Pushing Back on BAK

Why did you bring the issue of benzalkonium chloride (BAK) in eye drops to public attention in Denmark?
 

It’s very important to consider the well-being of every patient. In that sense, we need to know that every treatment comes with potential side effects. We know, for example, that non-adherence leads to the faster progression and thus the worsening of glaucoma. So, there’s a question about how we decrease these side effects and improve adherence.

Around 10 years ago, my patients were asking me about generics. They would show me different bottles of latanoprost and ask, “Are these all the same?” And I had to reply, “ I don’t actually know.” They were supposed to be the same treatment, but the bottle designs were different, the boxes were different. Together with a colleague, I began to purchase all the different generics of latanoprost and measured their physical and chemical properties. And we found significant differences in all of them, not so much with the active component, but with the inactive components. With topical medications such as eye drops, one of the inactive components is preservatives, in particular benzalkonium chloride (BAK).

We continued our studies and a more recent one showed that there was a difference between BAK-containing generics and brand-name eye drops in terms of the effect on human conjunctival goblet cell survival. The generic variant with BAK was very toxic, but the original brand name drops – with polyquad preservative – were much less toxic.

We found that in Denmark – and other countries – there are very few regulations to follow when you introduce a generic, certainly compared with all the phases you need to go through with a new branded medicine. As a result of our collaboration with Fight for Sight Denmark and the Danish Glaucoma Society, we instigated a change in the law. Now in Denmark, it is no longer legal to substitute BAK into a generic variant where the original brand name does not have it.

This change in the law took effect in March 2023. It shows that, for the sake of the patient, it’s good to actually speak up and say if something is wrong!

What do patients need to know about BAK?
 

There are other negative ingredients, but BAK is the “bad guy.” It’s one of the more toxic preservatives, and the one most commonly used in eye drops. First of all, we’re working to make patients aware of the existence of BAK in their eye drops. Then we’re asking the question, “Why would you put a toxin into an eyedrop for chronic use?” It’s not about efficacy; there's absolutely no reason for it. Fifty years ago, yes – the understanding was that BAK prevents bacterial growth, and could further facilitate the penetration of the active component into the eye. However, it has since been shown that there is no efficacy difference between BAK-free and BAK-containing eye drops.

In my opinion, the only case where BAK could perhaps be useful is in short-term antibiotics treatments as it kills bacteria. But generally, the more BAK comes into contact with the eye, the more toxic it becomes to the ocular surface. And the more side effects the patient suffers, the less adherent they become.

Across Europe we are seeing more use of preservative-free medication, but there are different prescribing patterns in different countries, so we need to continue to get our message out. In general, if patients are getting side effects from an eye drop, they should communicate this to their physician or eye doctor because it might not be the most appropriate treatment for them. Physicians should also be aware that if we use more eye drops, it’s better to use a combination where only one contains BAK, as opposed to all three. The less BAK, the better! And, generics are not the same as the original brand name or as the other generics.

How has the change in law translated into daily practice?
 

In Denmark, it means now that when you prescribe an eye drop and the patient goes to the pharmacy to get a generic variant, they cannot get a generic variant containing BAK because that is illegal. In terms of the effect on adherence, it is too early to measure the impact of this change as yet, but it is a step in the right direction. There are, however, still too few regulations for generics.

Do you have a taste for activism now?
 

I think it’s our duty to do what we think is the best for patients. We should engage them because, in the end, it’s patients that actually have the power. But they need to understand what opportunities they have, understand their disease and their choices, and know what is harmful. When something does not make sense or is causing harm, we should speak up, talk to the authorities, join forces with patient organizations and societies, and approach politicians because it is possible to actually make a difference.

We still need to do more research to convince the authorities to phase out BAK and work towards optimizing the requirements for generics much more than we do. I'm not against generics, of course, but it’s important that we are certain that generics are as efficient – and have no more side effects – than the original medication.

Miriam Kolko is senior consultant and glaucoma specialist at the Copenhagen University Hospital and Professor in Translational Eye Research at the Department of Drug Design and Pharmacology at the University of Copenhagen, Denmark. She is also president of the Danish Glaucoma Society and engaged in both the European Glaucoma Society and the World Glaucoma Association.

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