Latex Allergy Alerts in the Age of CPOE: Assessing the Risk From Injectable Medications

Latex allergies are a clear and present danger to many patients presenting to healthcare systems, with 4.3% of the general population worldwide having a documented allergy. ¹ The clinical presentation of these allergies can range from relatively mild, local cutaneous reactions to severe, generalized anaphylactoid reactions. The incidence also varies, with certain groups such as the elderly or those with certain comorbidities (eg, spina bifida) having a much higher risk.^1,2 Latex sensitization, defined as the presence of latex-specific antibodies in nonallergic individuals, is even more common, with an estimated prevalence exceeding 30%. ¹ Although much of the latex utilized in healthcare has been removed (eg, latex gloves) to mitigate this risk, latex remains present within much of the drug use process of injectable medications in particular, from the disposable syringes used to the rubber vial stoppers on medications.^3-5 And while these dry rubber products may release less latex proteins than dipped products, there is the potential that they may leach potential allergenic proteins into medications. ⁶ In a study of healthy volunteers, both with and without known latex allergies, 2 of 12 subjects with known latex allergies had positive skin reactions to an intradermal skin test solution that was in contact with an unpunctured natural rubber vial stopper. ⁵ An additional 5 of the 12 subjects had positive skin reactions to an intradermal skin test of the solution when the natural rubber vial stopper was punctured 40 times. While this has been a reported concern for years, with the Food and Drug Administration (FDA) issuing guidance regarding natural rubber latex in medical products, the wide-spread adoption of computerized prescriber order entry (CPOE) systems and more comprehensive electronic allergy repositories has increased the discourse on the topic, particularly on the frontlines of patient care.^7,8

There are multiple aspects that add to the complexity of this issue. For those patients with a known latex allergy and an individual injectable product that is documented to contain latex within its rubber stopper, CPOE systems are designed to generate a warning alert to the ordering provider. ⁹ It is well-documented that allergy alerts in general are often overridden, up to 97% in 1 study, with the most common reason being the patient has previously tolerated the medication. ¹⁰ Although this may be appropriate from the standpoint of the medication contained within the vial itself, it may not hold true for the variances in manufacturing packaging, hence leading to a false sense of security on the part of healthcare providers. However, often the scenario is far less clear in this setting. Though the medication package insert is intended to provide detailed information regarding the drug contents and safety warnings, sometimes they can fall short. One notable example is that of a female infant receiving Liposyn III, a product that neither the package insert nor the product’s website provided any caution of potential latex content. ¹¹ After an allergy/immunology consult, a latex allergy was suspected and the lipid emulsion was subsequently drawn into a syringe without going through the rubber stopper. Following this change in procedure, the patient did not have any further allergic reactions. Conversely, another case report details a patient with a documented latex allergy who was prescribed secukinumab and subsequently developed bilateral periorbital edema, lower extremity edema, and widely distributed eczematous eruptions. ¹² Despite the drug monograph documenting the existence of a natural rubber stopper in the product and cautioning against use in those with a documented latex allergy, the CPOE system failed to generate an alert to the prescribers upon ordering. These cases highlight the various challenges that exist with this issue and how the systems designed to limit the occurrence of these errors are not foolproof.

While drug allergies are commonly encountered, and there are a variety of ways to mitigate immunological responses to ensure patients receive optimal pharmacotherapy, the most agreed upon course of action for latex allergies however is avoidance. The American Society of Anesthesiologists (ASA) recommends avoiding latex exposure from birth and that health systems continually develop strategies to create a “latex-safe” environment. ¹³ Prior reports have suggested that pharmacologic prophylaxis with steroids and antihistamines can be effective, though allergic reactions have still occurred despite these actions. As such, the ASA does not recommend pharmacologic prophylaxis for latex hypersensitivity. A complete medical history and questionnaire, highlighting the specific allergic reaction on the patient’s record is recommended. They do note that with the ongoing effort to reduce the latex content in vial stoppers, they believe the risk of inducing an anaphylactic reaction is small. The American Association of Nurse Anesthetists (AANA) ¹⁴ also emphasizes maintaining a latex-safe environment. If it is not considered latex-safe, the operating room needs to be prepared the night before and all items containing latex must be removed. Similar to the ASA recommendation, a detailed patient history should be obtained, and any suspected latex allergy should undergo further testing with an allergist. In preparing a medication for a patient with latex allergy, they also recommend that the rubber vial stoppers should be punctured only once. Recommendations from the Association of Surgical Technologists are comparable with those of the AANA. The use of 1 puncture through the rubber vial stopper, known as the single-stick method, is recommended to avoid coring and contamination of the medication. ¹⁵ It is also recommended that surgical departments self-label the drugs that contain a vial stopper made of latex. Additionally, the removal of the vial stoppers is not recommended. There is no clear evidence that such a process prevents allergic reactions, and it has the potential to increase the risk of drug contamination. The Centers for Disease Control and Prevention (CDC) ¹⁶ has also issued guidance related to latex allergies. They stress that avoidance, if possible, is best for those patients who report a severe anaphylactic allergy to latex. Moreover, the CDC provides additional information about the latex contained within vaccine packaging in their textbook “Epidemiology and Prevention of Vaccine-Preventable Diseases,” commonly referred to as the “Pink Book.” ¹⁷ Although this information is derived from the manufacturers’ product labeling they still strongly recommend a review of the labeling included with the specific vaccine planned for administration in order to obtain the most up-to-date information. ¹⁶ Notably the recent COVID-19 vaccines are not included in this list, however Moderna, Pfizer, and Janssen all report that their vial stoppers for their vaccines are not made with natural rubber latex.^18-20 An unofficial database, latexdrugs.com, was created by pharmacists in 2003 to help providers have a resource to quickly determine the latex contents of injectable medications. ²¹ Though this may be a convenient resource to many, there are no guarantees that the information is up-to-date and accurate.

Moving forward, an official, up-to-date, and validated virtual database detailing the latex contents contained within injectable medications would be very beneficial to healthcare professionals at the bedside. In addition, further research into CPOE systems regarding effective modalities for reducing alert fatigue and improving alert appropriateness should continue to be a priority. While all allergy alerts within CPOE systems are subject to being ignored due to alert fatigue, they may be even more common with latex allergies due to prescribers’ lack of understanding regarding the sources of latex contained within medications. ¹⁰ Further research is also needed exploring the potential contamination of medications by vial stoppers and their contributions to allergic reactions. Currently, most studies involving latex allergies focus on latex gloves rather than medication vial stoppers. And while these studies have led to hospitals implementing measures to reduce latex allergen contamination and have led the FDA to ban the use of latex gloves, the contribution of medication vial stoppers to the problem has largely gone unaddressed.^3,22 Until such research and measures are taken, it is important for pharmacists at the bedside to continue to educate prescribers regarding latex allergy alerts and the potential sources of latex within medications. Pharmacists should also be cognizant of the potential correlation between repeated vial punctures and increased latex contamination when assessing for possible allergic drug reactions at the bedside. Finally, a thorough assessment of the medication labeling is always warranted in patients with documented latex allergies to ensure that any omissions from the CPOE system are identified prior to medication administration.