According to new research, regular use of certain erectile dysfunction drugs – phosphodiesterase type 5 inhibitors (PDE5 inhibitors) – may be associated with an increased risk of several adverse eye effects.
In a cohort study of 213,033 men, the risk of developing severe retinal detachment, retinal vascular occlusion or ischemic optic neuropathy increased by 85% in men who regularly took sildenafil (Viagra), tadalafil (Cialis ), vardenafil (Levitra), and avanafil (Stendra).
“The risk of these events is still rare and should not deter men from taking these medications unless they have pre-existing eye conditions, in which case they should talk to their doctor before starting these medications,” said lead author Mahyar Etminan, PharmD, MSc, an associate professor of ophthalmology at the University of British Columbia in Vancouver, said Medscape Medical News.
“However, if men taking these drugs experience visual changes, they should consult an eye doctor,” he added.
The results were published online April 7 in JAMA Ophthalmology.
Calculation of cases
Etminan and colleagues analyzed health insurance claims from the PharMetrics Plus database between 2006 and 2020. They looked at the risk of developing one of three eye conditions, comparing nonusers and regular users of sildenafil, tadalafil, vardenafil and avanafil. Regular users were defined as patients who received at least one prescription every 3 months in the year prior to ocular diagnosis.
Among 213,033 men who took the drugs, there were 1146 new cases of ocular adverse effects, with 278 cases of severe retinal detachment, 628 cases of retinal vascular occlusion and 240 cases of ischemic optic neuropathy. The average age was 64.6 years.
Patients with one of the three eye conditions were more likely to have hypertension, diabetes, cardiovascular disease or sleep apnea. The research team adjusted for these variables and found that patients were almost twice as likely as non-users to develop any of the eye problems.
Additionally, the research team found that the risk was even higher for patients who received five or more prescriptions for PDE5 inhibitors, suggesting dose response.
Overall, the number of eye diseases diagnosed was low relative to the population, with about 15.5 cases per 10,000 person-years. However, the research team concluded that regular users of PDE5 inhibitors should be “aware” of potential ocular adverse effects, particularly “given the popularity of these drugs”.
In 2020, there were about 20 million monthly prescriptions for PDE5 inhibitors in the United States, the study authors wrote. Sales have increased significantly during the pandemic, especially for tadalafil daily formulations.
Many case reports have shown an association between ocular adverse events and PDE5 inhibitors, and a few small studies have attempted to quantify the risks. However, the results are often contradictory and epidemiological data are not available on the risks of certain conditions such as retinal vascular occlusion or retinal detachment.
“The case reports look compelling at the individual level, but at the population level, it’s been hard to say if the association holds up,” said Nawaaz Nathoo, MD, BSc, ophthalmologist at Columbia University. -British. Medscape Medical News. Nathoo was not involved in this study.
In 2015, Nathoo and colleagues published a study on a potential link between PDE5 inhibitors and the risk of developing non-arteritic anterior ischemic optic neuropathy (NAION). They found no statistically significant association and struggled to explain how the drugs could cause these types of ocular adverse events.
Previous research has suggested an association between PDE5 inhibitors and optic nerve damage by compromised circulation, but the links have not been definitively established.
“There’s still no good mechanism to explain why this is happening, if there really is an association,” Nathoo said. “It’s one thing to say there’s a connection and another thing to explain why or how.”
For example, patients with erectile dysfunction who take PDE5 inhibitors are also more likely to develop certain eye problems, such as NAION, due to underlying vascular conditions such as hypertension and diabetes, Nathoo noted. .
At the same time, Etminan and his colleagues adjusted for these risk factors and separately analyzed men without underlying conditions, who consistently found an increased risk of eye conditions.
“We weren’t surprised but reassured that we were seeing the same signals from previous case reports and we were happy that, for the first time, we could quantify these risks in a large population of men,” Etminan said.
The monographs for sildenafil, tadalafil, vardenafil and avanafil include a warning about the risk of ischemic optic neuropathy, a serious eye condition that can lead to irreversible vision loss, Etminan and colleagues found. Retinal vascular occlusion is listed as a potential adverse event for sildenafil, tadalafil and vardenafil, but not for avanafil. None of the drug labels mention the risk of severe retinal detachment.
Based on their recent findings, Etminan and his colleagues would like to see drug companies update monographs. Physicians and patients should also be aware of the association if there is a problem.
“Ocular events may not be a priority for patients who need these types of drugs,” Nathoo said. “I don’t think patients need to be overly concerned about this initially, but it’s always important to consider adverse events, and it may be a good idea to withdraw a prescription if something happens.”
The study was funded by the University of British Columbia. Etminan and Nathoo did not disclose any relevant financial relationship.
JAMA Ophthalmol. Published online April 7, 2022. Full text
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