FDA label ad24a9ce-9ca4-47ea-bb66-44d7d1fd7722

Figure 1: Mean Sildenafil Plasma Concentrations in Healthy Male Volunteers. Figure

Figure 2: Mean Change from Baseline in Sitting Systolic Blood Pressure, Healthy Volunteers. Figure

Figure 3. Effect of VIAGRA and Placebo on Maintenance of Erection by Baseline Score. Figure Figure

Figure 4. Percentage of Patients Reporting an Improvement in Erections. Figure

WARNINGS There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VIAGRA, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. VIAGRA 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: Pharmacodynamics ). While this normally would be expected to be of little consequence in most patients, prior to prescribing VIAGRA, 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. Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including VIAGRA – 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 is no controlled clinical data on the safety or efficacy of VIAGRA 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) or hypertension (BP >170/110); • Patients with cardiac failure or coronary artery disease causing unstable angina; • Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases); • Patients with sickle cell or related anemias. Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA. 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. The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil ( 11-fold increase in AUC ). If VIAGRA is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil exposure. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200–800 mg). To decrease the chance of adverse events in patients taking ritonavir, a decrease in sildenafil dosage is recommended (see Drug Interactions , ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION ).

ADVERSE REACTIONS CLINICAL TRIALS VIAGRA was administered to over 3700 patients (aged 19–87 years) during pre-marketing clinical trials worldwide. Over 550 patients were treated for longer than one year. In placebo-controlled clinical studies, the discontinuation rate due to adverse events for VIAGRA (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature. In trials of all designs, adverse events reported by patients receiving VIAGRA were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies. When VIAGRA was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported: TABLE 2. ADVERSE EVENTS REPORTED BY ≥2% OF PATIENTS TREATED WITH VIAGRA AND MORE FREQUENT ON DRUG THAN PLACEBO IN PRN FLEXIBLE-DOSE PHASE II/III STUDIES Adverse Event Percentage of Patients Reporting Event VIAGRA N=734 PLACEBO N=725 Headache 16% 4% Flushing 10% 1% Dyspepsia 7% 2% Nasal Congestion 4% 2% Urinary Tract Infection 3% 2% Abnormal Vision Abnormal Vision: Mild and transient, predominantly color tinge to vision, but also increased sensitivity to light or blurred vision. In these studies, only one patient discontinued due to abnormal vision. 3% 0% Diarrhea 3% 1% Dizziness 2% 1% Rash 2% 1% Other adverse reactions occurred at a rate of >2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia. In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently. The following events occurred in <2% of patients in controlled clinical trials; a causal relationship to VIAGRA is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful: Body as a whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury. Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy. Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis. Hemic and Lymphatic: anemia and leukopenia. Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia. Musculoskeletal : arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis. Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia. Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis. Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes. Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia. POST-MARKETING EXPERIENCE Cardiovascular and cerebrovascular Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA, to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors (see WARNINGS for further important cardiovascular information). Special senses Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors (see PRECAUTIONS, Information for Patients ). Other events Other events reported post-marketing to have been observed in temporal association with VIAGRA and not listed in the clinical trial adverse reactions section above include: Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia. Urogenital: prolonged erection, priapism (see WARNINGS ), and hematuria. Special Senses: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/traction, paramacular edema and epistaxis. Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors (see PRECAUTIONS/Information for Patients ). Hemic and Lymphatic: Vaso-occlusive crisis: In a small, prematurely terminated study of REVATIO in patients with pulmonary hypertension (PH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with VIAGRA for ED is not known.

<table ID="_Refid_1e3b9a26-dfba-4ac8-9c49-bc7070d6a" width="100%"> <caption>TABLE 2. ADVERSE EVENTS REPORTED BY &#x2265;2% OF PATIENTS TREATED WITH VIAGRA AND MORE FREQUENT ON DRUG THAN PLACEBO IN PRN FLEXIBLE-DOSE PHASE II/III STUDIES</caption> <col width="40%"/> <col width="30%"/> <col width="30%"/> <thead> <tr> <th align="left" styleCode="Rrule Botrule Toprule " valign="top"> <content styleCode="bold">Adverse Event</content> </th> <th align="center" colspan="2" styleCode="Botrule Lrule Toprule " valign="top"> <content styleCode="bold">Percentage of Patients Reporting Event</content> </th> </tr> <tr> <th align="left" styleCode="Rrule Botrule " valign="top"/> <th align="left" styleCode="Rrule Botrule " valign="top"> <content styleCode="bold">VIAGRA</content> <content styleCode="bold">N=734</content> </th> <th align="left" styleCode="Botrule " valign="top"> <content styleCode="bold">PLACEBO</content> <content styleCode="bold">N=725</content> </th> </tr> </thead> <tbody> <tr> <td styleCode="Toprule " valign="top"> <paragraph>Headache</paragraph> </td> <td styleCode="Toprule " valign="top"> <paragraph>16%</paragraph> </td> <td styleCode="Toprule " valign="top"> <paragraph>4%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Flushing</paragraph> </td> <td valign="top"> <paragraph>10%</paragraph> </td> <td valign="top"> <paragraph>1%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Dyspepsia</paragraph> </td> <td valign="top"> <paragraph>7%</paragraph> </td> <td valign="top"> <paragraph>2%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Nasal Congestion</paragraph> </td> <td valign="top"> <paragraph>4%</paragraph> </td> <td valign="top"> <paragraph>2%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Urinary Tract Infection</paragraph> </td> <td valign="top"> <paragraph>3%</paragraph> </td> <td valign="top"> <paragraph>2%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Abnormal Vision<footnote ID="_Refida1j00e">Abnormal Vision: Mild and transient, predominantly color tinge to vision, but also increased sensitivity to light or blurred vision. In these studies, only one patient discontinued due to abnormal vision.</footnote> </paragraph> </td> <td valign="top"> <paragraph>3%</paragraph> </td> <td valign="top"> <paragraph>0%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Diarrhea</paragraph> </td> <td valign="top"> <paragraph>3%</paragraph> </td> <td valign="top"> <paragraph>1%</paragraph> </td> </tr> <tr> <td valign="top"> <paragraph>Dizziness</paragraph> </td> <td valign="top"> <paragraph>2%</paragraph> </td> <td valign="top"> <paragraph>1%</paragraph> </td> </tr> <tr> <td styleCode="Botrule " valign="top"> <paragraph>Rash</paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>2%</paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>1%</paragraph> </td> </tr> </tbody> </table>