OCULAR SAFETY OF VIAGRA (SILDENAFIL CITRATE): LONG-TERM STUDIES

Patients with erectile dysfunction and no history of eye disorder are described in detail elsewhere. Morales and associates have summarized the clinical safety of sildenafil in phase II/II clinical trials. In 6 flexible-dose studies comparing the efficacy of sildenafil (734 patients) with placebo (725 patients), abnormal vision was reported by 3% of those treated with study drug and 0% of those given placebo. The visual disturbances were most often described as a bluish tinge to vision or an increased brightness and sensitivity to lights. In 10 long-term, open-label extension studies involving 2,199 patients, the reported incidence of abnormal vision was somewhat lower (2%). A 52-week clinical trial conducted in 47 patients with erectile dysfunction was designed to monitor the long-term effects of sildenafil on visual function. Patients initially received sildenafil (Viagra) on a fixed-dose schedule (50 to 200 mg as needed) for 12-weeks, followed by a 40-week open-label flexible-dose period (25 to 100 mg as needed). Visual function was tested at baseline, 12 weeks, and 52 weeks.

Patients were not required to take a dose of sildenafil on the morning of their clinic visit; consequently, any changes to the visual function test results represented long-term rather than acute effects of sildenafil. No clinically significant changes were seen in visual acuity, contrast sensitivity, FM-100 hue test, photostress test, and slit-lamp examination. No serious visual adverse events or discontinuations occurred because of visual adverse events.

Concerning IOP, a strange focal cluster of 6 reports of “glaucoma” were issued from a single town in Germany prior to approval of the drug within that country (World Wide Safety, INTELRSG, 1998). Despite wide use of the drug within the United States and abroad, only occasional reports of glaucoma have been received. With respect to glaucoma, careful attention was paid to both the pupil and IOP during clinical development. For example, in 8 healthy male subjects receiving supratherapeutic doses of sildenafil (Viagra), there was no significant change in IOP 0.75 hours postdose. Monitoring of both pupil diameters and IOP during several clinical trials in the United States and abroad failed to demonstrate any effect whatsoever of sildenafil on either. In fact, as a demonstration of both the nature of single-event reporting and the inherent difficulty of attributing an event to the intake of a drug, a single report of an apparent cure of a 70-year-old patient with glaucoma of 9 years duration after sildenafil represents the most thoroughly documented case of an effect of sildenafil on IOP. Because medical therapy was insufficient to bring his pressure into the normal range, he required laser surgery, after which his pressures were serially recorded as 18 OD 19 OS applanation. Some time later, having taken a total of only three 100-mg doses of sildenafil, the patient returned to his ophthalmic consultant to find that his pressures now were 14 OD 13 OS applanation (personal communication, Dr Murray Maytom, Pfizer Inc) In the words of his ophthalmologist, “Based on the evidence at hand, one would be reluctant to give the credit to sildenafil, but as far as I can understand from the patient it has been the only factor that had changed or could have had an influence on what previously had always been a fairly stable problem.”

SUBPOPULATIONS

A retrospective analysis of combined data from 18 phase 2/3 studies (fixed- or flexible-dose, 4 to 26 weeks) evaluated visual adverse events in patients receiving sildenafil (5 to 200 mg) for the treatment of erectile dysfunction. Of the 2,722 patients who received sildenafil and the 1,552 patients who received placebo, 66 patients also had a history of eye disorders, which were described as diabetic retinopathy, glaucoma, and macular degeneration. A total of 9 visual adverse events were reported for these 66 patients, 7 from the 39 patients treated with sildenafil and 2 from the 27 patients treated with placebo. Of the 39 patients who received sildenafil, only 1 patient discontinued treatment because of a visual adverse event. This patient experienced moderate blurred vision and discontinued treatment with 10 mg of sildenafil on day 8 of treatment. Overall, sildenafil was generally well tolerated in this limited sample of patients with a history of eye disorders.

Leave a Reply

Your email address will not be published. Required fields are marked *

CAPTCHA image
*