ED medication comparison

The four oral medications FDA-approved for erectile dysfunction — sildenafil, tadalafil, vardenafil, and avanafil — all belong to the same class: phosphodiesterase type 5 (PDE5) inhibitors. They work by the same mechanism, they're all effective, and they share the same serious interactions. The differences come down to how fast they act, how long they last, their side effect patterns, and their cost.

This guide walks through each medication in depth, compares them in a single table, and lays out which one is typically a better fit for which situation. It draws on FDA prescribing information, the American Urological Association's ED guideline, and peer-reviewed data summarized by the National Institutes of Health.

The short answer

• Plan-ahead, occasional use, cheapest option: generic sildenafil (Viagra)
• Spontaneity, or a long weekend: tadalafil (Cialis) as-needed
• Continuous readiness or also treating enlarged prostate: daily low-dose tadalafil (2.5 mg or 5 mg)
• Fastest onset with fewest side effects: avanafil (Stendra)
• Didn't tolerate sildenafil but want short duration: vardenafil (Levitra)

How PDE5 inhibitors work

An erection begins with sexual arousal, which releases nitric oxide in the penis. Nitric oxide triggers production of cyclic GMP (cGMP), which relaxes smooth muscle and allows blood to flow into the corpus cavernosum. An enzyme called PDE5 breaks down cGMP — eventually ending the erection. PDE5 inhibitors block that enzyme, keeping cGMP levels high and making it easier to achieve and maintain an erection in response to normal sexual stimulation. Without arousal, they don't do much — they aren't aphrodisiacs.

Side-by-side comparison

Sildenafil (generic Viagra)

The original PDE5 inhibitor and still the most widely prescribed ED medication in the world. Sildenafil is the cheapest option by a wide margin and has the deepest body of research behind it.

Best for

• Planned, occasional use
• First-time ED patients who want to start cheap
• People who don't eat a heavy meal before sex

Dosing

Start 50 mg taken 30–60 minutes before sexual activity. Adjust to 25 mg or 100 mg based on response and tolerability. Max one dose per day. A high-fat meal can delay onset by an hour.

Side effects

Most common: headache (16%), flushing (10%), indigestion (7%), nasal congestion (4%), visual changes such as blue-tinted vision (3%). These are usually mild and transient.

Tadalafil (generic Cialis)

Tadalafil's long half-life (about 17.5 hours) makes it the only PDE5 inhibitor with a practical daily-use option. It's marketed informally as "the weekend pill" because a single 20 mg dose can cover up to 36 hours.

Best for

• Spontaneity — no timing a pill before sex
• Men with enlarged prostate (BPH) symptoms; daily tadalafil is FDA-approved for both
• Frequent sexual activity (more than twice a week)

Dosing

• As needed: 10 mg 30–60 minutes before sex, adjust 5–20 mg
• Daily: 2.5 mg or 5 mg once daily at the same time — steady state in ~5 days

Side effects

Headache (~15%), indigestion (~10%), back pain (~6%), muscle aches (~3%), nasal congestion. Back pain is more characteristic of tadalafil than the others and usually appears 12–24 hours after the dose.

Vardenafil (Levitra, Staxyn)

Vardenafil is chemically similar to sildenafil with a slightly different side-effect profile. Generic vardenafil is available but less commonly stocked — some pharmacies special-order it. Staxyn is an orally disintegrating version.

Best for

• People who tried sildenafil and had bothersome side effects (visual changes, flushing) and want another short-acting option
• Those who prefer a dissolving tablet (Staxyn)

Dosing

Start 10 mg about 60 minutes before sex; adjust 5–20 mg. High-fat meals reduce absorption.

Side effects

Very similar to sildenafil. Vardenafil can prolong QT interval on ECG at higher doses, so it's avoided in people with certain cardiac arrhythmias or who take medications that also prolong QT.

Avanafil (Stendra)

The newest of the four, approved by the FDA in 2012. Avanafil is designed for rapid onset and PDE5 selectivity, which translates to fewer off-target side effects.

Best for

• Fastest onset (effective in about 15 minutes)
• Lowest reported rate of visual disturbances and flushing
• Those who've had intolerable side effects on sildenafil or tadalafil

Dosing

Start 100 mg 15–30 minutes before sex; adjust 50–200 mg based on response.

Side effects

Fewest of the group — headache (~10%), flushing (~4%), nasal congestion (~3%). Back pain rates lower than tadalafil. The tradeoff is cost: avanafil remains substantially more expensive.

Who should not take PDE5 inhibitors

Other situations where PDE5 inhibitors are not appropriate, or need specialist input:

• Severe cardiovascular disease — unstable angina, recent heart attack or stroke (within 6 months), uncontrolled heart failure, severe hypotension
• Alpha-blocker use (doxazosin, terazosin) — can cause additive blood pressure drops; timing and dose adjustments are needed
• Severe liver or kidney impairment — dose reductions required
• Non-arteritic anterior ischemic optic neuropathy (NAION) — a rare vision-loss condition associated with PDE5 inhibitors; avoid in those with a prior episode
• Peyronie's disease or anatomical penile deformity — evaluate with a urologist first
• Sickle cell disease, multiple myeloma, leukemia — increased priapism risk
• HIV protease inhibitors, certain antifungals, or macrolide antibiotics (ritonavir, ketoconazole, clarithromycin) — these strongly raise PDE5 inhibitor levels; dose reductions required

Side effects to know

Across all four medications, common side effects are mild and short-lived: headache, facial flushing, nasal stuffiness, indigestion, and minor visual changes. Serious but rare side effects include:

• Priapism — an erection lasting more than 4 hours; a medical emergency. Go to the ER.
• Sudden hearing loss — rare; stop the medication and seek evaluation
• Sudden vision loss (NAION) — rare; stop immediately and see an ophthalmologist
• Severe hypotension — more likely with nitrates, alpha-blockers, or heavy alcohol

How to choose

A practical decision tree:

1. Are you taking nitrates or "poppers"? None of these are safe. Talk to a cardiologist first.
2. Do you want to plan each encounter or feel ready anytime? Plan = sildenafil or avanafil. Anytime = daily tadalafil.
3. Do you need the fastest onset? Avanafil.
4. Do you also have BPH (enlarged prostate) symptoms? Daily tadalafil treats both.
5. Is cost a factor? Generic sildenafil.

Most Bidwell providers start with sildenafil or tadalafil because of cost and the breadth of safety data, then adjust based on your response.

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