Orbactiv by The Medicines Company

On August 6, 2014, the FDA announced approval of Orbactiv (oritavancin) injection for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by species of Streptococci, Enterococcus faecalis, and Staphylococcus aureus, including methicillin-resistant strains of Staphylococcus aureus.^1,2

Orbactiv does not carry any black box warnings, although use of Orbactiv is contraindicated in patients with a history of hypersensitivity reactions to the active ingredient or any excipients in the formulation. In addition, use of intravenous (IV) unfractionated heparin sodium solution is contraindicated in patients who have received Orbactiv within the previous 48 hours because Orbactiv may affect the accuracy of activated partial thromboplastin time readings. Orbactiv treatment may also falsely elevate international normalized ratio readings for up to 24 hours after use.²

PHARMACOLOGY AND PHARMACOKINETICS

Orbactiv exerts concentrationdependent bactericidal activity by disrupting bacterial cell wall integrity through inhibition of polymerization and cross-linking of cell wall components known as peptidoglycans. Interfering with cell wall integrity ultimately leads to bacterial death.²

In 297 patients receiving a single dose of Orbactiv, the average elimination half-life was 245 hours. Orbactiv was extensively distributed in tissues, with an average volume of distribution of 87.6 liters. Dosage adjustment is not necessary in patients with mild to moderate hepatic impairment or mild to moderate renal impairment. Studies in patients with severe hepatic impairment or severe renal impairment have not been conducted.²

DOSAGE AND ADMINISTRATION

Each carton of Orbactiv contains a total of three 50-mL glass vials, each of which contains 400 mg of the active ingredient in a lyophilized powder for reconstitution. Before preparation, vials should be kept at room temperature. Once the IV solution is prepared, each 1200-mg dose in 1000 mL of 5% dextrose in sterile water should be infused over a period of at least 3 hours. The reconstituted solution may be kept at room temperature for up to 6 hours or may be kept under refrigeration for up to 12 hours. Importantly, this time includes the 3-hour infusion time.²

During preparation, Orbactiv should only be diluted in an infusion containing 5% dextrose in sterile water, and should never be diluted in normal saline. Dilution of Orbactiv in normal saline may lead to precipitation of the drug.²

CLINICAL TRIALS

Scientists evaluated the safety and efficacy of Orbactiv through 2 randomized, double-blind, multicenter, noninferiority trials. In each trial, patients with an ABSSSI received either 1 gram or 15 mg/ kg of vancomycin every 12 hours for 7 to 10 days or a single dose of Orbactiv 1200 mg infused over 3 hours. Patients with suspected gram-negative bacterial infections received aztreonam, and patients with suspected anaerobic bacterial infections received metronidazole. ²

Clinical response was defined as (1) no expansion of or a reduction in the ABSSSI lesion area, (2) no fever, and (3) no use of rescue antibacterial drugs within 48 to 72 hours of receiving treatment. In trial 1, among patients who were assessed 48 to 72 hours after initiating therapy, clinical response occurred in 82.3% of patients receiving Orbactiv versus 78.9% of patients receiving vancomycin. In trial 2, at the 48- to 72-hour assessment time point, clinical response occurred in 80.1% of patients receiving Orbactiv versus 82.9% of patients receiving vancomycin. In terms of clinical response, no statistically significant differences between treatments were detected.²

WARNINGS AND PRECAUTIONS

Orbactiv is a Pregnancy Category C medication. Levels of narrow therapeutic index medications may be affected by Orbactiv due to its weak inhibitory effects on CYP2C9 and CYP2C19, and weak induction of CYP3A4 and CYP2D6.²

Orbactiv may increase the risk of bleeding when coadministered with warfarin, and may interfere with the reliability of coagulation parameter readings. Patients with previous allergies to glycopeptide antibacterial medications such as vancomycin or telavancin should be monitored carefully due to the possibility of cross sensitivity.²

Use of Orbactiv may lead to Clostridium dificile—associated diarrhea. In clinical trials, osteomyelitis was more common among patients receiving Orbactiv than among patients receiving vancomycin. Patients receiving Orbactiv should be monitored for signs of osteomyelitis.²

Headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea were the adverse events most commonly associated with use of Orbactiv. Each of these adverse events occurred in at least 3% of patients receiving Orbactiv in clinical studies. For a complete discussion of potential adverse events and drug interactions with Orbactiv, please consult the product package insert.²

Michael R. Page, PharmD, RPh, earned his doctor of pharmacy degree at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

References:

• FDA approves Orbactiv to treat skin infections [press release]. FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm408475.htm. Accessed October 2014.
• Orbactiv (oritavancin) [package insert]. Parsippany, NJ: The Medicines Company; 2014.