HealthNovember 21, 2022

IV compatibility: Challenges, best practices, and the route ahead

By: Jacob Hirsekorn, PharmD
Administering medications or fluids via the intravenous (IV) route is essential for certain medical conditions, critically ill patients, and select medications. As often as it is used, the IV route of administration remains associated with a high risk of medication error.

According to studies, clinicians worldwide benefit from having access to IV compatibility data and decision support solutions to help them assess drug and solution compatibility and stability.

In practice, one of the most common IV drug questions is: Is Drug X compatible with Drug Y? A common scenario is also a Y-site safety consideration: If we only have one line, but we need to run two drugs, what are our options?

What are the biggest IV medication challenges?

In addition to USP 797 guidelines and NIOSH workplace safety guidelines for handling hazardous substances, US hospitals have established organizational policies and procedures designed to ensure safe IV drug preparation and administration practices. Organizations also prioritize training in accordance with those policies and procedures. However, challenges arise when IV drug compatibility and stability information is lacking, outdated, and inconsistent.

There are a variety of dosage forms and formulations, and the available product may vary depending on the country of origin. For example, an IV drug available as a powder for injection in the US may be an injection solution in a different country, each with their own unique drug properties.

Product labeling can also differ for IV drugs of the same dosage form depending on the manufacturer and/or country of origin. For example, a drug’s stability might be listed as 24 hours in US product labeling while the same drug’s stability might be listed as 12 hours in product labeling from a different country. While there will never be total consistency across national borders, navigating these inconsistencies can be challenging for clinicians.

Additionally, inactive ingredients, which may vary depending on the dosage form and formulation used, can affect the compatibility and stability of IV drugs.

Drug shortages affecting IV drugs

The problem of drug shortages has been well reported and grew quite a bit during the COVID-19 pandemic. Shortages of IV drugs have continued to be a significant concern.

For pharmacists, these shortages pose a unique set of challenges. Pharmacists in a hospital setting may have to attempt to figure out an alternative therapy; try to conserve extra IV drugs or to recalculate dosages using different concentrations based on what may be available; and also help to conserve IV supplies like tubing. For example, during a shortage of 5% albumin, pharmacists may have been faced with the challenge of using 25% albumin to make a 5% concentration in order to satisfy the prescribers’ original request.

Tips for using Trissel’s IV compatibility tool

Lexicomp® drug reference offers online and mobile access to the Trissel’s IV compatibility tool, incorporating data from the Trissel’s™ 2 Clinical Pharmaceutics Database by Lawrence A. Trissel. It can be utilized by clinicians in any hospital scenario, with the most common being critical care situations in which patients who are more likely to be on multiple drips, such as the ER and ICU. From outpatient infusion clinics to inpatient care, there are a variety of scenarios in which clinicians might have to prepare and/or administer an IV drug and need to check for drug compatibility or evaluate other pertinent drug information. The compatibility safety check is a key part of many clinicians’ routines.

There are two components of the Trissel’s IV compatibility database:

  • Compatibility results
  • Drug properties monographs

While nurses’ primary use is the compatibility results, pharmacists find value in both resources.

Consulting drug properties monographs allows pharmacists to drill down deeper than compatibility and find answers about IV drugs, including (but not limited to) preparation, stability, and storage that may not be pertinent to job responsibilities of other healthcare providers.

Using the compatibility results tool, clinicians can select IV drugs and/or solutions and receive an immediate overview of compatibility information in chart format with the following icons:

  • Green icon (indicating compatibility)
  • Red icon (indicating incompatibility)
  • Orange caution icon (indicating uncertain or variable results)

Nurses and other clinicians in busy patient care situations often want to quickly see a symbol for ease of decision-making. The compatibility chart is convenient and fast, but it isn’t always the whole story; there are often details that are important to consider when interpreting compatibility between IV drugs and/or solutions. Our goal is to provide clinicians with the information needed to make patient- and situation-specific decisions. This is especially important when presented with the orange caution sign, which can create a roadblock, as some clinicians see it and presume it indicates a lack of compatibility.

The orange caution sign: Understanding IV compatibility variables

The orange caution sign indicates uncertainty in compatibility or variables in the information that may require more consideration. There are a variety of situations that may result in the display of an orange caution sign. Examples include varying compatibility depending on the concentration or inactive ingredients, or conflicting compatibility results for a combination of IV drugs and/or solutions. While it is important to click on and read the details for all compatibility results, it is imperative for those that display the orange caution sign as this could be very helpful when interpreting compatibility results.

Here’s an example: The compatibility of the drug piperacillin sodium-tazobactam sodium and the solution lactated Ringer’s injection (LR) is dependent on whether the piperacillin sodium-tazobactam sodium formulation contains the inactive ingredient edetate disodium dihydrate (EDTA); those that do contain EDTA are reported to be compatible with LR, while those that do not are not compatible with LR. Therefore, if you search compatibility of piperacillin sodium-tazobactam sodium and LR, the chart will show the orange caution sign (uncertain/variable). However, if you click on it to read the details, you will learn that some formulations are stated to be compatible, which could apply to your patient and product used.

Next steps for IV drug compatibility

While we continually update the Lexicomp Trissel’s IV compatibility tool with data from the latest publications, IV compatibility and stability seems to be an area that isn’t studied and published as frequently as other topics in healthcare. Both opportunity and need for more attention and research in this field remain.

Questions abound from clinicians in practice regarding their clinical experience with IV drugs. More studies are needed to be able to potentially repeat these clinical experiences and publish the results, thus establishing best practice for this important aspect of patient care.

Learn About Trissel’s IV Compatibility Interactive Tool
Jacob Hirsekorn, PharmD
Clinical Content Consultant, Wolters Kluwer Health
Jacob Hirsekorn, PharmD, is a clinical content consultant at Wolters Kluwer Health, specializing in IV compatibility and medication patient education content. He received his degree from the University of Kansas and is also a practicing hospital pharmacist in the greater St. Louis area.
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