Sildenafil is a vasoactive agent that is commonly prescribed to treat erectile dysfunction (impotence) in men, and to reduce symptoms in patients with pulmonary arterial hypertension (PAH). By decreasing vascular resistance and relaxing muscles, sildenafil increases blood flow to particular areas of the body including the penis. Sildenafil belongs to the phosphodiesterase type 5 (PDE5) inhibitors drug class. Sildenafil may also be effective in male patients with ED related to diabetes mellitus1 or due to pelvic fracture urethral disruption.2 Sildenafil has been shown to be effective and well tolerated in patients on multidrug antihypertensive regimens and not associated with additional safety risks in these patients.3 According to ED treatment guidelines, oral phosphodiesterase type 5 inhibitors (PDE5 inhibitor) are considered first-line therapy.4 Final FDA approval for sildenafil for the treatment of ED was granted in March 1998. Sildenafil is the first oral therapy approved for treating early stages of PAH (pulmonary arterial hypertension).
Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cGMP. Cyclic guanosine monophosphate causes smooth muscle relaxation in the corpus cavernosum thereby allowing inflow of blood; the exact mechanism by which cGMP stimulates relaxation of smooth muscles has not been determined. Phosphodiesterase type 5 is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil enhances the effect of NO by inhibiting PDE5 thereby raising concentrations of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum and, at recommended doses, has no effect in the absence of sexual stimulation. Sildenafil can 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. However, the reduction in LES tone can worsen the symptoms of gastroesophageal reflux disease (GERD).9 Sildenafil has been shown to cross the blood-brain barrier and inhibit PDE5 in cerebral blood vessels. The areas of the brain that have the highest activity of PDE5 are the hippocampus, cerebral cortex, and basal ganglia. Although clinical studies have not proven this effect, inhibition of PDE5 by sildenafil in the brain may result in emotional, neurological, and psychological effects.
Do not take this medicine with any of the following medications: cisapride; methscopolamine nitrate; nitrates like amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, nitroglycerin; nitroprusside; other medicines for erectile dysfunction like tadalafil, vardenafil; other sildenafil products. Your health care provider needs to know if you have any of these conditions: bleeding disorders; eye or vision problems, including retinitis pigmentosa; Peyronie's disease, or history of priapism; heart disease, angina, a history of heart attack, irregular heartbeats, or other heart problems; high or low blood pressure; history of blood diseases; history of stomach bleeding; kidney disease; liver disease; stroke; an unusual or allergic reaction to sildenafil or other products. If you notice any changes in your vision while taking this drug, call your healthcare provider immediately. If you experience symptoms of nausea, dizziness, chest pain or arm pain upon initiation of sexual activity after taking this medicine, you should refrain from further activity and call your healthcare provider immediately. Do not use alcohol while using this medicine. Using this medicine does not protect you or your partner against HIV infection or other sexually transmitted infections.. Sildenafil is contraindicated in patients with a known hypersensitivity to any component of the tablet or injection. The safety and efficacy of combinations of sildenafil with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended. The use of sildenafil is not recommended in patients with pulmonary veno-occlusive disease (PVOD). Administration of sildenafil in this population may significantly worsen cardiovascular status. In addition, if signs of pulmonary edema occur during sildenafil administration, the possibility of associated PVOD should be considered. Sildenafil is contraindicated in patients who are currently on nitrate/nitrite therapy. Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of organic nitrates and nitrites. Patients receiving nitrates in any form are not to receive sildenafil. This includes any patient who receives intermittent nitrate therapies. It is unknown if it is safe for patients to receive nitrates once sildenafil has been administered. The American College of Cardiology recommends that sildenafil be used with caution in the following: patients with active coronary ischemia who are not taking nitrates (e.g., positive exercise test for ischemia); patients with congestive heart failure and borderline low blood pressure and borderline low volume status; patients on a complicated, multidrug, antihypertensive program; and patients taking drugs that can prolong the half-life of sildenafil. Patients with left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure can be particularly sensitive to the actions of sildenafil and other vasodilators. Doses of sildenafil above 25 mg should not be given within 4 hours of an alpha-blocker (e.g., doxazosin). Prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been associated with PDE5 inhibitor administration. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention. Sildenafil and other agents for the treatment of erectile dysfunction should be used with caution in patients with penile structural abnormality (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as such as sickle cell anemia, leukemia, multiple myeloma, polycythemia, or a history of priapism). Patients should be reminded that sildenafil, when used for erectile dysfunction, offers no protection against sexually transmitted disease. Sildenafil should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis. Sildenafil can decrease the tone of the lower esophageal sphincter and inhibit esophageal motility.9 Safety and efficacy of sildenafil has not been established in the treatment of pulmonary hypertension secondary to sickle cell disease. Vaso-occlusive crisis (sickle-cell crisis) requiring hospitalization has been reported more frequently in patients with pulmonary hypertension secondary to sickle cell disease who received sildenafil than by those who received placebo. Also, when using for erectile dysfunction, use sildenafil with caution in patients with sickle cell disease because the risk of priapism may be increased.
Sildenafil is classified as FDA pregnancy risk category B. There are no adequate and well-controlled studies of sildenafil in pregnant women. According to the manufacturers, Revatio should be used during pregnancy only if clearly needed;16 Sildenafil is not indicated for use in women.
It is not known if sildenafil or its metabolites are excreted in human breast milk. The prescribing information for Revatio recommends caution when the drug is administered to a nursing mother;16 Sildenafil is not indicated for use in women.11 Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Adverse reactions affecting the body as whole and occurring in < 2% of patients in controlled clinical trials of sildenafil include abdominal pain, accidental fall, accidental injury, allergic reaction (angioedema or anaphylactoid reactions), asthenia, chills, photosensitivity reaction, and shock. CNS and respiratory adverse reactions that occurred in < 2% of patients in clinical trials, include: abnormal dreams, asthma, ataxia, bronchitis, cough increased, depression, hypertonia, hyperesthesia, insomnia, laryngitis, neuralgia, neuropathy, pharyngitis, hyporeflexia, somnolence or drowsiness, sputum increased, tremor, and vertigo. Adverse reactions occurring in < 2% of patients in controlled clinical trials of sildenafil and affecting the digestive and urogenital systems include ejaculation dysfunction, orgasm dysfunction or anorgasmia, breast enlargement, colitis, cystitis, dysphagia, esophagitis, gastroenteritis, testicular swelling or genital edema, gingivitis, glossitis, abnormal liver function tests, nocturia, rectal hemorrhage, stomatitis, increased urinary frequency, urinary incontinence, vomiting, and dry mouth. Adverse reactions affecting the musculoskeletal system and occurring in < 2% of patients in controlled clinical trials of sildenafil include arthritis, arthrosis, bone pain, myasthenia, synovitis, tendon rupture, and tenosynovitis. Myalgia was reported by <= 7% of persons receiving sildenafil during clinical trials. A causal relationship to sildenafil therapy is uncertain.1116 Adverse reactions affecting the skin and appendages and occurring in < 2% of patients in controlled clinical trials of sildenafil include contact dermatitis, diaphoresis, exfoliative dermatitis, herpes simplex, pruritus, skin ulcer, and urticaria. During clinical trials, erythema was reported by 6% of sildenafil recipients. A causal relationship to sildenafil therapy is uncertain.11 16 Adverse reactions affecting hearing or otic special senses and occurring in < 2% of patients in controlled clinical trials of sildenafil include hearing loss, otalgia, and tinnitus. Ophthalmic adverse events reported by >= 2% of patients treated with sildenafil and which were more frequent on drug than placebo in clinical studies include visual impairment (3-11% vs. 0%) including mild and transient color tinge to vision and blurred vision (3% vs. 0%). Other ophthalmic adverse reactions occurring in < 2% of patients in controlled clinical trials of sildenafil include cataracts, conjunctivitis, mydriasis, ocular hemorrhage, ocular pain and photophobia.
Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.