PDE5 Inhibitors: Types, Uses, Side Effects & Comparison

Remote Pharmacy Research Team
August 28, 2025

Phosphodiesterase type 5 (PDE5) inhibitors are one of the most commonly prescribed treatments for erectile dysfunction (ED) and other related conditions. These medications work by improving blood flow to specific areas of the body, helping men achieve and maintain erections. They are also used in some cases to manage pulmonary arterial hypertension. Understanding how these drugs work, their different types, potential side effects, and how they compare to one another is essential before starting any treatment. In this guide, we’ll cover everything you need to know about PDE5 inhibitors and how they can support your sexual health.

What Are PDE5 Inhibitors and How Do They Work?

PDE5 inhibitors are a class of medications primarily prescribed to treat erectile dysfunction (ED) by improving blood flow to the penis. They work by blocking the enzyme phosphodiesterase type 5 (PDE5), which naturally breaks down cyclic guanosine monophosphate (cGMP).

When PDE5 is inhibited, cGMP levels remain elevated for longer periods, which relaxes smooth muscle cells and allows more blood to flow into the erectile tissue during sexual stimulation. This process helps men achieve and maintain stronger, longer-lasting erections.

Beyond ED, some PDE5 inhibitors are also prescribed for pulmonary arterial hypertension (PAH), a condition where high blood pressure affects the arteries in the lungs. By enhancing vasodilation, these medications improve blood circulation and reduce pressure in the pulmonary arteries.

Types of PDE5 Inhibitor Medications Compared

There are four main PDE5 inhibitors commonly prescribed for erectile dysfunction and other vascular-related conditions. While they all work by inhibiting the PDE5 enzyme to increase blood flow, each medication differs in onset time, duration, and potential side effects.

Tadalafil (Cialis / Adcirca)

Tadalafil is one of the most popular PDE5 inhibitors due to its long-lasting effects, which can last up to 36 hours. Often referred to as “the weekend pill,” it allows for greater spontaneity compared to other medications. It is also approved under the brand name Adcirca for treating pulmonary arterial hypertension.

  • Onset: Around 30 minutes
  • Duration: Up to 36 hours
  • Best for: Patients seeking flexibility and fewer timed doses

Sildenafil (Viagra / generic)

Sildenafil was the first PDE5 inhibitor introduced to the market under the brand name Viagra and remains one of the most prescribed medications for ED. It is also available in generic forms, making it more affordable.

  • Onset: 30 to 60 minutes
  • Duration: Around 4 to 6 hours
  • Best for: Patients who need a short-acting, cost-effective option

Avanafil (Stendra)

Avanafil is a newer PDE5 inhibitor designed to act faster and with fewer side effects compared to older drugs. Some users experience results in as little as 15 minutes, making it one of the fastest-acting medications in this class.

  • Onset: 15 to 30 minutes
  • Duration: 6 to 8 hours
  • Best for: Patients prioritizing rapid onset and fewer interactions

Vardenafil (Levitra)

Vardenafil, sold under the brand name Levitra, is similar to sildenafil but often preferred by patients who experience fewer side effects. It also tends to have slightly longer-lasting effects compared to Viagra.

  • Onset: 30 to 60 minutes
  • Duration: 6 to 8 hours
  • Best for: Patients who are sensitive to sildenafil or seeking a slightly longer duration

Uses of PDE5 Inhibitors

PDE5 inhibitors are primarily prescribed to improve blood flow by relaxing the smooth muscles in blood vessels. While they are most commonly associated with treating erectile dysfunction, their clinical applications extend beyond sexual health.

Erectile Dysfunction (ED)

PDE5 inhibitors are the first-line treatment for erectile dysfunction because they enhance blood flow to the penis, making it easier to achieve and maintain an erection during sexual stimulation.

Pulmonary Arterial Hypertension (PAH)

Medications like Tadalafil (Adcirca) and Sildenafil (Revatio) are also FDA-approved for treating PAH, a rare condition characterized by high blood pressure in the lungs’ arteries. By relaxing these blood vessels, PDE5 inhibitors reduce strain on the heart and improve exercise capacity.

Benign Prostatic Hyperplasia (BPH)

Tadalafil is sometimes prescribed to manage symptoms of BPH, such as frequent urination or difficulty starting urination, by relaxing the smooth muscle tissue around the bladder and prostate.

Common Side Effects of PDE5 Inhibitors

PDE5 inhibitors are generally considered safe and well-tolerated when used as prescribed. However, like any medication, they can cause side effects that vary in severity and frequency. Understanding these potential reactions can help you manage them effectively and decide when to seek medical guidance.

Mild and Common Side Effects

These are the most frequently reported side effects and typically resolve as the body adjusts to the medication:

  • Headache
  • Flushing (skin redness)
  • Nasal congestion
  • Dizziness or lightheadedness
  • Indigestion or upset stomach

Moderate Side Effects

Some people may experience more noticeable discomfort that should be monitored:

  • Vision changes
  • Tinnitus or mild hearing changes
  • Muscle and back pain (more common with Tadalafil)
  • Prolonged nasal congestion or sinus pressure

If these effects persist or interfere with daily life, discuss dosage adjustments with your doctor.

Rare but Serious Side Effects

Though uncommon, certain reactions require immediate medical attention:

  • Priapism
  • Severe vision loss
  • Sudden hearing loss
  • Severe allergic reactions such as rash, swelling, or difficulty breathing

These cases are rare but highlight the importance of consulting a healthcare provider before starting or combining PDE5 inhibitors with other medications.

Interaction-Related Risks

Combining PDE5 inhibitors with nitrate medications (e.g., nitroglycerin) or certain alpha-blockers can cause a dangerous drop in blood pressure. Always disclose your full medication list to your doctor before starting treatment.

Comparing Safety Profiles of Different PDE5 Inhibitors

While all PDE5 inhibitors share a similar mechanism of action, their safety profiles differ slightly based on half-life, potency, and how the body metabolizes them. Understanding these nuances helps patients and healthcare providers select the best option depending on individual needs and tolerance.

Tadalafil (Cialis / Adcirca)

  • Duration: Up to 36 hours, earning it the nickname “the weekend pill.”
  • Common Side Effects: Muscle aches and lower back pain occur more frequently than with other PDE5 inhibitors due to its longer activity.
  • Best For: Patients seeking flexibility in timing intercourse and those who prefer daily microdosing for chronic erectile dysfunction or benign prostatic hyperplasia (BPH).
  • Caution: Avoid high alcohol intake, as the combination can significantly lower blood pressure.

Sildenafil (Viagra / Generic)

  • Duration: Around 4 to 6 hours; quick onset within 30 to 60 minutes.
  • Common Side Effects: Headache, flushing, nasal congestion, and mild indigestion are the most reported.
  • Best For: Those who want a fast-acting, short-duration treatment, especially when intimacy is planned.
  • Caution: Should be avoided with fatty meals, which can delay absorption and effectiveness.

Avanafil (Stendra)

  • Duration: Approximately 6 hours but acts very quickly, sometimes in as little as 15 minutes.
  • Common Side Effects: Lower incidence of headaches and flushing compared to other PDE5 inhibitors, making it generally better tolerated.
  • Best For: Patients who prioritize minimal side effects and rapid onset.
  • Caution: Since it is newer, long-term safety data is somewhat more limited.

Vardenafil (Levitra)

  • Duration: Lasts 4 to 5 hours with onset similar to Sildenafil.
  • Common Side Effects: Flushing, nasal congestion, headache, and sometimes vision changes.
  • Best For: Men who do not respond well to Sildenafil but prefer a similar window of action.
  • Caution: Should be used cautiously in individuals with cardiac conditions due to potential blood pressure effects.

Key Takeaways

  • Avanafil tends to have the lowest risk of side effects overall.
  • Tadalafil provides the longest duration but may cause muscle aches more often.
  • Sildenafil and Vardenafil are reliable but have a higher chance of headaches and flushing.
  • Regardless of the choice, always consult a doctor before combining these drugs with nitrates or alcohol.

Real-Life Access: Prescriptions, Telehealth & Availability

Getting access to PDE5 inhibitors is easier than ever thanks to the rise of telehealth platforms and online pharmacies. While these medications traditionally required an in-person doctor’s visit, you can now consult with licensed healthcare providers remotely and receive your prescription without leaving home

Traditional Pharmacy vs Online Consultation

Traditionally, obtaining medications like Sildenafil, Tadalafil, or Avanafil meant scheduling a doctor’s appointment, undergoing an evaluation, and physically visiting a pharmacy to pick up your prescription. While effective, this process can be time-consuming and less discreet.

With Remote Pharmacy, the experience is far more convenient, confidential, and patient-focused. Our modern approach simplifies treatment while maintaining safety and privacy, ensuring you get the right medication without unnecessary steps.

Quick FAQs - Simplified Answers on PDE5 Inhibitors

Can You Use These If You Have Psychological ED?

Yes, you can, but effectiveness varies. PDE5 inhibitors like Sildenafil and Tadalafil primarily work on vascular issues, increasing blood flow to the penis. If psychological factors such as anxiety, stress, or relationship issues are the main cause, the medication may help partially, but it is often more effective when combined with therapy or counseling. A doctor’s assessment is highly recommended to determine the best approach.

Are Herbal Alternatives Safe?

Not always. Many herbal supplements marketed as “natural Viagra” are not FDA-regulated and may contain undisclosed or unsafe ingredients. Some even interact dangerously with heart medications or blood pressure treatments. If you’re considering herbal alternatives, always consult a healthcare provider first and stick to evidence-backed options when possible.

Is Daily Use Right for You?

Daily use of certain PDE5 inhibitors like Tadalafil (Cialis) can be safe and effective for some patients, especially those with chronic ED or benign prostatic hyperplasia (BPH). However, it’s not suitable for everyone, especially those with heart conditions, low blood pressure, or specific medication interactions. Always start under medical supervision to ensure the right dosage and avoid unnecessary risks.

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