Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 22 November 2019

Indication(s)

1 INDICATIONS AND USAGE SIVEXTRO is an oxazolidinone-class antibacterial drug indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (1.1) 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 susceptible bacteria. 1.1 Acute Bacterial Skin and Skin Structure Infections SIVEXTRO® is an oxazolidinone-class antibacterial 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. 1.2 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.

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

ESICM LIVES Highlights

ESICM LIVES Highlights

ESICM LIVES Congress 2018: Bringing you the latest news and insights from the 31st ESICM LIVES Congress, 20–24 October 2018 Paris, France.

Fibrinogen Deficiency in Bleeding

Fibrinogen Deficiency in Bleeding

Fibrinogen is important for blood clot formation and breakdown. It is the first coagulant factor to be reduced to critical levels during massive trauma, cardiac surgery and postpartum haemorrhage that involve excessive bleeding. Persistent fibrinogen deficiency can lead to bleeding complications and an increased risk in mortality. This learning zone looks at both congenital and acquired fibrinogen deficiencies including indications and techniques for diagnosis, trigger level for treatment and treatment options.

Optimising anti-TNF treatment using biosimilars

Optimising anti-TNF treatment using biosimilars

Biosimilars are uniquely placed to change clinical practice in the fields of gastroenterology, rheumatology, and dermatology. The adoption of biosimilars can improve patient access to the most appropriate treatment, at the optimum time, to ensure the best possible long-term disease outcomes.

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS None None (4)
Adverse reactions
6 ADVERSE REACTIONS The most common adverse reactions (≥2%) are nausea, headache, diarrhea, infusion- or injection-related adverse reactions, vomiting, and dizziness. (6) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice. Adverse reactions were evaluated for 1425 patients treated with SIVEXTRO in two Phase 2 and four Phase 3 clinical trials (three Phase 3 trials for 6 days of therapy and one Phase 3 trial for 7-21 days of therapy). The median age of patients treated with SIVEXTRO in the Phase 2 and Phase 3 trials was 44 years, ranging between 17 and 94 years old. The majority of patients treated with SIVEXTRO were male (66%) and White (67%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 37/1425 (2.6%) of patients treated with SIVEXTRO and in 25/1000 (2.5%) of patients treated with the comparator. SIVEXTRO was discontinued due to an adverse reaction in 14/1425 (1%) of patients and the comparator was discontinued due to an adverse reaction in 13/1000 (1.3%) of patients. Most Common Adverse Reactions The most common adverse reactions in patients treated with SIVEXTRO were nausea (7.1%), headache (4.5%), diarrhea (3.6%), vomiting (2.7%), and dizziness (1.6%). The median time of onset of adverse reactions was 5 days for both SIVEXTRO and linezolid with 12% occurring on the second day of treatment in both treatment groups. Table 2 lists selected adverse reactions occurring in at least 2% of patients treated with SIVEXTRO in clinical trials. Table 2: Selected Adverse Reactions Occurring in ≥2% of Patients Receiving SIVEXTRO in the Pooled Phase 3 ABSSSI Clinical Trials Adverse Reactions Pooled Phase 3 ABSSSI Clinical Trials SIVEXTRO (200 mg oral/intravenous once daily for 6 days) (N=1037) Linezolid (600 mg oral/intravenous twice daily for 10 days) (N=1000) Gastrointestinal Disorders Nausea 7% 10% Diarrhea 4% 5% Vomiting 3% 5% Nervous System Disorder Headache 5% 5% Dizziness 2% 2% Infusion- or Injection-Related Adverse Reactions Includes adverse reactions in the following body system or organ classes: General disorders and administration site conditions, infections and infestations, injury, poisoning and procedural complications, and vascular disorders, including but not limited to, phlebitis, injection- or infusion-site pain, injection- or infusion-site swelling, injection-site reaction, injection-site erythema, injection-site induration, and infusion-related reaction. 4% 2% The following selected adverse reactions were reported in SIVEXTRO-treated patients at a rate of less than 2% in these clinical trials: Blood and Lymphatic System Disorders: anemia Cardiovascular: palpitations, tachycardia Eye Disorders: asthenopia, vision blurred, visual impairment, vitreous floaters Immune System Disorders: drug hypersensitivity Infections and Infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic infection Investigations: hepatic transaminases increased (ALT increased, AST increased), gamma-glutamyltransferase (GGT) increased, white blood cell count decreased Nervous System Disorders: hypoesthesia, paresthesia, VIIth nerve paralysis Psychiatric Disorders: insomnia Skin and Subcutaneous Tissue Disorders: pruritus, urticaria, dermatitis Vascular Disorders: flushing, hypertension Laboratory Parameters Hematology laboratory abnormalities that were determined to be potentially clinically significant in the pooled Phase 3 ABSSSI clinical trials are provided in Table 3. Table 3: Potentially Clinically Significant Lowest Laboratory Values in the Pooled Phase 3 ABSSSI Clinical Trials Laboratory Assay Potentially Clinically Significant Values<75% (<50% for absolute neutrophil count) of lower limit of normal (LLN) for post-baseline measurements , Represents laboratory values within two days after the last dose of active drug SIVEXTRO (200 mg oral/intravenous once daily for 6 days) (n)Number of subjects with at least one post-baseline test result that are within two days after the last dose of active drug Linezolid (600 mg oral/intravenous twice daily for 10 days) (n) M = male; F = female Hemoglobin (<10.1 g/dL [M]) (<9 g/dL [F]) (994) 3.4% (957) 3.4% Platelet count (<112 × 103/mm3) (989) 2.1% (950) 3.8% Absolute neutrophil count (<0.8 × 103/mm3) (980) 0.4% (941) 0.6% Myelosuppression Phase 1 studies conducted in healthy adults exposed to SIVEXTRO for 21 days showed a possible dose and duration effect on hematologic parameters beyond 6 days of treatment. In the Phase 3 trials, clinically significant changes in these parameters were generally similar for both treatment arms (see Table 3). Peripheral and Optic Neuropathy Peripheral and optic neuropathy have been described in patients treated with another member of the oxazolidinone class for longer than 28 days. In Phase 3 trials, reported adverse reactions for peripheral neuropathy and optic nerve disorders were similar between both treatment arms (peripheral neuropathy 1.2% vs. 0.7% for tedizolid phosphate and linezolid, respectively; optic nerve disorders 0.3% vs. 0.1%, respectively). No data are available for patients exposed to SIVEXTRO for longer than 6 days.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION 200 mg administered once daily orally or as an intravenous (IV) infusion over 1 hour for six (6) days. (2.1) 2.1 Recommended Dosage The recommended dosage of SIVEXTRO is 200 mg administered once daily for six (6) days either orally (with or without food) or as an intravenous (IV) infusion in patients 18 years of age or older. The recommended dosage and administration is described in Table 1. Table 1: Dosage of SIVEXTRO Infection Route Dosage Frequency Infusion Time Duration of Treatment Acute Bacterial Skin and Skin Structure Infection (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. If patients miss a dose, they should take it 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, wait until their next scheduled dose. 2.2 Preparation and Administration of Intravenous Solution SIVEXTRO is supplied as a sterile, lyophilized powder for injection in single-use vials of 200 mg. Each 200 mg vial must be reconstituted with Sterile Water for Injection and subsequently diluted only with 0.9% Sodium Chloride Injection, USP. SIVEXTRO vials contain no antimicrobial preservatives and are intended for single use only. Preparation 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. Reconstitute the SIVEXTRO vial with 4 mL of Sterile Water for Injection. 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 storage time 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. Do not invert the vial during extraction. The reconstituted solution must be further diluted in 250 mL of 0.9% Sodium Chloride Injection, USP. Slowly inject the 4 mL of reconstituted solution into a 250 mL bag of 0.9% Sodium Chloride Injection, USP. Invert the bag gently to mix. Do NOT shake the bag as this may cause foaming. Administration Administer as an intravenous infusion only. Do not administer as an intravenous push or bolus. Do not mix SIVEXTRO with other drugs when administering. It is not intended for intra-arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. The intravenous bag containing the reconstituted and diluted intravenous solution should be inspected visually for particulate matter prior to administration. Discard if visible particles are observed. The resulting solution is clear and colorless to pale-yellow in color. After reconstitution and dilution, SIVEXTRO is to be administered via intravenous infusion using a total time of 1 hour. The total time from reconstitution to administration should not exceed 24 hours at room temperature or under refrigeration at 2°C to 8°C (36°F to 46°F). 2.3 Compatible Intravenous Solutions SIVEXTRO is compatible with 0.9% Sodium Chloride Injection, USP. 2.4 Incompatibilities SIVEXTRO for injection is incompatible with any solution containing divalent cations (e.g., Ca2+, Mg2+), including Lactated Ringer's Injection and Hartmann's Solution. Limited data are available on the compatibility of SIVEXTRO for injection with other intravenous substances, additives or other medications and they should not be added to SIVEXTRO single-use vials or infused simultaneously. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of SIVEXTRO with 0.9% Sodium Chloride Injection, USP.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, SIVEXTRO may cause fetal harm. Advise pregnant women of the potential risks to a fetus. (8.1) 8.1 Pregnancy Risk Summary Based on animal reproduction studies, SIVEXTRO may cause fetal harm when administered to pregnant women. The available data on the use of SIVEXTRO in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women of the potential risks to a fetus. Fetal developmental toxicities were observed in mice and rats treated with SIVEXTRO. In embryo-fetal studies in mice and rats, tedizolid phosphate was shown to produce fetal developmental toxicities in mice and maternal toxicity and fetal developmental toxicities in rats. Tedizolid phosphate administered orally during organogenesis to pregnant animals was associated with reduced fetal weights and an increased incidence of costal cartilage anomalies in the absence of maternal toxicity in mice; and maternal toxicity, decreased fetal weights, and increased skeletal variations in rats at plasma exposures approximately 4- and 6-times respectively, the human plasma exposure at the maximum recommended human dose (MRHD) of 200 mg/day. In female rats administered tedizolid phosphate during organogenesis through lactation, there was no evidence of fetal toxicity, developmental delays, or impaired reproduction in the offspring at plasma exposures approximately equivalent to the human plasma exposure at the MRHD. (see Data) The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In an embryo-fetal development study, tedizolid phosphate administered orally to pregnant mice at doses of 1, 5, and 25 mg/kg/day during organogenesis (Gestational Day [GD] 6 to GD15) was associated with fetal developmental effects occurring in the absence of maternal toxicity, including reduced fetal weights and an increased incidence of costal cartilage anomalies at the high dose (approximately 4-times the human plasma exposure at the MRHD based on plasma AUC comparison). Tedizolid phosphate administered orally at doses of 2.5, 5, and 15 mg/kg/day to pregnant rats during organogenesis (GD6 through GD17) was associated with maternal toxicity (reduced maternal body weights), decreased fetal weights, and increased skeletal variations including reduced ossification of the sternebrae, vertebrae, and skull at the high dose of 15 mg/kg/day (approximately 6-times the human plasma exposure at the MRHD based on plasma AUC comparison). The doses not associated with fetal toxicity in mice and maternal and fetal toxicity in rats were 5 and 2.5 mg/kg/day respectively (for both species approximately equivalent to the human plasma exposure at the MRHD based on plasma AUC comparison). In a pre-postnatal study, oral tedizolid phosphate administered to female rats at doses of 1.25, 2.5, and 3.75 mg/kg/day during gestation and lactation (GD6 through Lactational Day 20) was not associated with maternal toxicity, fetal toxicity, developmental delays, or impaired reproduction at doses up to the high dose of 3.75 mg/kg/day (approximately equivalent to the human plasma exposure at the MRHD based on plasma AUC comparison). 8.2 Lactation Risk Summary There is no information on the presence of tedizolid in human milk. Tedizolid is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. There are no data on the effects of SIVEXTRO on the breastfed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SIVEXTRO and any potential adverse effects on the breastfed child from SIVEXTRO or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients below the age of 18 have not been established. 8.5 Geriatric Use Clinical studies of SIVEXTRO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. No overall differences in pharmacokinetics were observed between elderly subjects and younger subjects.

Interactions

7 DRUG INTERACTIONS Orally administered SIVEXTRO inhibits Breast Cancer Resistance Protein (BCRP) in the intestine, which can increase the plasma concentrations of orally administered BCRP substrates, and the potential for adverse reactions. If possible, an interruption in the treatment of the co-administered BCRP substrate medicinal product should be considered during treatment with SIVEXTRO, especially for BCRP substrates with a narrow therapeutic index (e.g., methotrexate or topotecan). If coadministration cannot be avoided, monitor for adverse reactions related to the concomitantly administered BCRP substrates, including rosuvastatin. [See Clinical Pharmacology (12.3)]. SIVEXTRO (when administered orally) can increase the plasma concentrations of orally administered Breast Cancer Resistance Protein BCRP substrates. Monitor for adverse reactions related to the concomitant BCRP substrates if coadministration cannot be avoided. (7, 12.3)

More information

Category Value
Authorisation number NDA205436
Agency product number O7DRJ6R4DW
Orphan designation No
Product NDC 67919-040,67919-041
Date Last Revised 10-09-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 1540862
Storage and handling 16.1 Tablets SIVEXTRO tablets are yellow film-coated oval tablets containing 200 mg of tedizolid phosphate; each tablet is debossed with "TZD" on one side and "200" on the other side. They are supplied as follows: HDPE bottles of 30 tablets with child-resistant closure (NDC 67919-041-01) Unit dose blister packs of 6 tablets (NDC 67919-041-02)
Marketing authorisation holder Merck Sharp & Dohme Corp.