Tedizolid
tedizolid phosphate tablets and injection (Sivextro)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive organisms: MRSA, MSSA, S. pyogenes, S. agalactiae, S. anginosus group (including S. anginosus, S. intermedius, S. constellatus), and E. faecalis | Adults and pediatrics ≥12 years (200 mg); weight-band dosing available for younger pediatrics per 2025 FDA PI | Monotherapy | FDA Approved |
Tedizolid is the second FDA-approved oxazolidinone antibiotic, approved in 2014. It offers several advantages over linezolid for ABSSSI: once-daily dosing (owing to a longer half-life), a shorter 6-day treatment course, and a lower incidence of gastrointestinal side effects and myelosuppression at the approved duration. Tedizolid demonstrates four- to sixteen-fold greater in vitro potency against MRSA compared with linezolid and retains activity against some linezolid-resistant staphylococcal isolates. However, its approved indication is currently limited to ABSSSI; it is not FDA-approved for pneumonia, VRE infections, or other systemic Gram-positive infections.
MRSA osteomyelitis / prosthetic joint infection: Used as oral step-down for prolonged bone and joint infection courses, leveraging once-daily dosing and potentially lower myelosuppression risk than linezolid. Evidence quality: Low (case series, expert opinion).
Hospital-acquired / ventilator-associated pneumonia (MRSA): Evaluated in the VITAL trial (Phase 3, n=726). Tedizolid was noninferior to linezolid for day 28 all-cause mortality but did not demonstrate non-inferiority for investigator-assessed clinical response at test of cure. Not FDA-approved for pneumonia. Evidence quality: Moderate (Phase 3 trial with mixed results on co-primary endpoints).
VRE infections: In vitro activity against VRE including linezolid-resistant strains; used off-label when linezolid and daptomycin are not suitable. Evidence quality: Low (case series, in vitro data).
Dosing
Adult and Adolescent Dosing (≥12 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| ABSSSI (cellulitis, wound infection, major abscess) | 200 mg IV or PO once daily | 200 mg once daily × 6 days | 200 mg/day | Fixed 6-day course; no dose titration required IV-to-oral switch with no dose change (~91% oral bioavailability) |
| ABSSSI — IV-to-oral step-down | 200 mg IV once daily (minimum 1 day) | 200 mg PO once daily to complete 6 days total | 200 mg/day | In ESTABLISH-2, patients could switch to oral after minimum 1 day of IV Total duration remains 6 days regardless of route sequence |
Pediatric Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| ABSSSI — adolescents ≥12 years (≥35 kg) | 200 mg IV or PO once daily | 200 mg once daily × 6 days | 200 mg/day | Same as adult dosing Established in Phase 3 with 91 pediatric patients aged 12–17 |
| ABSSSI — younger pediatrics (<12 years / <35 kg) | Weight-band IV and oral dosing per 2025 FDA PI | Recent FDA label expansion (2025) includes weight-band dosing for patients from 1 kg; consult current Sivextro PI for specific dose tables Duration: 6 days total | ||
Tedizolid offers practical advantages over linezolid: once-daily dosing (vs twice daily), a shorter 6-day course (vs 10–14 days), and significantly fewer GI side effects (8.2% vs 12.2% for GI adverse events in pooled Phase 3 data). At the approved 6-day duration, tedizolid’s haematological safety profile is similar to placebo, whereas linezolid’s myelosuppression risk is duration-dependent and well-documented. However, tedizolid is only FDA-approved for ABSSSI, whereas linezolid covers pneumonia, VRE bacteremia, and other indications. Off-label use of tedizolid for longer durations carries unknown myelosuppression risk, though emerging case reports suggest it may be better tolerated than linezolid in extended courses.
Tedizolid phosphate is an inactive prodrug that is rapidly converted to the active moiety tedizolid by endogenous plasma phosphatases following both oral and IV administration. Systemic exposure to the parent prodrug (tedizolid phosphate) is negligible. All pharmacokinetic parameters and dosing refer to the active tedizolid.
Pharmacology
Mechanism of Action
Tedizolid is a second-generation oxazolidinone antibiotic that inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S ribosomal initiation complex. Compared to linezolid, tedizolid possesses an additional D-ring (methyltetrazole) that increases the number of hydrogen bonding interactions with the ribosome, resulting in four- to sixteen-fold higher in vitro potency against staphylococci. Tedizolid is primarily bacteriostatic against staphylococci and enterococci but demonstrates bactericidal activity against streptococci. Like linezolid, tedizolid is a reversible inhibitor of monoamine oxidase (MAO) in vitro, but at the approved clinical dose, it demonstrates substantially less MAO inhibition than linezolid in human challenge studies.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Prodrug rapidly converted to tedizolid; oral bioavailability ~91%; Tmax ~3 h; food does not affect extent of absorption | IV-to-oral switch requires no dose change; once-daily dosing supported by long half-life |
| Distribution | Vd ~100 L; protein binding ~80%; good tissue penetration into skin, soft tissue, and pulmonary epithelial lining fluid | Large Vd with high tissue penetration supports use in skin/soft tissue infections; concentrations in ELF exceed MIC for most Gram-positive pathogens |
| Metabolism | Primarily hepatic sulfate conjugation (Phase II reaction) to inactive metabolites; not CYP450-mediated; no autoinhibition of metabolism | Minimal CYP-mediated drug interaction potential; no inhibition or induction of CYP enzymes. Inhibits BCRP (breast cancer resistance protein) intestinally |
| Elimination | t½ ~12 h; ~18% excreted unchanged in urine; primarily fecal elimination; ~30% accumulation at steady state (reached in ~3 days) | No dose adjustment for renal or hepatic impairment; long half-life supports once-daily administration; dialysis not expected to significantly remove tedizolid |
Side Effects
Safety data from the ESTABLISH-1 and ESTABLISH-2 Phase 3 trials comparing tedizolid 200 mg once daily × 6 days versus linezolid 600 mg BID × 10 days for ABSSSI. Adverse events were generally mild. Pooled gastrointestinal adverse event rates were significantly lower with tedizolid (8.2%) than linezolid (12.2%; P=0.02).
| Adverse Effect | Tedizolid Incidence | Linezolid Comparator | Clinical Note |
|---|---|---|---|
| Nausea | 7% | 12% | Significantly lower than linezolid; usually mild; no dose adjustment needed |
| Headache | 5% | 6% | Similar between groups; non-specific |
| Diarrhea | 4% | 5% | Distinguish from C. difficile-associated diarrhea |
| Vomiting | 3% | 3% | Usually mild |
| Dizziness | 2% | 2% | Non-specific |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Infusion-site reactions (IV) | ~4% (IV patients) | Includes phlebitis, pain, erythema at infusion site; manage with site rotation |
| Peripheral neuropathy | 1.2% | Similar to linezolid (0.7%) in Phase 3; no data beyond 6-day course |
| Elevated hepatic transaminases | ~1–2% | Usually self-limiting; monitor if clinically indicated |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Myelosuppression (thrombocytopenia, anaemia, neutropenia) | Uncommon at 6-day course (similar to placebo); risk increases beyond 6 days (postmarketing reports) | Phase 1 data: dose- and duration-dependent beyond 6 days | Monitor CBC if extended beyond approved 6-day duration; at standard 6-day course, clinically significant changes similar between tedizolid and linezolid; neutropenia significantly lower with tedizolid (3% vs 7%, P=0.024) |
| Optic neuropathy | 0.3% (vs 0.1% linezolid in Phase 3) | Described for oxazolidinone class primarily with >28-day courses | No safety data beyond 6 days for tedizolid; prompt ophthalmology referral for any visual symptoms; discontinue if suspected |
| Peripheral neuropathy | 1.2% (vs 0.7% linezolid in Phase 3) | Oxazolidinone class effect; primarily with >28-day courses | Report numbness, tingling, or burning in extremities; discontinue promptly; may be irreversible |
| C. difficile-associated diarrhea | Rare | During or after treatment | Evaluate persistent diarrhea; test for C. difficile toxin; manage per guidelines |
Tedizolid’s favourable haematological safety profile is established only for its approved 6-day course. Phase 1 studies in healthy volunteers exposed to tedizolid for 21 days showed a dose- and duration-dependent effect on haematological parameters beyond 6 days of treatment, with 200 mg showing a profile similar to placebo while 400 mg showed changes comparable to linezolid 600 mg BID. Postmarketing reports of thrombocytopenia have been documented in patients treated for a median of 26.5 days (well beyond the approved 6-day duration). Clinicians using tedizolid off-label for extended courses should apply the same CBC monitoring principles used for linezolid.
Drug Interactions
Tedizolid is a weak, reversible MAO inhibitor in vitro. However, unlike linezolid, controlled human challenge studies with tedizolid at steady state showed no clinically meaningful interactions with pseudoephedrine (no significant BP or HR changes) and only a modest reduction in the tyramine pressor response threshold (325 mg tedizolid vs 425 mg placebo). Tedizolid is not metabolised by CYP450 enzymes and does not inhibit or induce them. The principal pharmacokinetic interaction is intestinal BCRP inhibition.
Monitoring
- CBC with DifferentialBaseline; not routinely required for 6-day course
Trigger-basedAt the approved 6-day duration, clinically significant haematological changes were similar between tedizolid and placebo. Weekly CBC monitoring is only necessary if treatment is extended beyond 6 days off-label, in patients with pre-existing cytopenias, or in patients on concurrent myelosuppressive agents. - Clinical Response48–72 hours after first dose
RoutineAssess for early clinical response: cessation of lesion spread and absence of fever. The primary endpoint in ESTABLISH-1 was early clinical response at 48–72 hours. Failure to respond warrants reassessment of diagnosis and culture data. - Visual SymptomsIf treatment extended beyond 6 days
Trigger-basedOptic neuropathy is a class effect of oxazolidinones, primarily with courses exceeding 28 days. No tedizolid-specific data beyond 6 days exists. Report any visual changes immediately.
Trigger-basedClass effect of oxazolidinones. Assess for numbness, tingling, or burning in extremities at each visit if off-label duration exceeds standard course.
RoutineMeasure and document lesion area. Improvement should be evident by 48–72 hours. Post-therapy evaluation at 7–14 days after completing treatment to confirm sustained response.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to tedizolid phosphate or any component of the formulation
Note: Unlike linezolid, the tedizolid FDA PI does not list concurrent MAOIs as a contraindication, reflecting its lower clinical MAO inhibition. However, patients on MAOIs were excluded from clinical trials, and caution remains appropriate.
Relative Contraindications (Specialist Input Recommended)
- Neutropenia (ANC <1,000 cells/mm³) — antibacterial activity of tedizolid was reduced in the absence of granulocytes in animal models; an alternative therapy should be considered in neutropenic patients (FDA PI)
- Concurrent serotonergic agents — excluded from clinical trials; theoretical serotonin syndrome risk; monitor closely if unavoidable
Use with Caution
- Concurrent oral BCRP substrates — tedizolid increases plasma concentrations of drugs transported by BCRP (rosuvastatin, methotrexate); monitor for substrate toxicity
- Treatment duration >6 days (off-label) — safety beyond 6 days is not established; myelosuppression and neuropathy risk is unknown but likely increases with duration based on class effect and Phase 1 data
- Pregnancy — fetal developmental toxicities observed in animal studies (reduced fetal weights, costal cartilage anomalies at 4–6× human exposure); use only if benefit clearly outweighs risk
The safety and efficacy of tedizolid in patients with neutropenia (neutrophil count <1,000 cells/mm³) have not been adequately evaluated. In an animal infection model, the antibacterial activity of tedizolid was reduced in the absence of granulocytes, requiring approximately 10-fold higher doses to achieve bacterial stasis in neutropenic versus non-neutropenic mice. An alternative therapy should be considered when treating patients with neutropenia who require an oxazolidinone.
Patient Counselling
Purpose of Therapy
Tedizolid is an antibiotic that treats serious skin infections caused by resistant bacteria, including MRSA. It can be given through a vein or taken as a tablet, and the full 6-day course must be completed even if the infection looks and feels better after a few days.
How to Take
Take one 200 mg tablet once a day, at the same time each day, with or without food, for exactly 6 days. If you miss a dose and it is within 8 hours of the usual time, take it as soon as possible. If more than 8 hours have passed, skip the missed dose and take the next dose at the usual time.
Sources
- Sivextro (tedizolid phosphate) — Full Prescribing Information. Merck Sharp & Dohme LLC. Revised 2025. FDA Label (2025)Most current FDA label including the 2025 pediatric expansion with weight-band dosing, BCRP interaction data, neutropenia warning, and adverse reaction incidences from Phase 3 trials.
- Sivextro (tedizolid phosphate) — Prescribing Information. Revised 2020. FDA Label (2020)Earlier label version with adult and adolescent dosing, PK parameters, and tyramine/pseudoephedrine challenge study results.
- Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. 2013;309(6):559–569. doi:10.1001/jama.2013.241ESTABLISH-1: Phase 3 RCT demonstrating non-inferiority of tedizolid 200 mg × 6 days versus linezolid 600 mg BID × 10 days for ABSSSI (oral-only study).
- 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)70737-6ESTABLISH-2: Phase 3 RCT confirming non-inferiority of tedizolid vs linezolid for ABSSSI with IV-to-oral step-down design.
- Shorr AF, Lodise TP, Corey GR, et al. Analysis of the Phase 3 ESTABLISH trials: tedizolid versus linezolid in acute bacterial skin and skin structure infection. Antimicrob Agents Chemother. 2015;59(2):864–871. doi:10.1128/AAC.03688-14Pooled analysis of ESTABLISH-1 and -2 including subgroup efficacy data by pathogen, with safety comparison showing lower GI AE rates with tedizolid.
- Wunderink RG, Roquilly A, Croce M, et al. A Phase 3, randomized, double-blind study comparing tedizolid phosphate and linezolid for treatment of ventilated gram-positive hospital-acquired or ventilator-associated bacterial pneumonia. Clin Infect Dis. 2021;73(3):e710–e718. doi:10.1093/cid/ciab032VITAL trial: tedizolid was noninferior to linezolid for day 28 all-cause mortality but did not demonstrate non-inferiority for investigator-assessed clinical response at test of cure in ventilated HAP/VAP.
- Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by IDSA for the treatment of MRSA infections in adults and children. Clin Infect Dis. 2011;52(3):e18–e55. doi:10.1093/cid/ciq146IDSA MRSA guideline positioning oxazolidinones among treatment options for Gram-positive infections; tedizolid not yet available at time of publication but relevant for therapeutic context.
- Shaw KJ, Barbachyn MR. The oxazolidinones: past, present, and future. Ann N Y Acad Sci. 2011;1241(1):48–70. doi:10.1111/j.1749-6632.2011.06330.xComprehensive review of oxazolidinone class development including the structural differences between linezolid and tedizolid that confer enhanced ribosomal binding.
- Zhanel GG, Love R, Adam H, et al. Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens. Drugs. 2015;75(3):253–270. doi:10.1007/s40265-015-0352-7Drug review covering tedizolid’s in vitro spectrum (4–16-fold more potent than linezolid vs MRSA), mechanism of action, and resistance profiles.
- Flanagan S, Fang E, Engel SM, Das AF, De Anda C, Prokocimer P. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy. 2014;34(9):891–900. doi:10.1002/phar.1458Definitive PK study establishing oral bioavailability (~91%), half-life (~12 h), minimal accumulation (28%), and similar PK parameters between IV and oral routes.
- Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet. 2001;358(9297):1975–1982. doi:10.1016/S0140-6736(01)06964-1Early review of the oxazolidinone class providing foundational pharmacological context for understanding tedizolid’s mechanism and spectrum.
- Lodise TP, Fang E, Engel SM, Das AF, Prokocimer P. Tedizolid pooled safety analysis: a comprehensive assessment from Phase 3 trials. Open Forum Infect Dis. 2014;1(Suppl 1):S406. doi:10.1093/ofid/ofu052.1073Pooled safety analysis across Phase 3 studies documenting the favourable GI and haematological safety profile of tedizolid at the 6-day approved duration.
- Ong V, Flanagan S, Fang E, et al. Absorption, distribution, metabolism, and excretion of the novel antibacterial prodrug tedizolid phosphate. Drug Metab Dispos. 2014;42(8):1275–1284. doi:10.1124/dmd.113.056697ADME study confirming prodrug conversion, sulfate conjugation as primary metabolic pathway, fecal elimination, and absence of CYP involvement.