ED Medications: What Are Your Options?

When men and their physicians discuss treating erectile dysfunction, one class of medication comes up first: PDE5 inhibitors. These drugs have transformed the treatment of ED since sildenafil (Viagra) was first approved in 1998. They're effective, relatively well-tolerated, and available at a range of price points.

Here's a clear breakdown of what's available and how they differ.

How PDE5 Inhibitors Work

An erection occurs when sexual stimulation triggers the release of nitric oxide in penile tissue, which produces a molecule called cGMP. cGMP relaxes smooth muscle and widens blood vessels in the penis, allowing blood to flow in and produce an erection.

PDE5 is an enzyme that breaks down cGMP. PDE5 inhibitors do exactly what their name says: they block PDE5. By blocking this breakdown, they allow cGMP to accumulate, amplifying and prolonging the physiological response to sexual stimulation.

This is an important point: PDE5 inhibitors don't cause erections on their own. They amplify the response to sexual stimulation. Without arousal, they don't work.

The Four Available PDE5 Inhibitors

Sildenafil (Viagra, generic)

The original. Available since 1998, now widely available as generic sildenafil at a fraction of the brand name cost.

• Takes effect: 30-60 minutes after dosing
• Duration: 4-6 hours
• Best taken: On an empty or light stomach (high-fat meals slow absorption)
• Most common doses: 25 mg, 50 mg, 100 mg

Tadalafil (Cialis, generic)

Known as "the weekend pill" because of its much longer duration.

• Takes effect: 30-45 minutes after dosing
• Duration: Up to 36 hours
• Food interaction: Minimal — can be taken with food
• Most common doses: 10 mg, 20 mg as needed; or 2.5-5 mg daily (low-dose continuous use)

Daily tadalafil (2.5-5 mg) is an option for men who prefer not to plan around a pill — you take it every day and the medication maintains steady blood levels. [A 2017 meta-analysis](https://pubmed.ncbi.nlm.nih.gov/28741090/) found tadalafil and sildenafil had similar efficacy and safety profiles, with most patients and their partners preferring tadalafil's longer duration.

Vardenafil (Levitra, generic)

Similar profile to sildenafil but slightly more selective.

• Takes effect: 25-60 minutes after dosing
• Duration: 4-8 hours
• Somewhat less affected by food than sildenafil

Avanafil (Stendra)

The newest in the class. Notable for its faster onset — some men notice effects in as little as 15-30 minutes — and potentially fewer side effects.

• Takes effect: 15-30 minutes after dosing
• Duration: 6 hours
• Currently only available as brand name (more expensive)

Side Effects

PDE5 inhibitors share a similar side effect profile:

• Headache (most common)
• Facial flushing
• Nasal congestion
• Indigestion
• Visual changes (sildenafil more commonly than others)
• Dizziness, particularly with positional changes

These are generally mild and temporary. Serious side effects are uncommon but exist.

The Critical Drug Interaction: Nitrates

PDE5 inhibitors are contraindicated with nitrates. Nitrates (including nitroglycerin, isosorbide dinitrate) used for chest pain lower blood pressure through a related mechanism. Combining them with PDE5 inhibitors can cause a dangerous, potentially life-threatening drop in blood pressure. [Hemodynamic studies](https://pubmed.ncbi.nlm.nih.gov/14609622/) have documented significant blood pressure drops when PDE5 inhibitors are co-administered with nitrates, and [review of cardiovascular effects](https://pubmed.ncbi.nlm.nih.gov/16884667/) confirms this interaction is absolute across all PDE5 inhibitors.

If you take any nitrate medications — or use poppers (amyl nitrite) recreationally — you cannot safely use PDE5 inhibitors. This is not a relative contraindication — it's absolute.

Which One Is Right for You?

The "best" PDE5 inhibitor is the one that works for you with the fewest side effects and best fits how you want to use it. Some considerations:

• If you want flexibility and low cost: sildenafil (generic is inexpensive)
• If you dislike timing around a pill: daily tadalafil
• If you want maximum spontaneity: avanafil
• If food often accompanies intimacy: tadalafil (minimal food interaction)

Your physician can help you weigh these and choose an appropriate starting dose based on your health history.

Ready to talk to a real doctor? Get started with Coral Health today.

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Sources

• Gong B et al. Tadalafil versus sildenafil in the treatment of erectile dysfunction: a systematic review and meta-analysis. International Urology and Nephrology, 2017. [PubMed](https://pubmed.ncbi.nlm.nih.gov/28741090/)
• Kloner RA. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. American Journal of Cardiology, 2003. [PubMed](https://pubmed.ncbi.nlm.nih.gov/14609622/)
• Prisant LM. Phosphodiesterase-5 inhibitors and their hemodynamic effects. Current Hypertension Reports, 2006. [PubMed](https://pubmed.ncbi.nlm.nih.gov/16884667/)