SIVEXTRO®

(tedizolid phosphate) 200 mg injection, for intravenous use; 200 mg tablet, for oral use

Professional Resources

Medical education video for SIVEXTRO

Acute bacterial skin and skin structure infections (ABSSSI): A roundtable case study discussion

In this educational video, Dr. David Talan, Dr. Amesh Adalja, and Dr. Warren Joseph discuss the outpatient treatment of ABSSSI.

Voice Talent, VOICE-OVER (VO): This promotional program was developed and paid for by Merck Sharp & Dohme, a subsidiary of Merck & Company, Incorporated. Voice Talent (VO): “Acute Bacterial Skin and Skin Structure Infections: A Roundtable Case Study Discussion” with doctors David Talan, Warren Joseph, and Amesh Adalja. Dr David Talan, ON CAMERA (OC): Thank you for joining our discussion, I’m Dr David Talan. Today, I am pleased to be joined by my colleagues Dr Warren Joseph and Dr Amesh Adalja. Dr Warren Joseph (OC): I’m glad to be here. Dr Amesh Adalja (OC): Thanks for having me. Dr David Talan (OC): Today’s discussion will be focused on the treatment of ABSSSI, or acute bacterial skin and skin structure infections, and appropriate settings of care. Let’s kick things off with an ABSSSI patient case that we may have seen before in our practices. Dr David Talan (VO): A 35-year-old man comes to your office today with a superficial but sizeable area of erythema on his right arm. Relevant past medical history includes sulfa allergy, a work-related skin abrasion, and close household contact with an individual that had a recent resolution of a MRSA abscess on the medial left thigh. The lesion area felt hot and painful upon palpation, there was no apparent pus upon visual examination. He also presented with lymphadenopathy and a fever of 100.4°F. Dr David Talan (OC): So, what are some initial thoughts about this patient? What’s the diagnosis and initial steps in caring for a patient like this gentleman? Dr Warren Joseph (OC): Well, starting with the classification of the infection, I would say the patient’s wound would be considered an ABSSSI based on the size of the lesion. More specifically, the infection appears to be cellulitis. Dr David Talan (OC): Absolutely, and the combined presence of fever, inflammation, induration of the bumps, and lymphatic involvement really solidifies the diagnosis of cellulitis. Dr Adalja, we start considering the antibiotic coverage we need for this infection, what are your thoughts? Dr Amesh Adalja (OC): For this patient, I suspect MRSA coverage would be needed for the following reason. The risk of MRSA is immediately increased due to the patient having work-related skin abrasions and having been in close household contact with an individual who had a recently resolved MRSA infection. Dr David Talan (OC): I agree with you. Based on our consensus on the diagnosis and likely pathogen for causing the infection, how would you proceed with this patient? Would you think that treatment would be more appropriate in the outpatient or inpatient setting? Dr Amesh Adalja (OC): If based purely on the patient’s presentation and the likelihood for MRSA, I would be inclined to treat him as an outpatient. It’s important to remember that the presence or magnitude of fever should not be the only deciding factor. In fact, neither precludes a patient from being treated as an outpatient. But, what makes me slightly hesitate with this decision is the patient’s history of a sulfa allergy. The availability of oral antibiotics typically used in the outpatient setting become much more limited. Dr Warren Joseph (OC): Well, I primarily work with patients in the outpatient setting, and am most comfortable treating patients this way. Dr Adalja is correct that the antibiotic choices become somewhat limited with the history of sulfa allergy, but I would start the patient in the outpatient setting on some form of empiric therapy that could be effective for suspected MRSA. Dr David Talan (OC): Thank you. Both of you raised very valid points. Choice of treatment setting has been an ongoing debate when it comes to the management of ABSSSI, but a recent study does suggest that a number of patients with certain characteristics of ABSSSI who present to the emergency room and are subsequently hospitalized can, in fact, be treated in the outpatient setting. Let’s talk a little more about how this discussion of treatment setting can impact our considerations for how to manage a case of ABSSSI. Dr David Talan (OC): I think my colleagues would agree that there are other factors to consider when making treatment decisions for ABSSSI patients. Dr David Talan (OC): For example, MRSA is definitely a challenge with ABSSSI. It’s prevalent in the hospital setting and increasingly found in the community. What are you looking for when selecting an antibiotic for skin infections that you suspect to be caused by MRSA? Dr Warren Joseph (OC): Because I generally practice in the outpatient setting, I’m on constant guard for potential cases of community-acquired MRSA. Dr Amesh Adalja (OC): Obviously, the antibiotic needs to have activity against MRSA, but it should also cover other possible common Gram-positive pathogens, as well. The dosage formulation of the antibiotic is less of a factor in the inpatient setting, but it’s nice to have options that allow patients to continue the same therapy from the inpatient to the outpatient setting. Dr Warren Joseph (OC): I agree, and with the outpatient setting, the dosage formulation and schedule actually become more important. Dr David Talan (OC): Thank you both for those insights. Much of what we’ve talked about thus far is very much in line with and applicable to the use of SIVEXTRO® (tedizolid phosphate), an antibiotic used to treat select Gram-positive organisms in ABSSSI. Let’s briefly review some product information, and then revisit the patient case we discussed earlier. Voice Talent (VO): SIVEXTRO (tedizolid phosphate) Indication: SIVEXTRO is an oxazolidinone-class antibacterial indicated for the treatment of adults with acute bacterial skin and skin structure infections, A-B-S-S-S-I or ABSSSI, caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis. Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of SIVEXTRO and other antibacterial drugs, SIVEXTRO should be used only to treat ABSSSI that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Voice Talent (VO): Selected Important Safety Information Patients with neutropenia: The safety and efficacy of SIVEXTRO in patients with neutropenia, defined as neutrophil counts less than 1000 cells/mm cubed, have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes. Alternative therapies should be considered when treating patients with neutropenia. Clostridium difficile–associated diarrhea, or CDAD, ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including SIVEXTRO. Evaluate all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible. Development of drug-resistant bacteria: Prescribing SIVEXTRO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Adverse reactions: The most common adverse reactions for SIVEXTRO are nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). Infusion site reactions (phlebitis) have been reported (3.1%) in patients receiving SIVEXTRO, when administered intravenously, particularly among Asian patients. Drug interactions with BCRP substrates: SIVEXTRO, when administered orally, can increase the plasma concentrations of orally administered Breast Cancer Resistance Protein, B-C-R-P, substrates and the potential for adverse reactions. Monitor for adverse reactions related to the concomitant BCRP substrates if coadministration cannot be avoided. Dr David Talan (OC): SIVEXTRO can be administered once daily for 6 days, either as a 200-mg oral tablet or as an intravenous infusion over 1 hour. With an absolute bioavailability of approximately 91%, no dose adjustment is necessary between IV and oral administration. Dr David Talan (VO): The efficacy of SIVEXTRO was established in two phase 3 trials, known as ESTABLISH-1 and ESTABLISH-2. Both ESTABLISH trials compared SIVEXTRO 200 mg once daily for 6 days with linezolid 600 mg every 12 hours for 10 days. ESTABLISH-1 evaluated an all-oral course, while ESTABLISH-2 studied an IV to oral switch Dr David Talan (VO): Patients with cellulitis or erysipelas, major cutaneous abscess, or wound infection were enrolled in the trials. Both studies required a minimum area of 75 cm2, at least 1 systemic or regional sign of infection, and suspicion or documentation of a Gram-positive infection. Dr David Talan (VO): The main exclusion criteria of the clinical trials were patients who received systemic antibiotics with Gram-positive coccal activity within the preceding 96 hours or for whom antibiotic therapy was ineffective for the primary ABSSSI site. Dr David Talan (VO): The primary end point of ESTABLISH-1 was early clinical response, defined as no increase from baseline lesion area at 48 to 72 hours after the first dose, and oral temperature of less than or equal to 37.6°C confirmed by a second temperature measurement within 24 hours in the intent-to-treat population. The secondary end point for both ESTABLISH-1 and ESTABLISH-2 was post-therapy evaluation 7 to 14 days after the end of treatment, which was an investigator-assessed clinical response. Dr David Talan (VO): The data from ESTABLISH-1 showed that SIVEXTRO efficacy was noninferior to linezolid for both the primary and secondary end points. Dr David Talan (VO): The most common adverse reactions for patients in the SIVEXTRO group in the two phase 3 trials were nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). In the 2 clinical trials, the number of patients who discontinued due to adverse events was similar between treatment groups with 0.5% in the SIVEXTRO group and 0.9% in the linezolid group. The incidence of serious adverse reactions in the 2 trials was also similar between the treatment groups with 1.8% occurring in the SIVEXTRO group vs 2.0% in the linezolid group. Dr David Talan (OC): Let’s return to the patient case. Based on the product characteristics and data, SIVEXTRO seems to be an appropriate option for the patient case we discussed earlier. What are your thoughts? Dr Warren Joseph (OC): I can see the utility of SIVEXTRO® (tedizolid phosphate) in our patient case. It has demonstrated noninferior efficacy to linezolid in ABSSSI and a low incidence of adverse reactions. The most common adverse reactions for patients in the SIVEXTRO group in the two phase 3 trials were nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). The ability for it to cover not only MRSA but also other Gram-positive bacteria is beneficial, as well. Dr Amesh Adalja (OC): Also, what about the once-daily dosing for the oral formulation? That, in combination with the short 6-day course, may be useful for appropriate patients in the outpatient setting. Dr David Talan (OC): Absolutely, so in summary, while the decision to treat patients with ABSSSI in the outpatient or inpatient setting can vary on a case-by-case basis, certain patients can be appropriately treated in the outpatient setting. In appropriate patients with ABSSSI, SIVEXTRO® (tedizolid phosphate) may be a potential treatment option. Before we close, I’d like to thank you both for joining me for this discussion. Dr Warren Joseph (OC): Thanks for having us. Dr Amesh Adalja (OC): It’s been a pleasure. Dr David Talan (VO): We hope you enjoyed this presentation and were able to gain some insight into our different perspectives. Before prescribing SIVEXTRO, please read the accompanying Prescribing Information. The Patient Information also is available. To learn more about SIVEXTRO, visit SIVEXTRO.com. Thank you for watching.

Indication

Indication: SIVEXTRO is an oxazolidinone-class antibacterial indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius and Streptococcus constellatus), and Enterococcus faecalis.

Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of SIVEXTRO and other antibacterial drugs, SIVEXTRO should be used only to treat ABSSSI that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Selected Safety Information

Patients with neutropenia: The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm3) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes. Alternative therapies should be considered when treating patients with neutropenia.

Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including SIVEXTRO. Evaluate all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.

Development of drug-resistant bacteria: Prescribing SIVEXTRO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse reactions: The most common adverse reactions for SIVEXTRO are nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). Infusion site reactions (phlebitis) have been reported (3.1%) in patients receiving SIVEXTRO (when administered intravenously), particularly among Asian patients.

Drug interactions with BCRP substrates: SIVEXTRO (when administered orally) can increase the plasma concentrations of orally administered Breast Cancer Resistance Protein (BCRP) substrates and the potential for adverse reactions. Monitor for adverse reactions related to the concomitant BCRP substrates if coadministration cannot be avoided.

Before prescribing SIVEXTRO, please read the accompanying Prescribing Information. The Patient Information also is available.

AINF-1180496-000404/18