Oritavancin's Role in ABSSSI Management

FEBRUARY 07, 2019

Experts Joe Reilly, PharmD, BS, BCGP, and Tom Lodise, PharmD, PhD, examine the biologic and economic rationale behind oritavancin in treating acute bacterial skin and skin structure infections.

Tom Lodise, PharmD, PhD: A newer agent in the treatment of patients with acute bacterial skin and skin structure infections is oritavancin. Oritavancin is a lipoglycopeptide. It has 3 distinct mechanisms of action. It inhibits cell wall synthesis as well as it destabilizes the cell membrane. It’s rapidly bactericidal. In time-kill studies, it has 3-log reduction within 1 to 2 hours, so a very bactericidal drug. And it’s currently indicated, as I mentioned before, for the treatment of adults with acute bacterial skin and skin structure infections.

The 1 thing that’s distinct with oritavancin relative to other drugs is that it’s a single-dose agent. So anytime you think about ideal therapy, you think about how you take 1 pill or 1 dose and your treatment course is set. Because out of need rather than choice, we’ve become accustomed to giving IV [intravenous] drugs multiple times a day or even taking oral drugs multiple times a day or even once a day for extended periods of time. So if we think about that ideal, a lot of those properties are really condensed in oritavancin as a single dose. It’s 1200 mg. No therapeutic drug monitoring, no adjustment for weight or patients with compromised renal function. So, again, it’s a really straightforward therapy, this single-dose agent for the treatment of adults with skin and soft tissue infections.

Joe Reilly, PharmD, BS, BCGP: Oritavancin is unique pharmacologically, and you could talk about it from an academic standpoint on how rapidly bactericidal it is, as Tom had mentioned, its different mechanisms on the cell wall synthesis, 2 distinct mechanisms just on cell wall synthesis, and the fact that it disrupts the cell membrane and dissipates that membrane potential. But I think what really matters most about this drug, in my opinion, is it’s a single dose. So when you give a patient an oritavancin infusion, you’ve ensured that they receive 10 days of IV antibiotics in 1 dose. So what that does is it takes away patient compliance. It takes away the need for patients to wind up having to get their prescription filled, pay for that prescription, and make the trip to the pharmacy. The hospital does this in many instances to prevent those money-losing admissions.

So in our institution, we’ll utilize oritavancin in the ED [emergency department] setting, in the obs [observation] unit, or in an infusion center to prevent admissions for patients who are only being admitted because they need an IV or so-called IV. It’s not just because they were unstable, but this allows us to prevent those money-losing admissions, and it’s best for the patient because they don’t have to continue outpatient antibiotics in the outpatient setting that can be associated with adverse effects [AEs] and problems.

Tom Lodise, PharmD, PhD: Joe, thank you for expanding upon that. One thing I do want to mention that comes up a lot is: How do you get away with a single dose? And a lot of this is due to its half-life. So what you find, as Joe mentioned, is you get a very concentrated exposure, particularly during the first 5 days of therapy. And as it goes into its gamma distribution phase, that terminal half-life, you have a prolonged exposure. So, again, it’s really based on its PK [pharmacokinetics] that it’s allowed for a single dose. And the 1 thing that always comes up is, if a person has an adverse event, is this going to persist for 2 or 3 weeks? So far in clinical trials, that has not been the case. It’s very similar to vancomycin, which was the comparator. If an AE did occur, it was usually within the first 2 days. And the average duration was 3 days. So what it does is it delivers that drug in that sweet spot where you want to have adequate drug exposure. But because drug concentrations drop significantly over time, a lot of those exposure-related adverse events are very consistent with what you would see with its comparator in clinical trials, vancomycin.

Joe Reilly, PharmD, BS, BCGP: Oritavancin can be given in the emergency department, it can be given in the observation unit, a doctor’s office, or anywhere an IV can be given. It’s given in a liter of D5W [dextrose 5% in water], given over a 3-hour infusion. And I think what’s best about using a drug like this is it optimizes to work for your system. So we would spend the money up front, the acquisition price on a drug like oritavancin, in order not to lose the money associated with a hospitalization. And we can give it to these patients. We don’t have to worry about them getting their prescriptions filled and unnecessary admissions.

Tom Lodise, PharmD, PhD: I think the 1 thing people always consider a drawback is that 3-hour infusion. Joe, I would argue that in someone who presents with a skin infection, clearly they were sick enough, they felt the need, to go to the ED thinking they may be hospitalized. So really having that drug over 3 hours gives you a chance to assess the patient, see how they’re responding. So it really shouldn’t be viewed as a deterrent.

Joe Reilly, PharmD, BS, BCGP: The 3-hour infusion, when people object to that, I would say, well, your alternative if you’re not going to use oritavancin is often to admit the patient. So we would rather give the drug in a setting where we can get reimbursed for the drug and prevent the money-losing admission. And we don’t have to necessarily worry about patients being compliant with their medications. There are some data looking at different posters that were done, IDSA [Infectious Diseases Society of America] and other places, that show when these patients are ensured to have 10 days of antibiotics in them, there are lower reinfection rates.

Tom Lodise, PharmD, PhD: And, again, when we think about going to an observation, you incur some cost when you initially go to the observation unit, but those patients are typically maintained for a skin infection 12 to 24 hours. So, again, why the 3-hour infusion is a little bit of a drawback, when you think about that site of care, particularly in an observation unit—it’s really not a deterrent.