The differences in subcutaneous formulation preparation and the corresponding impact on practice.
Adam M. Brufsky, MD, PhD: Preparing it, is it that you just prepare it like you normally do? How do you do it?
Tim Peterson, PharmD, BCOP: There's a fair difference in preparation for these agents. For rituximab, for instance, when we're preparing that, it actually comes in a solution, so initially you don't need to reconstitute. When we're giving rituximab intravenously you just dilute it, typically in D5N5 [dextrose 5% in normal saline], 250 cc, right? And that's basically all that needs to be done in the preparative regimen. For rituximab subcutaneously, it comes in 2 single dose ready-to-use vials. These come in either the 1600 mg dose or 1400 mg dose. And those doses are different based on the indication.
Adam M. Brufsky, MD, PhD: They're not in an injector?
Tim Peterson, PharmD, BCOP: Yes. As of right now it's a vial that just needs to be drawn up into a syringe. We typically will draw it up in the chemotherapy infusion suite. We will draw it up into a syringe and send it to the treatment suite.
Adam M. Brufsky, MD, PhD: It doesn't have to be reconstituted or anything like that?
Tim Peterson, PharmD, BCOP: There's no reconstitution, it's just drawing up the vial. Now the bigger difference is between trastuzumab's preparation.
Adam M. Brufsky, MD, PhD: Sure.
Tim Peterson, MD, PhD: Because you talked about the reconstitution that needs to be done with that. When we're giving trastuzumab intravenously it needs to be reconstituted with sterile water. And then it actually is further diluted in a bag of NS [normal saline] typically.
Adam M. Brufsky, MD, PhD: Right.
Tim Peterson, PharmD, BCOP: For trastuzumab, it has the same subcutaneous vial preparation basically. It comes in ready to use, single use, 600 mg vials. You draw it up, cap the syringe, label it, and send it off to the treatment suite. So you can imagine that from a pharmacy standpoint, the preparative time involved, particularly with trastuzumab, is significantly reduced.
Adam M. Brufsky, MD, PhD: At least I know from the trastuzumab literature, people have done time studies. Have you guys thought about that? Have you done any internal time studies or know what's going on there with this?
Matthew J. Matasar, MD: We've looked at the different practice level metrics specifically for the use of subcutaneous rituximab. And what we've done is we've looked at 2 different time periods in 2 different eras, if you will—the era when we were only relying upon intravenous [IV] rituximab, and the era following the availability of subcutaneous rituximab—to look at a number of different practice level metrics in measuring the impact of that changeover. Looking at changes in chair utilization rate, chair time, pharmacy time, and all of the different ways that you could imagine such a transition impacting the conduct of care at the practice level.
Adam M. Brufsky, MD, PhD: And you found, I'm assuming, that you saved an enormous amount of time.
Matthew J. Matasar, MD: It's interesting. On a patient-by-patient level you can see there are obviously dramatic changes. The most obvious change is the chair time for the patient, where they're getting 5 to 7 minutes of injection instead of an intravenous approach that may take anywhere from 90 minutes upward toward 3 or 4 hours. When you actually try to look at the impact on the center as a whole, even looking at the MSK [Memorial Sloan Kettering] lymphoma centric clinics, it's harder to see individual changes of rituximab IV that we replaced with subcutaneous rituximab. It doesn't seem to impact global measures of productivity or chair availability, simply because it's only 1 treatment of many.
Adam M. Brufsky, MD, PhD: Right.
Matthew J. Matasar, MD: I think the lesson we learned there is that for us to make a major impact at how a practice works at the macro level, it is going to require a lot of drugs like rituximab changing over to more patient availability.
Adam M. Brufsky, MD, PhD: I see your point, it's such a small area, I get it.