Sildenafil: uses, appearance and warnings

Sildenafil tablets are indicated for the treatment of erectile dysfunction. Sildenafil tablets are phosphodiesterase-5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED) ( 1 )

Sildenafil tablets, USP are supplied as white, oval shaped, biconvex, film coated tablets containing sildenafil citrate, USP equivalent to 25 mg, 50 mg, or 100 mg of sildenafil. Tablets are plain on one side and debossed with ‘B9’, ‘C1’, or ‘436’ on the other to indicate the dosage strengths. Tablets: 25 mg, 50 mg, 100 mg ( 3 )

Sildenafil tablets, USP are supplied as: 25 mg Tablets: White, oval shaped, biconvex, film coated tablets, plain on one side and debossed with 'B9' on the other side. Bottle of 30 Tablets with child-resistant closure NDC 59746-434-30 Bottle of 90 Tablets with child-resistant closure NDC 59746-434-90 Bottle of 500 Tablets NDC 59746-434-05 100 Unit-dose Tablets (10 x 10) NDC 59746-434-03 50 mg Tablets: White, oval shaped, biconvex, film coated tablets, plain on one side and debossed with 'C1' on the other side. Bottle of 30 Tablets with child-resistant closure NDC 59746-435-30 Bottle of 90 Tablets with child-resistant closure NDC 59746-435-90 Bottle of 100 Tablets with child-resistant closure NDC 59746-435-01 Bottle of 500 Tablets NDC 59746-435-05 100 Unit-dose Tablets (10 x 10) NDC 59746-435-03 100 mg Tablets: White, oval shaped, biconvex, film coated tablets, plain on one side and debossed with '436' on the other side. Bottle of 30 Tablets with child-resistant closure NDC 59746-436-30 Bottle of 90 Tablets with child-resistant closure NDC 59746-436-90 Bottle of 100 Tablets with child-resistant closure NDC 59746-436-01 Bottle of 500 Tablets NDC 59746-436-05 100 Unit-dose Tablets (10 x 10) NDC 59746-436-03 Recommended Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature] .

Administration of sildenafil to patients using nitric oxide donors, such as organic nitrates or organic nitrites in any form. Sildenafil was shown to potentiate the hypotensive effect of nitrates ( 4.1 , 7.1 , 12.2 ) Known hypersensitivity to sildenafil or any component of tablet ( 4.2 ) Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 4.3 ) 4.1 Nitrates Consistent with its known effects on the nitric oxide/cGMP pathway [see Clinical Pharmacology (12.1 , 12.2 )] , sildenafil was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated. After patients have taken sildenafil, it is unknown when nitrates, if necessary, can be safely administered. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [see Dosage and Administration (2.3) , Drug Interactions (7.1) , and Clinical Pharmacology (12.2) ] . 4.2 Hypersensitivity Reactions Sildenafil is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in sildenafil tablets and REVATIO, or any component of the tablet. Hypersensitivity reactions have been reported, including rash and urticaria [see Adverse Reactions (6.1) ]. 4.3 Concomitant Guanylate Cyclase (GC) Stimulators Do not use sildenafil in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including sildenafil, may potentiate the hypotensive effects of GC stimulators.

Patients should not use sildenafil if sexual activity is inadvisable due to cardiovascular status ( 5.1 ) Patients should seek emergency treatment if an erection lasts >4 hours. Use sildenafil with caution in patients predisposed to priapism ( 5.2 ) Patients should stop sildenafil and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non arteritic anterior ischemic optic neuropathy (NAION). Sildenafil should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a "crowded" optic disc may also be at an increased risk of NAION. ( 5.3 ) Patients should stop sildenafil and seek prompt medical attention in the event of sudden decrease or loss of hearing ( 5.4 ) Caution is advised when sildenafil is co-administered with alpha-blockers or anti-hypertensives. Concomitant use may lead to hypotension ( 5.5 ) Decreased blood pressure, syncope, and prolonged erection may occur at higher sildenafil exposures. In patients taking strong CYP inhibitors, such as ritonavir, sildenafil exposure is increased. Decrease in sildenafil dosage is recommended ( 2.4 , 5.6 ) 5.1 Cardiovascular There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including sildenafil, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Sildenafil has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), [see Clinical Pharmacology (12.2) ] . While this normally would be expected to be of little consequence in most patients, prior to prescribing sildenafil, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity. Use with caution in patients with the following underlying conditions which can be particularly sensitive to the actions of vasodilators including sildenafil – those with left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. There are no controlled clinical data on the safety or efficacy of sildenafil in the following groups; if prescribed, this should be done with caution. Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; Patients with resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg); Patients with cardiac failure or coronary artery disease causing unstable angina. 5.2 Prolonged Erection and Priapism Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of sildenafil tablets. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. Sildenafil should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). However, there are no controlled clinical data on the safety or efficacy of sildenafil in patients with sickle cell or related anemias. 5.3 Effects on the Eye Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged ≥ 50. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare post-marketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [ see Adverse Reactions (6.2) ] . Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including sildenafil, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including sildenafil, for this uncommon condition. …

The following are discussed in more detail in other sections of the labeling: Cardiovascular [see Warnings and Precautions (5.1) ] Prolonged Erection and Priapism [see Warnings and Precautions (5.2) ] Effects on the Eye [ see Warnings and Precautions (5.3) ] Hearing Loss [see Warnings and Precautions (5.4) ] Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives [see Warnings and Precautions (5.5) ] Adverse Reactions with the Concomitant Use of Ritonavir [see Warnings and Precautions (5.6) ] Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies [see Warnings and Precautions (5.7) ] Effects on Bleeding [see Warnings and Precautions (5.8) ] Counseling Patients About Sexually Transmitted Diseases [see Warnings and Precautions (5.9) ] The most common adverse reactions reported in clinical trials (≥ 2%) are headache, flushing, dyspepsia, abnormal v …

Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. …