tedizolid phosphate 200 MG Injection [Sivextro]

INDICATIONS AND USAGE SIVEXTRO is an oxazolidinone antibacterial indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible microorganisms in adult and pediatric patients (at least 26 weeks gestational age and weighing at least 1 kg) ( 1.1 ) Usage to Reduce Development of Drug-Resistant Bacteria 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 or prevent infections that are proven or strongly suspected to be caused by bacteria. 1.1 Acute Bacterial Skin and Skin Structure Infections SIVEXTRO ® is indicated for the treatment of 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 , in adult and pediatric patients (at least 26 weeks gestational age and weighing at least 1 kg). 1.2 Usage to Reduce Development of Drug-Resistant Bacteria 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 or prevent infections that are proven or strongly suspected to be caused by 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.

DOSAGE AND ADMINISTRATION Do not administer SIVEXTRO Tablets to pediatric patients weighing less than 35 kg. ( 2.1 ) Adult Patients Intravenous and Oral Dosage : 200 mg administered once daily orally or as an intravenous (IV) infusion over 1 hour for 6 days as specified in Table 1 in the full prescribing information. ( 2.2 ) Pediatric Patients Intravenous Dosage (at least 26 weeks gestational age and weighing at least 1 kg): Weight-based dosing as an intravenous infusion as specified in Table 2 in the full prescribing information. ( 2.3 ) Pediatric Patients Oral Dosage (weighing greater than or equal to 35 kg): Weight-based dosing as an oral tablet administered once daily as specified in Table 3 in the full prescribing information. ( 2.3 ) 2.1 Important Administration Instructions for Pediatric Patients Weighing Less than 35 kg Do not administer SIVEXTRO Tablets to pediatric patients weighing less than 35 kg [see Dosage and Administration 2.3 ]. 2.2 Recommended Dosage for Adult Patients The recommended dosage of SIVEXTRO is 200 mg administered once daily for six (6) days either as an oral tablet (with or without food) or as an intravenous (IV) infusion in adult patients. The recommended dosage and administration of SIVEXTRO in adult patients are described in Table 1 . Table 1: Recommended Dosage of SIVEXTRO for Adult Patients Infection Route Dose Frequency Infusion Time Duration of Treatment Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Intravenous 200 mg Once daily 1 hour 6 days Oral 200 mg Once daily Not Applicable No dose adjustment is necessary when changing from intravenous to oral SIVEXTRO. 2.3 Recommended Dosage for Pediatric Patients Recommended Dosage of SIVEXTRO for Injection for Pediatric Patients: Intravenous Dosage The recommended intravenous dosage of SIVEXTRO for Injection for pediatric patients (at least 26 weeks gestational age and weighing at least 1 kg) is presented in Table 2 . Table 2: Recommended Intravenous Dosage of SIVEXTRO for Injection for Pediatric Patients Weight Band (kg) Dose Frequency Infusion Time Duration of Treatment Pediatric Patients Weighing Less than 2 kg 1 to less than 2 Recommended Dosage for 1 kg to less than 2 kg is based on actual body weight. 3 mg/kg Twice daily 1 hour 6 days Pediatric Patients Weighing at Least 2 kg 2 to less than 3 6 mg Twice daily 1 hour 6 days 3 to less than 6 12 mg 6 to less than 10 20 mg 10 to less than 14 30 mg 14 to less than 20 40 mg 20 to less than 35 60 mg Pediatric Patients Weighing at Least 35 kg Greater than or equal to 35 200 mg Once daily 1 hour 6 days Recommended Dosage of SIVEXTRO Tablets for Pediatric Patients: Oral Dosage The recommended oral dosage of SIVEXTRO Tablets for pediatric patients is presented in Table 3 . SIVEXTRO Tablets can be administered with or without food. Do not administer SIVEXTRO Tablets to pediatric patients weighing less than 35 kg. Table 3: Recommended Oral Tablet Dosage of SIVEXTRO for Pediatric Patients Weight Band (kg) Dose Frequency Duration of Treatment Greater than or equal to 35 200 mg Once daily 6 days No dose adjustment is necessary when changing from intravenous to oral SIVEXTRO. 2.4 Recommendations Regarding Missed Doses(s) For Once Daily Oral Dosing of SIVEXTRO Tablets If patients miss a dose, administer the dose as soon as possible anytime up to 8 hours prior to their next scheduled dose. If less than 8 hours remain before the next dose, instruct the patients to wait until their next scheduled dose. 2.5 Preparation and Administration of Intravenous Solution SIVEXTRO is supplied as a sterile, lyophilized powder for injection in single-dose vials of 200 mg. Each 200 mg vial must be reconstituted with Sterile Water for Injection and subsequently diluted with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. SIVEXTRO vials contain no antimicrobial preservatives and are intended for single dose only. Discard any unused portion. Preparation of SIVEXTRO for Injection Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The contents of the vial should be reconstituted using aseptic technique as follows: Note: To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution. For Adults and Pediatric Patients Weighing at Least 35 kg: Reconstitute the SIVEXTRO vial with 4 mL of Sterile Water for Injection to provide a concentration of 50 mg/mL in each vial. Gently swirl the contents and let the vial stand until the cake has completely dissolved and any foam disperses. Inspect the vial to ensure the solution contains no particulate matter and no cake or powder remains attached to the sides of the vial. If necessary, invert the vial to dissolve any remaining powder and swirl gently to prevent foaming. The reconstituted solution is clear and colorless to pale-yellow in color; the total time from reconstitution to the end of administration should not exceed 24 hours at either room temperature or under refrigeration at 2°C to 8°C (36°F to 46°F). Tilt the upright vial and insert a syringe with appropriately sized needle into the bottom corner of the vial and remove 4 mL of the reconstituted solution for the 200 mg dose. Do not invert the vial during extraction. The reconstituted solution must be further diluted in 250 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Slowly inject the required volume of reconstituted solution as determined in Step 2 into a 250 mL bag of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Invert the bag gently to mix. Do NOT shake the bag as this may cause foaming. For Pediatric Patients Weighing Less than 35 kg: Reconstitute the SIVEXTRO vial with 4 mL of Sterile Water for Injection to provide a concentration of 50 mg/mL in each vial. Gently swirl the contents and let the vial stand until the cake has completely dissolved and any foam disperses. Inspect the vial to ensure the solution contains no particulate matter and no cake or powder remains attached to the sides of the vial. If necessary, invert the vial to dissolve any remaining powder and swirl gently to prevent foaming. The reconstituted solution is clear and colorless to pale-yellow in color; the total time from reconstitution to the end of administration should not exceed 24 hours at either room temperature or under refrigeration at 2°C to 8°C (36°F to 46°F). Prepare a stock solution (100 mL of 0.8 mg/mL tedizolid phosphate): Tilt the upright vial and insert a syringe with appropriately sized needle into the bottom corner of the vial and remove 1.6 mL of the reconstituted solution and add it to an infusion bag containing 98.4 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Do not invert the vial during extraction. Prepare the required volume of stock solution for infusion: Refer to Table 4 to convert the dose in mg to the appropriate volume of stock solution to be administered. Transfer this volume of stock solution to an adequately sized infusion bag or infusion syringe. It may be necessary to round to the nearest graduation mark of an appropriately sized syringe for smaller volumes. The total time from reconstitution to the end of administration should not exceed 24 hours at either room temperature or under refrigeration at 2°C to 8°C (36°F to 46°F). Table 4: Preparation of SIVEXTRO for Injection for Pediatric Patients Weighing 1 kg to Less than 35 kg from the 100 mL Stock Solution of 0.8 mg/mL Tedizolid Phosphate Body Weight (kg) Amount of SIVEXTRO per dose (given twice daily) Volume of stock solution (0.8 mg/mL) to be transferred to an adequately sized infusion bag or infusion syringe Pediatric Patients Weighing Less than 2 kg 1 to less than 2 3 mg/kg Volume (mL) = Weight (kg) x 3.75 mL/kg Pediatric Patients Weighing at Least 2 kg 2 to less than 3 6 mg 7.5 mL 3 to less than 6 12 mg 15 mL 6 to less than 10 20 mg 25 mL 10

WARNINGS AND PRECAUTIONS Serotonin Syndrome: Monitor patients taking SIVEXTRO concomitantly with serotonergic agents for signs of serotonin syndrome. If signs or symptoms of serotonin syndrome occur, consider discontinuing SIVEXTRO and/or concomitant serotonergic agents. ( 5.1 ) Patients with neutropenia: The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm 3 ) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes. Consider alternative therapies in neutropenic patients. ( 5.2 ) Clostridioides difficile -Associated Diarrhea: Evaluate if diarrhea occurs. ( 5.3 ) 5.1 Serotonin Syndrome Spontaneous reports of serotonin syndrome have been observed with the co-administration of oxazolidinones, including SIVEXTRO, and serotonergic agents. Commonly used serotonergic agents include serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, buspirone, serotonin 5-HT1 receptor agonists (triptans), and opioids, including meperidine. Symptoms associated with serotonin syndrome may include hyperthermia, diaphoresis, agitation, hyperreflexia, clonus, pyrexia, opsoclonus, muscle rigidity, tremor, and hypertonia. Monitor patients for the emergence of serotonin syndrome with the concomitant use of SIVEXTRO and serotonergic agents. If signs or symptoms of serotonin syndrome occur, consider discontinuing SIVEXTRO and/or concomitant serotonergic agents as clinically appropriate and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome when SIVEXTRO is used concomitantly with serotonergic agents. 5.2 Patients with Neutropenia The safety and efficacy of SIVEXTRO in patients with neutropenia (neutrophil counts <1000 cells/mm 3 ) have not been adequately evaluated. In an animal model of infection, the antibacterial activity of SIVEXTRO was reduced in the absence of granulocytes [see Clinical Pharmacology (12.2) ] . Alternative therapies should be considered when treating patients with neutropenia and ABSSSI. 5.3 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents including SIVEXTRO, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon and may permit overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug 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. Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.4 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.

CONTRAINDICATIONS None. None ( 4 )

Mechanism of Action Tedizolid is an antibacterial drug [see Microbiology (12.4) ] .