Clinical Trials
VIAGRA (sildenafil citrate) 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 (sildenafil citrate) (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 (sildenafil citrate) 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 (sildenafil citrate) 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 (sildenafil citrate) AND MORE FREQUENT ON DRUG THAN PLACEBO IN PRN FLEXIBLE-DOSE PHASE II/III STUDIES
| Adverse Event | Percentage of Patients VIAGRA N=734 |
Reporting Event PLACEBO N=725 |
| Headache | 16% | 4% |
| Flushing | 10% | 1% |
| Dyspepsia | 7% | 2% |
| Nasal Congestion | 4% | 2% |
| Urinary Tract Infection | 3% | 2% |
| Abnormal Vision† | 3% | 0% |
| Diarrhea | 3% | 1% |
| Dizziness | 2% | 1% |
| Rash | 2% | 1% |
| †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. | ||
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 (sildenafil citrate) 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 (sildenafil citrate) . 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 (sildenafil citrate) without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA (sildenafil citrate) and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA (sildenafil citrate) , 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 (sildenafil citrate) . 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 (sildenafil citrate) , to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors (see PATIENT INFORMATION).
Other events
Other events reported post-marketing to have been observed in temporal association with VIAGRA (sildenafil citrate) 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 (sildenafil citrate) . 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 PATIENT INFORMATION).
