Tadalafil, a drug used to treat erectile dysfunction and sold under the brand name Cialis, may raise the risk of glaucoma, a serious eye condition, according to a large comparative study published online in the British Journal of Ophthalmology.
The drug is also prescribed to treat sudden urinary urgency and frequency linked to an enlarged prostate. Researchers said patients who take tadalafil long term for this purpose may need careful monitoring of their eye health, particularly those with risk factors for glaucoma, such as a family history of the condition or elevated eye pressure, known as ocular hypertension.
Tadalafil belongs to a class of drugs called phosphodiesterase type 5 inhibitors, or PDE5 inhibitors, the same class as sildenafil, sold as Viagra. These drugs have previously been linked to various eye problems, including conditions affecting the optic nerve and the macula, the part of the retina responsible for sharp, detailed vision, the researchers said. Evidence linking PDE5 inhibitors to a higher glaucoma risk has so far been fragmentary and inconclusive, they added, particularly for tadalafil when used for lower urinary tract symptoms, which typically involves long-term daily dosing.
Study of nearly 75,000 men
To build a stronger evidence base, researchers set out to determine whether tadalafil, a long-acting PDE5 inhibitor, is associated with a higher glaucoma risk when prescribed for urinary tract symptoms tied to an enlarged prostate, a condition known as benign prostatic hyperplasia.
They drew on anonymized data from 73,854 men aged 40 and older in the TriNetX Analytics Network, a global collaborative research database. Half of the men had been prescribed tadalafil or another PDE5 inhibitor for up to five years, between January 2012 and December 2022, to treat their symptoms. The other half had not received these drugs.
The researchers assessed the likelihood that both groups of men would develop glaucoma, ocular hypertension, or begin treatment for glaucoma after five years. Men were matched on shared background characteristics, including age, ethnicity, smoking status and alcohol-related disorders, as well as underlying conditions such as cardiovascular disease, diabetes, cancer, high cholesterol, kidney function, obesity and chronic obstructive pulmonary disease, and other prescribed medications.
Findings show higher risk across measures
The analysis found that men prescribed tadalafil had a significantly higher likelihood of developing glaucoma, at 22%, compared with men who had not been prescribed the drug. They were also 32% more likely to develop ocular hypertension, 33% more likely to develop primary open-angle glaucoma, the most common form of the disease, and 33% more likely to begin treatment for glaucoma.
A closer look showed these associations held among men who developed glaucoma within one, three or six months of starting tadalafil. The pattern was consistent across patients over 50, patients who were white, and those with the various underlying conditions included in the study.
Researchers urge caution, not alarm
The study was observational, so the researchers said no definitive conclusions can be drawn about cause and effect. They acknowledged several limitations, including that they could not account for changes in prescriptions and medication use, or the development of other underlying conditions, over time. Most study participants were white, they added, so the findings may not apply to men of other ethnic backgrounds.
Even so, the researchers wrote that the findings suggest chronic PDE5 inhibition may influence eye physiology, which they said warrants further investigation into the mechanisms involved.
They stressed that the findings do not contraindicate the use of tadalafil. Instead, they said, the results highlight the importance of an initial ophthalmological evaluation and regular follow-up, especially for patients with pre-existing glaucoma, ocular hypertension, a family history of glaucoma, high myopia, or those who require long-term therapy.
