ED medication refers to prescription drugs that treat erectile dysfunction by increasing blood flow to the penis. The most common type is a class of oral pills called PDE5 inhibitors, which include four FDA-approved options. Non-oral alternatives also exist for people who can’t take pills or don’t respond to them.
How ED Medication Works
An erection starts in the brain. Visual, physical, or mental arousal triggers nerve signals that release a chemical called nitric oxide into the tissue of the penis. Nitric oxide sets off a chain reaction: it activates an enzyme that produces a molecule called cGMP, which relaxes the smooth muscle lining the blood vessels and spongy tissue inside the penis. As that muscle relaxes, blood flows in and an erection forms.
The body also produces an enzyme called PDE5, whose job is to break down cGMP and end the erection. In men with erectile dysfunction, this breakdown happens too quickly or the cGMP signal is too weak to produce a firm erection. PDE5 inhibitors block that cleanup enzyme, allowing cGMP to accumulate and sustain the erection longer. One critical detail: these drugs only work when you’re sexually aroused. Without that initial nitric oxide release from arousal, there’s no cGMP to protect, and the medication does nothing.
The Four Oral ED Medications
Four PDE5 inhibitors are currently approved for ED in the United States:
- Sildenafil (Viagra): The original, approved in 1998. Starting dose is 50 mg, with a maximum of 100 mg per day. Best taken about an hour before sexual activity. Peak blood levels occur around 60 minutes after swallowing the pill.
- Tadalafil (Cialis): Known for its long duration. Starting dose is 10 mg, maximum 20 mg. Takes longer to reach peak levels (about two hours), but its effects can last up to 36 hours, earning it the nickname “the weekend pill.” Also available in a low daily dose for continuous use.
- Vardenafil: Similar profile to sildenafil. Starting dose of 10 mg, maximum 20 mg. Reaches peak levels in about 60 minutes.
- Avanafil (Stendra): The newest option, designed for speed. It can start working in as little as 15 minutes, with peak levels at 30 to 45 minutes. Its shorter half-life of 3 to 5 hours means side effects also tend to clear faster.
Generic versions of sildenafil, vardenafil, and tadalafil are available, which has brought prices down significantly. All four require a prescription, and the maximum dosing frequency for each is once per day.
How to Choose Between Them
The main practical differences come down to timing and flexibility. If you want something you can take well in advance and not worry about a narrow window, tadalafil’s long duration gives the most flexibility. If spontaneity matters and you want the fastest possible onset, avanafil works in roughly half the time of sildenafil. Sildenafil and vardenafil sit in the middle, effective for most men with a roughly one-hour lead time.
Prescribing information for sildenafil notes that a high-fat meal can delay absorption and reduce peak blood levels, though clinical testing has found no significant loss of effectiveness when taken shortly before or with food. Tadalafil is generally less affected by meals. These are the kinds of real-world details worth discussing with a prescriber when picking the best fit for your routine.
Common Side Effects
Because PDE5 inhibitors relax blood vessels throughout the body (not just in the penis), the most frequent side effects are related to blood flow changes. Based on pharmacovigilance data and FDA labeling, the most commonly reported ones include:
- Headache: Reported in roughly 10 to 28% of users depending on the drug and dose
- Flushing: A warm, red feeling in the face or chest, affecting about 5 to 17%
- Indigestion: Reported in about 3 to 11%
- Visual changes: A bluish tint or increased light sensitivity, more common with sildenafil
These side effects are typically mild and fade as the drug leaves your system. Avanafil’s shorter half-life means side effects generally resolve faster than with longer-acting options like tadalafil.
The Nitrate Warning
The single most important safety rule with ED medication is to never combine it with nitrate drugs. Nitrates are commonly prescribed for chest pain (angina) and work by donating nitric oxide to relax blood vessels. Adding a PDE5 inhibitor on top of that creates a double hit: more nitric oxide plus blocked cGMP breakdown. The result can be a severe, dangerous drop in blood pressure.
In controlled studies, nearly half of participants who took sildenafil followed by a nitrate one hour later experienced dizziness, and several needed to be placed flat with their legs elevated to restore blood pressure. The recommended minimum gap between the two drugs is 24 hours, though for tadalafil, which stays active longer, prescribers often advise an even wider window. If you take any form of nitrate, including short-acting tablets or sprays for occasional chest pain, PDE5 inhibitors are not safe for you.
Non-Oral Alternatives
For men who don’t respond to pills or can’t take them due to drug interactions, a medication called alprostadil offers a different approach. Rather than working through the nitric oxide pathway, alprostadil directly relaxes the smooth muscle and blood vessels in the penis.
It comes in two forms. The first is an injection delivered with a fine needle directly into the side of the penis. The second is a tiny pellet inserted into the urethral opening. The injection typically produces an erection within 5 to 20 minutes, while the pellet works in 5 to 10 minutes. Either way, the erection lasts roughly 30 to 60 minutes. Injections are limited to three times per week with at least 24 hours between uses. The pellets can be used up to twice in a 24-hour period.
The idea of a penile injection understandably gives most people pause, but the needles are very small, and many men who switch to injections after pills fail report satisfaction with the results. A healthcare provider will walk you through the technique and supervise your first dose to find the right amount.
Getting ED Medication Safely
All ED medications in the U.S. require a prescription. This is partly because a provider needs to screen for contraindications like nitrate use, and partly because erectile dysfunction itself can be an early sign of cardiovascular disease, diabetes, or other conditions worth investigating.
The FDA warns that many online pharmacies sell ED drugs without requiring a prescription, and these products may contain the wrong active ingredient, too much or too little of the drug, or harmful contaminants. Some have been found to contain completely different medications. A legitimate online pharmacy will always require a valid prescription and will be licensed in the state where it operates. Telehealth services that include a consultation with a licensed provider before prescribing are a convenient and legal option, but any site that lets you buy pills with no medical evaluation at all is a red flag.