Background

Following the publication of a report in the Journal of Laryngology and Otology (April 2007), FDA conducted a search of its adverse event reporting system for cases of hearing loss in patients taking phosphodiesterase type 5 (PDE5) inhibitors. Twenty-nine postmarketing reports of sudden hearing loss defined as new hearing loss occurring over a period of 3 days or less following the last dose, both with and without tinnitus and dizziness, were identified. Sudden hearing loss was also reported in a few patients in clinical trials of these drugs. The labeling for Viagra, Levitra and Cialis was revised to address this new safety information. Revatio is sildenafil citrate marketed for treatment of pulmonary arterial hypertension (PAH) and FDA is working with the sponsor to revise labeling for this drug.

Recommendations

For Pulmonary Arterial Hypertension

* Physicians should advise their patients with pulmonary arterial hypertension (PAH) who experience sudden hearing loss while taking Revatio to seek prompt medical attention.
* Patients should be told NOT to discontinue treatment without consulting their physician.
* Physicians should explain to their patients that pulmonary arterial hypertension is a life-threatening condition and there is a risk of decompensation of their pulmonary arterial hypertension if they stop taking Revatio and are not provided with other treatment options.

For Erectile Dysfunction

* Physicians who prescribe Viagra, Levitra or Cialis for erectile dysfunction should advise their patients to immediately stop taking the drug if they experience any sudden decrease or loss of hearing and seek prompt medical attention.

Information for the Patient

Patients with Pulmonary Arterial Hypertension should:

* NOT stop taking Revatio if you experience any sudden decrease or loss of hearing.
* Seek prompt medical attention; call your healthcare provider

Patients with Erectile Dysfunction should:

* Immediately stop taking the drug if you experience any sudden decrease or loss of hearing
* Seek prompt medical attention

Data Summary

FDA’s analysis included all cases of hearing loss or impairment reported in clinical trials and in the post marketing setting for each of the products Viagra (sildenafil citrate); Levitra (vardenafil HCl); Cialis (tadalafil) and Revatio. Sildenafil use by patients with pulmonary arterial hypertension is both continuous and at a higher dose than for men taking sildenafil intermittently for erectile dysfunction.

From the postmarketing reports, we identified a total of 29 cases of sudden hearing loss that showed a temporal relationship to dosing with a PDE5 inhibitor. Sudden hearing loss was also reported in a few patients in clinical trials of these drugs. In many cases, medical conditions and other factors may have contributed to the adverse event.
Viagra:

Clinical trials:

A total of 5 sildenafil treated patients, of the approximately 25,000 sildenafil-treated patients from all clinical studies combined, experienced sudden hearing loss in temporal relation to dosing.

Post-marketing reports:

Fifteen of the postmarketing cases of sudden hearing loss had a temporal relationship and occurred in men ranging in age from 44 to 85. In 5 of the 15 cases, sudden hearing loss occurred after the first dose. Nine of the 15 cases were unilateral, one was bilateral and 5 did not specify. Sudden hearing loss was temporary (lasting 24 hrs to 2 weeks) in 4 of the 15 cases. In 8 cases, the sudden hearing loss was ongoing, and in 3 cases it was not reported if the sudden hearing loss was temporary or ongoing.

Levitra:

Clinical Trials:

A total of 3 of the approximately 16,000 patients treated with vardenafil in all clinical studies combined experienced sudden hearing loss in temporal relation to dosing.

Post-marketing reports:

Five of the postmarketing cases of sudden hearing loss had a temporal relationship and occurred in men ranging in age from 38 to 74. In 2 of the 5 cases, sudden hearing loss occurred after the first dose. Two of the 5 cases were unilateral, 1 was bilateral and 2 did not specify. In 3 of the 5 cases, the sudden hearing loss was temporary, and in 2 cases the sudden hearing loss was ongoing.

Cialis:

Clinical trials:

A total of 4 of the approximately 18,000 patients treated with tadalafil in all clinical studies combined experienced sudden hearing loss in temporal relation to dosing.

Post-marketing reports:

Five of the postmarketing cases of sudden hearing loss had a temporal relationship and occurred in men ranging in age from 58 to 71. In 3 of the 5 cases, sudden hearing loss occurred after the first dose. Two of the 5 cases were unilateral, 2 were bilateral and 1 did not specify. In 2 of the 5 cases, the sudden hearing loss was temporary, in 2 cases the sudden hearing loss was ongoing, and in 1 case it was not reported whether the sudden hearing loss was temporary or ongoing.

Revatio:

Sildenafil use by patients with PHA is both continuous and at a higher dose than for men taking sildenafil intermittently for erectile dysfunction.

Clinical Trials:

A total of 5 sildenafil-treated patients among the approximately 660 patients enrolled in all clinical studies reported hearing loss/impairment, including sudden hearing loss. Four of these cases occurred in an open-label extension study. Sildenafil therapy was continued in all 5 cases. In 2 cases, the sudden hearing loss resolved (2 months in one case, 1 day in the other). In 3 cases, the hearing impairment was still present at the end of the study.

Post-marketing reports:

A total of 4 reports of sudden hearing loss were received and occurred in 3 women and 1 man ranging in age from 36 to 63. The time to onset of sudden hearing loss ranged from less than 3 weeks to 11 months after beginning Revatio therapy and all could be reasonably associated with the use of the drug. All 4 cases involved unilateral hearing loss and were ongoing. Revatio therapy was continued for three of the reported cases and discontinued in 1 case.