Erectile dysfunction (ED) is a common condition in which a man has difficulty getting or maintaining an erection firm enough for sexual activity. ED can occur occasionally because of stress, tiredness or alcohol, but persistent erectile difficulties may be linked to conditions such as diabetes, high blood pressure, cardiovascular disease, hormonal problems, anxiety or certain medicines.
Medicines in this group include sildenafil, tadalafil, vardenafil and avanafil. They work by improving blood flow to the penis when a man is sexually stimulated.
If you have recently been diagnosed with ED or are learning about treatment options, this beginner’s guide explains what PDE5 inhibitors are, how they work, how the different medicines compare and the important precautions you should know.
What Are PDE5 Inhibitors?
PDE5 inhibitors are medicines commonly prescribed for erectile dysfunction.
PDE5 stands for phosphodiesterase type 5, an enzyme found in various tissues of the body, including blood vessels in the penis.
The four commonly used PDE5 inhibitors for erectile dysfunction are:
These medicines belong to the same drug class, but they differ in how quickly they start working, how long their effects may last, how they interact with food and how frequently they can be taken.
PDE5 inhibitors are considered an important oral treatment option for men with ED when there are no contraindications to their use.
How Do PDE5 Inhibitors Work?
An erection involves a series of signals between the brain, nerves and blood vessels.
When a man becomes sexually stimulated, the body releases nitric oxide in the penis. This promotes production of a chemical called cyclic guanosine monophosphate (cGMP).
cGMP helps relax smooth muscle in penile blood vessels. As these blood vessels relax and widen, more blood can flow into the penis, helping produce an erection.
The PDE5 enzyme normally breaks down cGMP.
PDE5 inhibitor medicines temporarily reduce the activity of this enzyme. As a result, cGMP can remain active for longer, supporting blood vessel relaxation and improving the erectile response.
Do PDE5 inhibitors automatically cause an erection?
No.
PDE5 inhibitors do not automatically produce an erection. Sexual stimulation is still required for them to work.
They also do not normally:
increase sexual desire
act as an aphrodisiac
permanently cure erectile dysfunction
protect against sexually transmitted infections
prevent pregnancy
They help support the body’s natural erectile response during sexual stimulation.
Types of PDE5 Inhibitors for Erectile Dysfunction
Although all PDE5 inhibitors work in a similar way, their timing and duration differ.
PDE5 inhibitorTypical time before sexual activityApproximate durationSildenafilAround 30–60 minutesAround 4 hoursTadalafilAround 30–60 minutesUp to 36 hoursVardenafilAround 60 minutesAround 4–5 hoursAvanafilAround 15–30 minutes depending on doseAround 4–5 hours
These figures are approximate. The response can differ between individuals depending on dose, food, other medicines, medical conditions and other factors.
Sildenafil
Sildenafil is one of the best-known PDE5 inhibitors.
It is generally taken before anticipated sexual activity. It may begin working within approximately 30 to 60 minutes, and its erectile-supporting effects commonly last for several hours.
A high-fat meal may delay its absorption and make it take longer to start working.
Sildenafil may be suitable for men who prefer an ED medicine taken only when needed rather than every day.
Tadalafil
Tadalafil is known for having a considerably longer period of action.
Its effects can last for up to 36 hours, although this does not mean a man will have an erection continuously for 36 hours. It simply means the medicine may help support an erection during sexual stimulation within that period.
Tadalafil can be prescribed either:
when needed before sexual activity, or
as a lower-dose daily treatment in appropriate patients.
Because of its longer duration, some men prefer tadalafil because it allows greater flexibility around the timing of sexual activity.
Vardenafil
Vardenafil is another PDE5 inhibitor used to treat erectile dysfunction.
It is generally taken approximately 60 minutes before sexual activity and normally should not be taken more frequently than directed by the prescriber.
Like other PDE5 inhibitors, vardenafil increases penile blood flow during sexual stimulation rather than creating an erection automatically.
Food can sometimes influence how quickly some forms of vardenafil are absorbed.
Avanafil
Avanafil is another PDE5 inhibitor used for erectile dysfunction.
Depending on the prescribed dose, it may be taken approximately 15 to 30 minutes before sexual activity, making it one of the faster-acting medicines in this group.
As with other PDE5 inhibitors, sexual stimulation is necessary for avanafil to produce its intended effect.
Sildenafil vs Tadalafil vs Vardenafil vs Avanafil: Which Is Better?
There is no single PDE5 inhibitor that is best for every man.
The most appropriate medicine may depend on factors including:
how quickly you want the medicine to work
how long you want the treatment window to last
how frequently you have sexual activity
whether you prefer daily or as-needed treatment
other health conditions
other medicines you take
previous side effects
individual response
cost and availability
Clinical guidance indicates that commonly used PDE5 inhibitors are effective treatments for many men with erectile dysfunction, although individual responses can vary.
A healthcare professional can help determine which option and dose are appropriate for you.
How Effective Are PDE5 Inhibitors?
PDE5 inhibitors help many men with erectile dysfunction, but they do not work equally well for everyone.
Treatment response may be influenced by the underlying cause of ED.
For example, erectile dysfunction can be associated with:
high blood pressure
obesity
nerve damage
hormonal problems
prostate surgery
psychological conditions
certain medications
Correct use of the medicine is also important.
A man may mistakenly assume that the treatment has failed if he takes it incorrectly, does not allow enough time for it to work or expects an erection without sexual stimulation.
If one PDE5 inhibitor does not provide the expected result, a healthcare professional may review the dose, timing, medical conditions and other medicines before deciding whether another treatment is appropriate.
Common Side Effects of PDE5 Inhibitors
Most medicines can cause side effects, and PDE5 inhibitors are no exception.
Common effects may include:
headache
facial flushing
indigestion or upset stomach
stuffy or runny nose
dizziness
Some side effects differ between individual medicines.
For example, tadalafil may sometimes cause muscle or back discomfort, while sildenafil and vardenafil can occasionally cause visual changes.
Most side effects are temporary, but persistent or troublesome symptoms should be discussed with a healthcare professional.
Who Should Not Take PDE5 Inhibitors?
PDE5 inhibitors are not appropriate for everyone.
One of the most important precautions involves nitrate medicines.
PDE5 inhibitors and nitrates
Men taking nitrates for chest pain or certain heart conditions generally must not use PDE5 inhibitors.
Examples of nitrate medicines include:
nitroglycerin
isosorbide mononitrate
isosorbide dinitrate
Combining nitrates with PDE5 inhibitors can cause a potentially dangerous fall in blood pressure.
PDE5 inhibitors can also interact with other medicines, including some treatments for blood pressure, prostate conditions, fungal infections and HIV.
They should also not be combined with the soluble guanylate cyclase stimulator riociguat, because this combination can cause excessive lowering of blood pressure.
Always tell your doctor or pharmacist about prescription medicines, over-the-counter medicines and supplements you use before starting ED treatment.
PDE5 Inhibitors and Alpha-Blockers
Some men with prostate enlargement or high blood pressure take medicines known as alpha-blockers.
Combining an alpha-blocker with a PDE5 inhibitor can lower blood pressure further in some people.
This does not necessarily mean the medicines can never be used together, but dose selection and timing may require medical supervision.
Do not change either medicine without discussing it with your healthcare provider.
When Should You Seek Medical Help?
Most PDE5 inhibitor side effects are mild, but certain symptoms require urgent medical attention.
Seek immediate medical care for:
An erection lasting longer than four hours
An erection lasting more than four hours is known as priapism.
It can damage penile tissue if it is not treated promptly.
Sudden loss of vision
Rarely, sudden vision changes or loss of vision have been reported with PDE5 inhibitor use.
Seek medical attention immediately if this happens.
Sudden hearing loss
Sudden reduction or loss of hearing, sometimes accompanied by ringing in the ears or dizziness, also requires prompt medical attention.
Chest pain
If chest pain occurs during or after sexual activity, seek urgent medical attention.
Tell the healthcare professional that you have taken a PDE5 inhibitor and when you took it. Do not take nitrate medication unless medical professionals who know about your PDE5 inhibitor use instruct you appropriately.
Can You Take More Than One PDE5 Inhibitor Together?
You should not combine sildenafil, tadalafil, vardenafil or avanafil on your own.
Taking multiple ED medicines together can increase the risk of:
dangerously low blood pressure
dizziness
fainting
headache
priapism
other adverse effects
If your current ED medicine does not seem effective, speak with your healthcare professional instead of increasing the dose or combining treatments yourself.
Can Alcohol Affect PDE5 Inhibitors?
Large amounts of alcohol can make erectile dysfunction worse and may also increase dizziness or blood-pressure-lowering effects associated with ED medicines.
Limiting excessive alcohol consumption can therefore be important both for treatment safety and erectile health.
Lifestyle factors such as smoking, physical inactivity, excess weight and heavy alcohol use can also contribute to erectile dysfunction.
What If PDE5 Inhibitors Do Not Work?
PDE5 inhibitors are not the only treatment for erectile dysfunction.
If oral medicines are unsuitable or ineffective, other options may include:
addressing underlying medical conditions
reviewing medicines that may contribute to ED
psychological counselling or sex therapy
vacuum erection devices
injectable medicines
urethral medicines
penile implants in selected patients
Lifestyle changes such as increasing physical activity, maintaining a healthy weight, stopping smoking and reducing excessive alcohol consumption may also improve erectile health.
Persistent ED should therefore be medically evaluated rather than treated only as a sexual-performance issue.
Why You Should Not Ignore Persistent Erectile Dysfunction
Occasional erection difficulties are common.
However, ED that occurs repeatedly may sometimes be an early sign of another medical condition.
Conditions associated with erectile dysfunction include diabetes, heart and blood vessel disease, obesity and certain hormonal or neurological disorders.
A medical evaluation can help identify contributing factors while determining the most suitable treatment.
Frequently Asked Questions About PDE5 Inhibitors
1. Are PDE5 inhibitors the same as Viagra?
Viagra is a brand of sildenafil, which is one type of PDE5 inhibitor.
Other PDE5 inhibitors include tadalafil, vardenafil and avanafil.
2. Do PDE5 inhibitors increase testosterone?
No. PDE5 inhibitors do not directly increase testosterone levels.
Men who have erectile dysfunction caused partly by testosterone deficiency may require separate evaluation and treatment.
3. Can PDE5 inhibitors increase sexual desire?
PDE5 inhibitors do not normally increase libido or sexual desire.
Their purpose is to improve the physical erectile response to sexual stimulation.
4. Which PDE5 inhibitor lasts the longest?
Among the commonly used PDE5 inhibitors, tadalafil has the longest duration of action, with effects potentially lasting for up to 36 hours.
5. Which PDE5 inhibitor works the fastest?
Avanafil may begin working relatively quickly and, depending on the prescribed dose, can be taken approximately 15 to 30 minutes before sexual activity. Individual response varies.
6. Can I take a PDE5 inhibitor every day?
Certain tadalafil regimens may be prescribed for daily use.
Whether daily treatment is appropriate depends on your health, treatment goals, other medications and your doctor’s assessment.
Do not begin daily ED medication without medical guidance.
Final Thoughts
PDE5 inhibitors are among the most widely used oral treatments for erectile dysfunction.
Sildenafil, tadalafil, vardenafil and avanafil all work by supporting the natural process that increases blood flow to the penis during sexual stimulation. However, they differ in how quickly they act, how long their effects last and how they should be taken.
For many men, choosing the right PDE5 inhibitor involves balancing effectiveness, duration, convenience, side effects and existing medical conditions.
Most importantly, ED medicine should not be viewed as a substitute for medical assessment. Persistent erectile dysfunction can sometimes indicate an underlying cardiovascular, metabolic, hormonal or psychological problem that also requires attention.
Before taking a PDE5 inhibitor, particularly if you have heart disease, low blood pressure or take nitrates, alpha-blockers or other prescription medicines, speak with a qualified healthcare professional.