According to published reports, the FDA has received 50 case reports of blindness and vision loss with sildenafil (VIAGRA), the first drug approved to treat erectile dysfunction (ED).  [COULDN’T FIND THIS IN THE FDA REPORT ON THEIR SITE 10/9/5] The Food and Drug Administration (FDA) is conducting an investigation into the connection between sildenafil and the condition known as non-arteritic anterior ischemic optic neuropathy (NAION), which can cause blindness. Similar invesigations are also being made into vardenafil (LEVITRA), and tadalafil (CIALIS). A smaller number of reports have been received for vardenafil and tadalafil, which are newer to the market.  

The FDA approved sildenafil in March 1998. At that time, we invoked our Five Year Rule. The Five Year Rule became the Seven Year Rule after new data showed that the majority of drug withdrawls and safety-based label changes occurred within seven years of a drug’s release (see Worst Pills, Best Pills News June 2002).

The FDA approved vardenafil in August 2003. Tadalafil was approved in November of that same year. The Seven Year Rule applies to both vardenafil and tadalafil.

The original 1998 professional product labeling, or package insert, for sildenafil stated that in some studies, as many at 11 percent of men using the drug experienced abnormal vision. A color tinge was the most common report, but increased sensitivity to light and blurred vision were also reported.  

Shortly after the FDA’s reviews of the drug were made public in 1998, Public Citizen petitioned the FDA to make major changes to the drug’s professional product labeling. This petition focused on important safety issues seen with use of the drug in studies conducted before approval, including vision problems.   

Sildenafil works by inhibiting an enzyme called phosphodiesterase. Forms of this enzyme are found in many parts of the body, including the eye. Some scientists think that changes in this enzyme can lead to some types of a serious disorder called retinitis pigmentosa, which can cause retinal degeneration and loss of vision. Phosphodiesterase controls the level of a particular chemical messenger in the retina by breaking it down as it is formed. This function is extremely important. High levels of this chemical messenger can damage the retina of the eye, leading to eventual blindness.

Visual disturbances were reported in studies of sildenafil that Pfizer submitted to the FDA to support the drug’s approval. In one single-dose study that tested doses of sildenafil ranging from 100 to 800 milligrams, about half of the men taking doses greater than 100 milligrams experienced visual disturbances. (Sildenafil is approved to be prescribed in doses of 25, 50 and 100 mg.) The disturbances included difficulty seeing in dim light, color aberration, and color tinges. Another study of sildenafil in healthy male volunteers showed that starting at 100 milligrams, men taking the drug had difficulty differentiating between different colors that increased as the dose of the drug increased.

A third study looked at visual function in eight normal males and eight men with diabetic retinopathy, a serious eye condition seen in diabetics. Both groups were given either 200 milligrams of sildenafil or a placebo [4 TIMES THE NORMAL DOSE]. In the sildenafil group, a test called the photopic electroretinogram (ERG) showed a 50 percent reduction in the response to blue light at 1.25 hours and at five hours after taking the drug.

In the petition, we noted that a 125-pound man taking 100 milligrams of sildenafil would be getting twice the dose per pound as a 250-pound man taking the same dose.

Public Citizen wrote a letter supplementing the petition to the FDA on August 20, 1998. In it, we again noted that sildenafil works by blocking the enzyme phosphodiesterase and the potential effects of phosphodiesterase inhibition.

The letter noted several important unanswered questions about sildenafil. When sildenafil is taken repeatedly, will the chemical messenger regulated by phosphodiesterase rise to toxic levels in some individuals, incurring the potential for retinal damage? How will vision be monitored in people using the drug? Will those with pre-existing retinal diseases be at increased risk of further retinal damage? The letter  asked that the FDA immediately convene an advisory committee to review the various serious problems related to the use of sildenafil.

The editors of the highly respected Medical Letter on Drugs and Therapeutics, written for physicians and pharmacists and noted for their independence from drug company influence, reviewed vision loss associated with the use of sildenafil in their June 20, 2005 issue. The Medical Letter editors reported that 14 cases of vision loss associated with use of sildenafil have been published in the medical literature. All of these men experienced NAION with blurred vision, a loss of the ability to see in particular parts of the eye, or both.

In some of these men, the loss was progressive and occurred over days or weeks. The loss of vision was generally first noticed within 24 hours of taking 25, 50 or 100 milligrams of sildenafil. Some had been using the drug for months or years; others had taken only one or a few doses. Five men noticed the loss of vision on awakening the next morning. Four others noticed vision loss within 90 minutes of taking the drug. One patient had vision loss in both eyes. Vision loss due to NAION was partial but permanent, which is the usual outcome with this condition.  

The Medical Letter editors also noted that NAION had also occurred in a few men taking tadalafil. In one case, the patient reported that transient visual field loss occurred with the first four doses of the drug, and became permanent after the fifth dose.

The editors concluded:

“Acute loss of vision due to NAION has been reported in some men taking sildenafil (Viagra), but there is no proof of cause and effect.”

This conclusion is scientifically appropriate, since postmarketing and published case reports do not prove a cause and effect relationship. However, despite the absence of “gold standard” proof that sildenafil, vardenafil, or tadalafil cause NAION and possible blindness, the reports of NAION associated with the use of these drugs in conjunction with the FDA investigation mean that there is every reason to warn men of the possibility of harm from the use of these drugs. This is true for drugs that do not treat life-threatening conditions and especially true in the case of the erectile dysfunction drugs, which may be used for recreational purposes at higher than the FDA-approved doses.

What You Can Do

You should not use sildenafil, vardenafil, or tadalafil for recreational purposes because there is no medical benefit to be gained. The possible harm from these drugs, no matter how small, will always outweigh a lack of medical benefit. If you experience any visual problems while using these drugs, notify your doctor immediately.

Attempts to confirm this on line requires the spending of hundreds of dollars in subscription fees since the major source is a Dutch capitalist company, in it for the money.  However, Pub Med provides abstracts from their extensive library—a good PR move.  And searching them rather than Google Scholar proved fruitful.  JK wasted an hour with Google Scholar.  

Viagra (sildenafil citrate) Information

FDA ALERT [07/2005]:

A small number of men have lost eyesight in one eye some time after taking Viagra, Cialis, or Levitra. This type of vision loss is called non-arteritic anterior ischemic optic neuropathy (NAION). NAION causes a sudden loss of eyesight because blood flow is blocked to the optic nerve.

We do not know at this time if Viagra, Cialis, or Levitra causes NAION. NAION also happens in men who do not take these medicines. People who have a higher chance for NAION include those who:

·         have heart disease

·         are over 50 years old

·         have diabetes

·         have high blood pressure

·         have high cholesterol

·         smoke

·         have certain eye problems

FDA has approved new labels for Viagra, Cialis, and Levitra to include information on possible eyesight loss (NAION).

At this time, it is not possible to determine whether these oral medicines for erectile dysfunction were the cause of the loss of eyesight or whether the problem is related to other factors such as high blood pressure or diabetes, or to a combination of these problems. The new labeling information is available along with additional information for healthcare providers and consumers online at:

At another FDA page:

FREQUENTLY ASKED QUESTIONS CONCERNING VIAGRA

As with any drug products, there are side effects of the product in some people. The most commonly reported side effects in patients treated with Viagra during the testing of the product were: headache, flushing, stomach ache, and mild and temporary visual changes (color perception changes, light perception changes, and blurred vision).

At http://www.fda.gov/cder/drug/InfoSheets/HCP/sildenafilHCP.pdf

“Most, but not all of these patients had underlying anatomic or vascular risk factors for development of NAION…it is not possible to determine whether these events are related directly to the use of PDE-5 inhibitors, to patient’s underlying vascular risk factors or other factors.

Studies shows that Viagra produced no effect on color vision

Effects of sildenafil on blue-on-yellow and white-on-white Humphrey perimetry in 3 months regular use.

Dundar SO, Topalo Gcaron Lu A, Dundar M, Kocak I.

Eye. 2005 Jul 29.

1Department of Ophthalmology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.

Purpose:  To assess the effects of sildenafil on blue-on-yellow (B/Y) and white-on-white (W/W) Humphrey perimetry in a group of men with erectile dysfunction in 3 months regular use.MethodsIn this prospective study, 14 patients with erectile dysfunction received 50 mg doses of sildenafil (Viagra, Pfizer) two times per week regularly for 3 months. Patients underwent best-corrected visual acuity (BCVA), colour vision, anterior segment and fundus examination, and B/Y and W/W Humphrey perimetry in each eye before and after sildenafil treatment. Changes in mean deviations (MD) were compared separately for both eyes. 

Results:  No significant changes from baseline were observed in BCVA and colour vision after sildenafil treatment. The anterior segment and fundus examinations revealed no abnormalities. There was no change on B/Y and W/W Humphrey visual field. MD values of B/Y and W/W Humphrey perimetry remained nonsignificant for both eyes after 3 months regular use of sildenafil (P=0.133, and 0.092, respectively, for right, and P=0.221 and 0.925, respectively, for left eyes).  ConclusionOral sildenafil used regularly for 3 months produced no effect on B/Y and W/W Humphrey perimetry.  Eye advance online publication, 29 July 2005; doi:10.1038/sj.eye.6702017.

PMID: 16052253 [PubMed - as supplied by publisher]

Ocular safety of Viagra, (sildenafil citrate).

Laties AM, Fraunfelder FT.

Scheie Eye Institute, Philadelphia, USA.

To date, sildenafil citrate (Viagra) gives every evidence of being a safe drug for the eye despite a series of expressed concerns. A review of how its ocular safety profile has been identified offers insights into the strengths and weaknesses of present systems and resources for judging the ocular safety of Viagra or, for that matter, of any new drug. Such insights include: The great value of careful, informed assessment of preclinical information gleaned from laboratory experiments. By and large, such assessments point the way toward appropriate clinical evaluation. For Viagra, early in its development it was noted that besides exerting a major inhibitory effect on the intended target, the vascular-associated enzyme phosphodiesterase 5 (PDE5), the drug also exerts a lesser but definite inhibitory effect on the closely related PDE6, located in the retina. For this reason, preclinical evaluation of the drug included electroretinography plus postmortem histology. In addition, an extended eye examination was incorporated into clinical protocols. The often chaotic but invaluable information stream that becomes available once marketing approval has been gained and large populations begin to use a drug. False alarms, misattribution, and erroneous information are the order of the day. Nevertheless, as information accumulates, patterns of response clarify and the true nature of special susceptibility for subpopulations, if any, becomes apparent. A role for the astute clinician remains: Subtle changes or unusual risks for subpopulations can be missed entirely for long periods of time. A manifest need for improvement in evaluation of postmarketing side-effects. This need has led to the establishment of a new discipline: pharmacoepidemiology. In ophthalmology, the National Registry of Drug Induced Ocular Side-Effects maintains a constant and invaluable surveillance. Examples are supplied to illustrate each of these major points: Our presentation will include data gleaned from clinical trials plus postmarketing information on the incidence, duration, and type of color vision defects observed at different doses of Viagra.

More studies

Int Ophthalmol. 2004 Mar;25(2):69-72.

Acute effects of sildenafil on Humphrey visual field and intraocular pressure.

Ermis SS, Inan UU, Samli M, Ozturk F.

CONCLUSIONS: No significant effect of sildenafil was seen on visual field and intraocular pressure in healthy subjects.

Am J Ophthalmol. 2004 May;137(5):842-9.

Visual short-term effects of Viagra: double-blind study in healthy young subjects.

Jagle H, Jagle C, Serey L, Yu A, Rilk A, Sadowski B, Besch D, Zrenner E, Sharpe LT.

Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant.

OTHER STUDIES CONFIRMED THIS CONCLUSION & ITS SAFE FOR THE HEART!

Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease.

Conti CR, Pepine CJ, Sweeney M.

‘Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5-200 mg) or placebo for 4-24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question ("Did the treatment improve your erections?"). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.

Available over the counter as STAMINA Rx and Spontane ES.  

(Today, the Food and Drug Administration (FDA) is warning consumers not to purchase or consume the following products: SIGRA, STAMINA Rx and STAMINA Rx for Women, Y-Y, Spontane ES and Uroprin, manufactured by NVE, Inc., in Newton, N.J. and distributed by Hi-Tech in Norcross, Ga. These products, which are being marketed as dietary supplements, actually contain a prescription drug ingredient that poses possible health risks. The products are being sold over-the-counter and are claiming to increase stamina, confidence and performance.)