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Branded formulation improves glaucoma care
Compounded drops can help increase compliance and reduce side effects.
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As a doctor in a busy medical office complex, the management of glaucoma patients is a standard part of my practice. As these patients are typically on at least one, and often several, medications, compliance issues frequently arise.
The cost of brand-name medications is always a concern, as is the reality of managing multiple administrations of eye drops daily. Compliance issues have been well documented and become an increasing problem the more drops a patient must use.
To combat cost, many patients must turn to generic medications. While this may help on one front, it creates several concerning issues on others. It also does not address the confusion and inconvenience that come with multiple medications and daunting dosing schedules.
Simplifying the regimen
Compounded formulations are advantageous on many levels, but some physicians may have concerns such as the inability to guarantee formulation consistency. However, if the medications are coming from a single, reputable source, those fears should dissipate.
I have found that Simple Drops, Imprimis Pharmaceutical’s line of compounded glaucoma formulations, provides the benefits of cost-efficient generic medications with the quality of a brand name. I typically prescribe either the Lat (latanoprost) drop or tim-lat (timolol and latanoprost), administered once a day in the morning. If my patients require further pressure-lowering intervention, they may need surgery, and I will often recommend laser surgical intervention or, if they also have cataracts, micro-invasive glaucoma surgery.
For those who need a little extra lowering, however, the compounded drops are highly beneficial. Having two different mechanisms of action in the same drop is far more convenient and cost-effective for the patient. Additionally, these formulations are preservative-free, which minimizes the toxicity to the ocular surface.
Benefits of preservative-free
One of the most significant benefits of the Simple Drops formulations is the fact that they are preservative free. Each formulation is provided in a bottle that allows for a one-way valve system, preventing the risk of contamination.
Most medications contain a preservative such as benzalkonium chloride (BAK). While the preservative is intended to destabilize the epithelium to some degree to aid drop penetration, this effect is a double-edged sword, particularly when working with a surface that is already compromised. The toxicity of the preservative can wreak havoc with the ocular surface, including creating or exacerbating existing dry eye and ocular surface disease (OSD).
Several studies have shown the prevalence of OSD ranging between 30% and 70% in glaucoma patients (Moss et al., Rossi et al., Labbe et al., Ghosh et al., Valente et al., Leung et al.), with a notable association found between the prevalence of OSD and the number of BAK-preserved medications used by the patient. (Pisella et al.) These patients are also twice as likely to have lissamine green staining of the bulbar conjunctiva and are more likely to experience a decrease in or cessation of compliance due to adverse reactions such as superficial punctate keratitis, corneal erosion and conjunctival allergy.
With compliance and the health of the ocular surface already significant concerns, particularly as many of my patients suffer from other lid and ocular surface disorders, eliminating preservatives that will only heighten these issues is essential to ensuring controlled, stable outcomes and avoiding other complications that frequent dosing may cause.
Knowing your sources
One of the biggest issues faced by patients needing medications, glaucoma patients in particular, is the often-unaffordable cost of brand-name drugs. Many turn to generic versions out of necessity or insurance policies. However, while the price may be more manageable, the quality of the medications may be subpar and can result in adverse events and unstable outcomes.
Knowing where prescribed drugs are manufactured is vital. Generic medications are only required to have the same active ingredients as their brand name counterparts. Differing levels of excipients such as preservatives, pH and tonicity adjusters, antioxidants, and buffers, which are not regulated, can interfere with the efficacy and safety of medications. These formulaic inconsistencies often associated with a generic may render the drug less effective and even toxic.
Studies have also shown that the concentration of active ingredients in generic formulations may decrease when exposed to adverse temperatures and tend to contain higher levels of particulate matter (Olthoff et al., Moss et al.), which can lead to inconsistent dosage concentration.
Additionally, generics manufactured in other countries may differ from their American-made counterparts, resulting in less potent medications and possible negative outcomes. Furthermore, generic medications will likely vary in packaging, including the size of the eyedropper, which can affect dosage size, even in instances when the ingredients are equivalent.
As a case in point, I had a patient who purchased his medications from a budget pharmacy, and the formulations he would receive changed about every quarter due to the vendor obtaining supplies from different manufacturers. As a result, his pressure fluctuated, and it became necessary to increase the frequency of his visits to attempt to manage his pressure. He was the first patient I placed on the Simple Drops Lat (latanoprost) formulation, and I immediately noticed that his pressure was better maintained and more consistent.
Having a single-source supplier that is responsible for formulation eliminates safety and efficacy concerns and can provide a sense of stability in manufacturing and the efficacy and safety profiles. I can now confidently prescribe medications knowing that my patients will receive uniform formulations.
Reimbursement
In my practice, we have the drops directly shipped to the patient. The patient pays Imprimis, and we help file for reimbursement with their insurance company.
Imprimis says it will provide the patient with a receipt and information they can submit to their insurance company. Some will have coverage for compound medications; some will not. Imprimis says its intention is to keep the cost of the combined medications below the cost of the co-pays for multiple medications.
Some clinicians have said that if patients question the cost of the compound, they will send them to the pharmacy with a prescription for the branded drug and tell them to return if it is more expensive. According to Imprimis, in most cases, the patients return for a prescription for the branded medication.
- References:
- Bagnis A, et al. Saudi Journal of Ophthalmology. 2011;doi:10.1016/j.sjopt.2011.08.004.
- Brechue WF, et al. Invest Ophthalmol Vis Sci. 1993;PMID:8325759.
- Cantor LB. Glaucoma Research Foundation. May 2014. www.glaucoma.org/treatment/generic-medications-are-they-the-same.php. Accessed October 23, 2017.
- Ghosh S, et al. Clin Experiment Ophthalmol. 2012;doi:10.1111/j.1442-9071.2012.02781.x.
- Inoue K. Clinical Ophthalmology. 2014;doi:10.2147/OPTH.S44708.
- Kahook M, et al. Curr Eye Res. 2012;doi:10.3109/02713683.2011.631722.
- Karmel M. American Academy of Ophthalmology. June 2011. http://development.aao.org/publications/eyenet/201106/upload/CUcomp-June-2011.pdf. Accessed May 6, 2015.
- Labbe A, et al. Cornea. 2012;doi:10.1097/ICO.0b013e31823f8cb6.
- Leung EW, et al. J Glaucoma. 2008;doi:10.1097/IJG.0b013e31815c5f4f.
- Levinson BA, et al. J Cataract Refract Surg. 2008;doi:10.1016/j.jcrs.2007.08.028.
- Moss SE, et al. Arch Ophthalmol. 2000;doi:10.1001/archopht.118.9.1264.
- Olthoff CMG, et al. Ophthalmology. 2005;doi:10.1016/j.ophtha.2004.12.035.
- Pisella PJ, et al. Br J Ophthalmol. 2002;86:418–423.
- Roberts CW, et al. J Ocul Pharmacol Ther. 2007;doi:10.1089/jop.2006.0070.
- Robin AL, et al. Ophthalmology. 2005;doi:10.1016/j.ophtha.2004.12.026.
- Rossi GC, et al. Eur J Ophthalmol. 2013;doi:10.5301/ejo.5000220.
- Valente C, et al. J Ocul Pharmacol Ther. 2011;doi:10.1089/jop.2010.0133.
- Weir RE, et al. Br J Ophthalmol. 2005;doi:10.1136/bjo.2004.059519.
- Zore M, et al. Br J Ophthalmol. 2013;doi:10.1136/bjophthalmol-2012-302245.
- For more information:
- Agustin L. Gonzalez, OD, FAAO, ABCMO, practices at Eye and Vision’s North Texas Center for Dry Eye and Ocular Surface Disease. He also founded a dry eye clinic in the North Texas area and has a special interest in cornea and external disease. Gonzalez is a member of the Primary Care Optometry News Editorial Board. He can be reached at: gonzalez.agu@gmail.com.
- Disclosure: Gonzalez reports no relevant financial disclosures.
Perspective
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J. James Thimons, OD
Dr. Gonzalez addresses an important issue in today’s ophthalmic marketplace, and that is the daily challenges that face clinicians and patients in attaining access to the therapeutic agents that are prescribed to treat the myriad of diseases that eye care providers encounter. The frequency of these concerns has escalated from occasional to constant for many practices, and the dreaded prior authorization form has become the bane of our existence. The concept of using compounded agents to address some of these concerns is an interesting and potentially useful alternative, but I believe it should be considered with some caution due to their “off label” status and the relative lack of practitioner experience in this area.
Compounding, while appealing, has had its concerns as well. The 2017 PEW Charitable Trusts report indicates 50 errors were identified between 2001 and 2017, resulting in 1,227 adverse events, including 99 deaths. This is exacerbated by the fact that only 30% of the states require sterile compounding pharmacies to report adverse events, thus, indicating the current data is most likely much lower than actual outcomes. Additionally, with many of the “combo” agents like Tim, Brim, Dor and Lat, there is zero clinical experience to guide practitioners’ selections in regard to the IOP efficacy of a complex combined product.
While compounding does offer some appealing positives such as ease of access, reduction/elimination of preservatives, relative consistency of product and, to some degree, cost savings, I believe that there are other alternatives that are available that serve the patient and doctor equally well. Bausch + Lomb has developed a unique relationship with Walgreen’s pharmacies that guarantees very low fixed prices for commercial insurance. Akorn has a similar program for their preservative-free glaucoma agents with Eagle pharmacy located in Florida. Other providers such as Novartis and Allergan provide coupon support that, when used appropriately, can provide access to their products at significantly reduced rates.
I use compounding pharmacy services weekly and rely on them for unique one-of-a-kind products that are not available commercially. The same concerns for adverse events are present, but the benefits outweigh the risks in patients in which drugs such as fortified vancomycin, tobramycin and cephalexin are used in treatment of severe microbial disease. Additionally, there is a large body of peer-reviewed literature to support their use.
I do believe that a time will come when companies like Imprimis will become mainstays of the ophthalmic treatment armamentarium, but I do not believe that in regard to glaucoma therapy they have achieved that status yet. A rapid way to acceptance in that regard would be their willingness to conduct head-to-head trials of their products vs. current branded agents to demonstrate the same efficacy and safety.
- Reference:
- PEW Charitable Trusts. U.S. illnesses and deaths associated with compounded medications or repackaged medications, 2001-20017. Posted June 23, 2017. Accessed March 27, 2018. http://www.pewtrusts.org/en/multimedia/data-visualizations/2017/us-illnesses-and-deaths-associated-with-compounded-medications-or-repackaged-medications.
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