Information for Healthcare Professionals: Tadalafil (marketed as Cialis) (7/2005)
To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program using the contact information at the bottom of this sheet.
advise patients to stop use of all PDE-5 inhibitors and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, which can result in permanent loss of vision.
discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators such as PDE-5 inhibitors.
As of May 18, 2005, a total of 43 cases of ischemic optic neuropathy (ION) among patients using the marketed PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) 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.
The four cases associated with tadalafil use are summarized below:
Table 1: Demographic characteristics of 4 cases of ischemic optic neuropathy reported in association with tadalafil
Mean 57.5 years, Median 59 years (range, 45 to 67 years)
Male 4 cases
Time to Onset†
≤ 2 hrs – 1 case; 45 hrs – 1 case; 48-72 hrs – 1 case; ≤ 7 days – 1 case
20mg - 3 cases; Unknown/Not Reported – 1 case
Recurrent ocular symptoms
Source of Report
US 3 cases; Foreign 1 case
2004 - 2 cases; 2005 – 2 cases
Disabled – 1 case (No outcome reported in 3 cases)
† time to onset after last tadalafil administration
All four cases 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.