Unknown drug side effects often pose a risk to patient safety. However, in rare cases, an unexpected adverse event can open the door to a new therapeutic indication. Understanding when this shift happens – and how pharmacovigilance specialists can support it – is essential. This article explores a recent literature review uncovered by the DrugCard platform, highlighting the intriguing case of mydriasis caused by local anesthetics. Could this unexpected adverse event turn into a beneficial therapeutic tool?

When an Adverse Event Becomes Useful

An adverse event is usually an unwelcome surprise. Yet history shows us that unintended drug effects sometimes reveal valuable medical applications. For example, sildenafil, initially developed for angina, became revolutionary for erectile dysfunction. Similarly, the sedative thalidomide, after its infamous past, found a role in treating multiple myeloma.

The case of mydriasis caused by local anesthetics might follow a similar path. Once again, an adverse event could reveal an unexpected benefit.

The DrugCard Platform Discovery: Mydriasis and Local Anesthetics

A review identified by the DrugCard platform found 14 articles describing 26 patients with mydriasis after local anesthetic use, mostly during dental procedures, blepharoplasty, and photocoagulation. Additionally, eight articles (168 patients) reported intentional mydriasis induced by local anesthetics via intracameral injection, topical drops, and sub-Tenon administration.

Only two studies mentioned adverse events. Corneal epithelial damage and edema occurred at very high doses of lidocaine, but no adverse events were seen at doses producing maximum mydriasis. Another study reported reversible and clinically insignificant corneal effects, even at large doses.

Although mydriasis remains classified as an unexpected adverse event in anesthetic SmPCs, its off-label ophthalmic use shows promise. Local anesthetics may offer a safer, faster alternative to traditional mydriatics, improving patient comfort and recovery.

Understanding Why This Adverse Event Happens

The review highlights a proposed mechanism centred on the ciliary ganglion. Local anesthetics are thought to block nerve transmission or exert a neurotoxic effect on neurons innervating the ciliary ganglion. This blockade mimics tonic Adie’s pupil features, which are characterized by persistent pupil dilation, sluggish reaction to light, loss of accommodation, and denervation hypersensitivity.

This plausible mechanism strengthens the link between local anesthetics and the unexpected adverse event of mydriasis. Understanding why this happens is the first step toward considering a new therapeutic application.

Benefits If This Adverse Event Becomes a New Indication

If validated, the adverse event of mydriasis could offer several clinical advantages compared to traditional mydriatic agents:

• Rapid pupil dilation, minimizing surgical preparation time
• Faster postoperative recovery of normal pupil size
• Reduced risk profile, as some traditional mydriatics are linked to systemic adverse events
• A single-agent approach combining anesthesia, akinesia, and mydriasis – simplifying drug regimens

For ophthalmologists and surgeons, these benefits could significantly enhance surgical efficiency and patient comfort.

The Pharmacovigilance Role in Monitoring Adverse Events

From a pharmacovigilance perspective, this situation highlights the balance between off-label use and new indication approval. While clinicians may already exploit the beneficial unexpected adverse event, formal approval requires clinical evidence proving safety, efficacy, and a positive benefit-risk balance.

Moreover, increasing off-label use without regulatory clarity can expose patients to new risks. That is why pharmacovigilance systems must stay vigilant. Monitoring real-world data, tracking adverse events, and reviewing literature – like the DrugCard discovery – are vital to identifying emerging patterns early.

Conclusion: From Side Effect to Therapeutic Tool?

An unexpected adverse event is not always an endpoint. As seen in the case of mydriasis induced by local anesthetics, it can sometimes be the start of a promising therapeutic development.

Pharmacovigilance specialists face two challenges: ensuring patient safety while recognizing responsible opportunities to expand clinical applications. Monitoring adverse events, supporting risk communication, and collaborating with regulatory agencies help ensure that any transition from adverse events to therapeutic indications is safe and scientifically sound.