Does Zyvox (linezolid) cause side effects?

Zyvox (linezolid) is a synthetic antibiotic effective against bacteria such as Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and others. It is effective against Staphylococcus aureus isolates that are resistant to other antibiotics. 

Zyvox prevents bacteria from growing by interfering with their ability to make proteins. Because proteins are made differently in people and bacteria, Zyvox does not interfere with production of proteins in humans.

Zyvox is used to treat nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant isolates) or Streptococcus pneumoniae community-acquired pneumonia caused by Streptococcus pneumoniae, or Staphylococcus aureus (methicillin-susceptible isolates only), complicated and uncomplicated skin and skin structure infections such as diabetic foot infections, and vancomycin-resistant Enterococcus faecium infections.

Common side effects of Zyvox include

Serious side effects of Zyvox include

Drug interactions of Zyvox include monoamine oxidase inhibitors (MAOI) because Zyvox blocks the breakdown of compounds that are normally broken down by monoamine oxidase enzymes, which increases the levels of these compounds in the body and can increase the risk of side effects. 

Zyvox should not be combined with antidepressants such as paroxetine, fluoxetine, amitriptyline, nortriptyline, bupropion; pain medications like methadone, tramadol, and meperidine; dextromethorphan, St. John's wort, cyclobenzaprine, and mirtazapine. Such combinations lead to high serotonin levels, which may cause confusion, high blood pressure, tremor, hyperactivity, coma, and death. 

Zyvox should not be combined with pseudoephedrine, phenylephrine, ephedrine, and phenylpropanolamine because the combination can cause an acute hypertensive episode. 

Monoamine oxidase also breaks down tyramine, a chemical present in aged cheese, wines, and other aged foods. Since Zyvox inhibits monoamine oxidase, it decreases the breakdown of tyramine from ingested food, thus increasing the level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a hypertensive crisis. 

Patients treated with MAOIs and Zyvox should adhere to recommended dietary modifications that reduce the intake of tyramine. 

Zyvox has not been adequately studied in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

It is unknown if Zyvox is excreted in breast milk. Consult your doctor before breastfeeding.

What are the important side effects of Zyvox (linezolid)?

Common side effects of linezolid include:

Other possible side effects of linezolid include:

Possible serious side effects of linezolid include:

Cases of hypoglycemia have been reported during treatment with linezolid in patients with diabetes who are receiving insulin or oral hypoglycemic medications.

People who are taking drugs that may increase blood pressure should not receive linezolid or should be monitored closely for potential increases in blood pressure.

Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections since more people in the linezolid treated groups died in an investigational study of patients with these catheter-related bloodstream infections.

Like other antibiotics, linezolid may cause Clostridium difficile associated diarrhea or colitis.

Linezolid may suppress the bone marrow. Therefore, complete blood cell counts should be obtained weekly and discontinuation of treatment should be considered in patients who develop or have worsening bone marrow suppression.

Peripheral and optic neuropathy may occur, most often in patients treated for longer than 28 days. Patients who experience visual impairment should be evaluated immediately.

To reduce the risk of serotonin syndrome patients taking serotonergic antidepressants should only receive linezolid if other options are not available.

Zyvox (linezolid) side effects list for healthcare professionals

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 Zyvox 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 Zyvox-treated and 19.6% of comparator-treated patients experienced at least one drug-related adverse event. For all other indications, 20.4% of Zyvox -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 Zyvox.

Table 2: Incidence (%) of Treatment-Emergent Adverse Reactions Occurring in >1% of Adult Patients Treated with Zyvox in Comparator-Controlled Clinical Trials

ADVERSE REACTIONSUncomplicated Skin and Skin Structure InfectionsAll Other Indications
Zyvox 400 mg by mouth every 12 hours
(n=548)
Clarithromycin 250 mg by mouth every 12 hours
(n=537)
Zyvox 600 mg every 12 hours
(n=1498)
All Other Comparators*
(n=1464)
Headache8.88.45.74.4
Diarrhea8.26.18.36.4
Nausea5.14.56.64.6
Vomiting2.01.54.32.3
Dizziness2.63.01.81.5
Rash1.11.12.32.6
Anemia0.402.11.4
Taste alteration1.82.01.00.3
Vaginal moniliasis1.81.31.10.5
Oral moniliasis0.501.71.0
Abnormal liver function tests0.40.21.60.8
Fungal infection1.50.20.30.2
Tongue discoloration1.300.30
Localized abdominal pain1.30.61.20.8
Generalized abdominal pain0.90.41.21.0
* 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 Zyvox-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 Zyvox-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 Zyvox 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.

Of the pediatric patients treated for uSSSIs, 19.2% of Zyvox-treated and 14.1% of comparator-treated patients experienced at least one drug-related adverse event. For all other indications, 18.8% of Zyvox-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 > 1% of Pediatric Patients (and >1 Patient) in Either Treatment Group in Comparator-Controlled Clinical Trials

ADVERSE REACTIONSUncomplicated Skin and Skin Structure Infections*All Other Indications†,
Zyvox
(n=248)
Cefadroxil
(n=251)
Zyvox
(n=215)
Vancomycin
(n=101)
Diarrhea7.88.010.812.1
Vomiting2.96.49.49.1
Headache6.54.00.90
Anemia005.67.1
Thrombocytopenia004.72.0
Nausea3.73.21.90
Generalized abdominal pain2.42.80.92.0
Localized abdominal pain2.42.80.51.0
Loose stools1.60.82.33.0
Eosinophilia0.40.81.91.0
Pruritus at non-application site0.80.41.42.0
Vertigo1.20.400
* Patients 5 through 11 years of age received Zyvox 10 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received Zyvox 600 mg by mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours.
† Patients from birth through 11 years of age received Zyvox 10 mg/kg intravenously by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6-24 hours, depending on age and renal clearance.

Of the pediatric patients treated for uSSSIs, 1.6% of Zyvox-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 0.9% of Zyvox-treated and 6.1% of comparator-treated patients.

Laboratory Abnormalities

  • Zyvox 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 Zyvox 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 Zyvox 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 Zyvox and 0.4% with cefadroxil.
  • Thrombocytopenia associated with the use of Zyvox appears to be dependent on duration of therapy (generally greater than 2 weeks of treatment).
  • The platelet counts for most patients returned to the normal range/baseline during the follow-up period.
  • No related clinical adverse events were identified in Phase 3 clinical trials in patients developing thrombocytopenia.
  • Bleeding events were identified in thrombocytopenic patients in a compassionate use program for Zyvox; the role of linezolid in these events cannot be determined.
  • Changes seen in other laboratory parameters, without regard to drug relationship, revealed no substantial differences between Zyvox and the comparators.
  • These changes were generally not clinically significant, did not lead to discontinuation of therapy, and were reversible.
  • The incidence of adult and pediatric patients with at least one substantially abnormal hematologic or serum chemistry value is presented in Tables 4, 5, 6, and 7.

Table 4: Percent of Adult Patients who Experienced at Least One Substantially Abnormal* Hematology Laboratory Value in Comparator-Controlled Clinical Trials with Zyvox

Laboratory AssayUncomplicated Skin and Skin Structure InfectionsAll Other Indications
Zyvox 400 mg every 12 hoursClarithromycin 250 mg every 12 hoursZyvox 600 mg every 12 hoursAll Other Comparators†,
Hemoglobin (g/dL)0.90.07.16.6
Platelet count (x 103/mm³)0.70.83.01.8
WBC (x 103/mm³)0.20.62.21.3
Neutrophils (x 103/mm³)0.00.21.11.2
* <75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; <75% (<50% for neutrophils) of LLN and of baseline for values abnormal at baseline.
† 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.

Table 5: Percent of Adult Patients who Experienced at Least One Substantially Abnormal* Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with Zyvox

Laboratory AssayUncomplicated Skin and Skin Structure InfectionsAll Other Indications
Zyvox 400 mg every 12 hoursClarithromycin 250 mg every 12 hoursZyvox 600 mg every 12 hoursAll Other Comparators†,
AST (U/L)1.71.35.06.8
ALT (U/L)1.71.79.69.3
LDH (U/L)0.20.21.81.5
Alkaline phosphatase (U/L)0.20.23.53.1
Lipase (U/L)2.82.64.34.2
Amylase (U/L)0.20.22.42.0
Total bilirubin (mg/dL)0.20.00.91.1
BUN (mg/dL)0.20.02.11.5
Creatinine (mg/dL)0.20.00.20.6
* >2 x Upper Limit of Normal (ULN) for values normal at baseline; >2 x ULN and >2 x baseline for values abnormal at baseline.
† 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.

Table 6: Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal* Hematology Laboratory Value in Comparator-Controlled Clinical Trials with Zyvox

Laboratory AssayUncomplicated Skin and Skin Structure Infections†All Other Indications‡
ZyvoxCefadroxilZyvoxVancomycin
Hemoglobin (g/dL)0.00.015.712.4
Platelet count (x 103/mm³)0.00.412.913.4
WBC (x 103/mm³)0.80.812.410.3
Neutrophils (x 103/mm³)1.20.85.94.3
* <75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline; <75% (<50% for neutrophils) of LLN and <75% (<50% for neutrophils, <90% for hemoglobin if baseline <LLN) of baseline for values abnormal at baseline.
† Patients 5 through 11 years of age received Zyvox 10 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received Zyvox 600 mg by mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours.
‡ Patients from birth through 11 years of age received Zyvox 10 mg/kg intravenously by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6-24 hours, depending on age and renal clearance.

Table 7: Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal* Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with Zyvox

Laboratory AssayUncomplicated Skin and Skin Structure Infections†All Other Indications‡
ZyvoxCefadroxilZyvoxVancomycin
ALT (U/L)0.00.010.112.5
Lipase (U/L)0.41.2
Amylase (U/L)0.61.3
Total bilirubin (mg/dL)6.35.2
Creatinine (mg/dL)0.40.02.41.0
* >2 x Upper Limit of Normal (ULN) for values normal at baseline; >2 x ULN and >2 (>1.5 for total bilirubin) x baseline for values abnormal at baseline.
† Patients 5 through 11 years of age received Zyvox 10 mg/kg by mouth every 12 hours or cefadroxil 15 mg/kg by mouth every 12 hours. Patients 12 years or older received Zyvox 600 mg mouth every 12 hours or cefadroxil 500 mg by mouth every 12 hours.
‡ Patients from birth through 11 years of age received Zyvox 10 mg/kg intravenously/by mouth every 8 hours or vancomycin 10 to 15 mg/kg intravenously every 6-24 hours, depending on age and renal clearance.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Zyvox. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

  • Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia); sideroblastic anemia.
  • Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision.
  • Lactic acidosis. Although these reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days, these events have also been reported in patients receiving shorter courses of therapy.
  • Serotonin syndrome has been reported in patients receiving concomitant serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and Zyvox.
  • Convulsions.
  • Anaphylaxis, angioedema, and bullous skin disorders including severe cutaneous adverse reactions (SCAR) such as toxic epidermal necrolysis and Stevens-Johnson syndrome.
  • Superficial tooth discoloration and tongue discoloration have been reported with the use of linezolid. The tooth discoloration was removable with professional dental cleaning (manual descaling) in cases with known outcome.
  • Hypoglycemia, including symptomatic episodes.

What drugs interact with Zyvox (linezolid)?

Monoamine Oxidase Inhibitors

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase.

Adrenergic And Serotonergic Agents

Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Summary

Zyvox (linezolid) is a synthetic antibiotic effective against bacteria such as Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and others. Common side effects of Zyvox include diarrhea, vomiting, headache, nausea, abdominal pain, loose stools, increased white blood cells (eosinophilia), itching, and dizziness. Zyvox has not been adequately studied in pregnant women. It is unknown if Zyvox is excreted in breast milk.

Treatment & Diagnosis

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Medically Reviewed on 9/23/2020
References
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.