Practice Pearl 4: Calculating Dose for SQ Formulations

Practical considerations regarding the dosing of subcutaneous formulations

Adam M. Brufsky, MD, PhD: So the first thing that people ask is, "Is there a loading dose when you use subcutaneous formulation?" With IV [intravenous] dosing with trastuzumab, you have to use a loading dose. Is there a loading dose with subcutaneous dosing?

Tim Peterson, PharmD, BCOP: So there's no loading dose for either of the available subcutaneous formulations right now. For rituximab, it's either the 1400 mg for non-Hodgkin lymphoma or 1600 mg, which is the dose equivalent to 500 mg/m² for CLL [chronic lymphocytic leukemia]. That's 600 mg for trsatuzumab. Subcutaneous is on the order of an 8 mg/kg loading dose, but there's no loading dose required for either of the subcutaneous formulations.

Adam M. Brufsky, MD, PhD: At all. And again, there's really no weight-adjusted dosing in this, is there?

Tim Peterson, PharmD, BCOP: No.

Matthew J. Matasar, MD: There's not.

Adam M. Brufsky, MD, PhD: And I think from the HannaH trial, and I'm assuming from the lymphoma data, the BMI [body mass index] really doesn't matter. I guess it really doesn't. Do you think it matters at all?

Matthew J. Matasar, MD: I think there's concern in lymphoma that for the upper extremes, there may be a cross point.

Adam M. Brufsky, MD, PhD: Someone with a BMI of 40.

Matthew J. Matasar, MD: Right. With over 40 BMI in somebody who you really think needs the full rituximab, I think some people would be more comfortable giving weight-based testing.

Adam M. Brufsky, MD, PhD: That's a good point. And at the lower end, do you also have trouble too? Were some of the patients BMIs emaciated or quasi-emaciated? Maybe some of the BMIs were 15, 16 or something like that?

Matthew J. Matasar, MD: Remember that the dose of 375 mg/m² rituximab is purely for historical purposes. There's no knowledge that that is the right dose. Some people believe that more would actually be better, although that work is going to be very hard to ever accomplish in the clinic. So for patients with a lower range of BMI where you're going to be effectively giving them a higher dose, I don't think that lymphoma doctors would worry about giving too much rituximab.

Adam M. Brufsky, MD, PhD: If someone is not a lymphoma person, the thing I worry about with rituximab is reaction, right—infusion site reaction or the overall reaction—not quite anaphylactic but whatever reaction you get. Is there any more worry with the subcutaneous dosing than with the IV?

Matthew J. Matasar, MD: There isn't. With rituximab, everybody's gotten through their first dose intravenously. You never give it to the person subcutaneously because everybody reacts to the first dose of IV rituximab. Once you've gotten through that first IV exposure, you already have Rituxan on board at that point.

Adam M. Brufsky, MD, PhD: That's important to know. Because that would be the fear for somebody, just bringing that out, that you would give a subcutaneous dose and you can't stop it. With IV, you can stop it the minute someone starts reacting. But with a subcutaneous dose, you're done.

Matthew J. Matasar, MD: Right.

Adam M. Brufsky, MD, PhD: And that's never been a problem as far as you know?

Matthew J. Matasar, MD: You have to give it intravenously, and it has to be fully tolerated.

Adam M. Brufsky, MD, PhD: Got it.

Matthew J. Matasar, MD: If you don't get through the first dose with IV, you go back to IV. If you've given the first dose of IV but they still have a circulating clone of more than 30,000 cells per milliliter, you're going to go IV again. You have to be confident enough that they have Rituxan on board and they're well saturated so you can give it subcutaneously without worries about generating some sort of severe reaction.

Adam M. Brufsky, MD, PhD: It's going to be interesting in the breast cancer field now that this is out, what we're going to do. Because we don't have all of this. Traditionally the reaction to trastuzumab really hasn't been bad. It's usually diarrhea; occasionally with the first dose, you get fever and chills because you're introducing a foreign protein. But other than that, you really don't see it. So it will be really intresting to see how people adapt to it.

Tim Peterson, PharmD, BCOP: And that speaks to an important distinction in that trastuzumab is the subcutaneous formulation that doesn't require an initial IV dose. The first dose of trasuzumab can be subcutaneous as opposed to rituximab, which requires that IV dose.

Adam M. Brufsky, MD, PhD: Right. And it should be OK. It's just going to be really interesting to see what happens in those infusion site reactions that we get, or not just site but infusion reactions that you sometimes get.