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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Tedizolid: Drug information

Tedizolid: Drug information
(For additional information see "Tedizolid: Patient drug information" and see "Tedizolid: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Sivextro
Pharmacologic Category
  • Antibiotic, Oxazolidinone
Dosing: Adult

Skin and soft tissue infection (alternative agent):

Note: Reserve for patients with or at risk for methicillin-resistant S. aureus infection who cannot receive preferred agents (Spelman 2021).

Oral, IV: 200 mg once daily (Moran 2014; Prokocimer 2013). Total duration of therapy is ≥5 days; may extend up to 14 days depending on severity and clinical response (IDSA [Stevens 2014]; Spelman 2021).

Missed doses: Administer as soon as possible any time up to 8 hours prior to the next scheduled dose; if less than 8 hours remain before the next dose, wait until the next scheduled dose.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

(For additional information see "Tedizolid: Pediatric drug information")

Skin and skin structure infections: Children ≥12 years and Adolescents: Oral, IV: 200 mg once daily for 6 days.

Dosing: Renal Impairment: Pediatric

No dosage adjustment necessary; not removed by hemodialysis.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Geriatric

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous, as phosphate [preservative free]:

Sivextro: 200 mg (1 ea)

Tablet, Oral, as phosphate:

Sivextro: 200 mg

Generic Equivalent Available: US

No

Administration: Adult

Oral: Administer with or without food.

Intravenous: Administer as an IV infusion over 1 hour; do not administer as an IV push or bolus. Not for intra-arterial, IM, intrathecal, intraperitoneal, or subcutaneous administration. If the same IV line is to be used for sequential infusion of other drugs or solutions, the line should be flushed with NS before and after tedizolid infusion.

Administration: Pediatric

Oral: Administer with or without food.

Missed dose: Administer as soon as possible if ≥8 hours until next scheduled dose; otherwise, wait until next scheduled dose. All 6 doses should be administered even if a dose is missed.

Parenteral: IV: Administer as an IV infusion over 1 hour; do not administer as an IV push or bolus. Not for intra-arterial, IM, intrathecal, intraperitoneal, or subcutaneous administration. If the same IV line is to be used for sequential infusion of other drugs or solutions, the line should be flushed with NS before and after tedizolid infusion.

Usual Infusion Concentrations: Adult

200 mg in 250 mL (concentration: 0.8 mg/mL) of NS only

Use: Labeled Indications

Skin and soft tissue infections: Treatment of adults and pediatric patients ≥12 years of age with acute bacterial skin and soft tissue infections caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Flushing (<2%), hypertension (<2%), palpitations (<2%), phlebitis (adolescents: 3%), tachycardia (<2%)

Dermatologic: Dermatitis (<2%), pruritus (<2%), urticaria (<2%)

Endocrine & metabolic: Increased gamma-glutamyl transferase (<2%)

Gastrointestinal: Clostridioides difficile colitis (<2%), diarrhea (4%), nausea (7%), oral candidiasis (<2%), vomiting (1% to 3%)

Genitourinary: Vulvovaginal infection (fungal: <2%)

Hematologic & oncologic: Anemia (<2%), decreased platelet count (<112,000/mm3: 1% to 2%), decreased white blood cell count (<2%)

Hepatic: Increased serum alanine aminotransferase (≤3%), increased serum aspartate aminotransferase (≤3%), increased serum transaminases (≤3%)

Hypersensitivity: Hypersensitivity reaction (<2%)

Local: Injection site reaction (≤4%)

Nervous system: Dizziness (2%), facial nerve paralysis (<2%), headache (5%), hypoesthesia (<2%), insomnia (<2%), paresthesia (<2%), peripheral neuropathy (1%)

Ophthalmic: Asthenopia (<2%), blurred vision (<2%), visual impairment (<2%), vitreous opacity (<2%)

Miscellaneous: Infusion related reaction (≤4%)

<1%:

Hematologic & oncologic: Decrease in absolute neutrophil count (<800/mm3)

Ophthalmic: Optic neuropathy

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Neutropenia: Not recommended for use in patients with neutrophil counts <1000 cells/mm3. Alternative therapies should be considered when treating patients with neutropenia and acute bacterial skin and skin structure infections (ABSSI).

Metabolism/Transport Effects

Inhibits BCRP/ABCG2

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

BCRP/ABCG2 Substrates: Tedizolid may increase the serum concentration of BCRP/ABCG2 Substrates. Risk C: Monitor therapy

Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rimegepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rimegepant. Risk X: Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Sympathomimetics: Tedizolid may enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification

Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification

Pregnancy Considerations

Adverse events were observed in animal reproduction studies.

Breast-Feeding Considerations

It is not known if tedizolid is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Baseline complete blood count (CBC) with differential

Mechanism of Action

After conversion from the prodrug, tedizolid phosphate, tedizolid binds to the 50S bacterial ribosomal subunit. This prevents the formation of a functional 70S initiation complex that is essential for the bacterial translation process and subsequently inhibits protein synthesis. Tedizolid is bacteriostatic against enterococci, staphylococci, and streptococci (Kisgen 2014).

Pharmacodynamics and Pharmacokinetics

Absorption: Oral: Well absorbed.

Distribution: Vdss:

Adolescents 12 to 17 years of age (mean weight: 55.3 kg): 54.2 ± 10.2 L (Bradley 2016).

Adults: 67 to 80 L.

Protein binding: 70% to 90%.

Metabolism: Tedizolid phosphate is converted by phosphatases to tedizolid (active, parent drug); no other significant circulating metabolites.

Bioavailability: Oral: ~91%.

Half-life elimination:

Adolescents 12 to 17 years of age: ~6.6 to 8.3 hours (Bradley 2016).

Adults: ~12 hours.

Time to peak: Oral: ~3 hours; IV: 1 to 1.5 hours.

Excretion: Feces (82%) and urine (18%), both as inactive sulfate conjugates. Less than 3% excreted in feces or urine as parent drug.

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Anti-infective considerations:

Parameters associated with efficacy:

S. aureus: fAUC24/minimum inhibitory concentration; goal: ~20 to 50 (bacteriostasis); ~35 to 105 (1-log kill) (Lepak 2012; Louie 2011).

Expected drug exposure in patients with normal renal function:

Cmax (peak):

Single dose, 200 mg:

Adolescents 12 to 17 years of age: Oral: 2.23 ± 0.55 mg/L; IV: 3.85 ± 1.51 mg/L (Bradley 2016).

Adults, BMI <30 kg/m2: Oral: 2.3 mg/L; IV: 2.9 mg/L (Flanagan 2017).

Adults, BMI ≥30 kg/m2: Oral: 1.9 mg/L; IV: 2.5 mg/L (Flanagan 2017).

Multiple dose (steady state), 200 mg once daily:

Adults: Oral: 2.2 ± 0.6 mg/L; IV: 3 ± 0.7 mg/L.

AUC:

Single dose, 200 mg: AUC0 to ∞:

Adolescents 12 to 17 years of age: Oral: 25.2 ± 9.2 mg•hour/L; IV: 27.8 ± 7.3 mg•hour/L (Bradley 2016).

Adults, BMI <30 kg/m2: Oral: 28.5 mg•hour/L; IV: 28.7 mg•hour/L (Flanagan 2017).

Adults, BMI ≥30 kg/m2: Oral: 25.4 mg•hour/L; IV: 25.4 mg•hour/L (Flanagan 2017).

Multiple dose (steady state), 200 mg once daily: AUC24:

Adults: Oral: 25.6 ± 8.5 mg•hour/L; IV: 29.2 ± 6.2 mg•hour/L.

Postantibiotic effect: Staphylococcus spp. (including methicillin-resistant): 0.05 to 0.7 hours; Enterococcus spp. (including vancomycin-resistant): 0.1 to 1.3 hours (Locke 2014).

Pricing: US

Solution (reconstituted) (Sivextro Intravenous)

200 mg (per each): $369.29

Tablets (Sivextro Oral)

200 mg (per each): $463.60

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Cubizolid (EG);
  • Sivextro (BB, CR, CZ, DE, DK, DO, EE, ES, FI, GB, GT, HN, HR, HU, IE, KR, KW, LT, NI, NL, NO, PA, PH, PL, RO, SE, SI, SK, SV);
  • Tedimerp (EG);
  • Trcarezolid (EG);
  • Zolidocyrl (EG)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Bradley JS, Flanagan SD, Arrieta AC, Jacobs R, Capparelli E, Prokocimer P. Pharmacokinetics, safety and tolerability of single oral or intravenous administration of 200 mg tedizolid phosphate in adolescents. Pediatr Infect Dis J. 2016;35(6):628-633. doi:10.1097/INF.0000000000001096 [PubMed 26910588]
  2. Flanagan SD, Bien PA, Munoz KA, et al. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food and comparison of two solid forms of the prodrug. Pharmacother. 2014;34:240-250. [PubMed 23926058]
  3. Flanagan S, Minassian SL, Passarell JA, Fiedler-Kelly J, Prokocimer P. Pharmacokinetics of tedizolid in obese and nonobese subjects. J Clin Pharmacol. 2017;57(10):1290-1294. doi:10.1002/jcph.928 [PubMed 28510339]
  4. Kisgen JJ, Mansour H, Unger NR, et al. Tedizolid: a new oxazolidinone antimicrobial. Am J Health-Sys Pharm. 2014;71:621-633. [PubMed 24688035]
  5. Lepak AJ, Marchillo K, Pichereau S, Craig WA, Andes DR. Comparative pharmacodynamics of the new oxazolidinone tedizolid phosphate and linezolid in a neutropenic murine Staphylococcus aureus pneumonia model. Antimicrob Agents Chemother. 2012;56(11):5916-5922. doi:10.1128/AAC.01303-12 [PubMed 22964254]
  6. Locke JB, Zurenko GE, Shaw KJ, Bartizal K. Tedizolid for the management of human infections: in vitro characteristics. Clin Infect Dis. 2014;58(suppl 1):S35-S42. doi:10.1093/cid/cit616 [PubMed 24343830]
  7. Louie A, Liu W, Kulawy R, Drusano GL. In vivo pharmacodynamics of torezolid phosphate (TR-701), a new oxazolidinone antibiotic, against methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains in a mouse thigh infection model. Antimicrob Agents Chemother. 2011;55(7):3453-3460. doi:10.1128/AAC.01565-10 [PubMed 21502615]
  8. Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14(8):696-705. doi:10.1016/S1473-3099(14)70737-6 [PubMed 24909499]
  9. O’Riordan WO, Green S, Mehra P, et al. Tedizolid phosphate for the management of acute bacterial skin and skin structure infections: efficacy summary. Clin Inf Dis. 2014;58(S1):S43-50. [PubMed 24343832]
  10. Prokocimer P, Bien P, Surber J, et al. Phase 2, randomized, double-blind, dose ranging study evaluating the safety, tolerability, population pharmacokinetics and efficacy of oral torezolid phosphate in patients with complicated skin and skin structure infections. Antimicrob Agents Chemother. 2011;55:583-592. [PubMed 21115795]
  11. Prokocimer P, De Anda C, Fang E, et al. Tedizolid phosphate vs. linezolid for treatment of acute bacterial skin and skin structure infections. The ESTABLISH-1 randomized trial. JAMA. 2013;309:559-569. [PubMed 23403680]
  12. Sivextro (tedizolid) [prescribing information]. Whitehouse Station, NJ: Merck; October 2020.
  13. Spelman D, Baddour LM. Cellulitis and skin abscess in adults: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 11, 2021.
  14. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu444 [PubMed 24973422]
  15. Urbina O, Ferrandez O, Espona M, et al. Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections. Drug Design Dev and Ther. 2013;7:243-265. [PubMed 23589680]
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