This article was originally published in a sponsored newsletter.

Low-dose atropine is an effective therapy used “off-label” for slowing myopia progression in children. In the U.S., it must be obtained directly from a compounding pharmacy. Compounding pharmacies are not held to the same strict guidelines by the U.S. Food and Drug Administration (FDA) as commercial drug manufacturers. Rather, they operate under the authority of their state boards of pharmacy, which do not require the same rigorous testing as commercial products. As a result, the quality, stability, and sterility of low-dose atropine may be affected.

Researchers surveyed 26 compounding pharmacies across 19 states regarding their low-dose atropine products.¹ They found that only 38% of pharmacies recommended refrigerating their product versus storing it at room temperature. The median bottle size was 5ml, and the beyond-use date was 65 days (IQR: 45 to 158 days). Generally, a 5ml bottle should last about 50 days with once-nightly bilateral use.

Half of the compounding pharmacies used commercially available 1% atropine to prepare their low-dose products, 38% used powered atropine, 8% used either depending on availability, and 4% (one pharmacy) stated this information was proprietary. The inactive ingredients added to these preparations can affect their overall stability. Among the pharmacies surveyed, some reported using only artificial tears (42%), whereas others used saline (23%), and the remainder used more than one ingredient. Dilution of preservatives, such as benzalkonium chloride (BAK), with these non-preserved inactive ingredients also presents a concern because they may be ineffective in maintaining the product's sterility. Most smaller compounding pharmacies do not have the capability to do analytical testing of their products routinely, but FDA-approved products must undergo extensive testing for sterility, efficacy, and stability until the expiration date.

The same research group proceeded to obtain 24 samples of 0.01% atropine from nine different compounding pharmacies.² They sent the samples to be analyzed 30 days after receipt and found a wide variety of formulations. The median pH of the samples was 6.9, close to that of the ocular surface. Atropine is stable at lower pH levels (3 to 6), but most ophthalmic solutions are closer to neutral (6.6 to 7.8). At higher pH levels, atropine degrades faster to tropic acid, which has no antimuscarinic properties.² Samples from two pharmacies had tropic acid concentrations greater than the U.S. Pharmacopeia (USP) limit, indicating the breakdown of atropine. While the lower pH levels may cause stinging or discomfort for patients, the solution is more stable.

In that study, at the 30-day mark, the median percent concentration of atropine was 7% less than target and six samples had less than 90% of target. The concentration should be within 10% of the prescribed or labeled concentration. Given that 0.01% is the lowest concentration of atropine used clinically, these findings pose concerns for efficacy. Research is still developing as to the best or most effective concentration, but results may be skewed if the concentration that eyecare providers prescribe is not what patients receive.

These issues with the stability of low-dose atropine leads to inconsistent products for patients, and the variable quality of products may be a public health risk. With increasing prescribing of low-dose atropine for myopia management, there is a need for a commercial product that can be held to higher standards of regulation.

1. Richdale K, Tomiyama ES, Novack GD, Bullimore MA. Compounding of Low-Concentration Atropine for Myopia Control. Eye Contact Lens. 2022 Dec 1;48:489-492.

2. Richdale K, Skidmore KV, Tomiyama ES, Bullimore MA. Compounded 0.01% Atropine-What’s in the Bottle? Eye Contact Lens. 2023 Jun 1;49:219-223.