Practice Pearl 1: The Benefits of a Flat Dose

Experts consider the reasoning behind flat dosing of subcutaneous formulations, as well as its added benefit.

Adam M. Brufsky, MD, PhD: New subcutaneous formulations are becoming available for medications commonly used intravenously. This Pharmacy Times® Best Practices Practice Pearls is designed to identify the implications of a transition from intravenous [IV] to subcutaneous dosing on health care resources and patient quality of life. This panel of experts will discuss the efficacy and safety between the formulations as well as the challenges faced by institutions in implementing this transition. Having well thought-out administration procedures should help provide a smooth transition process.

I am Dr Adam Brufsky, MD, PhD, professor of medicine, associate chief of the Division of Hematology/Oncology at the University of Pittsburgh School of Medicine, and co-director of a comprehensive breast cancer center of the University of Pittsburgh in Pittsburgh, Pennsylvania. Joining me today on this distinguished panel are Dr Matthew Matasar, MD, associate member of the lymphoma service and medical site director at Memorial Sloan Kettering Cancer Center Bergen in New York, New York; and Dr Tim Peterson, PharmD, BCOP, clinical pharmacy specialist at Memorial Sloan Kettering Cancer Center in New York, New York. Thank you so much for joining us, and now let’s begin.

When we talk about these drugs, what are the challenges to providers? I think people don’t understand at least that some of these IV medicines could become subcutaneous. And what does it mean? People just think, “Oh, it’s just a marketing gimmick.” But what are really the issues here? Let’s start, go ahead Matt.

Matthew J. Matasar, MD: Thanks. It is an interesting inflection point that we find ourselves in at the clinic right now in oncology with the emergence of these new subcutaneous formulations. These are medicines that we as oncologists have been using comfortably and consistently for years, medicines like rituximab in intravenous formulation and trastuzumab’s intravenous formulation. And now we have emerging options to give these medicines subcutaneously. The subcutaneous treatment really has both advantages and disadvantages to it that we as oncologists need to be more understanding and aware of and comfortable discussing with our patients.

Adam M. Brufsky, MD, PhD: Right. What do you think as a pharmacist? To the average guy in the street, how do you give a big antibody subcutaneously? Why would it work? What are the challenges for pharmacists? How do they prepare this? Is there anything different that you do with this?

Tim Peterson, PharmD, BCOP: Sure. The big thing when we have these first oncology agents that are being developed subcutaneously is their formulation with hyaluronidase, which allows better tissue distribution of the antibody therapy. These medications are given in such a way that they’re flat dosed. We’re no longer using weight-based dosing for these agents. Rituximab is a weight-based medication on the order of our BSA [body surface area] that we calculate for patients. Trastuzumab on the other hand is weight-based based on the kilogram basis.

Adam M. Brufsky, MD, PhD: Right.

Tim Peterson, PharmD, BCOP: All of these agents that are developed with hyaluronidase for subcutaneous formulations are flat dose. These bring into effect different preparative regimens that we need to do for pharmacists in the chemotherapy suite, including differences in our reconstitution and that sort of thing from a pharmacy standpoint.

Adam M. Brufsky, MD, PhD: Let me ask this question to both of you. So it’s a flat dose. I’m a breast cancer specialist, so I know trastuzumab. You’re a lymphoma specialist, you guys are familiar with rituximab. And I’m so used to how we get the vial with the 440 mg in it, and we worry about wastage and all this, and now we’re just blowing that all away, right? We’re just giving a flat dose.

Matthew J. Matasar, MD: Right.

Adam M. Brufsky, MD, PhD: And we’re OK with this.

Matthew J. Matasar, MD: At least in lymphoma, there’s the question on the pharmacy end on the weight side, which is super important. But on the clinical side we have pretty good PK [pharmacokinetic] data looking at absorption and levels of rituximab with flat-based dosing across a pretty wide range of body size, BSA, BMI [body mass index] calculi, as well as age, creatinine clearance, and other sorts of measures in metabolism. And we see that, other than at the extremes—for most of us who lie in the middle—exposure when you’re giving a flat dose of subcutaneous rituximab is as good or better than you would achieve with weight-based dosing at 375 mg/m² for instance.

Adam M. Brufsky, MD, PhD: Right. So you’re giving a flat dose, and I think with trastuzumab it’s 600 mg. I don’t know what it is for rituximab, but for trastuzumab it is 600 mg. The thing is, can you get away with less? How did they choose 600 mg? Why did they choose 600 mg, do you guys know? I honestly don’t.

Matthew J. Matasar, MD: I know how the lymphoma dosing got chosen, which was basically trying to jigger it so that you could come up with dosing that would reliably give as good, or a smidgen better, results than you would get with 375 mg/m², and there are 2 different doses.

Adam M. Brufsky, MD, PhD: The MFD, the minimum flat dose.

Matthew J. Matasar, MD: There you go, a new term.

Adam M. Brufsky, MD, PhD: For the MFD, the minimum flat dose.