Linezolid
Tablet, Film Coated · Oral, Intravenous
Uses
Linezolid injection is an oxazolidinone-class antibacterial indicated in adults and children for the treatment of the following infections caused by susceptible Gram-positive bacteria: Nosocomial pneumonia ( 1.1 ); Community-acquired pneumonia ( 1.2 ); Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis ( 1.3 ); Vancomycin-resistant Enterococcus faecium infections. ( 1.4 ) Limitations of Use: ( 1.5 )
• Linezolid injection is not indicated for the treatment of Gram-negative infections.
• The safety and efficacy of Linezolid formulations given for longer than 28 days have not been evaluated in controlled clinical trials. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Linezolid injection formulations and other antibacterial drugs, Linezolid injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.6 ) 1.1 Nosocomial Pneumonia Linezolid injection is indicated for the treatment of nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates) or Streptococcus pneumoniae [ see Clinical Studies (14) ]. 1.2 Community-acquired Pneumonia Linezolid injection is indicated for the treatment of community-acquired pneumonia caused by Streptococcus pneumoniae , including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible isolates only) [ see Clinical Studies (14) ]. 1.3 Complicated Skin and Skin Structure Infections Linezolid injection is indicated for the treatment of complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis, caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , or Streptococcus agalactiae . Linezolid injection has not been studied in the treatment of decubitus ulcers [ see Clinical Studies (14) ]. 1.4 Vancomycin-resistant Enterococcus faecium Infections Linezolid injection is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia [ see Clinical Studies (14) ]. 1.5 Limitations of Use
• Linezolid injection is not indicated for the treatment of Gram-negative infections. It is critical that specific Gram-negative therapy be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected [ see Warnings and Precautions (5.4) ].
• The safety and efficacy of Linezolid formulations given for longer than 28 days have not been evaluated in controlled clinical trials [ see Clinical Studies (14) ]. 1.6 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Linezolid injection and other antibacterial drugs, Linezolid injection should be used only to treat or prevent infections 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.
Dosage and administration
Dosage, Route, and Frequency of Administration Infection Pediatric Patients (Birth through 11 Years of Age) Adults and Adolescents (12 Years and Older) Duration (days) Nosocomial pneumonia ( 1.1 ) 10 mg/kg intravenously every 8 hours 600 mg intravenously every 12 hours 10 to 14 Community-acquired pneumonia, including concurrent bacteremia ( 1.2 ) Complicated skin and skin structure infections ( 1.3 ) Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia ( 1.4 ) 10 mg/kg intravenously every 8 hours 600 mg intravenously every 12 hours 14 to 28
• Pediatric Patients-The recommended dose is 10 mg per kg intravenously every 8 hours. Linezolid injection in a single-dose container should be used only in pediatric patients who require the entire 600 mg dose and not any fraction thereof. ( 2.1 ) 2.1 General Dosage and Administration The recommended dosage for Linezolid injection for the treatment of infections is described in Table 1. No dose adjustment is necessary when switching from intravenous to oral administration. Table 1. Dosage Guidelines for Linezolid Injection Dosage, Route, and Frequency of Administration Recommended Duration of Treatment (consecutive days) Infection Due to the designated pathogens [ see Indications and Usage (1) ] Pediatric Patients Neonates less than 7 days : Most pre-term neonates less than 7 days of age (gestational age less than 34 weeks) have lower systemic linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg every 8 hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg every 8 hours by 7 days of life [ see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3) ] . (Birth through 11 Years of Age) Adults and Adolescents (12 Years and Older) Nosocomial pneumonia 10 mg/kg intravenously every 8 hours 600 mg intravenously every 12 hours 10 to 14 Community-acquired pneumonia, including concurrent bacteremia Complicated skin and skin structure infections Vancomycin-resistant Enterococcus faecium infections , including concurrent bacteremia 10 mg/kg intravenously every 8 hours 600 mg intravenously every 12 hours 14 to 28 The maximum dose for pediatric patients should not exceed the recommended adult dose. The recommended dose is 10 mg per kg intravenously every 8 hours. Linezolid injection in a single-dose container should be used only in pediatric patients who require the entire 600 mg dose and not any fraction thereof. 2.2 Intravenous Administration Linezolid injection is supplied in single-dose, ready-to-use container [ see How Supplied/Storage and Handling (16) ]. Parenteral drug products should be inspected visually for particulate matter prior to administration. Check for minute leaks by firmly squeezing the bag. If leaks are detected, discard the solution, as sterility may be impaired . Keep the containers in the overwrap until ready to use. Store at room temperature. Protect from freezing. Linezolid injection may exhibit a yellow color that can intensify over time without adversely affecting potency. Linezolid injection should be administered by intravenous infusion over a period of 30 to 120 minutes. Do not use this intravenous container in series connections . Additives should not be introduced into this solution. If Linezolid injection is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each product. Discard unused portion. If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of Linezolid injection with an infusion solution compatible with Linezolid injection and with any other drug(s) administered via this common line. 2.3 Compatibilities Compatible intravenous solutions include 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP, and Lactated Ringer's Injection, USP. 2.4 Incompatibilities Physical incompatibilities resulted when Linezolid injection was combined with the following drugs during simulated Y-site administration: amphotericin B, chlorpromazine HCl, diazepam, pentamidine isothionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole. Additionally, chemical incompatibility resulted when Linezolid injection was combined with ceftriaxone sodium.
Dosage forms and strengths
Linezolid injection: 600 mg/300 mL (2 mg/mL) linezolid in single-dose, ready-to-use flexible plastic container in a foil laminate overwrap. Injection: 600 mg/300 mL (2 mg/mL) linezolid. ( 3 )
Contraindications
• Known hypersensitivity to linezolid or any of the other product components. ( 4.1 )
• Patients taking any monoamine oxidase inhibitors (MAOI) or within two weeks of taking an MAOI. ( 4.2 ) 4.1 Hypersensitivity Linezolid injection is contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components . 4.2 Monoamine Oxidase Inhibitors Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g., phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product.
Warnings and precautions
• Myelosuppression: Monitor complete blood counts weekly. Thrombocytopenia has been reported more often in patients with severe renal and in patients with moderate to severe hepatic impairment. Consider discontinuation in patients who develop or have worsening myelosuppression. ( 5.1 )
• Peripheral and Optic Neuropathy: Reported primarily in patients treated for longer than 28 days. If patients experience symptoms of visual impairment, prompt ophthalmic evaluation is recommended. ( 5.2 )
• Serotonin Syndrome: Monitor patients taking Linezolid injection concomitantly with serotonergic agents for signs of serotonin syndrome. If signs or symptoms of serotonin syndrome occur, consider discontinuing Linezolid injection and/or concomitant serotonergic agents. ( 5.3 )
• A mortality imbalance was seen in an investigational study in linezolid-treated patients with catheter-related bloodstream infections. ( 5.4 )
• Clostridioides difficile- Associated Diarrhea: Evaluate if diarrhea occurs. ( 5.5 )
• Potential interactions producing elevation of blood pressure: monitor blood pressure. ( 5.6 )
• Rhabdomyolysis: If signs or symptoms of rhabdomyolysis are observed, discontinue Linezolid injection and initiate appropriate therapy. ( 5.9 )
• Hypoglycemia: Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. ( 5.10 )
• Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Monitor serum sodium levels regularly in patients at risk of hyponatremia and/or SIADH. ( 5.11 ) 5.1 Myelosuppression Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment levels. Thrombocytopenia has been reported more often in patients with severe renal impairment, whether or not on dialysis, and in patients with moderate to severe hepatic impairment. Complete blood counts should be monitored weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, those with pre-existing myelosuppression, those with severe renal impairment or moderate to severe hepatic impairment, those receiving concomitant drugs that produce bone marrow suppression, or those with a chronic infection who have received previous or concomitant antibacterial drug therapy. Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression [ see Adverse Reactions (6.2) ]. 5.2 Peripheral and Optic Neuropathy Peripheral and optic neuropathies have been reported in patients treated with linezolid, primarily in those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration. Visual blurring has been reported in some patients treated with linezolid for less than 28 days. Peripheral and optic neuropathy has also been reported in children. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Visual function should be monitored in all patients taking Linezolid injection for extended periods (≥3 months) and in all patients reporting new visual symptoms regardless of length of therapy with Linezolid injection. If peripheral or optic neuropathy occurs, the continued use of Linezolid injection in these patients should be weighed against the potential risks. 5.3 Serotonin Syndrome Spontaneous reports of serotonin syndrome including fatal cases associated with the concomitant use of linezolid and serotonergic agents have been reported. 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 Linezolid injection and serotonergic agents or with use of Linezolid injection in patients with carcinoid syndrome. If signs or symptoms of serotonin syndrome occur, consider discontinuing Linezolid injection and/or concomitant serotonergic agents as clinically appropriate and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome when Linezolid injection is used concomitantly with serotonergic agents. 5.4 Mortality Imbalance in an Investigational Study in Patients With Catheter-Related Bloodstream Infections, Including Those With Catheter-Site Infections An imbalance in mortality was seen in patients treated with linezolid relative to vancomycin/dicloxacillin/oxacillin in an open-label study in seriously ill patients with intravascular catheter-related infections [78/363 (21.5%) vs. 58/363 (16.0%); odds ratio 1.426, 95% CI 0.970, 2.098]. While causality has not been established, this observed imbalance occurred primarily in linezolid-treated patients in whom either Gram-negative pathogens, mixed Gram-negative and Gram-positive pathogens, or no pathogen were identified at baseline, but was not seen in patients with Gram-positive infections only. Linezolid is not approved and should not be used for the treatment of patients with catheter-related bloodstream infections or catheter-site infections. Linezolid has no clinical activity against Gram-negative pathogens and is not indicated for the treatment of Gram-negative infections.
Side effects
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Myelosuppression [ see Warnings and Precautions (5.1) ]
• Peripheral and Optic Neuropathy [ see Warnings and Precautions (5.2) ]
• Serotonin Syndrome [ see Warnings and Precautions (5.3) ]
• Clostridioides difficile -Associated Diarrhea [ see Warnings and Precautions (5.5) ]
• Lactic Acidosis [ see Warnings and Precautions (5.7) ]
• Convulsions [ see Warnings and Precautions (5.8) ]
• Rhabdomyolysis [ see Warnings and Precautions (5.9) ]
• Hypoglycemia [ see Warnings and Precautions (5.10) ]
• Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) [ see Warnings and Precautions (5.11) ] Most common adverse reactions (>5% of adult and pediatric patients treated with Linezolid injection) include diarrhea, vomiting, headache, nausea, and anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults The safety of linezolid formulations was evaluated in 2,046 adult patients enrolled in seven Phase 3 comparator-controlled clinical trials, who were treated for up to 28 days. For all indications, 20.4% of linezolid-treated and 14.3% of comparator-treated patients experienced at least one drug-related adverse event. Table 2 shows the incidence of all-causality, treatment-emergent adverse reactions reported in at least 1% of adult patients in these trials by dose of linezolid. Table 2. Incidence (%) Treatment-Emergent Adverse Reactions Occurring in greater than 1% of Adult Patients Treated with Linezolid in Comparator-Controlled Clinical Trials ADVERSE REACTIONS Linezolid 600 mg every 12 hours (n = 1498) All Other Comparators Comparators included cefpodoxime proxetil 200 mg by mouth every 12 hours; ceftriaxone 1 g intravenously every 12 hours; dicloxacillin 500 mg by mouth every 6 hours; oxacillin 2 g intravenously every 6 hours; vancomycin 1 g intravenously every 12 hours. (n = 1464) Headache 5.7 4.4 Diarrhea 8.3 6.4 Nausea 6.6 4.6 Vomiting 4.3 2.3 Dizziness 1.8 1.5 Rash 2.3 2.6 Anemia 2.1 1.4 Taste alteration 1.0 0.3 Vaginal moniliasis 1.1 0.5 Oral moniliasis 1.7 1.0 Abnormal liver function tests 1.6 0.8 Fungal infection 0.3 0.2 Tongue discoloration 0.3 0 Localized abdominal pain 1.2 0.8 Generalized abdominal pain 1.2 1.0 Discontinuations due to drug-related adverse events occurred in 2.1% of linezolid-treated and 1.7% of comparator-treated patients. The most common reported drug-related adverse events leading to discontinuation of treatment were nausea, headache, diarrhea, and vomiting. Pediatric Patients The safety of linezolid formulations was evaluated in 215 pediatric patients ranging in age from birth through 11 years, and in 248 pediatric patients aged 5 through 17 years (146 of these 248 were age 5 through 11 and 102 were age 12 to 17). These patients were enrolled in two Phase 3 comparator-controlled clinical trials and were treated for up to 28 days. In the study of hospitalized pediatric patients (birth through 11 years) with Gram-positive infections, who were randomized 2 to 1 (linezolid: vancomycin), mortality was 6.0% (13/215) in the linezolid arm and 3.0% (3/101) in the vancomycin arm. However, given the severe underlying illness in the patient population, no causality could be established. For all indications, 18.8% of linezolid-treated and 34.3% of comparator-treated patients experienced at least one drug-related adverse event. Table 3 shows the incidence of all-causality, treatment-emergent adverse reactions reported in more than 1% of pediatric patients (and more than 1 patient) in either treatment group in the comparator-controlled Phase 3 trials. Table 3. Incidence (%) of Treatment-Emergent Adverse Reactions Occurring in greater than 1% of Pediatric Patients (and greater than 1 Patient) in Either Treatment Group in Comparator-Controlled Clinical Trials Patients from birth through 11 years of age received linezolid 10 mg/kg intravenously and/or by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6–24 hours, depending on age and renal clearance. ADVERSE REACTIONS Linezolid (n = 215) Vancomycin (n = 101) Diarrhea 10.8 12.1 Vomiting 9.4 9.1 Headache 0.9 0 Anemia 5.6 7.1 Thrombocytopenia 4.7 2.0 Nausea 1.9 0 Generalized abdominal pain 0.9 2.0 Localized abdominal pain 0.5 1.0 Loose stools 2.3 3.0 Eosinophilia 1.9 1.0 Pruritus at non-application site 1.4 2.0 Vertigo 0 0 For all indications, discontinuations due to drug-related adverse events occurred in 0.9% of linezolid-treated and 6.1% of comparator-treated patients. Laboratory Abnormalities Linezolid has been associated with thrombocytopenia when used in doses up to and including 600 mg every 12 hours for up to 28 days. In Phase 3 comparator-controlled trials, the percentage of adult patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 2.4% (range among studies: 0.3 to 10.0%) with linezolid and 1.5% (range among studies: 0.4 to 7.0%) with a comparator. In a study of hospitalized pediatric patients ranging in age from birth through 11 years, the percentage of patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 12.9% with linezolid and 13.4% with vancomycin. In an outpatient study of pediatric patients aged from 5 through 17 years, the percentage of patients who developed a substantially low platelet count was 0% with linezolid and 0.4% with cefadroxil.
Drug interactions
Monoamine oxidase inhibitors and potential for interaction with adrenergic and serotonergic agents. ( 4.2 , 5.3 , 5.6 , 7 , 12.3 ) 7.1 Monoamine Oxidase Inhibitors Linezolid is a reversible, nonselective inhibitor of monoamine oxidase [ see Contraindications (4.2) and Clinical Pharmacology (12.3) ]. 7.2 Adrenergic and Serotonergic Agents Linezolid has the potential for interaction with adrenergic and serotonergic agents [ see Warnings and Precautions (5.3 , 5.6) and Clinical Pharmacology (12.3) ].
Use in specific populations
8.1 Pregnancy Risk Summary Available data from published and postmarketing case reports with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered during organogenesis, linezolid did not cause malformations in mice, rats, or rabbits at maternal exposure levels approximately 6.5 times (mice), equivalent to (rats), or 0.06 times (rabbits) the clinical therapeutic exposure, based on AUCs. However, embryo-fetal lethality was observed in mice at 6.5 times the estimated human exposure. When female rats were dosed during organogenesis through lactation, postnatal survival of pups was decreased at doses approximately equivalent to the estimated human exposure based on AUCs ( see Data ). The background risk of major birth defects and miscarriage for the indicated populations 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 to 4% and 15 to 20%, respectively. Data Animal Data In mice, embryo-fetal toxicities were observed only at doses that caused maternal toxicity (clinical signs and reduced body weight gain). An oral dose of 450 mg/kg/day given from Gestation Day (GD) 6–16 (6.5 times the estimated human exposure based on AUCs) correlated with increased postimplantational embryo death, including total litter loss, decreased fetal body weights, and an increased incidence of costal cartilage fusion. Neither maternal nor embryo-fetal toxicities were observed at doses up to 150 mg/kg/day. Fetal malformations were not observed. In rats, fetal toxicity was observed at 15 and 50 mg/kg/day administered orally from GD 6–17 (exposures 0.22 times to approximately equivalent to the estimated human exposure, respectively, based on AUCs). The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights. Fetal malformations were not observed. Maternal toxicity, in the form of reduced body weight gain, was seen at 50 mg/kg/day. In rabbits, reduced fetal body weight occurred only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) when administered at an oral dose of 15 mg/kg/day given from GD 6‑20 (0.06 times the estimated human exposure based on AUCs). Fetal malformations were not observed. When female rats were treated with 50 mg/kg/day (approximately equivalent to the estimated human exposure based on AUCs) of linezolid during pregnancy and lactation (GD 6 through Lactation Day 20), survival of pups was decreased on postnatal days 1 to 4. Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss. 8.2 Lactation Risk Summary Linezolid is present in breast milk. Based on data from available published case reports, the daily dose of linezolid that the infant would receive from breastmilk would be approximately 6% to 9% of the recommended therapeutic infant dose (10 mg/kg every 8 hours). There is no information on the effects of linezolid on the breastfed infant; however, diarrhea and vomiting were the most common adverse reactions reported in clinical trials in infants receiving linezolid therapeutically [ see Adverse Reactions (6.1) ] and (see Clinical Considerations ) . There is no information on the effects of linezolid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for linezolid and any potential adverse effects on the breastfed child from linezolid or from the underlying maternal condition. Clinical Considerations Advise lactating women to monitor a breastfed infant for diarrhea and vomiting. 8.3 Females and Males of Reproductive Potential Infertility Males Based on findings from studies in rats, linezolid may reversibly impair fertility in male patients [ see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of linezolid for the treatment of pediatric patients with the following infections are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from a comparator-controlled study of Gram-positive infections in pediatric patients ranging in age from birth through 11 years [ see Indications and Usage (1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ]:
• nosocomial pneumonia
• complicated skin and skin structure infections
• community-acquired pneumonia (also supported by evidence from an uncontrolled study in patients ranging in age from 8 months through 12 years)
• vancomycin-resistant Enterococcus faecium infections Linezolid injection in a single-dose container should be used only in pediatric patients who require the entire 600 mg dose and not any fraction thereof. Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended. The pharmacokinetics of linezolid have been evaluated in pediatric patients from birth to 17 years of age. In general, weight-based clearance of linezolid gradually decreases with increasing age of pediatric patients. However, in preterm (gestational age <34 weeks) neonates <7 days of age, linezolid clearance is often lower than in full-term neonates <7 days of age.
Pregnancy
8.1 Pregnancy Risk Summary Available data from published and postmarketing case reports with linezolid use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered during organogenesis, linezolid did not cause malformations in mice, rats, or rabbits at maternal exposure levels approximately 6.5 times (mice), equivalent to (rats), or 0.06 times (rabbits) the clinical therapeutic exposure, based on AUCs. However, embryo-fetal lethality was observed in mice at 6.5 times the estimated human exposure. When female rats were dosed during organogenesis through lactation, postnatal survival of pups was decreased at doses approximately equivalent to the estimated human exposure based on AUCs ( see Data ). The background risk of major birth defects and miscarriage for the indicated populations 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 to 4% and 15 to 20%, respectively. Data Animal Data In mice, embryo-fetal toxicities were observed only at doses that caused maternal toxicity (clinical signs and reduced body weight gain). An oral dose of 450 mg/kg/day given from Gestation Day (GD) 6–16 (6.5 times the estimated human exposure based on AUCs) correlated with increased postimplantational embryo death, including total litter loss, decreased fetal body weights, and an increased incidence of costal cartilage fusion. Neither maternal nor embryo-fetal toxicities were observed at doses up to 150 mg/kg/day. Fetal malformations were not observed. In rats, fetal toxicity was observed at 15 and 50 mg/kg/day administered orally from GD 6–17 (exposures 0.22 times to approximately equivalent to the estimated human exposure, respectively, based on AUCs). The effects consisted of decreased fetal body weights and reduced ossification of sternebrae, a finding often seen in association with decreased fetal body weights. Fetal malformations were not observed. Maternal toxicity, in the form of reduced body weight gain, was seen at 50 mg/kg/day. In rabbits, reduced fetal body weight occurred only in the presence of maternal toxicity (clinical signs, reduced body weight gain and food consumption) when administered at an oral dose of 15 mg/kg/day given from GD 6‑20 (0.06 times the estimated human exposure based on AUCs). Fetal malformations were not observed. When female rats were treated with 50 mg/kg/day (approximately equivalent to the estimated human exposure based on AUCs) of linezolid during pregnancy and lactation (GD 6 through Lactation Day 20), survival of pups was decreased on postnatal days 1 to 4. Male and female pups permitted to mature to reproductive age, when mated, showed an increase in preimplantation loss.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of linezolid for the treatment of pediatric patients with the following infections are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from a comparator-controlled study of Gram-positive infections in pediatric patients ranging in age from birth through 11 years [ see Indications and Usage (1) , Clinical Pharmacology (12.3) and Clinical Studies (14) ]:
• nosocomial pneumonia
• complicated skin and skin structure infections
• community-acquired pneumonia (also supported by evidence from an uncontrolled study in patients ranging in age from 8 months through 12 years)
• vancomycin-resistant Enterococcus faecium infections Linezolid injection in a single-dose container should be used only in pediatric patients who require the entire 600 mg dose and not any fraction thereof. Pharmacokinetic information generated in pediatric patients with ventriculoperitoneal shunts showed variable cerebrospinal fluid (CSF) linezolid concentrations following single and multiple dosing of linezolid; therapeutic concentrations were not consistently achieved or maintained in the CSF. Therefore, the use of linezolid for the empiric treatment of pediatric patients with central nervous system infections is not recommended. The pharmacokinetics of linezolid have been evaluated in pediatric patients from birth to 17 years of age. In general, weight-based clearance of linezolid gradually decreases with increasing age of pediatric patients. However, in preterm (gestational age <34 weeks) neonates <7 days of age, linezolid clearance is often lower than in full-term neonates <7 days of age. Consequently, preterm neonates <7 days of age may need an alternative linezolid dosing regimen of 10 mg/kg every 12 hours [ see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) ]. In limited clinical experience, 5 out of 6 (83%) pediatric patients with infections due to Gram-positive pathogens with minimum inhibitory concentrations (MICs) of 4 mcg/mL treated with linezolid had clinical cures. However, pediatric patients exhibit wider variability in linezolid clearance and systemic exposure (AUC) compared with adults. In pediatric patients with a sub-optimal clinical response, particularly those with pathogens with MIC of 4 mcg/mL, lower systemic exposure, site and severity of infection, and the underlying medical condition should be considered when assessing clinical response [ see Clinical Pharmacology (12.3) and Dosage and Administration (2) ].
Geriatric use
8.5 Geriatric Use Of the 2,046 patients treated with linezolid in Phase 3 comparator-controlled clinical trials, 589 (29%) were 65 years or older and 253 (12%) were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Overdosage
In the event of overdosage, supportive care is advised, with maintenance of glomerular filtration. Hemodialysis may facilitate more rapid elimination of linezolid. In a Phase 1 clinical trial, approximately 30% of a dose of linezolid was removed during a 3-hour hemodialysis session beginning 3 hours after the dose of linezolid was administered. Data are not available for removal of linezolid with peritoneal dialysis or hemoperfusion. Clinical signs of acute toxicity in animals were decreased activity and ataxia in rats and vomiting and tremors in dogs treated with 3,000 mg/kg/day and 2,000 mg/kg/day, respectively.
Description
Linezolid injection contains linezolid, which is a synthetic antibacterial agent of the oxazolidinone class. The chemical name for linezolid is ( S )- N -[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl] methyl]-acetamide. The empirical formula is C 16 H 20 FN 3 O 4 . Its molecular weight is 337.35, and its chemical structure is represented below: Linezolid injection is supplied as a ready-to-use sterile isotonic solution for intravenous infusion. Each container contains 600 mg of linezolid in 300 mL of a clear, colorless to slightly yellow aqueous solution. Inactive ingredients include: citric acid anhydrous USP 1.92 mg/mL, sodium chloride USP 9 mg/mL, sodium hydroxide NF 0.76 mg/mL, and water for injection USP. Sodium hydroxide NF and/or hydrochloric acid NF are used to adjust the pH. The sodium (Na + ) content is 3.98 mg/mL (52 mEq/300 mL container). Chemical Structure
Mechanism of action
12.1 Mechanism of Action Linezolid is an antibacterial drug [ see Microbiology (12.4) ].
How supplied
Linezolid injection is available in a single-dose, ready-to-use flexible plastic container in a foil laminate overwrap. The container is available in the following package size: Unit of sale Concentration NDC 0409-4883-01 Case of 10 single-dose VisIV TM flexible plastic containers 600 mg/300 mL (2 mg/mL) NDC 0409-4883-10 Case of 10 single-dose freeflex ® flexible plastic containers 600 mg/300 mL (2 mg/mL) Store at 20 to 25°C (68 to 77°F), excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Protect from light. It is recommended that the containers be kept in the overwrap until ready to use. Protect containers from freezing.
Storage
Store at 20 to 25°C (68 to 77°F), excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature]. Protect from light. It is recommended that the containers be kept in the overwrap until ready to use. Protect containers from freezing.
Patient information
Important Administration Instructions Advise patients that Linezolid injection may be taken with or without food. Peripheral and Optic Neuropathy Advise patients to inform their physician if they experience changes in vision while taking Linezolid injection [ see Warnings and Precautions (5.2) ]. Serotonin Syndrome Advise patients to inform their physician if taking serotonergic agents, including serotonin reuptake inhibitors or other antidepressants and opioids. Advise patients of the increased risk of serotonin syndrome when Linezolid injection is used concomitantly with serotonergic agents [ see Warnings and Precautions (5.3) ]. Potential Interactions Producing Elevation of Blood Pressure
• Advise patients to inform their physician if they have a history of hypertension.
• Advise patients to avoid large quantities of foods or beverages with high tyramine content while taking Linezolid injection. Foods high in tyramine content include those that may have undergone protein changes by aging, fermentation, pickling, or smoking to improve flavor, such as aged cheeses, fermented or air-dried meats, sauerkraut, soy sauce, tap beers, and red wines. The tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated.
• Advise patients to inform their physician if taking medications containing pseudoephedrine HCl, such as cold remedies and decongestants [ see Warnings and Precautions (5.6) ]. Lactic Acidosis Advise patients to inform their physician if they experience repeated episodes of nausea or vomiting while receiving Linezolid injection [ see Warnings and Precautions (5.7) ]. Convulsions Advise patients to inform their physician if they have a history of seizures or convulsions [ see Warnings and Precautions (5.8) ]. Rhabdomyolysis Advise patients to inform their physician if they experience signs and symptoms of rhabdomyolysis including muscle pain, tenderness or weakness and dark urine [ see Warnings and Precautions (5.9) ]. Hypoglycemia Advise patients to inform their physician if they have diabetes mellitus. Hypoglycemic reactions, such as diaphoresis and tremulousness, along with low blood glucose measurements may occur when treated with linezolid. If such reactions occur, patients should contact a physician or other health professional for proper treatment [ see Warnings and Precautions (5.10) ]. Hyponatremia and/or SIADH Advise patients at risk for hyponatremia to inform their physician if they experience signs and symptoms of hyponatremia and/or SIADH, including confusion, somnolence, generalized weakness, and respiratory distress [ see Warnings and Precautions (5.11) ]. Antibacterial Resistance Patients should be counseled that antibacterial drugs including Linezolid injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When linezolid injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by linezolid or other antibacterial drugs in the future. Diarrhea Diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible [ see Warnings and Precautions (5.5) ]. Infertility Advise male patients that linezolid may reversibly impair fertility [ see Use in Specific Populations (8.3) ].
Label text from the FDA structured product label by Hospira, Inc. (revised Jun 19, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Linezolid in 33 products
Linezolid NDC products (33)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-8044 | Linezolid 600 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 62332-183 | Linezolid 600 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-183 | Linezolid 600 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Limited | ANDA |
| 60687-754 | Linezolid 100 mg/5mL Granule, For Suspension | American Health Packaging | ANDA |
| 60687-309 | Linezolid 600 mg/1 Tablet, Film Coated | American Health Packaging | ANDA |
| 67877-419 | Linezolid 600 mg/1 Tablet, Film Coated | Ascend Laboratories, LLC | ANDA |
| 71335-2565 | Linezolid 600 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 63629-8576 | Linezolid 600 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 31722-749 | Linezolid 600 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-865 | Linezolid 100 mg/5mL Granule, For Suspension | Camber Pharmaceuticals, Inc. | ANDA |
| 65145-181 | Linezolid 600 mg/300mL Injection, Solution | Caplin Steriles Limited | ANDA |
| 62135-442 | Linezolid 600 mg/1 Tablet | Chartwell RX, LLC | ANDA |
| 67046-1576 | Linezolid 600 mg/1 Tablet, Film Coated | Coupler LLC | ANDA |
| 55150-242 | Linezolid 600 mg/300mL Injection, Solution | Eugia US LLC | ANDA |
| 63323-713 | Linezolid 2 mg/mL Injection, Solution | Fresenius Kabi USA, LLC | ANDA |
| 0143-9534 | Linezolid 600 mg/300mL Injection, Solution | Hikma Pharmaceuticals USA Inc. | ANDA |
| 0054-0319 | Linezolid 100 mg/5mL Powder, For Suspension | Hikma Pharmaceuticals USA Inc. | ANDA |
| 66298-7131 | Linezolid 2 mg/mL Injection, Solution | Hp Halden Pharma AS | ANDA |
| 43386-022 | Linezolid 600 mg/1 Tablet | Lupin Pharmaceuticals,Inc. | ANDA |
| 33342-352 | Linezolid 600 mg/1 Tablet, Coated | Macleods Pharmaceuticals Limited | ANDA |
| 0904-6553 | Linezolid 600 mg/1 Tablet, Film Coated | Major Pharmaceuticals | ANDA |
| 66794-219 | Linezolid 600 mg/300mL Injection, Solution | Piramal Critical Care Inc | ANDA |
| 66794-236 | Linezolid 600 mg/300mL Injection | Piramal Critical Care Inc. | ANDA |
| 70518-4034 | Linezolid 600 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 64980-561 | Linezolid 600 mg/1 Tablet | Rising Pharma Holdings, Inc. | ANDA |
| 0781-3433 | Linezolid 600 mg/300mL Injection, Solution | Sandoz Inc | ANDA |
| 0781-3431 | Linezolid 200 mg/100mL Injection, Solution | Sandoz Inc | ANDA |
| 85766-231 | Linezolid 600 mg/1 Tablet, Film Coated | Sportpharm LLC | ANDA |
| 85766-075 | Linezolid 600 mg/1 Tablet | Sportpharm LLC | ANDA |
| 57664-682 | Linezolid 200 mg/100mL Injection, Solution | Sun Pharmaceutical Industries, Inc. | ANDA |
| 57664-683 | Linezolid 600 mg/300mL Injection, Solution | Sun Pharmaceutical Industries, Inc. | ANDA |
| 0409-4883 | Linezolid 2 mg/mL Injection, Solution | Hospira, Inc. | NDA |
| 59762-1308 | Linezolid 100 mg/5mL Suspension | Mylan Pharmaceuticals Inc. | NDA AUTHORIZED GENERIC |
Linezolid recalls
- D-0703-2018 May 9, 2018 · Class II · Terminated
Lack of Assurance of Sterility; confirmed customer report of a leaking bags and mold found between the outer bag and the overwrap - D-0337-2018 Feb 14, 2018 · Class I · Terminated
Presence of Particulate Matter; white particulate matter identified as mold was found in one bag
Frequently asked questions
What is Linezolid used for?
Linezolid injection is an oxazolidinone-class antibacterial indicated in adults and children for the treatment of the following infections caused by susceptible Gram-positive bacteria: Nosocomial pneumonia ( 1.1 ); Community-acquired pneumonia ( 1.2 ); Complicated skin and skin structure infections, including diabetic foot infections, without concomitant osteomyelitis ( 1.3 );…
What are the side effects of Linezolid?
The following clinically significant adverse reactions are described elsewhere in the labeling: • Myelosuppression [ see Warnings and Precautions (5.1) ] • Peripheral and Optic Neuropathy [ see Warnings and Precautions (5.2) ] • Serotonin Syndrome [ see Warnings and Precautions (5.3) ] • Clostridioides difficile -Associated Diarrhea [ see Warnings and Precautions (5.5) ] • Lactic Acidosis [ see… See the full label for the complete list.
Who makes Linezolid?
Linezolid is listed by 26 labelers in the FDA NDC directory, including A-S Medication Solutions, Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, American Health Packaging.
Has Linezolid been recalled?
The FDA enforcement database lists 2 recalls for Linezolid, most recently D-0703-2018 (class ii): Lack of Assurance of Sterility; confirmed customer report of a leaking bags and mold found between the outer bag and the overwrap