Watch for Seizures in Men Taking High-Dose PDE-5 Inhibitors

BMJ

A spate of case reports indicate a likely connection between higher-than-recommended doses of phosphodiesterase type 5 (PDE-5) inhibitors and epileptic seizures. The most recent report (. 2006; 333: 785) describes an otherwise healthy 60-year-old man who took a 40-mg dose of vardenafil (Levitra), because he felt the prescribed 10-mg dose was not correcting his erectile dysfunction (ED). About 3 hours later, he had a tonic-clonic seizure that was observed by relatives.

Extensive evaluation at the hospital included neurologic examination, brain magnetic resonance imaging (MRI), and electroencephalography after a period of sleep deprivation, but no other possible cause of his seizure could be found. Cardiovascular (CV) disease was ruled out with stress electrocardiography, echocardiography, cardiac scan with dipyridamole test, and Doppler ultrasonography. A link to the PDE-5 inhibitor was deemed the only likely explanation.

Despite being told to stop taking vardenafil, 2 months later he took the drug again, at a dose of 30 mg, and had a recurrent tonic-clonic seizure episode after 4 hours.

Rev Neurol [Paris].

Earlier this year, a report in a French journal ( 2006; 162:651-652) described a 78-year-old man who had 2 partial epileptic seizures—each after taking 10 mg of vardenafil. He had no history of epilepsy, and brain MRI at the hospital was negative for preexisting lesions.

BMJ.

In 2002, Israeli researchers reported 2 cases of epileptic seizures associated with the PDE-5 inhibitor sildenafil (Viagra) ( 2002; 325: 869). A 63-year-old man with a history of hypertension who was otherwise healthy had a first tonic-clonic seizure 3 hours after taking 50 mg of sildenafil for the first time. Results of extensive neurologic and CV evaluations were normal. Although he was advised to stop taking sildenafil, he decided to try it again 3 months later, only to suffer the same fate—a tonic-clonic seizure 4 hours after taking the drug. In men older than 65 years, the initial recommended dose for sildenafil is 25 mg.

In the second Israeli case, an otherwise healthy 54-year-old man had a first tonic-clonic seizure about 4.5 hours after taking his first-ever dose of sildenafil. Again, workup was negative.

Although 4 cases of epileptic seizures were reported during the clinical trials of sildenafil, none could be directly attributed to the drug. No such events were reported during clinical trials of vardenafil or of tadalafil (Cialis), and the latter has so far not been associated with seizures.

PDE-5 inhibitors are thought to provide temporary resolution of ED by increasing the effects mediated by nitric oxide. Since research has shown that nitric oxide also has an effect on seizure threshold, nitric oxide may be the common factor here.

Regardless of the mechanisms involved, physicians should be aware of and should warn their patients of the possibility of seizures in men who are taking these drugs.