How Does Avanafil Work to Treat ED?

How Does Avanafil Work to Treat Erectile Dysfunction?

Published: 6 November 2026

How does avanafil work? Avanafil is a phosphodiesterase type 5 (PDE5) inhibitor that works by relaxing blood vessels in the penis, allowing increased blood flow during sexual stimulation to help achieve and maintain an erection [6]. It is the fastest-acting oral ED treatment licensed in the UK, marketed as Spedra, and can start working in as little as 15–30 minutes [11]. Unlike some older ED medicines, avanafil is highly selective for the PDE5 enzyme, which may reduce the risk of certain side effects while delivering effective results when sexual arousal is present.

Understanding How Avanafil Works: The PDE5 Mechanism

To understand how avanafil works, it helps to know what happens during a normal erection. Sexual stimulation triggers the release of nitric oxide in the penis, which activates an enzyme called guanylate cyclase. This enzyme increases levels of cyclic guanosine monophosphate (cGMP), a chemical messenger that relaxes smooth muscle in the penile arteries and allows blood to flow in, producing an erection [6].

The enzyme phosphodiesterase type 5 (PDE5) breaks down cGMP, which naturally ends the erection. In men with erectile dysfunction, this breakdown can happen too quickly or blood flow may be insufficient. Avanafil blocks PDE5, preventing the breakdown of cGMP and allowing it to accumulate. This prolongs the relaxation of blood vessels and enhances blood flow to the penis when sexual stimulation occurs [6].

Crucially, avanafil does not cause an erection on its own—sexual arousal is still required to trigger the release of nitric oxide and start the process. This means avanafil supports the body's natural response rather than forcing an artificial reaction [11].

How Quickly Does Avanafil Work Compared to Other ED Treatments?

One of the key advantages of avanafil is its rapid onset of action. Clinical trials have shown that avanafil can start working in as little as 15–30 minutes after taking a tablet, making it the fastest-acting PDE5 inhibitor available in the UK [11]. This is significantly quicker than sildenafil (Viagra), which typically takes about one hour, or tadalafil (Cialis), which requires at least 30 minutes [3][4].

The speed of avanafil is particularly useful for men who prefer more spontaneity, as it allows less planning time before sexual activity. However, the actual onset can vary between individuals depending on factors such as whether the tablet is taken with food, individual metabolism, and overall health [6].

Despite its fast action, avanafil's effects do not last as long as tadalafil, which can remain effective for up to 36 hours. Avanafil's duration is more comparable to sildenafil and vardenafil, typically lasting around 4–6 hours [6][11]. This makes it ideal for on-demand use rather than daily dosing.

Taking Avanafil for Best Results

Avanafil is available in 50mg, 100mg, and 200mg tablets. The usual starting dose is 100mg, taken about 15–30 minutes before sexual activity, with a maximum of one dose per day [6]. Your prescriber may adjust the dose depending on how well it works and whether you experience any side effects.

Avanafil can be taken with or without food, although a very heavy or high-fat meal may slow its absorption slightly. Avoiding excessive alcohol is important, as alcohol can worsen erectile dysfunction and increase the risk of side effects such as dizziness or low blood pressure [6].

How Does Avanafil Work Differently from Sildenafil and Tadalafil?

All PDE5 inhibitors—avanafil, sildenafil, tadalafil, and vardenafil—work by the same basic mechanism of blocking the PDE5 enzyme. However, they differ in their selectivity, speed, and duration of action [6]. Avanafil is highly selective for PDE5, meaning it has less effect on other phosphodiesterase enzymes found elsewhere in the body, such as PDE6 in the retina or PDE11 in skeletal muscle [11].

This selectivity may reduce the likelihood of certain side effects. For example, sildenafil's action on PDE6 can occasionally cause temporary visual disturbances such as a blue tinge to vision, whereas avanafil's higher selectivity makes this less common [6][11]. Similarly, the risk of muscle aches—sometimes associated with tadalafil due to PDE11 activity—may be lower with avanafil.

In terms of onset, avanafil is the fastest, while tadalafil offers the longest duration. Sildenafil and vardenafil sit somewhere in between. The choice between these medicines often comes down to personal preference, lifestyle, and how your body responds. All are effective treatments and require a prescription following a clinical assessment [2][6].

Who Can Use Avanafil and How Does It Work Safely?

Avanafil is licensed for adult men with erectile dysfunction and is only available on prescription after a consultation with a UK-registered prescriber [6]. It is not suitable for everyone. You must not take avanafil if you use nitrate medicines (such as GTN spray, isosorbide mononitrate, or isosorbide dinitrate) for angina, nicorandil, riociguat, or recreational drugs known as 'poppers' (amyl or alkyl nitrites). Combining avanafil with these can cause a dangerous drop in blood pressure [6].

Men taking alpha-blockers for prostate problems or high blood pressure (such as doxazosin or tamsulosin) can usually use avanafil, but must be stable on the alpha-blocker and start on the lowest dose of avanafil to minimise the risk of dizziness or fainting [6]. If you take medicines that strongly inhibit the liver enzyme CYP3A4—such as ritonavir, cobicistat, ketoconazole, itraconazole, or clarithromycin—avanafil is usually contraindicated or requires significant dose adjustment, so your prescriber will review your current medicines carefully [6].

Avanafil is not suitable if sexual activity is inadvisable due to serious heart conditions (recent heart attack or stroke, unstable angina, severe heart failure), very low blood pressure, previous sudden vision loss (NAION), or certain inherited eye disorders [6]. Always disclose your full medical history and all current medicines during your consultation.

Common Side Effects and What to Expect

Like all medicines, avanafil can cause side effects, though not everyone experiences them. The most common include headache, flushing (redness of the face), nasal congestion, and back pain [6]. These are usually mild and short-lived. Dizziness can occur, especially if you also take blood-pressure medicines or alpha-blockers, so it's important to stand up slowly and avoid driving if affected.

Rare but serious side effects include an erection lasting more than four hours (priapism), sudden loss of vision or hearing, or chest pain during sex. If any of these occur, seek urgent medical help immediately [6]. Most men tolerate avanafil well, and side effects often lessen with continued use.

How Does Avanafil Work with Other Medications?

Understanding how avanafil works with other medications is essential for safe use. As mentioned, avanafil must never be combined with nitrates, nicorandil, riociguat, or poppers due to the risk of severe low blood pressure [6]. If you take alpha-blockers, your prescriber will ensure you are stable on that treatment and will start avanafil at the lowest dose [6].

Potent CYP3A4 inhibitors significantly increase avanafil levels in the blood, raising the risk of side effects. These include HIV medicines (ritonavir, cobicistat), antifungals (ketoconazole, itraconazole), and some antibiotics (clarithromycin). Avanafil is generally contraindicated with these medicines, or the dose must be carefully adjusted [6]. Conversely, CYP3A4 inducers such as rifampicin, carbamazepine, phenytoin, and St John's wort can reduce avanafil's effectiveness, so your prescriber may recommend an alternative ED treatment.

Other blood-pressure medicines can add to the blood-pressure-lowering effect of avanafil, which is usually manageable but must be declared during your consultation. Grapefruit juice can also raise avanafil levels and should be avoided [6]. For any medicine not listed here, do not assume the combination is safe—your prescriber and pharmacist will check every current medicine during your consultation, and you should never stop or change a prescribed medicine without professional advice.

How Does Avanafil Work in Practice: Getting Treatment at Cured Pharmacy

At Cured Pharmacy, avanafil is available as Spedra following an online consultation reviewed by a UK-registered prescriber. The consultation involves answering questions about your medical history, current medicines, and overall health to ensure avanafil is safe and appropriate for you. This process is required by law for all prescription medicines and helps protect your safety [2].

If approved, your prescription is dispensed by our GPhC-registered pharmacy (GPhC 9012511) and delivered discreetly to your door. Spedra (avanafil) is priced at £20.95, or £16.76 for your first order with code Ednew. We also offer other PDE5 inhibitors, including Sildenafil from £0.45 (£0.36 with Ednew), Tadalafil from £7.95 (£6.36 with Ednew), and Vardenafil at £16.95 (£13.56 with Ednew), allowing you to choose the treatment that best suits your lifestyle and preferences.

If you are experiencing erectile dysfunction for the first time, it is important to see your GP as well. ED can be an early warning sign of underlying conditions such as heart disease, diabetes, or high blood pressure, and addressing these can improve both your general health and your sexual function [1][2]. Treatment with avanafil or other PDE5 inhibitors can be very effective, but it works best as part of a holistic approach that includes healthy lifestyle choices and management of any underlying health issues.

Lifestyle Factors That Support How Avanafil Works

While avanafil is highly effective, lifestyle factors play an important role in erectile function. Regular exercise, a balanced diet, maintaining a healthy weight, and not smoking all improve blood flow and cardiovascular health, which directly supports erectile function [1][2]. Reducing alcohol intake and managing stress or anxiety can also make a significant difference.

Avanafil works by enhancing the body's natural response to sexual stimulation, so addressing psychological factors—such as performance anxiety or relationship issues—can improve outcomes. Some men benefit from combining medication with counselling or psychosexual therapy [2]. Your GP or a specialist can provide guidance and referrals if needed.

Scientific References

1. NHS. (n.d.). Erectile dysfunction (impotence). NHS website. https://www.nhs.uk/conditions/erection-problems-erectile-dysfunction/ [accessed 6 November 2026]
2. National Institute for Health and Care Excellence. (n.d.). Erectile dysfunction. Clinical Knowledge Summaries. https://cks.nice.org.uk/topics/erectile-dysfunction/ [accessed 6 November 2026]
3. Joint Formulary Committee. (n.d.). Sildenafil. British National Formulary. NICE. https://bnf.nice.org.uk/drugs/sildenafil/ [accessed 6 November 2026]
4. Joint Formulary Committee. (n.d.). Tadalafil. British National Formulary. NICE. https://bnf.nice.org.uk/drugs/tadalafil/ [accessed 6 November 2026]
5. Joint Formulary Committee. (n.d.). Avanafil. British National Formulary. NICE. https://bnf.nice.org.uk/drugs/avanafil/ [accessed 6 November 2026]
6. National Institute for Health and Care Excellence. (2014). Erectile dysfunction: avanafil (ESNM45). https://www.nice.org.uk/advice/esnm45 [accessed 6 November 2026]

Information on this page is for educational purposes only and is not medical advice. Prescription treatments require clinical assessment by a UK-registered prescriber. Always consult a qualified healthcare professional before starting or changing any medication.

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