The Food and Drug Administration ( FDA ) has approved new labeling for Cialis ( Tadalafil ), Viagra ( Sildenafil ), and Levitra ( Vardenafil ) regarding postmarketing reports of vision loss related to NAION ( non-arteritic anterior ischemic optic neuropathy ).

Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including: low cup to disc ratio ( “crowded disc” ), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking.

Given the small number of events, the large number of users of PDE-5 inhibitors and the fact that this event occurs in a similar population to those who do not take these medicines, it is not possible to determine whether these events are related directly to the use of PDE-5 inhibitors, to the patient’s underlying vascular risk factors or anatomical defects, to a combination of these factors, or other factors.

As of May 18, 2005, a total of 43 cases of ischemic optic neuropathy ( ION ) among patients using the PDE-5 inhibitors have been reported to the FDA’s Adverse Event Reporting System.

Since approval, 38 cases have been identified in association with Sildenafil, 4 cases have been identified in association with Tadalafil and one case has been identified in association with Vardenafil.

Most of these cases ( 25/43 ) appear to be the non-arteritic anterior ischemic optic neuropathy ( NAION ) subtype.
Thirty-six of the 43 cases reported accompanying visual loss, and 26 of these 36 cases reported the visual loss as continuing or permanent.
Most of the patients in these cases reported vascular risk factors for NAION that overlap with vascular risk factors for erectile dysfunction ( such as age over 50, low cup to disc ratio, hypertension, diabetes, smoking, etc ), making direct attribution to PDE-5 inhibitors not possible.

However, the clinical attributes of some of the cases ( e.g., a temporal relationship in 19 Sildenafil cases, 4 Tadalafil cases, and the one Vardenafil case, and the report of recurrent ocular symptoms that might reflect NAION in five sildenafil cases and one Tadalafil case ), raise concern in regard to the role of PDE-5 inhibitors.

Viagra

The majority of Sildenafil cases ( 21/38 ) appear to be cases of NAION.
It was not possible to definitively subtype ( e.g. arteritic vs nonarteritic, posterior vs anterior ) the remaining 17 ischemic optic neuropathy cases because of limited information that was provided.

Thirty-one of the 38 cases reported accompanying vision loss that was continuing or permanent in 22 cases.
Visual loss was not documented in the remaining 7 cases.
In nineteen of the 38 cases, diminished vision or vision loss was reported from “immediately” after to 36 hours after Sildenafil administration.
Twenty-nine of the 38 cases reported one or more of the following risk factors for developing NAION: history of hypertension in 14 cases, history of hyperlipidemia in 12 cases, a low cup to disk ratio or “crowded disc” in 11 cases, history of diabetes in 6 cases, history of coronary artery disease in 3 cases, history of smoking in 3 cases, history of hypotension in 1 case, and previous history of ION in 1 case.

Cialis

All four cases, associated with Tadalafil use, reported vision loss that was continual or permanent.
All four were reported from within 2 hrs to 7 days from Tadalafil administration.
Three of the 4 cases reported one or more of the following risk factors for developing ION: a low cup to disk ratio or “crowded disc” in 3 cases, recent post-operative hypotension in 1 case, and history of hyperlipidemia in 1 case.

Levitra

One case associated with Vardenafil use was reported to FDA in 2004.
A male patient in his mid-50s with no documented hypertension, diabetes and hyperlipidemia took 10mg Vardenafil for the first time and experienced vision loss in his left eye the next morning.
The patient lost central vision in his left eye, reportedly due to transient ischemia.
It is unknown if the vision loss reversed or persisted.

FDA is aware of 6 additional cases of vision loss following Vardenafil administration, reported as serious adverse events in the Bayer Global Drug Safety Database.

Source: FDA, 2005


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