How Do Tadalafil and Sildenafil Work, and Can You Combine Them?

Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are the most common medicines used to treat erectile dysfunction (ED). The two most widely used are tadalafil (brand name Cialis) and sildenafil (brand name Viagra). Understanding how these medicines work, their differences, and whether they can be safely combined is important for making informed decisions about ED treatment.
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​How Do Tadalafil and Sildenafil Work?
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Both tadalafil and sildenafil help men with ED by increasing blood flow to the penis, making it easier to get and keep an erection. They do this by blocking an enzyme called phosphodiesterase type 5 (PDE5). When PDE5 is blocked, another chemical called cyclic GMP (cGMP) builds up, which relaxes the blood vessels in the penis and allows more blood to flow in when a man is sexually aroused.[1][2][3][4][5]
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- Sildenafil usually starts working within 30–60 minutes and lasts for about 4–6 hours.
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- Tadalafil can start working in as little as 30 minutes, but its effects last much longer—up to 36 hours. Tadalafil can also be taken as a low-dose pill every day, which allows for more spontaneous sexual activity.[6][3]
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​What Are the Main Differences Between Tadalafil and Sildenafil?
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- How long they last: Tadalafil lasts much longer in the body than sildenafil.
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- How they are taken: Sildenafil is usually taken as needed, about an hour before sex. Tadalafil can be taken as needed or as a low-dose pill every day.
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- Food interactions: Sildenafil may work more slowly if taken with a heavy or fatty meal. Tadalafil is not affected by food.[6][3]
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- Side effects: Both medicines can cause headaches, flushing, stuffy nose, and upset stomach. Tadalafil may be more likely to cause back pain or muscle aches, while sildenafil may be more likely to cause vision changes.[1][3][5]
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​Can Tadalafil and Sildenafil Be Combined?
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Combining tadalafil and sildenafil is not routinely recommended, and the U.S. Food and Drug Administration (FDA) advises against taking more than one PDE5 inhibitor at the same time due to the risk of side effects like low blood pressure.[6] However, some studies have looked at using both medicines together in men who do not respond well to one medicine alone.
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- A clinical trial found that men with severe ED who took daily tadalafil 5 mg plus sildenafil 50 mg as needed had better improvement in erectile function than those who took tadalafil alone, without an increase in side effects.[7]
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- A large review of studies found that combining two ED treatments, including two PDE5 inhibitors, can help some men who do not respond to one medicine alone, especially those with more difficult-to-treat ED. The risk of side effects was not higher than with one medicine, but the improvement in erectile function was usually small.[8]
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- The American Urological Association recommends starting with one PDE5 inhibitor and adjusting the dose as needed. Combination therapy may be considered for men who do not respond to one medicine, but this should be done under close medical supervision.[4]
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​Important Safety Information
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- Never take tadalafil or sildenafil with nitrates (medicines for chest pain) or certain blood pressure medicines, as this can cause dangerous drops in blood pressure.[9][10][6][3]
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- Combining tadalafil and sildenafil should only be considered if single therapy does not work, and only under the guidance of a healthcare provider.
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- Do not take more than the prescribed dose of any ED medicine.
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- Tell your healthcare provider about all medicines and supplements you are taking.
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​Summary
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Tadalafil and sildenafil are both effective treatments for ED, but they differ in how long they last and how they are taken. Most men do well with one medicine alone. Combining them may help some men with severe or difficult-to-treat ED, but this should only be done with medical supervision due to the risk of side effects. Always follow your healthcare provider’s instructions and never combine ED medicines on your own.[7][8][1][9][10][2][6][3][4][5]
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