but may take more time to kick in. So, how do you know which one is right for you?
In this article, you’ll learn how these medicines act in the body, how quickly they work, how long they last, and what to expect with each.
| 🔑 Key Takeaways ➤ Tadalafil is the only one that helps with urinary issues by relaxing muscles in the bladder and prostate. ➤ Vardenafil can start working in as little as 10 minutes, while sildenafil and tadalafil usually take 30 to 60 minutes. ➤ Tadalafil lasts up to 36 hours, but sildenafil and vardenafil wear off after about 18 hours. ➤ You can take tadalafil every day at a low dose or just when needed, but sildenafil and vardenafil are only for on-demand use. ➤ Vardenafil comes in orodispersible tablets that dissolve quickly, unlike the other two. ➤ While all three drugs are effective, tadalafil may offer a more convenient option for many men ➤ Tadalafil may cause muscle aches more often, while vardenafil can affect color vision in some people. ➤ Sildenafil and vardenafil should not be taken more than once a day, but tadalafil offers a flexible daily option. ➤ Only tadalafil and sildenafil are approved to treat both erectile dysfunction and pulmonary hypertension, while vardenafil is mainly for erectile issues. |
Mechanism of Action
Sildenafil, tadalafil, and vardenafil all work in a similar way—they block an enzyme called PDE5, which helps relax muscles and improve blood flow, especially in the penis and lungs. The main difference is that tadalafil also helps with urination by relaxing muscles in the prostate and bladder.
Mechanism of Action of Sildenafil
Sildenafil works by acting as a competitive inhibitor of the enzyme phosphodiesterase type 5 (PDE5), which normally breaks down cyclic guanosine monophosphate (cGMP). cGMP is the molecule that helps relax smooth muscle in blood vessels. When PDE5 is inhibited, cGMP is preserved and even accumulates. This buildup leads to increased activity of cGMP-dependent protein kinase, which then reduces calcium levels inside smooth muscle cells, increases potassium outflow, and deactivates myosin light chain kinase. All of these changes cause the smooth muscle in the penis and lungs to relax.
In the penis, this leads to erection by allowing blood to fill the cavernosal spaces. In the lungs, it eases the flow of blood through the pulmonary arteries, lowering pulmonary pressure.
So, sildenafil helps improve blood flow by keeping cGMP around longer. For people with erectile dysfunction or pulmonary arterial hypertension, that’s essential—because both conditions need better blood flow where it counts.
Mechanism of Action of Tadalafil
Tadalafil also works by selectively inhibiting phosphodiesterase type 5 (PDE5). This enzyme is found in smooth muscle cells, including those in the penis, pulmonary arteries, and the prostate. By blocking PDE5, tadalafil prevents the breakdown of cGMP, which is produced when nitric oxide is released during sexual stimulation. Higher cGMP levels lead to the relaxation of the smooth muscle in the corpus cavernosum, allowing increased blood flow and an erection.
But tadalafil doesn’t stop there—it also promotes vasodilation in the lungs, lowering blood pressure in pulmonary arteries, and relaxes smooth muscles in the bladder and prostate, which can help men with benign prostatic hyperplasia urinate more easily.
Mechanism of Action of Vardenafil
According to the American Society of Health-System Pharmacists, vardenafil is also a phosphodiesterase type 5 (PDE5) inhibitor. Like the others, it blocks the action of PDE5, which breaks down cGMP. During sexual stimulation, nitric oxide is released and activates an enzyme that converts GTP to cGMP. This molecule is key to relaxing smooth muscles and allowing more blood to flow into the penis.
By stopping the breakdown of cGMP, vardenafil makes sure there’s enough of it to keep blood vessels open and the smooth muscles relaxed, which helps produce and maintain an erection.
Vardenafil helps enhance the natural process of getting an erection—but only if there is sexual stimulation. It doesn’t work in the absence of sexual arousal, and it won’t increase desire or act as an aphrodisiac. Its effects are focused and specific to how your body responds to sexual signals.
Onset and Duration
Sildenafil, tadalafil, and vardenafil all start working within about 30 to 60 minutes, but vardenafil can work in as little as 10 minutes for some people. Tadalafil lasts the longest—up to 36 hours—while sildenafil and vardenafil usually last up to 18 hours.
Onset and Duration of Sildenafil
Sildenafil begins to take effect within 30 minutes after taking it. The medication is generally taken around 1 hour before sexual activity. Its effects can last up to 18 hours. However, patients are advised not to exceed one dose per day.
The medication can be taken 30 minutes to 4 hours before intercourse, and while the onset can occur within half an hour, the intensity of action may vary depending on individual response.
Onset and Duration of Tadalafil
Tadalafil usually starts working within 30 to 60 minutes, though one study adds that its onset may occur in as little as 15 minutes in some men — although fewer than 40% respond that early, and most reach effectiveness closer to 2 hours after ingestion. Because of this variability, patients should not be advised to expect rapid results, as doing so may lead to anxiety or disappointment.
Tadalafil’s most unique feature is its long half-life of 17.5 hours, which provides a therapeutic window of up to 36 hours with a single dose. This extended duration allows for more flexibility in timing sexual activity and reduces the pressure of precise scheduling.
Onset and Duration of Vardenafil
In a large at-home, randomized controlled trial, the participants achieved intercourse in as early as 10 minutes after dosing with vardenafil 10 mg or 20 mg.
Within 25 minutes of ingestion, approximately 50–53% of men on vardenafil had at least one successful sexual attempt, compared to 26% on placebo. A statistically significant effect was noted from 10–11 minutes post-dose onward, depending on the dose.
Further analysis from pivotal trials found that both orodispersible (ODT) and film-coated tablets of vardenafil offer comparable rapid onset. Within the first 15 minutes, the mean success rate for intercourse was 62.5% for vardenafil ODT compared to 29.4% for placebo.
In the 16–30 minute window, success rates rose to over 65%, with the majority of intercourse attempts initiated during this period resulting in successful outcomes.
Dosing
Sildenafil and vardenafil are taken only when needed and no more than once a day, usually about an hour before sex. Tadalafil can be taken the same way or once daily, making it the only one approved for both regular and as-needed use.
Sildenafil Dosing Frequency
Sildenafil is typically taken on demand, approximately 1 hour before sexual activity, though it may be effective anywhere from 30 minutes to 4 hours after dosing. It is not intended for regular daily use and should not be taken more than once in a 24-hour period.
This flexible timing is designed to support planned intercourse while minimizing unnecessary exposure.
Tadalafil Dosing Frequency
Tadalafil offers two distinct dosing options:
- On-demand dosing, typically at 10 mg, taken at least 30 minutes before sexual activity.
- Once-daily dosing, usually at 2.5 mg or 5 mg, taken at the same time each day, regardless of planned sexual activity.
Tadalafil’s long half-life allows it to maintain effective drug levels with daily use. This makes tadalafil the only PDE5 inhibitor with both on-demand and continuous dosing approvals.
Vardenafil Dosing Frequency
Vardenafil is prescribed on demand, with recommended doses of 10 mg or 20 mg taken roughly 25 to 60 minutes before sexual activity. While multiple formulations exist—including orodispersible tablets (ODT) and film-coated tablets—the dosing frequency remains the same: not more than once daily. There is no approved once-daily regimen, unlike with tadalafil.
Efficacy
According to a study comparing these three medications, sildenafil showed high success rates in a 24-week study, with 77% of men reporting improved erections at 50 mg and 84% at 100 mg.
Vardenafil was found to be similarly effective but has a slight edge because it doesn’t affect color vision, a rare side effect linked to sildenafil due to its effect on phosphodiesterase-6.
Tadalafil also showed equal effectiveness to sildenafil but stands out for its much longer duration of action, which allows for greater flexibility. In comparison studies, more men preferred tadalafil over sildenafil, likely because of this extended effect.
This suggests that while all three drugs are effective, tadalafil may offer a more convenient option for many men.
Side Effects
Sildenafil, tadalafil, and vardenafil all share common mild side effects like headache, flushing, and indigestion, but serious problems like vision or hearing loss and long-lasting erections are rare. Tadalafil may also cause muscle aches, and vardenafil may lead to flu-like symptoms or color vision changes.
Side Effects of Sildenafil
Sildenafil can cause a range of side effects, although most people only experience mild symptoms, especially when taking it short term for erectile dysfunction.
Common side effects include:
- Headache
- Nausea
- Flushing or hot flushes
- Indigestion
- Stuffy nose
- Dizziness
You might not feel all of them, and they often go away quickly. Still, if any symptom persists or worsens, it’s best to tell your doctor.
Serious side effects are rare. These include:
- Sudden decrease or loss of vision
- Chest pain, especially during or after sexual activity
- Painful or prolonged erection lasting more than 2 hours
- Seizures or fits
- A serious allergic reaction, known as anaphylaxis
Anaphylaxis may involve swelling of the lips, mouth, throat, or tongue; trouble breathing or swallowing; confusion or fainting; pale or blue lips, skin, or extremities; and an itchy, raised, blistered, or peeling rash. These symptoms need emergency care right away.
Side Effects of Tadalafil
Tadalafil is generally well tolerated. Most people don’t have issues, especially when using it short term. But like all medicines, side effects can still happen.
Common side effects include:
- Headache
- Nausea
- Flushing or hot flushes
- Indigestion
- Stuffy nose
- Muscle aches
These symptoms usually go away when the medicine is stopped. But if one of them sticks around or makes you uncomfortable, talk to a doctor.
Serious side effects are rare. These include:
- Sudden loss of vision or hearing
- Painful or prolonged erection lasting more than 2 hours
- Seizure or fit
- Chest pain
If chest pain happens and you’re taking nitrates, do not use them. Call 999 immediately instead.
Tadalafil may also cause a severe allergic reaction (anaphylaxis). Signs include sudden swelling of the face, lips, tongue, or throat; rapid or difficult breathing; tightness in the throat; pale or blue skin; confusion or fainting; and rashes that are swollen, itchy, blistered, or peeling. Call emergency services at once if you notice any of these.
Side Effects of Vardenafil
Vardenafil can bring both mild and serious side effects. It is important to follow the dosage instructions carefully and to be aware of what your body is telling you.
Common side effects include:
- Headache
- Upset stomach
- Heartburn
- Flushing
- Stuffy or runny nose
- Flu-like symptoms
These symptoms are usually not serious. But if any of them become hard to handle or don’t go away, contact your healthcare provider.
Some side effects may be more serious. These include:
- Erection that lasts longer than 4 hours
- Sudden and severe vision loss or blurred vision
- Color vision changes, such as seeing a blue tint or having trouble seeing in low light
- Sudden hearing loss, sometimes with dizziness or ringing in the ears
- Swelling of the face, lips, tongue, or limbs
- Hoarseness
- Difficulty breathing or swallowing
- Fainting
- Rash or hives
Permanent vision or hearing loss has happened in some people who took vardenafil or similar drugs, though it’s not confirmed if the medication caused it. If you suddenly lose your vision or hearing, stop taking the medicine and call your doctor immediately.
Wrap Up
Tadalafil lasts longer and can be taken daily, making it more flexible. Vardenafil may act faster and even comes in quick-dissolving tablets. Sildenafil remains a popular option with reliable results. But they also come with side effects, and some may suit you better than others.
Not sure which one to try? Talk to a doctor who can guide you based on your health needs, lifestyle, and any other conditions you may have.
Frequently Asked Questions
Can food affect how well the pills work?
Yes, especially for Vardenafil. A high-fat meal can slow it down. Tadalafil isn’t affected by food much.
Is one better for diabetics?
Vardenafil has shown good results in men with diabetes. Always check with your doctor for what’s best for you.
What if Sildenafil doesn’t work for me?
Make sure you’re taking it the right way and talk to your doctor about your testosterone levels. You might try Tadalafil or Vardenafil instead.
Are there special risks with Tadalafil?
Yes. Because it lasts so long, if you need heart meds like nitrates, it can be dangerous. Always talk to your doctor first.
Can younger and older men use different pills?
Younger men might prefer Tadalafil for more flexibility. Older men with other health issues may do better with Sildenafil or Vardenafil.
Why would someone switch from one pill to another?
You might want a longer effect, fewer side effects, or better results. Everyone’s body is different, so it’s about finding the right fit for you.
Sources
- Smith, B. P., & Babos, M. (2023). Sildenafil. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK558978/
- American Society of Health-System Pharmacists. (2022, January 15). Vardenafil. MedlinePlus. U.S. National Library of Medicine. Retrieved from https://medlineplus.gov/druginfo/meds/a603035.html
- National Health Service. (2022, November 11). Common questions about tadalafil. NHS. Retrieved from https://www.nhs.uk/medicines/tadalafil/common-questions-about-tadalafil/
- Coward, R. M., & Carson, C. C. (2008). Tadalafil in the treatment of erectile dysfunction. Therapeutics and Clinical Risk Management, 4(6), 1315–1330. https://doi.org/10.2147/tcrm.s3336
- Montorsi, F., Padma-Nathan, H., Buvat, J., Schwaibold, H., Beneke, M., Ulbrich, E., Bandel, T.-J., & Porst, H.; Vardenafil Study Group. (2004). Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: A randomized, double-blind, placebo-controlled trial. The Journal of Sexual Medicine, 1(2), 168–178. https://doi.org/10.1111/j.1743-6109.2004.04025.x
- Debruyne, F. M. J., Gittelman, M., Sperling, H., Börner, M., & Beneke, M. (2011). Time to onset of action of vardenafil: A retrospective analysis of the pivotal trials for the orodispersible and film-coated tablet formulations. The Journal of Sexual Medicine, 8(10), 2912–2923. https://doi.org/10.1111/j.1743-6109.2011.02462.x
- Doggrell, S. A. (2005). Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opinion on Pharmacotherapy, 6(1), 75–84. https://doi.org/10.1517/14656566.6.1.75