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If you’re weighing tadalafil vs avanafil, you’re probably trying to figure out one specific thing: which one is less likely to give you a headache, flushing, or a stuffy nose the next morning. That’s the question most patients actually ask at the pharmacy counter, even if they phrase it differently.
Both drugs are PDE5 inhibitors, the same class as sildenafil (Viagra) and vardenafil. Both are FDA-approved for erectile dysfunction. But they behave very differently in the body, and the side-effect profile reflects that.
The short version: avanafil tends to cause fewer and shorter-lasting side effects. Tadalafil tends to work longer and offer more flexibility. The right pick depends on what you’re optimizing for.
How Tadalafil vs Avanafil Actually Work
Both medications block phosphodiesterase type 5, the enzyme that breaks down cGMP in penile smooth muscle. Block the enzyme, blood vessels relax, blood flow improves, and an erection becomes possible with sexual stimulation.
The difference is selectivity and half-life. Avanafil (brand name Stendra) is the newest PDE5 inhibitor, approved by the FDA in 2012. It’s more selective for PDE5 than for related enzymes (PDE6 in the retina, PDE11 in skeletal muscle), which is the main reason it tends to cause fewer visual side effects and less back pain.
Tadalafil (brand name Cialis) is the long-acting one. Its half-life is about 17.5 hours, compared with roughly 5 hours for avanafil. That’s why tadalafil earned the "weekend pill" nickname, and why it’s also approved for daily dosing and for BPH. If you want a deeper look at that dual use, our piece on whether tadalafil can treat both BPH and ED walks through the evidence.
Side Effect Profiles Compared
Here’s where the comparison gets practical. According to MedlinePlus and the FDA prescribing information, the most common side effects of each drug look like this.
Tadalafil, common side effects:
- Headache (about 11 to 15% of users)
- Back pain or muscle aches (roughly 6%, often delayed 12 to 24 hours)
- Indigestion or reflux
- Nasal congestion
- Flushing
- Limb pain
Avanafil, common side effects:
- Headache (about 7 to 10%)
- Flushing (around 3 to 10%)
- Nasal congestion
- Mild back pain (under 3%)
- Less commonly, dizziness
The back pain difference is notable. Tadalafil’s longer half-life and weaker selectivity against PDE11 are the suspected reasons some men get that dull lower-back ache the day after. Avanafil’s tighter selectivity largely sidesteps that problem.
Visual disturbances, like blue-tinged vision, show up more with sildenafil and vardenafil than with either tadalafil or avanafil. Both of the drugs we’re comparing here are relatively kind to the eyes.
Onset, Duration, and Real-World Use
Avanafil is fast. It can start working in 15 to 30 minutes, with some men responding in as little as 15. That’s the fastest onset of any oral ED drug currently on the market.
Tadalafil is slower to start, usually 30 to 45 minutes, but lasts up to 36 hours. For couples who don’t want to plan around a pill, that’s a meaningful advantage. The trade-off is that any side effect you get also sticks around longer. A headache from avanafil might be gone by morning. A headache from tadalafil could linger into the next day.
If you’re trying to decide between dosing strategies, our breakdown of tadalafil daily versus on-demand dosing is worth a read. Daily low-dose tadalafil tends to smooth out the side-effect peaks and is often better tolerated than higher on-demand doses.
Drug Interactions and Safety Concerns
Both drugs share the same critical contraindication: never combine with nitrates (nitroglycerin, isosorbide). The combination can cause a dangerous drop in blood pressure. The American Heart Association has clear guidance on this for patients with cardiovascular disease.
Other interactions to flag with your prescriber:
- Alpha-blockers for BPH or blood pressure (tamsulosin, doxazosin)
- Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin)
- Other PDE5 inhibitors (don’t stack them)
- Significant alcohol intake, especially with tadalafil
Men with severe liver disease, recent stroke, unstable angina, or significant low blood pressure shouldn’t take either drug without specialist input. For a broader comparison across the whole class, our overview of the top 10 ED pills lays out the pros and cons side by side.
If cost is a factor, generic tadalafil is widely available and usually inexpensive. Generic avanafil exists but is less common and often more expensive at retail. You can compare prices on generic tadalafil and avanafil at edrugstore.com to see what fits your budget.
So Which Has Fewer Side Effects?
The honest answer in the tadalafil vs avanafil comparison: avanafil generally wins on side-effect frequency and duration, especially for back pain, muscle aches, and the lingering "next-day" feeling. Multiple clinical trials, including data summarized in PubMed-indexed reviews, show avanafil’s discontinuation rates due to side effects sit in the low single digits.
That said, "fewer side effects" is not the same as "better drug for you." Most patients I see end up choosing tadalafil because the 36-hour window matters more to them than the modest difference in side-effect profile. A small subset who get bad back pain or who want the fastest onset switch to avanafil and stay there.
The Bottom Line
In the tadalafil vs avanafil decision, avanafil offers a slightly cleaner side-effect profile and faster onset, while tadalafil offers far longer duration and more dosing flexibility. Both are effective for most men with ED, and both are safe when used as prescribed and screened for interactions.
If side effects from tadalafil have been bothering you, ask your prescriber whether a lower daily dose, or a switch to avanafil, makes sense for your situation. And if you’ve never tried either, talk to your pharmacist about which profile fits your health history, your other medications, and what you actually want out of treatment.
This article is for informational purposes only and is not medical advice. Always consult a licensed pharmacist or physician before starting, stopping, or changing any medication.
References
- FDA Drug Approvals and Databases, official approval status and prescribing information for PDE5 inhibitors.
- MedlinePlus: Tadalafil, NIH-curated patient information on dosing and side effects.
- American Heart Association: Cardiac Medications, guidance on nitrate interactions with ED drugs.
- PubMed, peer-reviewed clinical trial data on avanafil tolerability and discontinuation rates.
Dr Steven Schlosser
Dr. Schlosser graduated from Lafayette College Phi Beta Kappa and attended Georgetown Medical School. He had 4 years of medical residency training at Tufts University in Boston in both Gynecology and Internal Medicine. He has had a spotless medical career for the past 40+ years and is Board Certified. Learn More