The most common side effects of tadalafil are headache, indigestion, back pain, muscle aches, flushing, and a stuffy or runny nose. In clinical trials, headache was the most frequent, affecting up to 15% of people taking the higher 20 mg dose. Most of these side effects are mild and resolve within a few hours, though muscle-related symptoms can linger up to 48 hours.
Common Side Effects and How Often They Occur
Clinical trials involving thousands of participants give a clear picture of what to expect. At the 20 mg as-needed dose, 15% of men reported headaches (compared to 5% on placebo), 10% experienced indigestion, and about 3% had muscle aches. At the lower 5 mg daily dose, these numbers drop noticeably: headache occurs in roughly 4 to 6% of users, indigestion in about 2 to 5%, and muscle aches in 1 to 2%.
Other commonly reported effects include flushing (a warm, red feeling in the face or chest), nasal congestion, and back pain. Back pain and muscle aches tend to follow a distinct pattern: they typically show up 12 to 24 hours after taking the medication and resolve within 48 hours. The other common side effects, like headache and flushing, usually fade within a few hours.
Why Tadalafil Causes Muscle Aches
Tadalafil works by blocking an enzyme called PDE5, which helps relax blood vessels and improve blood flow. But it also has some cross-reactivity with a related enzyme, PDE11, found in skeletal muscle tissue. This cross-reactivity is what causes the back pain and muscle aches that are somewhat unique to tadalafil compared to similar medications. It’s not a sign of injury or damage, just an unwanted ripple effect of how the drug interacts with your body.
Daily Dosing vs. As-Needed Dosing
Tadalafil has an unusually long half-life of about 17.5 hours, which is why it can be taken as a low daily dose (2.5 or 5 mg) rather than only before sexual activity (10 or 20 mg). The daily approach tends to produce fewer and milder side effects. Research has found a trend toward fewer side effects with the 5 mg daily dose compared to 20 mg on demand, along with better compliance. If side effects are bothering you on a higher dose, the daily low-dose option may be worth discussing.
The Nitrate Interaction: A Serious Risk
The most dangerous interaction with tadalafil involves nitrate medications, commonly prescribed for chest pain (nitroglycerin, isosorbide). Combining the two can cause a severe, potentially life-threatening drop in blood pressure. Here’s why: both tadalafil and nitrates work through the same pathway to relax blood vessels. Together, they cause an excessive buildup of a signaling molecule that triggers extreme vasodilation, meaning your blood vessels open far wider than they should. In studies, this combination caused standing systolic blood pressure to drop below 85 mmHg in significantly more people than placebo, with the dangerous interaction lasting up to 24 hours after taking tadalafil.
This is not a theoretical concern. If you take any form of nitrate medication, tadalafil is strictly off-limits. Even recreational nitrate use (poppers) carries the same risk.
Blood Pressure Effects With Other Medications
Because tadalafil lowers blood pressure slightly on its own, there’s been concern about combining it with alpha-blockers, which are often prescribed for enlarged prostate symptoms. The good news: studies have found that combining tadalafil 20 mg with certain alpha-blockers (alfuzosin and tamsulosin, specifically) did not produce clinically meaningful blood pressure drops in middle-aged men. The combination showed a positive safety profile. That said, the interaction can vary depending on which alpha-blocker you take, so your prescriber will factor this in.
Rare but Serious Side Effects
A few rare complications deserve attention because they require immediate action.
Priapism is an erection lasting longer than four hours that is unrelated to sexual stimulation. The concerning type involves trapped blood that becomes oxygen-deprived, causing the penis to become fully rigid, tender, and painful. This is a medical emergency because prolonged oxygen deprivation can cause permanent tissue damage. It’s rare with tadalafil, but the long duration of the drug’s effects means you should be aware of it.
Sudden vision changes, including a sudden decrease or loss of vision in one or both eyes, have been reported in a small number of people taking PDE5 inhibitors. This may be linked to a condition affecting blood flow to the optic nerve. People with an inherited eye condition called retinitis pigmentosa are at higher risk and generally should not use tadalafil.
Sudden hearing loss, sometimes with ringing in the ears or dizziness, has also been reported rarely.
Who Should Avoid Tadalafil
Beyond the nitrate restriction, several cardiovascular conditions make tadalafil unsafe. You should not take it if you’ve had a heart attack within the last three months, heart failure within the last six months, a stroke within the last six months, or if you have uncontrolled high or low blood pressure, uncontrolled irregular heartbeat, severe chest pain, or certain structural heart valve problems. These conditions make the blood pressure effects of tadalafil unpredictable and potentially dangerous.
People with retinitis pigmentosa or other retinal disorders are also advised against using it, given the small but real risk of vision complications.