Sildenafil

Sildenafil, most widely known by the brand name Viagra, is a drug prescribed for erectile dysfunction and pulmonary arterial hypertension. Doctors may also use it off-label to treat some symptoms of secondary Raynaud's phenomenon. Whether it works for sexual dysfunction in women remains uncertain. It can be taken by mouth, injected into a vein, or dissolved under the tongue. When swallowed, it typically starts working within twenty minutes and its effects last about two hours.

Common side effects include headaches, heartburn, and facial flushing. People with cardiovascular disease should use it cautiously. Rare but serious risks include vision changes, hearing loss, and priapism—a prolonged erection that can damage the penis. Sildenafil must not be taken with nitric oxide donors like nitroglycerin, because this combination can cause a dangerous drop in blood pressure.

The drug works by blocking an enzyme called phosphodiesterase 5 (PDE5), which normally breaks down cGMP—a molecule that helps regulate blood flow in the penis. Sexual arousal is still required for the drug to have an effect; it does not create or increase arousal on its own. It also widens blood vessels in the lungs.

Pfizer originally developed sildenafil in 1989 while researching treatments for angina. It gained approval for medical use in the United States and European Union in 1998. By 2023, it was the 151st most prescribed medication in the U.S., with over 3 million prescriptions. Generic versions are available, and in the United Kingdom it is sold as a pharmacy medicine.

**Medical uses**

**Erectile dysfunction** – Sildenafil’s main use is for erectile dysfunction, meaning the inability to maintain an erection sufficient for intercourse. It has become a standard treatment, including for men with diabetes.

**Antidepressant-associated erectile dysfunction** – Early evidence suggests sildenafil may help men whose erectile problems are caused by antidepressants.

**Pulmonary hypertension** – While sildenafil improves certain disease markers in people with pulmonary arterial hypertension, it does not appear to reduce the risk of death or serious side effects.

**Raynaud's phenomenon** – Sildenafil and similar PDE5 inhibitors are used off-label to reduce blood vessel spasms and treat severe ischemia and ulcers in the fingers and toes of people with secondary Raynaud’s. They moderately reduce how often and how long these spasms occur, though as of 2016 their broader role in Raynaud’s was unclear.

**Altitude sickness** – Sildenafil has shown some potential to improve exercise performance at high altitudes, but its overall effectiveness is not clear.

**High-altitude pulmonary edema** – The drug has been studied for this condition, but its use is currently not recommended.

**Adverse effects** – In clinical trials, the most common side effects were headache, flushing, indigestion, nasal congestion, and vision problems such as light sensitivity and blurriness. Some users reported seeing everything with a blue tint (cyanopsia). This happens because sildenafil, though selective for PDE5, also slightly affects PDE6, an enzyme in the retina. This can cause color vision abnormalities. Some people also experienced blurriness and loss of peripheral vision. In July 2005, the FDA updated labeling for sildenafil and similar drugs to note rare post-marketing reports of sudden vision loss, while stating it was not possible to determine whether the drugs caused it or if other factors like high blood pressure or diabetes were responsible. A careful review of pooled clinical trial data found no evidence of increased risk for a specific type of optic nerve damage or other eye problems linked to PDE5 inhibitor use. Rare but serious post-marketing side effects include prolonged erections, severe low blood pressure, heart attack, irregular heart rhythms, stroke, increased eye pressure, and sudden hearing loss. In October 2007, the FDA required stronger warnings on all PDE5 inhibitors about the potential risk of sudden hearing loss.

**Interactions** – People taking protease inhibitors for HIV should be cautious, as these drugs slow the breakdown of sildenafil, raising its levels in the blood and increasing side effects. Those on protease inhibitors should take no more than 25 mg of sildenafil every 48 hours. Other drugs that interfere with sildenafil’s metabolism include erythromycin and cimetidine, both of which can extend its half-life. Taking sildenafil at the same time as an alpha blocker (used for high blood pressure or prostate conditions) can cause low blood pressure, but this effect is avoided if the two are taken at least four hours apart.

**Contraindications** – Sildenafil should not be used with nitric oxide donors, organic nitrites, or nitrates, including nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, sodium nitroprusside, and alkyl nitrites.