Practice Pearl 4: Dosing Complications and Various Dosage Vials


A review of the dosing challenges and various dosage vials for emicizumab.


  • Practice Pearl 4: Calculating Doses for Individualized Treatment
  • Practice Pearl 3: Complications and Pain Management With Hemophilia

Luigi Brunetti, PharmD, MPH: Now we'll switch gears. I think we provided some context for our audience and something to mull over and think about. But for emicizumab, what is the standard dosing for emicizumab? Is there a useful dosing calculator for emicizumab or Hemlibra?

Robert F. Sidonio, Jr, MD: I'll let you start with that.

Giles Slocum, PharmD: Perfect. There is that load, as we've talked about, and this is a 3 mg/kg subcutaneous injection that's going to be done every 7 days for the first 28 days. And at that point, after that load is complete, you have 3 different dosing schemes. You have a once weekly injection, a once every 2 weeks injection, and a once every 4 week injection. It's 1.5 mg/kg for the once weekly dosing; 3 mg/kg is for the every 2 weeks dosing regimen; and then we have a 6 mg/kg for every 4 weeks dosing. There is a dosing calculator on their website that is available. What's nice about that is there are 4 different vial sizes for this, and we'll get into that, but it helps distinguish which vials you'll potentially need to use with that dosing calculator.

Robert F. Sidonio, Jr, MD: They looked at the dosing regimens on study, and they didn't see a lot of difference. There may have been a slight tendency to bleed more with the less infrequent injections, which makes sense. And in children, the arms were very limited. And so for us we generally dose weekly or every other week, or every 2 weeks. For the younger children, if you're starting an infant on it, you often are having to dose monthly. And so we're having this debate about rounding up and rounding down, and they certainly don't talk too much about that on the website, or at least endorsed by the company, because that's something that we have to make a decision about. But I think it's important to remember on the original Japanese study, they were looking at doses as low as 0.3 mg/kg and 1 mg/kg.

The biggest challenge that we have now is the patients who are aging and gaining weight, and now I have to decide whether I want to throw away half of a vial, or is it safe enough to round up and that dose is OK? That's where the challenge is. And so if someone's dose is drifting a little bit, if they're not bleeding, we leave it alone and tell the family, "He's dosed technically below the label. If you have any increased bleeding, we probably should round up." That's where we're struggling with this idea about vial wastage. And I know they're potentially working on another smaller vial, which would help us a lot with the children.

It's also important to understand when you talk with the patients, particularly the older ones, that they may have to do more than 1 injection. Because some of them get surprised by that and you don't want them to be surprised. If they're doing a monthly injection, they're most likely doing 2 injections. They just need to think about that, "Do I want to do 2 injections once a month, or is it better to do 1 injection every 2 weeks?"

Luigi Brunetti, PharmD, MPH: Right. So anything over 2 mL is going to essentially be 2 injections.

Robert F. Sidonio, Jr, MD: Yes, exactly.

Luigi Brunetti, PharmD, MPH: And that leads to how you had mentioned the vial sizes, there are 4 vial sizes. How does that potentially complicate the dosing?

Giles Slocum, PharmD: Yes, I would say it can potentially complicate it. Within those 4 vial sizes, there are 2 concentrations. The smallest increment that we have is a 30 mg/mL concentration. And then the last 3 are the 150 mg/mL, but all those volumes are a little bit different. So you have the 150 mg and 1 mL; a 105 mg and 0.7 mL; and then a 60 mg and 0.4 mL. So it does get a little bit interesting with the volume and obviously, depending on what your dose comes up with given your weight at that time, you may be using a partial of 1 and a partial of another, and then getting to a volume. If it exceeds 2 mL, then you're going to obviously need 2 syringes.

So it's not super straightforward when you talk about it in person, but there are dosing cards and an online calculator that help differentiate and tell you exactly how much of what you need.

Robert F. Sidonio, Jr, MD: Correct.

Luigi Brunetti, PharmD, MPH: I don't know if you've used those online calculators, but I think they're immensely helpful because not only does it calculate the dose for you when you insert the patient's weight, but it actually provides you options in terms of what dosage vials to use to combine, as well as what size syringe is needed. One calculator gives you that information. I think it's very useful.

Robert F. Sidonio, Jr, MD: It's useful as a backup too because I often will try to do the math. I'll say, let me come up with multiple scenarios. And then I say, I think this will work. And I’ll often now go back to the calculator and look and make sure our math is correct. Because remember, we often have to write 1 script for the loading dose and then another script for the maintenance dose, because I think it can be confusing if you put all of it on 1 prescription.

And so that becomes a little challenging. And that’s why we bring them in the first couple of times. Then we often bring them back relatively soon after they got started, because I think there can be some initial confusion on this. And thankfully, they’re all different color vials. And the other challenge is that they don’t want us to mix the different concentrations. I personally don’t think that’s an issue if you’re using the entire vial. I don’t know why that matters to be honest. But I can understand why they’re concerned about mixing 2 different concentrations, particularly if you don’t utilize the whole vial, because there can definitely be some math errors going on in there.

Giles Slocum, PharmD: Yes.

Luigi Brunetti, PharmD, MPH: There is a nice dosing video, a patient-focused video, that can be helpful for patients to refer back to, even after they’re sent home from the HTC [hemophilia treatment center].

Robert F. Sidonio, Jr, MD: Yes, it’s good training, and we often ask them to tell us what they’re doing and how they’re doing it. We often will watch them in clinic and if they’re due for doses, we say, “Hey, can we just watch you do it?” Ideally these families are giving it on a Sunday night when it’s a low-key evening before school, and so it’s always nice to refresh them on how to do these things.

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