Sildenafil

What is sildenafil?

Sildenafil is a prescription drug belonging to a class of drugs known as phosphodiesterase type 5 (PDE5) inhibitors. PDE5 enzymes regulate the signaling pathway in the normal physiological processes related to blood flow. They bind to and activate receptors located in the arteries of the lungs and the corpus cavernosum of the penis. PDE5 inhibitors prevent the binding of these enzymes to their target receptors. This inhibition initiates a series of metabolic events resulting in the relaxation of smooth muscle in the blood vessel walls, allowing the vessels to dilate and increasing the flow of blood to those areas.¹ ²

What You Need To Know About Erectile Dysfunction

Sildenafil is sold under the brand name Viagra for the treatment of erectile dysfunction (ED), while prescriptions for pulmonary arterial hypertension (PAH) are for the brands Revatio and Liqrev. The generic drug sildenafil is available for both indications.

What is sildenafil used to treat?

Sildenafil has been approved by the US Food and Drug Administration (FDA) for the treatment of ED in adults and PAH in adults and children aged one year and older.³ ⁴

In ED, sildenafil indirectly promotes the activity of nitric oxide, a compound naturally released during sexual stimulation that increases blood flow to the genitalia. Because the drug relies on nitric oxide, it will not trigger spontaneous erections.

The drug works similarly in PAH to improve blood flow through the arteries bringing blood from the heart to the lungs. It allows these vessels to dilate, counteracting the high pressures that prevent healthy blood flow to the lungs in PAH.

Sildenafil has been used off-label for treating female sexual arousal disorder and high-altitude sickness, but these uses are not US FDA-approved.⁵

Dosage forms and strengths

Sildenafil is available as a tablet, an oral suspension, and a liquid for intravenous injection.⁶

Tablets are available in the following dosing strengths (generic, Viagra, Revatio):

• 20mg

• 25mg

• 50mg

• 100mg 

The oral suspension is formulated in one concentration (generic, Revatio, Liqrev): 

• 10mg/mL

The solution for injection is available in one strength (generic, Revatio): 

• 10mg/12.5mL

How do you take sildenafil?

The dosage for sildenafil varies with the indication being treated.⁷

For ED, the recommended adult dosing options for sildenafil (generic, Viagra) are as follows:

• An initial dose of 50mg once a day as needed, and it can be taken 30 minutes to four hours before sexual activity (recommended one hour prior)

• The dose may be adjusted up or down based on effectiveness and tolerance

• Maximum dosing frequency is once per day

These are the adult dosing recommendations for the treatment of PAH (generic, Revatio, Liqrev):

• An initial oral dose of 20mg three times daily, spaced 4–6 hours apart 

• A maximum oral dose of 240mg per day 

• Pediatric dosing is based on age and weight

• Injections are administered by a medical professional in a healthcare setting 

Your prescriber will adjust your sildenafil dose according to the recommendations for your condition and your unique needs.

Seeing results

Sildenafil can produce an erection within 30 minutes. Its duration of action can last up to 18 hours. One study found the median time to onset of an erection was 27 minutes, with the shortest time to action at 12 minutes and the longest at 70 minutes.⁸ ⁹

Who should not take sildenafil?

Sildenafil is not suitable for everyone, and some people may need to take additional measures to ensure they can use the drug safely. Inform your doctor if you¹⁰ ¹¹ ¹²

• Have had an allergic reaction to sildenafil or a similar drug

• Are taking nitrate-based drugs for chest pain (Nitrostat, Isordil) or for recreational use (“poppers”) 

• Smoke cigarettes

• Have a history of priapism (a painful, prolonged erection)

• Have had a heart attack or stroke

Or if you have any of the following medical conditions:

• Severe liver disease

• Pulmonary veno-occlusive disease (PVOD)

• Bleeding disorders

• Aortic stenosis

• Congestive heart failure

• Heart rhythm disorders 

• Coronary artery disease

• Very high or low blood pressure

• Diabetes

• High cholesterol

• Sickle cell disease, multiple myeloma, and leukemia 

• Peyronie disease or penile deformity

• Active stomach ulcer

• Hearing loss

• Vision loss related to non-arteritic anterior ischemic optic neuropathy (NAION) and other eye conditions

These lists may be incomplete, and other conditions may affect your body’s handling of sildenafil. Inform your doctor of all your medical conditions before taking sildenafil.

Potential side effects of sildenafil

Sildenafil can cause side effects. Most are mild and resolve without intervention, but some are severe and demand urgent medical attention.¹³ ¹⁴

Common side effects

The most common side effects associated with sildenafil are:

• Headache

• Dizziness

• Upset stomach, nausea

• Indigestion

• Flushing

• Stuffy or runny nose, nosebleeds

• Visual changes, including blurred vision, changes in color perception, and light sensitivity

• Muscle aches

• Back or limb pain

• Diarrhea

• Rash

• Numbness and tingling

Less common and severe side effects of sildenafil

Some of the less common and more severe adverse effects of sildenafil include the following:¹⁵ ¹⁶

• Hearing loss, ringing in the ears

• Sudden vision loss affecting one or both eyes

• Fainting or lightheadedness

• Very low blood pressure

• Chest pain

• Shortness of breath

• Priapism

• Vaso-occlusive crisis in patients with PAH due to sickle cell disease

• Buildup of fluid in the lungs and worsening of condition in people with PVOD

Overdose

Any of the adverse effects outlined above may indicate an overdose. If you suspect you may have taken too much sildenafil, seek medical care immediately, even if you don’t have any symptoms.¹⁷

Allergy information

Some people are allergic to the active or inactive ingredients in sildenafil. Symptoms of a drug allergy may include any of the following:

• Hives 

• Rash 

• Itching 

• Swollen blisters 

• Wheezing

• Trouble breathing 

• Tightness in the chest 

• Swelling in the face, lips, mouth, and tongue

• Vomiting

• Loss of consciousness 

If you experience any symptoms of a drug allergy while taking sildenafil, stop taking the drug immediately. Call your doctor or seek emergency medical attention, depending on the severity of your symptoms.

Long-term use of sildenafil

Sildenafil treats ED and PAH, but it’s not a cure. As such, it’s commonly prescribed for long-term use. In a study examining the long-term safety of sildenafil, less than 4% experienced treatment-related adverse effects that led to a change in dosage or discontinuation of treatment.¹⁸

While it’s possible to develop tolerance to many drugs, that’s not the case with sildenafil. In a study on the treatment for radiation-related ED in people with prostate cancer, researchers found that over 90% of participants reported the drug was still effective over the four-year study period.¹⁹

Sildenafil and pregnancy

Sildenafil has been designated a category B drug in pregnancy by the US FDA. While animal studies did not demonstrate a risk to the fetus, there are no adequate studies assessing the risk in humans.²⁰

Despite the uncertainty, sildenafil is considered a relatively safe drug during pregnancy. A 2018 review of literature revealed that some babies whose mothers had taken sildenafil while pregnant had increased birth weights, which was considered a beneficial effect.²¹

Your doctor will weigh the potential risks against the benefits in your case when deciding if you should take the drug while pregnant.

Sildenafil and breastfeeding

Limited research indicates that sildenafil does appear in breastmilk but in doses that would not be considered harmful to the infant.²²

Missed doses

If you take sildenafil for ED, you’ll take it as needed, so you won’t have to worry about missed doses. However, if you have PAH and miss a dose of the medication, take it as soon as you remember unless it’s nearly time for your next dose. If that’s the case, skip the missed dose and take the next one as scheduled. Never double your dose to make up for a missed one.

Drug interactions

Sildenafil is known to have interactions with the drugs listed below:²³ 

• Nitrates, such as nitroglycerin (Nitrostat), isosorbide dinitrate, isosorbide mononitrate, and street drugs called “poppers”²⁴

• Guanylate cyclase stimulators like riociguat (Adempas)²⁵

• HIV drugs, including saquinavir (Invirase), atazanavir (Reyataz), and ritonavir (Norvir)

• Antibiotics like erythromycin, tobramycin (Tobrex), and clarithromycin²⁶

• Antifungal drugs, such as itraconazole (Sporanox) and ketoconazole (Nizoral) 

• Alpha-blockers, including doxazosin (Cardura), silodosin (Rapaflo), alfuzosin (UroXatral), and terazosin

• Blood pressure drugs like amlodipine (Pacerone), amiloride, atenolol (Tenormin), and captopril

• Other drugs used to treat ED like tadalafil (Cialis), vardenafil, and avanafil (Stendra)

• Mifepristone (Mifeprex, Korlym)

• St. John’s wort

This list of interactions isn’t complete. Discuss all medications you take regularly or occasionally with your doctor before starting sildenafil.

Can I drink alcohol while taking sildenafil?

Drinking alcohol while taking sildenafil can result in low blood pressure and other adverse effects. Evidence suggests this is not cause for concern in people consuming low-to-moderate amounts of alcohol, but it’s unclear if the same is true for people drinking higher volumes. Speak with your doctor about the risk level based on your situation.²⁷

What to discuss with your doctor before starting sildenafil

Sildenafil is available by prescription only, so you’ll need to meet with your doctor before you start taking it. At your appointment, you should discuss all of the following topics that apply to you:²⁸

• Heart problems, such as heart failure, a recent heart attack or heart surgery, chest pain (particularly during sexual activity), or an irregular heartbeat

• History of a stroke

• Circulation problems

• High cholesterol

• Low or high blood pressure

• Liver or kidney disease

• Diabetes

• Stomach ulcer or history of gastrointestinal bleeding

• History or family history of severe vision loss or eye disease

• History of an allergic reaction to sildenafil or a similar medication

• Bleeding disorder

• Blood cell disease, such as sickle cell anemia or multiple myeloma

• Penile deformity 

• History of priapism

• All of your medications, along with any supplements, vitamins, or herbs you take regularly or occasionally

• Any upcoming surgeries or dental procedures

• Pregnancy, breastfeeding, or any plans for conceiving

Stopping sildenafil

If you take sildenafil as needed for ED, it’s unlikely you’ll experience any physical withdrawal effects when you stop. However, research on patients taking the drug recreationally indicates there’s a risk of psychological dependence. Beyond that, it’s essential to note that your symptoms will return when you stop taking the medication, so you may want to discuss alternative treatment options with your doctor.²⁹

If you take sildenafil daily for PAH and wish to stop, seek guidance from your doctor on how to do so safely. Evidence suggests that suddenly stopping the medication may trigger a rapid worsening of your condition, a decline in physical exercise performance, and acute right heart failure.³⁰

Drug approval history

• 1998: The US FDA approved sildenafil for treating ED³¹

• 2005: Sildenafil was granted US FDA approval for the treatment of PAH³²

Tips for taking sildenafil

The following tips can help you take sildenafil safely while maximizing its effectiveness:³³

• For ED, it’s best to take sildenafil an hour before engaging in sexual activity. However, you can take it as early as four hours or as late as 30 minutes before.

• Do not combine multiple ED treatments without consulting your doctor.

• Ask your doctor about consuming grapefruit or grapefruit juice while taking this medication.

• If you take the oral solution, prepare it by shaking the bottle vigorously for at least 30 seconds and measuring the dose with a device intended for measuring medications. Household spoons are not adequately precise.

• If you need emergency medical treatment for a heart problem, inform your care team that you’re taking sildenafil. They may need to know when you took your last dose.

Frequently asked questions

What does sildenafil do for ED?

Sildenafil is a commonly prescribed treatment for ED or sexual impotence. It blocks the enzyme PDE5 and increases blood flow to the penis during sexual stimulation.

How does sildenafil treat PAH?

Sildenafil treats PAH by relaxing and reducing the pressure in blood vessels in the lungs, allowing for increased blood flow.

How long does sildenafil’s effect last?

It takes about thirty minutes for sildenafil to work. And its action continues for a couple of hours, possibly up to a maximum of four hours.³⁴