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FAQ

Hearing loss and PDE5 inhibitors

Phosphodiesterase type 5 (PDE5) inhibitors including sildenafil (Viagra®), vardenafil (Levitra®) and tadalafil (Cialis®) are indicated for use in men with erectile dysfunction. In addition, sildenafil (Revatio®), at a different dosing schedule, is indicated for improvement in exercise ability in patients with pulmonary arterial hypertension (PAH). Inhibition of PDE5 prevents breakdown of cyclic guanosine monophosphate thereby relaxing smooth muscle in the corpus cavernosum allowing inflow of blood which results in penile erection. The efficacy in PAH is also based on smooth muscle relaxation that occurs within the pulmonary vasculature via increased levels of cyclic guanosine monophosphate through PDE5 inhibition. Common side effects of these agents include headache, flushing, dyspepsia, nasal congestion and/or rhinitis.

In the April 2007 issue of The Journal of Laryngology and Otology, Mukherjee and colleagues describe the course of a 44 year old man’s progressive hearing loss after starting sildenafil 50 mg for erectile dysfunction. The symptoms began with a ringing sensation in the right ear 5 days after taking sildenafil which spread to the left ear 2 days later. The ringing sound progressed from low to high pitched and eventually led to difficulty hearing and understanding spoken words. Fifteen days after starting the medication, the patient reported absolute hearing loss that did not resolve after discontinuing the medication. Management with a corticosteroid (prednisolone 1 mg/kg/day for 1 month) and inhaled oxygen and carbon dioxide (8 times daily for 5 days) did not reverse the symptoms and no improvement was observed at 6 months. The authors were not able to identify any other cause of hearing loss and postulate sildenafil as the cause of cochleotoxicity.

Although the incidence of hearing loss was low in clinical trials, this published case report prompted the Food and Drug Administration (FDA) to search its own adverse events database for reports of sudden hearing loss associated with use of PDE5 inhibitors. A summary of the 29 postmarketing reports received by the FDA are given in the table below. Sudden hearing loss was defined as new loss of hearing over 3 days or less after the last dose. In certain cases, dizziness and tinnitus were accompanying symptoms. Of the 25 patients using the drugs for erectile dysfunction, 10 cases of hearing loss occurred after the first dose. In patients with pulmonary arterial hypertension, sudden hearing loss occurred from less than 3 weeks to 11 months after starting sildenafil. Although a temporal relation exists between the occurrence of hearing loss and initiation of the drug, it is unclear whether the effects are solely due to the drug, other medical conditions, risk factors or a combination of these. Outside of discontinuation of the medication, management of patients with ongoing symptoms is unclear.

Description of postmarketing reports of sudden hearing loss with PDE5 inhibitors.

Due to these postmarketing reports of sudden decrease or loss of hearing, the FDA has requested manufacturers of PDE5 inhibitors to revise the labeling of these agents. The FDA recommends prescribers to counsel patients taking PDE5 inhibitors for erectile dysfunction to discontinue use of the drug immediately if hearing loss occurs. However, PAH patients taking Revatio® who develop hearing loss should consult their providers immediately and should not discontinue the medication without first discussing other treatment options with their providers.

References
Wickersham R, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons; 2008.

Mukherjee B, Shivakumar T. A case of sensorineural deafness following ingestion of sildenafil. J Laryngol Otol 2007 Apr;121(4):395-7.

Anon. Information for Healthcare Professionals Sheet for Viagra, Levitra and Cialis. Food and Drug Administration. Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/ED_HCP.htm Accessed 12/3/2007.