Linezolid 100 mg/5mL Granule, For Suspension — NDC 31722-865-25 (Billing 31722-0865-25)
This is a package of Linezolid 100 mg/5mL Granule, For Suspension from Camber Pharmaceuticals, Inc., marketed since Oct 2022 and currently FDA-listed; retail pharmacies pay about $2.74 per mL (NADAC). It is this product's only package size.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 045132
- GCN: 26871
- GPI-14 (Medi-Span): 16230040001920
- HICL (First Databank): 021157
- AHFS class code: 08:12.28.24
- RxCUI (RxNorm): 311345
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Oxazolidinone Antibacterial class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It treats certain bacterial infections caused by Gram-positive bacteria. These include hospital- and community-acquired pneumonia, skin infections, and vancomycin-resistant Enteroc...
- Take it exactly as prescribed, usually every 8 or 12 hours, by mouth or through a vein. You can take it with or without food. Finish the full course your prescriber gave you.
- Diarrhea, nausea, vomiting and headache are the most common. Dizziness, rash and taste changes also happen. Call your doctor if they are severe or don’t go away.
- Call for blurred vision or color changes, numbness or tingling, severe diarrhea, repeated vomiting, seizures, or unusual bleeding. Also call for high fever, stiff muscles, agitatio...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Linezolid — tap one for details:
Linezolid may be associated with lower levels of 7 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2.736 | $410.37 / 150 ml |
| Medicaid paysCMS SDUD · 12 mo | $2.13 | $318.93 / 150 ml |
| Medicare drug plans payPart D · Q2 2026 | $2.68 | $401.39 / 150 ml |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 31722-0865-25 You're viewing this Main listing | 1 BOTTLE, GLASS in 1 CARTON / 150 mL in 1 BOTTLE, GLASS | 2022-10-31 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Linezolid 100 mg/5mL 00054-0319-50 | Hikma | 150 ml | $2.736 | AB | Availability likely | — |
| Linezolid 100 mg/5mLthis 31722-0865-25 | Camber | 1 bottle | $2.736 | AB | Availability likely | — |
| Linezolid 100 mg/5mL 60687-0754-05 | American | 1 bottle | $2.736 | AB | Availability likely | — |
| Zyvox 100 mg/5mL 00009-5136-01 | Pharmacia | 150 ml | — | AB | Discontinued | — |
| Linezolid 100 mg/5mL 59762-1308-01 | Mylan | 150 ml | — | AB | Discontinued | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Linezolid for oral suspension 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 ); Uncomplicated skin and skin structure infections ( 1.4 ); Vancomycin-resistant Enterococcus faecium infections.
( 1.5 ) Limitations of Use ( 1.6 ): • Linezolid for oral suspension 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 formulations and other antibacterial drugs, linezolid should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
( 1.7 )
1.1Nosocomial Pneumonia Linezolid for oral suspension is indicated for the treatment of nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates) or Streptococcus pneumoniae [ see Clinical Studies (14) ].
1.2Community-acquired Pneumonia Linezolid for oral suspension 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) ].
1.3Complicated Skin and Skin Structure Infections Linezolid for oral suspension 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 for oral suspension has not been studied in the treatment of decubitus ulcers [ see Clinical Studies (14) ].
1.4Uncomplicated Skin and Skin Structure Infections Linezolid for oral suspension is indicated for the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes [ see Clinical Studies (14) ].
1.5Vancomycin-resistant Enterococcus faecium Infections Linezolid for oral suspension is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia [ see Clinical Studies (14) ].
1.6Limitations of Use Linezolid for oral suspension 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 for oral suspension formulations given for longer than 28 days have not been evaluated in controlled clinical trials [ see Clinical Studies (14) ].
1.7Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of linezolid for oral suspension and other antibacterial drugs, linezolid for oral suspension 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 ▾
2 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 10 mg/kg intravenous or oral every 8 hours 600 mg intravenous or oral 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 intravenous or oral every 8 hours 600 mg intravenous or oral every 12 hours 14 to 28 Uncomplicated skin and skin structure infections less than 5 yrs: 10 mg/kg oral every 8 hours 5 to 11 yrs: 10 mg/kg oral every 12 hours Adults: 400 mg oral every 12 hours Adolescents: 600 mg oral every 12 hours 10 to 14
2.1General Dosage and Administration The recommended dosage for linezolid formulations for the treatment of infections is described in Table 1. Table 1. Dosage Guidelines for Linezolid for Oral Suspension Infection * Dosage, Route and Frequency of Administration Recommended Duration of Treatment (consecutive days) Pediatric Patients † (Birth through 11 Years of Age) Adults and Adolescents (12 Years and Older) Nosocomial pneumonia 10 mg/kg intravenously or oral ‡ every 8 hours 600 mg intravenously or oral ‡ 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 or oral ‡ every 8 hours 600 mg intravenously or oral ‡ every 12 hours 14 to 28 Uncomplicated skin and skin structure infections less than 5 yrs: 10 mg/kg oral ‡ every 8 hours 5 to 11 yrs: 10 mg/kg oral ‡ every 12 hours Adults: 400 mg oral‡ every 12 hours Adolescents: 600 mg oral ‡ every 12 hours 10 to 14 * Due to the designated pathogens [ see Indications and Usage (1) ] † 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) ]. ‡ Oral dosing using either linezolid tablets or linezolid for oral suspension [ see How Supplied/Storage and Handling (16) ].
No dose adjustment is necessary when switching from intravenous to oral administration.
2.5Constitution of Oral Suspension Linezolid for oral suspension is supplied as a powder/granule for constitution. Gently tap bottle to loosen powder. Add a total of 123 mL distilled water in two portions.
After adding the first half, shake vigorously to wet all of the powder. Then add the second half of the water and shake vigorously to obtain a uniform suspension. After constitution, each 5 mL of the suspension contains 100 mg of linezolid.
Before using, gently mix by inverting the bottle 3 to 5 times. Do not shake . Store constituted suspension at room temperature.
Use within 21 days after constitution.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Linezolid for oral suspension: White or off white to brown granule/powder. When constituted as directed, each bottle will contain 150 mL of a suspension providing the equivalent of 100 mg of linezolid per each 5 mL. • For oral suspension: 100 mg of linezolid per each 5 mL. ( 3 )
⛔ Contraindications ▾
4 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 )
4.1Hypersensitivity Linezolid formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components .
4.2Monoamine 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 Cautions ▾
5 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 serotonergic agents, including antidepressants and opioids, for signs of serotonin syndrome.
Patients taking serotonergic antidepressants should receive linezolid for oral suspension only if no other therapies are available. Discontinue serotonergic antidepressants and monitor patients for signs and symptoms of both serotonin syndrome and antidepressant discontinuation. ( 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 ) Hypoglycemia: Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents.
( 5.9 ) Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): Monitor serum sodium levels regularly in patients at risk of hyponatremia and/or SIADH. ( 5.10 ) Phenylketonuria: Linezolid for oral suspension contains phenylalanine which can be harmful to patients with phenylketonuria. ( 5.11 )
5.1Myelosuppression 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.Completeblood 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 )].
5.2Peripheral 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 for extended periods (≥ 3 months) and in all patients reporting new visual symptoms regardless of length of therapy with linezolid.
If peripheral or optic neuropathy occurs, the continued use of linezolid in these patients should be weighed against the potential risks.
5.3Serotonin Syndrome Spontaneous reports of serotonin syndrome including fatal cases associated… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (>5% of adult and/or pediatric patients treated with linezolid) include: diarrhea, vomiting, headache, nausea, and anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Private Limited at 1-886-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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. Of the patients treated for uncomplicated skin and skin structure infections (uSSSIs), 25.4% of linezolid -treated and 19.6% of comparator-treated patients experienced at least one drug-related adverse event.
For all other 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 (%) of Treatment–Emergent Adverse Reactions Occurring in >1% of Adult Patients Treated with Linezolid in Comparator-Controlled Clinical Trials ADVERSE REACTIONS Uncomplicated Skin and Skin Structure Infections All Other Indications Linezolid 400 mg by mouth every 12 hours (n=548) Clarithromycin 250 mg by mouth every 12 hours (n=537) Linezolid 600 mg every 12 hours (n=1498) All Other Comparators * (n=1464) Headache 8.8 8.4 5.7
4.4Diarrhea 8.2 6.1 8.3
6.4Nausea 5.1 4.5 6.6
4.6Vomiting 2 1.5 4.3
2.3Dizziness 2.6 3 1.8
1.5Rash 1.1 1.1 2.3
2.6Anemia 0.4 0 2.1
1.4Taste alteration 1.8 2 1
0.3Vaginal moniliasis 1.8 1.3 1.1
0.5Oral moniliasis 0.5 0 1.7 1 Abnormal liver function tests 0.4 0.2 1.6
0.8Fungal infection 1.5 0.2 0.3
0.2Tongue discoloration 1.3 0 0.3 0 Localized abdominal pain 1.3 0.6 1.2
0.8Generalized abdominal pain 0.9 0.4 1.2 1 * 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. Of the patients treated for uSSSIs, 3.5% of linezolid -treated and 2.4% of comparator-treated patients discontinued treatment due to drug-related adverse events. For all other indications, 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% (13/215) in the linezolid arm and 3 % (3/101) in the vancomycin arm. However, given the severe underlying illness in the patient population, no causality could be established. Of the pediatric patients treated for uSSSIs, 19.2% of linezolid-treated and 14.1% of comparator-treated patients experienced at least one drug-related adverse event.
For all other 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-caus… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Monoamine oxidase inhibitors and potential for interaction with adrenergic and serotonergic agents. ( 4.2 , 5.3 , 5.6 , 7 , 12.3 )
7.1Monoamine Oxidase Inhibitors Linezolid is a reversible, nonselective inhibitor of monoamine oxidase [ see Contraindications (4.2) and Clinical Pharmacology (12.3) ].
7.2Adrenergic 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 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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 to 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 to 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 to 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.
8.2Lactation 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.
8.3Females and Males of R… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy 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 to 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 to 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 to 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 ▾
8.4Pediatric 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 The safety and effectiveness of linezolid for the treatment of pediatric patients with the following infection have been established in a comparator-controlled study in pediatric patients ranging in age from 5 through 17 years [ see Clinical Studies (14) ]: uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes 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 ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Linezolid is an antibacterial drug [see Microbiology (12.4) ].
12.2Pharmacodynamics In a randomized, positive- and placebo-controlled crossover thorough QT study, 40 healthy subjects were administered a single linezolid 600 mg dose via a 1 hour IV infusion, a single linezolid 1,200 mg dose via a 1 hour IV infusion, placebo, and a single oral dose of positive control. At both the 600 mg and 1,200 mg linezolid doses, no significant effect on QTc interval was detected at peak plasma concentration or at any other time.
12.3Pharmacokinetics The mean pharmacokinetic parameters of linezolid in adults after single and multiple oral and intravenous doses are summarized in Table 8. Plasma concentrations of linezolid at steady-state after oral doses of 600 mg given every 12 hours are shown in Figure 1. Table 8.
Mean (Standard Deviation) Pharmacokinetic Parameters of Linezolid in Adults Dose of Linezolid C max mcg/mL C min mcg/mL T max hrs AUC * mcg•h/mL t 1/2 hrs CL mL/min 400 mg tablet single dose † every 12 hours 8.10 (1.83) 11 (4.37) --- 3.08 (2.25) 1.52 (1.01) 1.12 (0.47) 55.10 (25) 73.40 (33.50) 5.20 (1.50) 4.69 (1.70) 146 (67) 110 (49) 600 mg tablet single dose every 12 hours 12.70 (3.96) 21.20 (5.78) --- 6.15 (2.94) 1.28 (0.66) 1.03 (0.62) 91.40 (39.30) 138 (42.10) 4.26 (1.65) 5.40 (2.06) 127 (48) 80 (29) 600 mg IV injection ‡ single dose every 12 hours 12.90 (1.60) 15.10 (2.52) --- 3.68 (2.36) 0.50 (0.10) 0.51 (0.03) 80.20 (33.30) 89.70 (31) 4.40 (2.40) 4.80 (1.70) 138 (39) 123 (40) 600 mg oral suspension single dose 11 (2.76) --- 0.97 (0.88) 80.80 (35.10) 4.60 (1.71) 141 (45) * AUC for single dose = AUC 0 to ∞ ; for multiple dose = AUC 0 to Ʈ † Data dose-normalized from 375 mg ‡ Data dose-normalized from 625 mg, intravenous dose was given as 0.5-hour infusion.
C max = Maximum plasma concentration; C min = Minimum plasma concentration; T max = Time to C max ; AUC = Area under concentration-time curve; t 1/2 = Elimination half-life; CL = Systemic clearance Figure 1. Plasma Concentrations of Linezolid in Adults at Steady-State Following Oral Dosing Every 12 Hours (Mean ± Standard Deviation, n=16) Absorption Linezolid is extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
Therefore, linezolid may be given orally or intravenously without dose adjustment. Linezolid may be administered without regard to the timing of meals. The time to reach the maximum concentration is delayed from 1.5 hours to 2.2 hours and C max is decreased by about 17% when high fat food is given with linezolid.
However, the total exposure measured as AUC 0 to ∞ is similar under both conditions. Distribution Animal and human pharmacokinetic studies have demonstrated that linezolid readily distributes to well-perfused tissues. The plasma protein binding of linezolid is approximately 31% and is concentration-independent.
The volume of distribution of linezolid at steady-state averaged 40 to 50 liters in healthy adult volunteers. Linezolid concentrations have been determined in various fluids from a limited number of subjects in Phase 1 volunteer studies following multiple dosing of linezolid. The ratio of linezolid in saliva relative to plasma was 1.2 to 1 and the ratio of linezolid in sweat relative to plasma was 0.55 to 1.
Metabolism Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite (B). Formation of metabolite A is presumed to be formed via an enzymatic pathway whereas metabolite B is mediated by a non-enzymatic chemical oxidation mechanism in vitro . In vitro studies have demonstrated that linezolid is minimally metabolized and may be mediated by human cytochrome P450.
However, the metabolic pathway of linezolid i… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Linezolid is an antibacterial drug [see Microbiology (12.4) ].
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.3Oral Suspension Linezolid for oral suspension is available as a dry, white or off-white to brown granule/powder. When constituted as directed, each bottle will contain 150 mL of a suspension providing the equivalent of 100 mg of linezolid per each 5 mL. Linezolid for oral suspension is supplied as follows: 100 mg/5 mL in 250 mL glass bottles NDC 31722-865-25
16.4Storage and Handling Store at 25ºC (77ºF); excursions permitted to 15 to 30ºC (59 to 86ºF) [see USP Controlled Room Temperature]. Protect from light. Keep bottles tightly closed to protect from moisture.
📋 Description ▾
11 DESCRIPTION Linezolid for oral suspension contain linezolid USP, 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 for oral suspension is supplied as white or off white to brown granule/powder for constitution into a suspension for oral administration. Following constitution, each 5 mL contains 100 mg of linezolid. Inactive ingredients are anhydrous citric acid powder, aspartame, carboxymethylcellulose sodium, colloidal silicon dioxide, glycyrrhizinate ammonium, hypromellose, mannitol, microcrystalline cellulose, sodium benzoate, sodium chloride, sucrose, trisodium citrate dihydrate, xanthan gum, and flavors [ see Patient Counseling Information (17) ].
The sodium (Na + ) content is 8.18 mg/5 mL. Linezolidstructure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Important Administration Instructions Advise patients that linezolid for oral suspension 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 for oral suspension [ see Warnings and Precautions (5.2) ] . Serotonin Syndrome Advise patients to inform their physician if taking serotonergic agents, including serotonin re-uptake inhibitors or other antidepressants and opioids [ 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 for oral suspension. 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 or phenylpropanolamine 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 for oral suspension [ 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) ]. 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 (5.9) ] . 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 (5.10) ]. Phenylketonuria Advise patients with phenylketonuria (PKU) that each 5 mL of the 100 mg/5 mL linezolid for oral suspension contains 20 mg phenylalanine.
The other linezolid for oral suspension formulations do not contain phenylalanine. Phenylalanine can be harmful to patients with phenylketonuria. Contact your physician or pharmacist when prescribed with linezolid for oral suspension [ see Warnings and Precautions (5.11) ].
Antibacterial Resistance Patients should be counseled that antibacterial drugs including linezolid for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When linezolid for oral suspension 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 for oral suspension 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 occur… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics The mean pharmacokinetic parameters of linezolid in adults after single and multiple oral and intravenous doses are summarized in Table 8. Plasma concentrations of linezolid at steady-state after oral doses of 600 mg given every 12 hours are shown in Figure 1. Table 8.
Mean (Standard Deviation) Pharmacokinetic Parameters of Linezolid in Adults Dose of Linezolid C max mcg/mL C min mcg/mL T max hrs AUC * mcg•h/mL t 1/2 hrs CL mL/min 400 mg tablet single dose † every 12 hours 8.10 (1.83) 11 (4.37) --- 3.08 (2.25) 1.52 (1.01) 1.12 (0.47) 55.10 (25) 73.40 (33.50) 5.20 (1.50) 4.69 (1.70) 146 (67) 110 (49) 600 mg tablet single dose every 12 hours 12.70 (3.96) 21.20 (5.78) --- 6.15 (2.94) 1.28 (0.66) 1.03 (0.62) 91.40 (39.30) 138 (42.10) 4.26 (1.65) 5.40 (2.06) 127 (48) 80 (29) 600 mg IV injection ‡ single dose every 12 hours 12.90 (1.60) 15.10 (2.52) --- 3.68 (2.36) 0.50 (0.10) 0.51 (0.03) 80.20 (33.30) 89.70 (31) 4.40 (2.40) 4.80 (1.70) 138 (39) 123 (40) 600 mg oral suspension single dose 11 (2.76) --- 0.97 (0.88) 80.80 (35.10) 4.60 (1.71) 141 (45) * AUC for single dose = AUC 0 to ∞ ; for multiple dose = AUC 0 to Ʈ † Data dose-normalized from 375 mg ‡ Data dose-normalized from 625 mg, intravenous dose was given as 0.5-hour infusion.
C max = Maximum plasma concentration; C min = Minimum plasma concentration; T max = Time to C max ; AUC = Area under concentration-time curve; t 1/2 = Elimination half-life; CL = Systemic clearance Figure 1. Plasma Concentrations of Linezolid in Adults at Steady-State Following Oral Dosing Every 12 Hours (Mean ± Standard Deviation, n=16) Absorption Linezolid is extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
Therefore, linezolid may be given orally or intravenously without dose adjustment. Linezolid may be administered without regard to the timing of meals. The time to reach the maximum concentration is delayed from 1.5 hours to 2.2 hours and C max is decreased by about 17% when high fat food is given with linezolid.
However, the total exposure measured as AUC 0 to ∞ is similar under both conditions. Distribution Animal and human pharmacokinetic studies have demonstrated that linezolid readily distributes to well-perfused tissues. The plasma protein binding of linezolid is approximately 31% and is concentration-independent.
The volume of distribution of linezolid at steady-state averaged 40 to 50 liters in healthy adult volunteers. Linezolid concentrations have been determined in various fluids from a limited number of subjects in Phase 1 volunteer studies following multiple dosing of linezolid. The ratio of linezolid in saliva relative to plasma was 1.2 to 1 and the ratio of linezolid in sweat relative to plasma was 0.55 to 1.
Metabolism Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite (B). Formation of metabolite A is presumed to be formed via an enzymatic pathway whereas metabolite B is mediated by a non-enzymatic chemical oxidation mechanism in vitro . In vitro studies have demonstrated that linezolid is minimally metabolized and may be mediated by human cytochrome P450.
However, the metabolic pathway of linezolid is not fully understood. Excretion Nonrenal clearance accounts for approximately 65% of the total clearance of linezolid. Under steady-state conditions, approximately 30% of the dose appears in the urine as linezolid, 40% as metabolite B, and 10% as metabolite A.
The mean renal clearance of linezolid is 40 mL/min which suggests net tubular reabsorption. Virtually no linezolid appears in the feces, while approximately 6% of the dose appears in the feces as metabolite B, and 3% as metabolite A. A small degree of nonlinearity in clearance was observed with increasing do… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics In a randomized, positive- and placebo-controlled crossover thorough QT study, 40 healthy subjects were administered a single linezolid 600 mg dose via a 1 hour IV infusion, a single linezolid 1,200 mg dose via a 1 hour IV infusion, placebo, and a single oral dose of positive control. At both the 600 mg and 1,200 mg linezolid doses, no significant effect on QTc interval was detected at peak plasma concentration or at any other time.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Adults Nosocomial Pneumonia Adult patients with clinically and radiologically documented nosocomial pneumonia were enrolled in a randomized, multi-center, double-blind trial. Patients were treated for 7 to 21 days. One group received ZYVOX I.V.
Injection 600 mg every 12 hours, and the other group received vancomycin 1 g every 12 hours intravenously. Both groups received concomitant aztreonam (1 to 2 g every 8 hours intravenously), which could be continued if clinically indicated. There were 203 linezolid-treated and 193 vancomycin-treated patients enrolled in the study.
One hundred twenty-two (60%) linezolid-treated patients and 103 (53%) vancomycin-treated patients were clinically evaluable. The cure rates in clinically evaluable patients were 57% for linezolid-treated patients and 60% for vancomycin-treated patients. The cure rates in clinically evaluable patients with ventilator-associated pneumonia were 47% for linezolid-treated patients and 40% for vancomycin-treated patients.
A modified intent-to-treat (MITT) analysis of 94 linezolid-treated patients and 83 vancomycin-treated patients included subjects who had a pathogen isolated before treatment. The cure rates in the MITT analysis were 57% in linezolid-treated patients and 46% in vancomycin-treated patients. The cure rates by pathogen for microbiologically evaluable patients are presented in Table 12.
Table 12. Cure Rates at the Test-of-Cure Visit for Microbiologically Evaluable Adult Patients with Nosocomial Pneumonia Pathogen Cured Linezolid n/N (%) Vancomycin n/N (%) Staphylococcus aureus 23/38 (61) 14/23 (61) Methicillin-resistant S. aureus 13/22 (59) 7/10 (70) Streptococcus pneumoniae 9/9 (100) 9/10 (90) Complicated Skin and Skin Structure Infections Adult patients with clinically documented complicated skin and skin structure infections were enrolled in a randomized, multi-center, double-blind, double-dummy trial comparing study medications administered intravenously followed by medications given orally for a total of 10 to 21 days of treatment.
One group of patients received linezolid I.V. Injection 600 mg every 12 hours followed by linezolid Tablets 600 mg every 12 hours; the other group received oxacillin 2 g every 6 hours intravenously followed by dicloxacillin 500 mg every 6 hours orally. Patients could receive concomitant aztreonam if clinically indicated.
There were 400 linezolid-treated and 419 oxacillin-treated patients enrolled in the study. Two hundred forty-five (61%) linezolid-treated patients and 242 (58%) oxacillin-treated patients were clinically evaluable. The cure rates in clinically evaluable patients were 90% in linezolid-treated patients and 85% in oxacillin-treated patients.
A modified intent-to-treat (MITT) analysis of 316 linezolid-treated patients and 313 oxacillin-treated patients included subjects who met all criteria for study entry. The cure rates in the MITT analysis were 86% in linezolid-treated patients and 82% in oxacillin-treated patients. The cure rates by pathogen for microbiologically evaluable patients are presented in Table 13.
Table 13. Cure Rates at the Test-of-Cure Visit for Microbiologically Evaluable Adult Patients with Complicated Skin and Skin Structure Infections Pathogen Cured Linezolid n/N (%) Oxacillin/Dicloxacillin n/N (%) Staphylococcus aureus 73/83 (88) 72/84 (86) Methicillin-resistant S. aureus 2/3 (67) 0/0 (-) Streptococcus agalactiae 6/6 (100) 3/6 (50) Streptococcus pyogenes 18/26 (69) 21/28 (75) A separate study provided additional experience with the use of linezolid in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections.
This was a randomized, open-label trial in hospitalized adult patients with documented or suspected MRSA infection. One group of patients received linezolid I.V. Injection 600 mg every 12 hours followed by linezolid Tablets 600 mg every 12 hours.
The other group of patients received vancomycin 1 g every 12 hours intravenously. Both group… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Lifetime studies in animals have not been conducted to evaluate the carcinogenic potential of linezolid. Neither mutagenic nor clastogenic potential was found in a battery of tests including: assays for mutagenicity (Ames bacterial reversion and CHO cell mutation), an in vitro unscheduled DNA synthesis (UDS) assay, an in vitro chromosome aberration assay in human lymphocytes, and an in vivo mouse micronucleus assay. Linezolid did not affect the fertility or reproductive performance of adult female rats given oral doses of up to 100 mg/kg/day for 14 days prior to mating through Gestation Day 7.
It reversibly decreased fertility and reproductive performance in adult male rats when given at doses ≥ 50 mg/kg/day, with exposures approximately equal to or greater than the expected human exposure level (exposure comparisons are based on AUCs). The reversible fertility effects were mediated through altered spermatogenesis. Affected spermatids contained abnormally formed and oriented mitochondria and were non-viable.
Epithelial cell hypertrophy and hyperplasia in the epididymis was observed in conjunction with decreased fertility. Similar epididymal changes were not seen in dogs. In sexually mature male rats exposed to drug as juveniles, mildly decreased fertility was observed following treatment with linezolid through most of their period of sexual development (50 mg/kg/day from days 7 to 36 of age, and 100 mg/kg/day from days 37 to 55 of age), with exposures up to 1.7 times greater than mean AUCs observed in pediatric patients aged 3 months to 11 years.
Decreased fertility was not observed with shorter treatment periods, corresponding to exposure in utero through the early neonatal period (gestation day 6 through postnatal day 5), neonatal exposure (postnatal days 5 to 21), or to juvenile exposure (postnatal days 22 to 35). Reversible reductions in sperm motility and altered sperm morphology were observed in rats treated from postnatal day 22 to 35.
13.2Animal Toxicology and/or Pharmacology Target organs of linezolid toxicity were similar in juvenile and adult rats and dogs. Dose- and time-dependent myelosuppression, as evidenced by bone marrow hypocellularity/decreased hematopoiesis, decreased extramedullary hematopoiesis in spleen and liver, and decreased levels of circulating erythrocytes, leukocytes, and platelets have been seen in animal studies. Lymphoid depletion occurred in thymus, lymph nodes, and spleen.
Generally, the lymphoid findings were associated with anorexia, weight loss, and suppression of body weight gain, which may have contributed to the observed effects. In rats administered linezolid orally for 6 months, non-reversible, minimal to mild axonal degeneration of sciatic nerves was observed at 80 mg/kg/day; minimal degeneration of the sciatic nerve was also observed in 1 male at this dose level at a 3-month interim necropsy. Sensitive morphologic evaluation of perfusion-fixed tissues was conducted to investigate evidence of optic nerve degeneration.
Minimal to moderate optic nerve degeneration was evident in 2 male rats after 6 months of dosing, but the direct relationship to drug was equivocal because of the acute nature of the finding and its asymmetrical distribution. The nerve degeneration observed was microscopically comparable to spontaneous unilateral optic nerve degeneration reported in aging rats and may be an exacerbation of common background change. These effects were observed at exposure levels that are comparable to those observed in some human subjects.
The hematopoietic and lymphoid effects were reversible, although in some studies, reversal was incomplete within the duration of the recovery period.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Lifetime studies in animals have not been conducted to evaluate the carcinogenic potential of linezolid. Neither mutagenic nor clastogenic potential was found in a battery of tests including: assays for mutagenicity (Ames bacterial reversion and CHO cell mutation), an in vitro unscheduled DNA synthesis (UDS) assay, an in vitro chromosome aberration assay in human lymphocytes, and an in vivo mouse micronucleus assay. Linezolid did not affect the fertility or reproductive performance of adult female rats given oral doses of up to 100 mg/kg/day for 14 days prior to mating through Gestation Day 7.
It reversibly decreased fertility and reproductive performance in adult male rats when given at doses ≥ 50 mg/kg/day, with exposures approximately equal to or greater than the expected human exposure level (exposure comparisons are based on AUCs). The reversible fertility effects were mediated through altered spermatogenesis. Affected spermatids contained abnormally formed and oriented mitochondria and were non-viable.
Epithelial cell hypertrophy and hyperplasia in the epididymis was observed in conjunction with decreased fertility. Similar epididymal changes were not seen in dogs. In sexually mature male rats exposed to drug as juveniles, mildly decreased fertility was observed following treatment with linezolid through most of their period of sexual development (50 mg/kg/day from days 7 to 36 of age, and 100 mg/kg/day from days 37 to 55 of age), with exposures up to 1.7 times greater than mean AUCs observed in pediatric patients aged 3 months to 11 years.
Decreased fertility was not observed with shorter treatment periods, corresponding to exposure in utero through the early neonatal period (gestation day 6 through postnatal day 5), neonatal exposure (postnatal days 5 to 21), or to juvenile exposure (postnatal days 22 to 35). Reversible reductions in sperm motility and altered sperm morphology were observed in rats treated from postnatal day 22 to 35.
📄 Recent Major Changes ▾
Warnings and Precautions, Myelosuppression (5.1) 7/2023
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Linezolid for Oral suspension 150 mL Container label Linezolid for Oral suspension 150 mL Container Carton linezolid-cntr-label linezolid-carton-label