Sildenafil(Viagra) vs Tadalafil(Cialis): Difference, Duration, Side Effects and Which Is Better

Sildenafil (Viagra) and tadalafil (Cialis) are the two most widely prescribed oral medications for erectile dysfunction (ED), a common condition in men characterized by difficulty achieving or maintaining an erection, due to physiological or psychological factors. Both drugs belong to a class of medications called phosphodiesterase type 5 (PDE5) inhibitors, which work by enhancing blood flow to the penis through the nitric oxide-cGMP pathway during sexual stimulation.

PDE5 is an enzyme found in the smooth muscle of blood vessels, particularly in the penis and lungs. It breaks down cyclic guanosine monophosphate (cGMP), a molecule that helps relax blood vessels and increase blood flow. By blocking PDE5, these drugs allow cGMP to build up, enhancing blood flow and supporting erections.They relax the smooth muscle in the penis, the corpus cavernosum, allowing for a firmer, longer-lasting erection. Erectile dysfunction is treated largely by the administration of these two medicines, providing a solution for men to regain their confidence in comfort.

Sildenafil, introduced by Pfizer in 1998, acts quickly and lasts for about 4 to 6 hours, while tadalafil, launched by Eli Lilly in 2003, has a longer duration (up to 36 hours), earning it the nickname “the weekend pill.” Clinical studies in the British Journal of Clinical Pharmacology, show that sildenafil reaches peak levels in 1-1.5 hours, whereas tadalafil peaks at around 2 hours and has a much longer half-life of 17.5 hours.

While both medications are effective for treating ED, tadalafil offers greater flexibility and spontaneity due to its longer effect, and many users report higher satisfaction and psychological well-being. Side effects differ slightly in both medicines. Sildenafil may cause vision-related side effects, while tadalafil more commonly causes back or muscle pain. Additionally, they are approved for benign prostatic hyperplasia (BPH) and both are approved for pulmonary arterial hypertension (PAH) under different brand names.

Understanding the differences such as duration, affordability, food and drug interactions can help you choose the best erectile dysfunction medication tailored to your health, lifestyle, and timing preferences.

For a better understanding of the differences between the drugs, refer to the table below.

What Is the Difference Between Sildenafil (Viagra) and Tadalafil (Cialis)?

Sildenafil and tadalafil are two of the most widely used phosphodiesterase type 5 (PDE5) inhibitors for the treatment of erectile dysfunction (ED). While both medications enhance blood flow to the penis and help men achieve and maintain erections, they differ significantly in how quickly they work, how long their effects last, and how they fit into different treatment plans. Understanding the key differences between sildenafil (commonly known by the brand name Viagra) and tadalafil (Cialis) can help patients choose the most suitable option for their lifestyle and needs.

Sildenafil:

Sildenafil citrate is a selective PDE5 inhibitor approved for the treatment of erectile dysfunction. It enhances nitric oxide-mediated vasodilation in the corpus cavernosum during sexual stimulation. Pfizer originally developed sildenafil in the early 1990s to treat angina (chest pain), but researchers soon discovered that it caused erections. This surprising effect led to sildenafil citrate tablets’ repurposing as a treatment for erectile dysfunction.

Tadalafil:

Tadalafil is a PDE5 inhibitor that enhances erectile function by boosting blood flow to the penis. Known for its extended half-life, tadalafil provides a longer duration of action compared to other ED medications, earning it the nickname “the weekend pill.” It was developed by ICOS Corporation in collaboration with Eli Lilly, following the commercial success of sildenafil. Tadalafil was approved by the U.S. Food and Drug Administration (FDA) in November 2003 under the brand name Cialis.

What Are the Medical Uses of Sildenafil and Tadalafil?

Sildenafil and tadalafil are both FDA-approved PDE5 inhibitors primarily used to treat erectile dysfunction (ED). Both drugs have received approval under the names – Revatio for sildenafil and Adcirca for tadalafil, for treating pulmonary arterial hypertension (PAH). Both are also used to treat benign prostatic hyperplasia (BPH), either alone or in combination with ED. These extended uses leverage the vasodilatory effects of the drugs on smooth muscle in the lungs and lower urinary tract.

Some off-label uses for these drugs occur in conditions like Raynaud’s phenomenon, Female Sexual Arousal Disorder (FSAD), and altitude sickness / High-Altitude Pulmonary Edema (HAPE).

To better illustrate the dosage differences between the two drugs, see the table below.

How Does Sildenafil Work Compared to Tadalafil?

Sildenafil (Viagra) and tadalafil (Cialis) are oral medications classified as phosphodiesterase type 5 (PDE5) inhibitors, commonly prescribed for the treatment of erectile dysfunction (ED). These drugs act by blocking the PDE5 enzyme, which is responsible for breaking down cyclic guanosine monophosphate (cGMP), a chemical messenger that plays a key role in the erectile process.

During sexual arousal, nitric oxide (NO) is released in the corpus cavernosum, the spongy tissue in the penis responsible for erection. This stimulates the production of cGMP, which causes the smooth muscles in the corpus cavernosum to relax, allowing blood vessels to dilate and increase blood flow to the penis. By inhibiting the breakdown of cGMP, sildenafil and tadalafil help maintain higher levels of this compound, resulting in improved erection firmness and duration in response to sexual stimulation.

A study in the British Journal of Clinical Pharmacology (2002), showed the pharmacokinetic analysis of sildenafil in healthy male volunteers. It revealed that oral administration of 50 mg sildenafil produced a peak plasma concentration of approximately 159 ng/mL, typically achieved at 1 to 1.5 hours post-dose. The drug displayed an average terminal half-life of about 4 hours. Additionally, a high-fat meal delayed absorption and reduced peak plasma concentration by around 29%, but had minimal effect on overall exposure.

A study in the British Journal of Clinical Pharmacology (2005), conducted pharmacokinetic assessments in healthy adults after single and multiple doses of tadalafil (2.5-20 mg). It found that tadalafil reached a mean peak plasma concentration of approximately 378 µg/L around 2 hours after a 20 mg dose, followed by a half-life of 17.5 hours. The research confirmed dose- and time-linear pharmacokinetics, unaffected by food intake, with relatively slow systemic clearance compared to other PDE5 inhibitors.

How Fast Does Sildenafil Work Compared to Tadalafil?

Sildenafil and tadalafil differ in how quickly they begin to work after ingestion, a factor that often influences patient preference and clinical use. While both are PDE5 inhibitors, their onset of action is shaped by pharmacokinetics, food interactions, and individual metabolism.

Sildenafil typically begins working within 30-60 minutes, with some users reporting effects as early as 12 minutes under ideal conditions. However, its absorption is delayed by high-fat meals, so it’s best taken on an empty stomach. Tadalafil generally starts working within 30-45 minutes, and its absorption is not significantly affected by food.

In clinical trials, sildenafil showed onset of action as early as 12-30 minutes, with peak effects around 60 minutes, while tadalafil became effective within 30-45 minutes, reaching peak concentration in 2 hours. Real-world data align with this, with most men experiencing sildenafil effects in 45-60 minutes and tadalafil in 30-60 minutes. However, tadalafil’s gradual and longer-lasting effects often make it feel smoother and less time-sensitive compared to the more distinct and short-acting response of sildenafil.

Which Lasts Longer: Sildenafil or Tadalafil?

When it comes to duration of action, tadalafil outlasts sildenafil. Sildenafil (Viagra) remains effective for about 4 to 6 hours after ingestion, though its peak effect usually occurs around the 1-hour mark. After this window, its blood concentration declines rapidly due to a shorter half-life of approximately 4 hours. This makes sildenafil a suitable choice for on-demand use, but it requires careful timing around sexual activity.

Tadalafil (Cialis) lasts significantly longer – up to 36 hours, earning it the nickname “the weekend pill.” It allows sustained plasma levels and therapeutic effects over an extended period of time. This prolonged action supports both on-demand and daily low-dose regimens, offering more flexibility and spontaneity in sexual activity.

Which Medication Gives a Harder Erection: Sildenafil or Tadalafil?

Both sildenafil and tadalafil are effective at improving erection hardness by enhancing blood flow to the penis, but neither has been proven to consistently produce a “harder” erection over the other.

Sildenafil produces a more intense peak effect due to its faster onset and shorter duration, making it feel more potent to some users. In contrast, tadalafil offers more natural-feeling, longer-lasting erections, which results in greater overall satisfaction and improved consistency, especially when taken daily. The effect differs from user to user. User preference is driven by timing flexibility, rather than erectile strength.

What Is the Usual Dosage of Sildenafil or Tadalafil?

The usual dosage of sildenafil is 50 mg, one hour prior to sexual activity. If ineffective, the dose may be increased to 100 mg per day. The standard dose of tadalafil is 10 mg, 30 minutes before sexual activity. The dose is reduced to 5 mg if necessary. Tadalafil has a longer duration of action (up to 36 hours), so a daily dose may not be required.

For the treatment of erectile dysfunction (ED), both sildenafil and tadalafil are taken orally, but their dosing regimens differ based on their pharmacokinetics and duration of action. Consult your doctor to determine your dose based on your age and health.

What Are the Side Effects of Tadalafil vs Sildenafil?

Both sildenafil and tadalafil are generally well-tolerated medications, but they cause similar side effects because they work through the same mechanism, as phosphodiesterase type 5 (PDE5) inhibitors.

However, the differences in how long these drugs stay in the body (duration of action) and how selectively they target PDE5 versus other types of PDE enzymes (like PDE1, PDE6, or PDE11) lead to slight variations in side effects. For example, sildenafil is more likely to cause visual disturbances due to its effect on PDE6, found in the retina, while tadalafil’s longer half-life and activity at PDE11 causes more muscle or back pain in some users.

Below is a table comparing common side-effects for both drugs.

Some adverse reactions reported for both drugs are priapism (prolonged erection lasting over 4 hours), sudden hearing loss, non-arteritic anterior ischemic optic neuropathy (NAION) – more commonly associated with sildenafil, severe hypotension – when combined with nitrates or alpha-blockers.

Sildenafil and tadalafil remain safe for consumption despite the side-effects listed above. But, always consult your doctor if the medication or dosage does not agree with you.

What Drugs Should Not Be Taken With Sildenafil or Tadalafil?

Sildenafil and tadalafil cause serious interactions when combined with certain medications or substances due to their vasodilatory effects. Most notably, nitrates and alpha-blockers should be avoided, as combining them with PDE5 inhibitors cause dangerous drops in blood pressure, leading to dizziness, fainting, or even cardiac events.

A study, published in the Journal of the American College of Cardiology (2000), investigated the interaction between sildenafil citrate (50 mg) and nitrate medications in men with stable angina. It showed that combining sildenafil with nitrate medications leads to significantly enhanced drops in blood pressure, increasing the risk of severe hypotension. As a result, sildenafil is contraindicated in patients who are taking nitrates.

In case of ongoing alpha-blocker medications, sildenafil or tadalafil must only be used with a physician’s guidance. The combination of the drugs with alpha-blockers may cause hypotension. 

Tadalafil is metabolized in the liver primarily by the enzyme CYP3A4. CYP3A4 is an essential enzyme predominantly located in the liver and intestines, where it is responsible for metabolizing a wide range of drugs and breaking down numerous compounds within the body. When this enzyme is inhibited by certain medications like ticagrelor, ketoconazole, itraconazole, or ritonavir, tadalafil breaks down more slowly, causing higher concentrations to remain in the bloodstream. This increases the risk of side effects, including headaches, flushing, low blood pressure, and prolonged erections.

On the other hand, CYP3A4 inducers like rifampin accelerate the metabolism of tadalafil, leading to lower drug levels and reduced effectiveness. This may make the medication less effective in treating erectile dysfunction or symptoms of benign prostatic hyperplasia. Due to these interactions, careful monitoring or dose adjustments are necessary.

A case report in the Journal of Forensic and Legal Medicine (2023), a rare case of death due to the combined effect of alcohol and sildenafil causing cerebrovascular hemorrhage was published. Heavy alcohol consumption is contraindicated with both sildenafil and tadalafil as it enhances vasodilatory side effects, dizziness, and hypotension.

For a comprehensive list of drugs to be avoided, refer below.

1. Nitrates (eg. nitroglycerin, isosorbide dinitrate) – can cause dangerous drops in blood pressure
2. Alpha-blockers (eg. tamsulosin, doxazosin) – may lead to low blood pressure and dizziness
3. Protease inhibitors (eg. ritonavir, saquinavir) – can raise drug levels and side effects
4. Antifungal medications (eg. ketoconazole, itraconazole) – may increase blood levels of the drug
5. Macrolide antibiotics (eg. erythromycin, clarithromycin) – can also increase blood levels
6. Certain seizure medications (eg. carbamazepine, phenytoin) – may reduce effectiveness.
7. Other ED medications – combining with other PDE5 inhibitors increases side effect risk

Which Food Interacts With Sildenafil or Tadalafil?

Sildenafil is known to be affected by food, especially high-fat meals, which delays its absorption and reduces its maximum plasma concentration. Tadalafil has low water solubility, but it is efficiently absorbed through the gastrointestinal tract and its absorption is not affected by food when taken orally. Grapefruit and grapefruit juice can interact with both sildenafil and tadalafil by increasing their blood levels, which may heighten the risk of side effects.

A pharmacokinetic study in the British Journal of Clinical Pharmacology (2002), reported that taking sildenafil with food, especially a high-fat meal, delayed its peak concentration by about one hour and reduced the maximum concentration by approximately 29%, while overall exposure dropped around 11%. These changes, though measurable, are generally not deemed clinically significant, but taking sildenafil on an empty stomach helps ensure faster onset.

Another study in the same journal described the pharmacokinetic effects of tadalafil. It showed that tadalafil follows a dose and time-dependent linear pharmacokinetic profile, meaning its absorption and concentration in the body increase proportionally with the dose. Unlike some other ED medications, its absorption is not influenced by food intake, and it is cleared from the body more slowly than most other PDE5 inhibitors.

Which Is Better: Sildenafil or Tadalafil for Erectile Dysfunction?

Both sildenafil (Viagra) and tadalafil (Cialis) are effective treatments for erectile dysfunction (ED), but the better option depends on individual needs, lifestyle, and health factors.

Sildenafil typically starts working in 30-60 minutes and lasts about 4-6 hours, making it a good option for occasional, planned use. However, it may be less effective if taken after a high-fat meal.

Tadalafil, on the other hand, begins to work in 30-45 minutes and lasts up to 36 hours, offering more spontaneity. It’s also approved for treating benign prostatic hyperplasia (BPH). Men who want a longer window of effectiveness or who experience urinary symptoms prefer tadalafil over sildenafil.

Which Is More Affordable: Cialis (Tadalafil) or Viagra (Sildenafil)?

Tadalafil might be slightly more affordable, due to its longer duration of action. However both drugs are priced approximately in the same range, and choice largely depends on user intent and convenience.

Cenforce 100 mg (Sildenafil) is generally priced at $0.85-$2.00 per tablet on most online pharmacy websites. It’s a common generic version of Viagra manufactured by Centurion Laboratories.

Vidalista 20 mg (Tadalafil) usually costs around $0.90-$2.00 per tablet, and is manufactured by Centurion Laboratories as well. Since tadalafil lasts longer, some users take it less frequently, which reduces overall cost.

Which Is Safer Sildenafil or Tadalafil?

Both sildenafil and tadalafil are considered safe and well-tolerated PDE5 inhibitors when used as prescribed, but they differ in duration, side-effects profile, and individual tolerability. A direct meta-analysis in the Journal of International Urology and Nephrology (2017), comparing tadalafil and sildenafil found no significant difference in erection firmness or success of intercourse between the two drugs. However, tadalafil’s longer half-life (~17.5 hours) offers a longer window of action (up to 36 hours), which many patients report as more natural and flexible. Tadalafil users also reported an increased occurrence of muscle pain, however flushing was noticeably lower than sildenafil users.

Can You Take Sildenafil and Tadalafil Together?

No, sildenafil and tadalafil should not be taken together. Both drugs belong to the same class, phosphodiesterase type 5 (PDE5) inhibitors, and combining them significantly increases the risk of adverse effects such as severe hypotension, dizziness, syncope, priapism, and cardiovascular events. Since both medications work by enhancing nitric oxide-mediated vasodilation, their effects are additive and potentially dangerous when used together. Clinical guidelines and pharmacological reviews explicitly advise against combining PDE5 inhibitors due to the lack of safety data and the risk of synergistic vasodilatory effects.

What Are The Best ED Treatments? 

The best ED treatments include oral medications, lifestyle changes, therapy, and medical devices, with oral PDE5 inhibitors like sildenafil and tadalafil offering the fastest and most reliable results.

For most men, oral PDE5 inhibitors (like sildenafil and tadalafil) are the first-line treatments due to their proven effectiveness and ease of use. However, non-drug treatments like vacuum pumps, penile injections, or lifestyle adjustments can work better in cases of severe ED, drug contraindications, or psychological triggers. A healthcare provider can help select the right treatment based on individual needs.

What Are The Best ED Pills?

The best ED pills include sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra), each offering different onset times, durations, and side effect profiles. Sildenafil is one of the best ED pills for rapid onset and short-term use. It begins working in 30 to 60 minutes and remains effective for about 4 to 6 hours. It’s ideal for men who want a fast-acting option for planned sexual activity.

Tadalafil offers a longer window of effectiveness, up to 36 hours, and can be taken daily at a lower dose. This makes it suitable for men who want more spontaneity or prefer a regular dosing schedule. Vardenafil is similar to sildenafil but may work better in men with diabetes or certain cardiovascular risks due to its slightly different chemical structure. It typically lasts 4 to 5 hours. Avanafil, the newest option, acts quickly (within 15–30 minutes) and has fewer side effects for some men.

All four options require sexual stimulation to work and are available by prescription. A healthcare provider can help determine the most appropriate pill based on age, health status, and frequency of use.

Which ED Medication Has The Longest-Lasting Effects?

Tadalafil (Cialis) has the longest-lasting effect among ED medications, staying active in the body for up to 36 hours. This long window makes it ideal for men who want greater flexibility and spontaneity in sexual activity. In contrast, sildenafil lasts for about 4 to 6 hours, depending on metabolism, food intake, and other factors. Vardenafil (Levitra) offers a similar duration to sildenafil, typically around 4 to 5 hours, but may work slightly better in men with diabetes. Avanafil (Stendra), a newer-generation PDE5 inhibitor, works quickly, within 15 to 30 minutes, and lasts around 6 hours, making it a balanced option between onset speed and duration.

Which Is More Effective: Sildenafil Or Vardenafil?

Sildenafil and vardenafil are both effective PDE5 inhibitors, but their subtle differences can affect which one works better for a specific user. Clinical data suggest that for many men, sildenafil vs vardenafil comparisons show similar success in achieving erections, though vardenafil may offer greater efficacy in individuals with diabetes or high cholesterol. Both drugs typically take effect within 30 to 60 minutes and last about 4 to 6 hours. However, vardenafil binds more selectively to the PDE5 enzyme, which may reduce side effects like visual changes that are sometimes reported with sildenafil. On the other hand, sildenafil is more widely available and often more affordable, making it a first choice for many doctors. Choosing between sildenafil vs vardenafil depends on how your body responds, what side effects you experience, and whether you have coexisting health conditions. A healthcare provider can help tailor the treatment based on personal needs.

What Are the Generic Options of Sildenafil Citrate?

Cenforce, commonly referred to as the “Blue Pill,” is the generic option of sildenafil citrate used to treat erectile dysfunction (ED) in men. Manufactured by Centurion Laboratories, it contains 100 mg of sildenafil citrate, the same active ingredient found in Viagra. This generic alternative is typically available in blister packs of 10 tablets. Some other generic options of Sildenafil Citrate include Kamagra, Fildena, Suhagra, and Silagra.

What Are the Generic Options of Tadalafil?

Vidalista is recognized as a generic alternative to tadalafil. It is manufactured by Centurion Laboratories. It contains tadalafil, a long-acting phosphodiesterase type 5 (PDE5) inhibitor that enhances blood flow to help men achieve and maintain erections. Each strip includes 10 tablets, and the effects last up to 36 hours, earning it the nickname “Weekend Pill.” Tadalafil reaches its peak concentration about 2 hours after intake. Other generic options of Tadalafil include brands like Tadacip, Cialis, Tadarise, and Apcalis.