Oritavancin Shows Similar Safety as Vancomycin
Published: Oct 14, 2014 | Updated: Oct 15, 2014
PHILADELPHIA – The new once-weekly antibiotic oritavancin appears to be as effective as 7-10 days of vancomycin infusion in treating skin and soft tissue infections – and its safety profile was similar to vancomycin, researchers reported here.
Treatment emergent adverse events occurred in 540 of the 976 patients receiving a single dose of oritavancin (55.3%) and in 559 of the 983 patients (56.9%) receiving vancomycin, in the pooled safety results of the SOLO trials, said G. Ralph Corey, MD, professor of medicine at Duke University School of Medicine.
There were two deaths in the patients in the oritavancin group and three in the controls. Additionally, there were 57 serious adverse events in oritavancin arm and 58 serious adverse events among patients who were receiving 7-10 days of vancomycin, Corey reported at IDWeek 2014.
He said the long half-life of oritavancin makes it possible to give a single dose that attacks pathogens – especially methicillin-resistant Staphylococcus aureus (MRSA) – for at least a week. But he told MedPage Todaythat 245-hour half-life also caused initial concerns, hence a study that specifically addressed adverse events.
"The first time I heard about this drug, I said, 'Oh my God, if you have an allergic reaction it's going to last forever'," he said. "So I asked, 'Am I comfortable doing this?' At the beginning I wasn't but after randomizing 2000 patients and seeing no prolonged adverse reactions and seeing that the side effects that occurred didn't last longer than vancomycin's adverse reactions, I am feeling more comfortable."
But he said that clinicians who use the drug (Orbactiv) – approved August 6 by the FDA – have to remain vigilant. "That doesn't mean that we shouldn't keep watching," he said. "For the long-acting drugs we have to keep looking at safety. I don't want to hurt anybody, but I do want to help people."
Corey predicted patients will prefer oritavancin when compared with vancomycin. "The difference is stunning," he said. "If I were a patient and I came into the emergency room and they said we can have a PICC (peripherally inserted central catheter) line put in, and it will be there for 7-10 days and you have to infuse yourself twice a day; you can't take showers; you have to be really careful and it may form a clot and it may get infected, or you can lay right here and have a 3-hour infusion and you can go home...which one would you rather have? I would just say, 'give me the infusion and let me go home.' To me this is a no-brainer," Corey said, in discussing his studies.
As far as fighting infection, he said outcomes between oritavancin and vancomycin in the double-blind, randomized Phase III studies were virtually identical. Among patients treated with oritavancin, 81.2% achieved the composite efficacy endpoint of cessation of spreading or reduction in the size of the baseline lesion, absence of fever and no need for rescue antibiotics while 80.9% of the patients on 7-10 days of vancomycin achieved that endpoint. The results fell well within the pre-specified noninferiority criteria of being less than 10% of the efficacy of vancomycin.
The researchers also noted that more MRSA patients on oritavancin achieved a secondary endpoint of reducing the size of the lesion by at least 20%. Corey and colleagues reported that 93.1% of the MRSA patients receiving oritavancin achieved that milestone compared with 87.1% of the MRSA patients receiving vancomycin (P=0.032).
"I think we can use this drug in other ways such as in bloodstream infections and bone infections – both of which require long-periods of therapy of 4-6 weeks," he said.
Oritavancin is a lipoglycopeptide characterized by concentration-dependent bactericidal activity against gram-positive pathogens including MRSA. The long half-life of oritavancin allows for a single intravenous 1200 mg dose and provides an important option to the management acute bacterial skin and skin structure infections, Corey said.
The SOLO trials enrolled 1959 patients. Treatment-emergent adverse events were defined as adverse events with onset or worsening severity at or after the first dose of study drug through the Safety Follow-up Visit (Day 60). Onset of an adverse event was calculated as the number of days from the initiation of the first infusion to the adverse event start date.
Dennis Stevens, MD, chief of infectious diseases at the VA Medical Center Boise, Idaho, told MedPage Today, "Oritavancin has a mechanism of action is similar to vancomycin and dalbavancin (Dalvance). These are agents that were developed primarily to be able to treat MRSA in skin and soft tissue infections.
"I think the importance of the oritavancin studies is that this is a medication that is given only once per week, and that is good and bad. The goodness of it is that it may be possible for physicians to treat a serious infection with one dose of an antibiotic and potentially be able to send the patient home earlier and save hospitalization and associated costs.
"The potential bad news is that many antibiotics – almost all drugs – have some side effects, so if you stop to think that this drug is going to be on board for a week and the patient has an adverse event...that's a problem," Stevens said.
"This study looked at the onset of adverse events with oritavancin compared to vancomycin and also the duration of the side effects, and there was no difference. I think this is reassuring for the possibility that patients might have longer adverse events with a drug like oritavancin."
The cost of oritavancin may be an issue in its use, Stevens said. Corey also agreed that how the drug is priced would ultimately affect how it is used in the community.
Stevens said that oritavancin adds to the arsenal of anti-MRSA drugs that are becoming available for the clinic. "I think we have been under the gun in terms of not developing antibiotics as quickly as we should have over the years and many pharmaceutical companies are not into the business of developing new antibiotics despite this explosion of resistance so we welcome new agents," he said. "I think oritavancin is certainly one. Dalbavancin, tedizolid (Sivextro), telavancin (Vibativ) and ceftaroline (Teflaro) are all new antibiotics that have potential efficacy against MRSA."
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