Pondering allergy drops and dry eye
Allergy drops and dry eye
So I happened across an allergy drop study today. Zerviate is an Rx allergy drop which received its FDA approval in 2017 as an Rx allergy drop. I clicked on the link to the abstract (scroll down and you’ll see it) in my feed, assuming that it showed up there because of dry eye being mentioned as a side effect of the drug in the study.
In fact, the absence of any mention of dry eye made me curious on several fronts. I’m not familiar with Zerviate at all, and it’s new, which made me wonder where it stood in terms of dry eye risk and also preservatives. So I had a look at the FDA paperwork. No mention of dry eye. That got me really curious, so I went and dug through the FDA files on the other major Rx allergy drops to compare them. Here is what I found.
What the FDA paperwork says about the side effects of allergy drops
Following is a sampling of information from various allergy eye drops’ FDA documentation.
First of all, most allergy drops contain benzalkonium chloride as preservative. Click here to see how they compare. Patanol, Pataday, Elestat and Zerviate were the worst offenders, at 0.01%.
Next, here are some examples of the variations in language they have about adverse experiences (note - for those where the non-ocular side effects were listed separately, I did not include those). This stuff is all over the map.
Patanol: “The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritis, rhinitis, sinusitis, and taste perversion.”
Pataday: “The following adverse experiences have been reported in 5% or less of patients: Ocular: blurred vision, burning or stinging, conjunctivitis, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, pain and ocular pruritus.”
Lastacaft: “The most frequent ocular adverse reactions, occurring in less than 4% of eyes treated with LASTACAFT®, were eye irritation, burning and/or stinging upon instillation, eye redness and eye pruritus.”
Alomide: “The most frequently reported ocular adverse experiences were transient burning, stinging, or discomfort upon instillation, which occurred in approximately 15% of the subjects. Other ocular events occurring in 1 to 5% of the subjects included ocular itching/pruritus, blurred vision, dry eye, tearing/discharge, hyperemia, crystalline deposits, and foreign body sensation. Events that occurred in less than 1% of the subjects included corneal erosion/ulcer, scales on lid/lash, eye pain, ocular edema/swelling, ocular warming sensation, ocular fatigue, chemosis, corneal abrasion, anterior chamber cells, keratopathy/keratitis, blepharitis, allergy, sticky sensation, and epitheliopathy.”
Elestat: “The most frequently reported ocular adverse reactions occurring in approximately 1-10% of patients were burning sensation in the eye, folliculosis, hyperemia, and pruritus. “
A simple abstract certainly can hide a multitude of sins. So much of dry eye is iatrogenic - caused by drugs - and SO MANY eye drops cause or worsen dry eye. These things need to be flagged so that we’re not simply exchanging one problem for another problem.
The Zerviate study
So here’s the study that prompted me to dig all that stuff up:
Safety of cetirizine ophthalmic solution 0.24% for the treatment of allergic conjunctivitis in adult and pediatric subjects. (Malhotra et al, Clinical Ophthalmology, February 2019.)
The studies reported here aimed to assess the safety and tolerability of cetirizine ophthalmic solution 0.24%, a new topical ophthalmic medication approved by the US Food and Drug Administration for the treatment of ocular itching associated with allergic conjunctivitis.
PATIENTS AND METHODS:
Three clinical studies evaluated cetirizine ophthalmic solution 0.24% administration: a Phase I prospective, single-center, open-label, pharmacokinetic (PK) study (N=11) evaluating single-dose administration and twice-daily (BID) administration for 1 week in healthy adults, and two Phase III, multi-center, randomized, double-masked, vehicle-controlled, parallel-group studies evaluating the safety and tolerability in adult and pediatric populations (2-18 years of age) for up to 6 consecutive weeks. The first safety and tolerability study evaluated cetirizine BID (study 1, N=512), while the second study examined cetirizine three times daily (TID) (study 2, N=516). Each study assessed best corrected visual acuity, slit-lamp biomicroscopy, IOP, dilated ophthalmoscopy, treatment-emergent adverse events, vital signs, urine pregnancy test, and physical examination (general health, head, eyes, ears, nose, and throat). The PK study also measured hematology, blood chemistry, and urinalysis, while the two Phase III studies additionally assessed corneal endothelial cell counts (ECC) and ECC density in a subset of subjects (via specular microscopy), and drug administration tolerability.
Bilateral administration of cetirizine ophthalmic solution 0.24% resulted in low systemic exposure in the PK study and was associated with a low incidence of mild adverse events. There were no drug-related severe or serious adverse events. The tolerability scores between the active and vehicle groups were comparable, demonstrating high comfort in the administration of cetirizine ophthalmic solution 0.24%.
Cetirizine ophthalmic solution 0.24% dosed BID or TID demonstrated an acceptable safety profile and was well-tolerated when administered to subjects aged ≥2 years.