Common and Serious Side Effects of Sildenafil Citrate

[15][16] In the United Kingdom, it is available as a pharmacy medicine. The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete sexual intercourse).

Its use is now one of the standard treatments for erectile dysfunction, including for males with diabetes mellitus.

Tentative evidence suggests that sildenafil may help males who experience antidepressant-induced erectile dysfunction. While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects.

• Sildenafil molecules work by relaxing smooth muscle tissue.
• This relaxation allows increased blood flow in blood vessels.
• It is less effective without sexual arousal.
• Some common brand names include Viagra, Revatio, and Kamagra.
• Sildenafil's patent expired, leading to numerous generics.
• Generic versions are usually more affordable.
• It’s important to follow prescription instructions strictly.
• Using more than the recommended dose can be dangerous.

Sildenafil and other PDE5 inhibitors are used off-label to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud's phenomenon;[9][21] these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes.

Index Words

There are risks to the mother and fetus from untreated pulmonary arterial hypertension. Limited clinical data preclude a clear determination of the risk of sildenafil to an infant during breast-feeding. Data from a case report describe the presence of sildenafil and its active metabolite in human milk. There is insufficient information on the effects of sildenafil on the breast-fed infant and no information on the effects of sildenafil on milk production. Sildenafil, sold under the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension.

Interaction médicamenteuse

[4][8] It is also sometimes used off-label for the treatment of certain symptoms in secondary Raynaud's phenomenon. [9] It is unclear if it is effective for treating sexual dysfunction in females. [8] It can be taken orally (swallowed by mouth), intravenously (injection into a vein), or through the sublingual route (dissolved under the tongue). [8][10] Onset when taken orally is typically within twenty minutes and lasts for about two hours. Common side effects include headaches, heartburn, and flushed skin.

How is sildenafil supplied (dosage forms)?

[8] Caution is advised in those with cardiovascular disease. [8] Rare but serious side effects include vision problems, hearing loss, and prolonged erection (priapism) that can lead to damage to the penis. [8] Sildenafil should not be taken sildenafil chewable tablets by people on nitric oxide donors such as nitroglycerin, as this may result in a serious drop in blood pressure. Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis. [8] It requires sexual arousal to work, and does not by itself cause or increase sexual arousal. [9] As of 2016,[update] their role more generally in Raynaud's was not clear.

Sildenafil has shown some potential for improving exercise performance at high altitudes. However, its overall efficacy is not clear.

Pregnancy & Lactation

[8] It also results in dilation of the blood vessels in the lungs. Pfizer originally discovered the medication in 1989 while looking for a treatment for angina. [11] It was approved for medical use in the United States and in the European Union in 1998. [5][8][11][12] In 2023, it was the 151st most commonly prescribed medication in the United States, with more than 3 million prescriptions. [13][14] It is available as a generic medication. Sildenafil has been studied for high-altitude pulmonary edema (HAPE), but its use is currently not recommended for that indication. In clinical trials, the most common adverse effects of sildenafil use included headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision.

Other Uses for Sildenafil

However, the ratio of the metabolite to sildenafil is higher in patients with pulmonary arterial hypertension (PAH). The metabolite is further metabolized to inactive compounds. Sildenafil is excreted as metabolites primarily in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Both sildenafil and its active metabolite have terminal half-lives of about 4 hours. Sildenafil concentrations at 24 hours post a single 100 mg oral dose average 2 ng/mL (compared to peak plasma concentrations of approximately 440 ng/mL).

Effets indésirables

While similar pharmacokinetic parameters were observed in healthy volunteers and patients with erectile dysfunction, the average steady-state concentrations were 20% to 50% higher and Cmin levels doubled in patients with PAH compared to healthy volunteers. Affected cytochrome P450 isoenzymes: CYP3A4 and CYP2C9Sildenafil is metabolized principally by the hepatic cytochrome P450 (CYP) 3A4; CYP2C9 is also involved to a lesser degree. Dosage reductions are recommended for patients receiving potent cytochrome CYP3A4 inhibitors. Sildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of about 41% (25% to 63%). Its pharmacokinetics are dose-proportional over the recommended dose range.

Recreational use

Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. Oral Suspension (Liqrev):When sildenafil is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 53%; the extent of absorption (AUC) is increased by 11%.Oral tablets and oral powder for suspension (Revatio, Viagra):When sildenafil is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. A 10 mg IV dose is predicted to provide a pharmacological effect of sildenafil and its N-desmethyl metabolite equivalent to that of a 20 mg PO dose. Limited data do not report a clear association with the use of sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy. No evidence of teratogenicity or embryofetal toxicity was observed in animal reproduction studies using sildenafil at doses 32- and 65-times the recommended human dose. [4] Some sildenafil users have complained of seeing everything tinted blue (cyanopsia). [24] This cyanopsia can be explained because sildenafil, while selective for PDE5, does have some affinity for PDE6, which is the phosphodiesterase found in the retina.

Dosing & Uses

The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil can also inhibit PDE5 present in esophageal smooth muscle, lung tissue, and brain tissue. Inhibition of PDE5 in lung tissue results in relaxation of pulmonary vascular smooth muscle and subsequently pulmonary vasodilation, thereby making sildenafil an effective agent in treating pulmonary hypertension. Inhibition of PDE5 present in esophageal smooth muscle can cause a marked inhibition of esophageal motility as well as a reduction in lower esophageal sphincter (LES) tone. These effects may be beneficial in certain motor disorders involving the esophagus such as diffuse spasm, nutcracker esophagus, and hypertensive LES.

What should I do if I miss a dose of sildenafil?

However, the reduction in LES tone can worsen the symptoms of gastroesophageal reflux disease (GERD). Sildenafil is one-tenth as potent for PDE6, an enzyme found in the retina, as it is for PDE5; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma concentrations of the drug. The mean steady state volume of distribution (Vss) is 105 L, indicating widespread tissue distribution. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.

Altitude sickness

Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.001% of the administered dose may appear in the semen of patients. Sildenafil is predominantly metabolized by hepatic cytochrome P450 (CYP) enzymes. One active metabolite with properties similar to the parent drug has been identified and is formed by N-desmethylation of sildenafil. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil and accounts for about 20% of the pharmacologic effects of sildenafil. Patients thus taking the drug may experience colorvision abnormalities. Some complained of blurriness and loss of peripheral vision. In July 2005, the US Food and Drug Administration (FDA) updated labeling for tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra) to reflect a small number of post-marketing reports of sudden vision loss, while acknowledging that "...it is not possible to determine whether these oral medicines for erectile dysfunction were the cause of the loss of eyesight or whether the problem is related to other factors such as high blood pressure or diabetes, or to a combination of these problems. "[25] A careful review of pooled data from clinical trials containing well documented information about the dose and duration of exposure to the drug for a large number of patients, yields no evidence for an increased risk of non-arteritic anterior ischemic optic neuropathy or other adverse ocular events associated with PDE5 inhibitor use. Rare but serious adverse effects found through postmarketing surveillance include prolonged erections, severe low blood pressure, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.

• Sildenafil works by inhibiting phosphodiesterase type 5 enzyme.
• This inhibition increases cGMP levels in the body.
• Elevated cGMP leads to smooth muscle relaxation.
• It promotes vasodilation in the corpus cavernosum.
• This process facilitates an erection during sexual activity.
• The drug’s pharmacokinetics allow for rapid absorption.
• Food intake can influence absorption rate.
• It is effective in men of various ages.

[4] In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, required a more prominent warning of the potential risk of sudden hearing loss. Care should be exercised by people who are also taking protease inhibitors for the treatment of HIV infection. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side effects.