Clinical Apprenticeship: Octreotide and Pantoprazole Compatibility

For some reason, there exists some disconnect between how some clinical pharmacists come by their knowledge. Almost as if it’s some secretive pact we hold where information is only exchanged under full moons in the middle of July. While there may be some mysterious goings-on I’m not aware of, the simple matter of truth is that in almost every circumstance, it’s just experience and knowing where to look. So today, I’m going to teach you how to look at any problem as if you’ve been through two years of residency and a few board certifications.

Let’s take the example of octreotide and pantoprazole. We’re not talking about clinical efficacy, whether you should be using it for upper vs lower GI bleed, and so on. We’re just talking about compatibility. In reality, it doesn’t matter what the question or issue is, this method is universal. It will work with every single problem that comes up in your clinical adventures.

Start broad

The first, most logical place to look is in an electronic form of Trissel’s IV Compatability. By the selection of resources I have access to, this occurs through Lexi-comp for me. Regardless of how you get there when searching for IV compatibility of octreotide and pantoprazole, the Trissels results yield a mixture of compatible and incompatible results. As confusing of a result as this is, it is not a result. It’s not an answer. But we wouldn’t stop here anyway. To investigate further, you have to consider your original question at hand and attempt to gain more specific details.

Re-state the question at hand

We aren’t asking whether any concentration of octreotide and pantoprazole are compatible, were asking whether a specific concentration is. Were also not asking whether they’re compatible in any diluent, were asking about compatibility in the specific diluent. So with these new details, we know that a standard octreotide infusion is 1 mg/mL in sodium chloride 0.9% (NS). Whereas the pantoprazole is 0.32 mg/mL in NS.

We didn’t (and couldn’t) input that data into the search function of Trissel’s, so we’ve got to do the searching on our own. This is simple enough to do by examining each entry in the details section of the Trissel’s report. In this specific case, we know that there were 2 compatible and 4 incompatible study results. With each study, we can find the concentration and diluent used for each drug in question.

As it turns out, zero (none) of the studies in question used NS as the diluent for octreotide. They were all dextrose 5% in water (D5W), despite octreotide being compatible in NS in concentrations ranging from 1.5 to 250 mcg/mL. Furthermore, zero of the studies cited use the concentration of octreotide in question. In this finding, we have to answer whether this compatibility can be extrapolated between diluents. Since it appears that both octreotide and pantoprazole are physically compatible in various concentrations in either solution, it would be reasonable to consider them interchangeable in the context of this question.

So now that we’ve resolved one issue with compatibility, we come back to the initial question. But based on this new information we must revise this question from a general inquiry to a more specific question: is pantoprazole 0.32 mg/mL in NS compatible with octreotide 1 mcg/mL in NS?

While the difference in the stated question may seem minuscule, it is incredibly important. Its importance rests in your ability to confidently guide bedside care vs punting the responsibility back to the team at the bedside to get another IV line (not to mention the pain, infection risk, and resource utilization that you’re wasting).

Question everything

With this new framing of the problem at hand, evaluating the available information and literature is the very next step. But instead of having to sit down and read numerous papers cover to cover, you can strategically identify which points to evaluate then systematically work backward through a manuscript to get the necessary information.

The description of the first study cited in the Trissel’s compatibility table states that octreotide 5 mcg/mL in D5W is incompatible in pantoprazole 0.16 to 0.4 mg/mL in NS. The reference provided was “Walker SE, Fau-Lun C, Wyllie A, et al, “Physical compatibility of pantoprazole with selected medications during simulated Y-site administration”, Can J Hosp Pharm, 2004; Volume 57: pp. 90-7.”

But this warrants further investigation. Remember, don’t assume you need to read this reference cover to cover- you have a specific question at hand. There’s an excellent book I recommend you read to help improve your reading efficiency. It’s called “How to read a book.” That’s not a joke. It’s a really helpful book. Nevertheless, with this specific question at hand, we must look at this study effectively and economically. In doing so, you learn that octreotide and pantoprazole were physically compatible when the octreotide concentration was less than 1.5 μg/mL… hmmm, that’s different than what Trissel’s reported.

This is where clinical pharmacist becomes a clinical pharmacist. Using your clinical experience and judgment, does this statement make sense with everything you’ve now researched? Or do you need to do further research? Your gut tells you that since a general report told you these items are not compatible, yet your own research USING THE SAME INFORMATION brought you to a different and opposing conclusion. That’s right, you need to confirm your suspicion.

The evidence double tap

So you found one paper that gave you a concrete answer. How would your confidence in your answer change if you had two papers that agreed? What about three?

The next two studies cited state octreotide 5 mcg/mL in D5W is compatible with pantoprazole 0.4 and 0.8 mg/mL in D5W, respectively. Not letting confirmation bias get the better of us, we similarly look at these papers individually and ultimately agree with their conclusions.

The fourth study listing the octreotide concentration of 7.5 mcg/mL in D5W is incompatible with pantoprazole 0.16 to 0.8 mg/mL in NS. Practicing the same investigation technique as before, looking at this specific study, we quickly realize its the exact same citation as in “Study 1,” hmmm… curious. Reading the specific study section related to pantoprazole and octreotide testing, we realize that the authors state that a color change (but never a precipitate) was observed with almost all of the combinations, in pantoprazole concentrations ranging from 0 to 0.80 mg/mL and octreotide concentrations ranging from 0 to 10.0 μg/mL. So the authors conducted an additional 62 sample analyses to further question this compatibility. What they observed was that for any compatible solutions, the final concentration of octreotide must be less than 1.5 μg/mL and pantoprazole at any final concentration less than 0.80 mg/mL.

In many cases such as this, further questioning the evidence either leads to strengthening your initial conclusion, or systematic dismantling of the argument at hand. In either case, your answer – and the answer you’ll give your colleagues at the bedside – is much more qualified and robust.

Summarize and communicate

We’ve learned a great deal from investigating the question, identifying the underlying question at hand, scrutinizing the evidence by questioning everything and executing a double-tap to strength test our initial conclusions. What we do now is the critical last step: communicating the answer.

Since we may have to redefine the question with the answer itself, as well as provide enough information to earn the trust of the team member on the receiving end there are many techniques and tactics to employ. But keeping it as simple and direct as possible can prevent you from being tuned out when your providing interesting information (that is, interesting to you), but not directly answering the question.

Simply stated, the answer to the initial question at hand is: “The available evidence supports our standard concentrations of octreotide and pantoprazole as compatible.” If follow up questions arise (How do you know they’re compatible? What would it look like if they aren’t compatible?) you’ve actually already prepared these by performing the detailed (but efficient) research we described above. You can even provide the primary literature reference. For anything, you didn’t look up, or already know simply answering “I’ll look into that and get back to you in 30 minutes” is an excellent answer. Since you’ve already learned a systematic method for investigating questions, a 30-minute turn around time is more than enough.

So let’s summarize. For any clinical problem that arises from clinical practice, taking a five-step systematic method for investigating and answering the question can help you perform better. Those five-steps are to:

  • Start broad – cast a wide next in your initial search for information
  • Re-state the question at hand – focus your research
  • Question everything – be skeptical, dive deep.
  • The evidence double-tap – One study is good, three are better. When only one is available, scrutinize it in depth
  • Summarize and communicate – get to the point, fast.

 

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Clinical Apprenticeship: Octreotide and Pantoprazole Compatibility

Clinical Apprenticeship: Octreotide and Pantoprazole Compatibility