1. How it works

• Sildenafil may be used to treat erectile dysfunction (ED or impotence) in men (Viagra brand) or pulmonary arterial hypertension in both men and women (Revatio brand), depending on the brand.
• Sildenafil blocks the action of an enzyme known as cGMP-specific phosphodiesterase type-5 (PDE-5). This enzyme breaks down cGMP, a substance that induces smooth muscles to relax. Blocking PDE-5 means increased levels of cGMP within the smooth muscles which promotes muscle relaxation and vasodilation (a widening of blood vessels).
• High levels of PDE-5 are found in the penis, lungs, and retina. PDE-5 is also found throughout the body within the smooth muscle cells of the blood vessels and muscles.
• Sildenafil belongs to the class of medicines known as selective phosphodiesterase (PDE) type 5 inhibitors.

2. Upsides

• Sildenafil (Viagra brand) increases blood flow to the penis following sexual stimulation. It does this by blocking the enzyme responsible for the breakdown of cGMP. cGMP is a substance that relaxes and widens blood vessels and smooth muscle cells. This allows men to keep an erection hard enough for sex.
• Sildenafil (Viagra brand) only works following sexual stimulation. It works within 30 to 60 minutes, but may be taken up to four hours before sexual activity.
• Sildenafil (Revatio brand) reduces high blood pressure associated with pulmonary arterial hypertension (PAH). This improves the ability to exercise in people with PAH and delays any worsening of their symptoms.
• Available orally and as an IV preparation for PAH. Available orally for ED.
• Revatio is available as a generic under the name of sildenafil (20mg tablet). There is also a generic version of Viagra available, under the name sildenafil, in 25mg, 50mg, and 100mg strengths.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dyspepsia, flushing, headache, indigestion, muscle or back pain, and visual disturbances are commonly reported.
• Other side effects include a drop in blood pressure, insomnia, nasal congestion, or a runny nose and nosebleeds. Sudden hearing loss has also been reported. Some people taking sildenafil have had bleeding events; however, it has not been established if this is related to sildenafil use.
• Rarely, may decrease blood flow to the optic nerve causing sudden vision loss. The risk is greater in people aged older than 50, with diabetes, heart disease, high blood pressure, high cholesterol, who smoke, or with certain pre-existing eye problems.
• Rarely, may cause other side effects or lead to painful erections lasting longer than four hours. See your doctor immediately if this happens.
• May not be suitable for some people including those with angina, chest pain, other heart conditions, liver or kidney problems, blood or bleeding disorders, stomach ulcers, certain eye conditions, or a physical deformity of the penis (such as Peyronie's disease).
• Higher dosages of sildenafil are associated with a higher risk of death in children with PAH. For this reason, the FDA does not recommend use in children aged less than 18 years.
• May interact with some medications including certain antibiotics and antifungals, herbal remedies, HIV medicines, nitrates, and drugs used in the treatment of high blood pressure or prostate disorders. Sildenafil should not be taken with other PDE-5 inhibitors.
• The dosage may need to be reduced in people with kidney or liver disease.
• More research is needed to establish if sildenafil has a role in sexual dysfunction in women.
• Sildenafil offers no protection against sexually transmitted diseases.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Sildenafil is used to treat erectile dysfunction (ED) and to reduce blood pressure in pulmonary arterial hypertension (PAH). It is taken when needed for ED and daily for PAH. A headache, stomach upsets, and flushing are the main side effects, and it should not be taken within 24 hours of a nitrate.

5. Tips

• If you are taking sildenafil (Viagra) for ED, do not take it more than once a day. Take an hour before sexual stimulation (range 30 minutes to 4 hours). If you take it with a high-fat meal it may delay how quickly it starts working.
• If you are taking sildenafil (Revatio) for PAH, take it as directed (the usual dosage is three times daily). You can take it either with or without food.
• Do not consume grapefruit or grapefruit products while taking sildenafil.
• Always talk to your doctor before taking ANY medication for ED. Some ED medications are not suitable for men with certain medical conditions, and your doctor can advise you on an alternative.
• Call your doctor immediately if you experience dizziness or feel nauseous during sexual activity, or develop pain, numbness, or tingling in your chest, arms, neck, or jaw.
• Do not take sildenafil if you are also taking a nitrate drug (such as nitroglycerin or isosorbide dinitrate/mononitrate) for chest pain or heart problems. Do not take sildenafil with recreational drugs such as "poppers". Taking these substances together can cause a sudden and dangerous drop in blood pressure.
• Always buy your ED medications from a reputable supplier as there are a lot of counterfeit products on the market.
• Certain lifestyle and psychological factors, such as smoking, drinking, and stress, can impact ED. Eliminating these - for example, staying more active, losing weight if you are overweight, reducing alcohol intake, stopping smoking, and reducing stress - may also help improve ED.
• Never take other ED medications at the same time as taking sildenafil. Do not take Viagra while taking Revatio and vice-versa.
• Seek urgent medical advice if an allergic reaction, sudden vision loss, or painful erections lasting more than four hours occur.
• Drinking alcohol after taking sildenafil may lower blood pressure and decrease sexual performance.
• If you are a woman of childbearing age taking sildenafil (brand Revatio) for PAH, then tell your doctor if you become pregnant or are intending to become pregnant. It is not known if sildenafil is distributed into breast milk.

6. Response and effectiveness

• Peak plasma concentrations of sildenafil are reached within 30 to 120 minutes of a single dose. Effects of sildenafil, when used for ED, are usually noticeable within 30 to 60 minutes of a single dose.
• When used to treat PAH, blood pressure-lowering effects are noticeable within one to two hours.

7. Interactions

Medicines that interact with sildenafil may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with sildenafil. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with sildenafil include:

• alpha-agonists (eg, clonidine, methyldopa)
• alpha-blockers (eg, alfuzosin, doxazosin, prazosin, tamsulosin, or terazosin)
• antibiotics, such as azithromycin, clarithromycin, erythromycin, metronidazole, norfloxacin, rifabutin, rifampin, or tetracycline
• antidepressants, such as desipramine, sertraline, or St. John's Wort
• antifungal medications, such as itraconazole, ketoconazole, or voriconazole
• beta-blockers such as atenolol or propranolol
• blood thinners, such as warfarin
• cimetidine
• cystic fibrosis medications, such as ivacaftor
• epilepsy medications, such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or primidone
• other erectile dysfunction medications (eg, alprostadil, Cialis, vardenafil)
• heart medications, such as amlodipine, amiodarone, atenolol, bosentan, candesartan, captopril, clonidine, diltiazem, enalapril, irbesartan, losartan, nifedipine, propranolol, sotalol, or verapamil
• hepatitis medications, such as boceprevir and simeprevir
• HIV medications (eg, atazanavir, delavirdine, efavirenz, fosamprenavir, indinavir, etravirine, ritonavir, nevirapine, saquinavir, or tipranavir)
• nitrates (eg, amyl nitrate, isosorbide dinitrate, isosorbide mononitrate, or nitroglycerin): separate administration by 24 hours
• tolbutamide
• others, such as aprepitant, butalbital, cimetidine, cyclosporine, riociguat, or imatinib.

Sildenafil is metabolized mainly by CYP3A4 and to some extent by CYP2C9. It also weakly inhibits CYP1A2, 2C(, 2C19, 2D^, 2E1, and 3A4. Any drug that is a substrate of one of these enzymes could potentially interact with sildenafil.

In addition, taking sildenafil with too much alcohol can lead to orthostatic hypotension, which is a drop in blood pressure when you go from a sitting or lying down position to standing. Symptoms include a headache, dizziness, or fainting when standing.

Antacids, such as magnesium hydroxide or aluminum hydroxide may also affect the absorption of sildenafil. Grapefruit juice may also increase the side effects of sildenafil.

Note that this list is not all-inclusive and includes only common medications that may interact with sildenafil. You should refer to the prescribing information for sildenafil for a complete list of interactions.