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Zyvox (Linezolid) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The safety of ZYVOX formulations was evaluated in 2046 adult patients enrolled in seven Phase 3 comparator-controlled clinical trials, who were treated for up to 28 days. In these studies, 85% of the adverse events reported with ZYVOX were described as mild to moderate in intensity. Table 6 shows the incidence of adverse events reported in at least 2% of patients in these trials. The most common adverse events in patients treated with ZYVOX were diarrhea (incidence across studies: 2.8% to 11.0%), headache (incidence across studies: 0.5% to 11.3%), and nausea (incidence across studies: 3.4% to 9.6%).

Table 6. Incidence (%) of Adverse Events Reported in ≥2% of Adult Patients in Comparator-Controlled Clinical Trials with ZYVOX
Event ZYVOX
(n=2046)
All Comparators *
(n=2001)
Diarrhea 8.3 6.3
Headache 6.5 5.5
Nausea 6.2 4.6
Vomiting 3.7 2.0
Insomnia 2.5 1.7
Constipation 2.2 2.1
Rash 2.0 2.2
Dizziness 2.0 1.9
Fever 1.6 2.1

Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; clarithromycin 250 mg PO q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.

Other adverse events reported in Phase 2 and Phase 3 studies included oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Table 7 shows the incidence of drug-related adverse events reported in at least 1% of adult patients in these trials by dose of ZYVOX.

Table 7. Incidence (%) of Drug-Related Adverse Events Occurring in >1% of Adult Patients Treated with ZYVOX in Comparator-Controlled Clinical Trials
Uncomplicated Skin and Skin Structure Infections All Other Indications
Adverse Event ZYVOX 400 mg PO q12h
(n=548)
Clarithromycin 250 mg PO q12h
(n=537)
ZYVOX 600 mg q12h
(n=1498)
All Other Comparators *
(n=1464)
% of patients with 1 drug-related adverse event 25.4 19.6 20.4 14.3
% of patients discontinuing due to drug-related adverse events † 3.5 2.4 2.1 1.7
Diarrhea 5.3 4.8 4.0 2.7
Nausea 3.5 3.5 3.3 1.8
Headache 2.7 2.2 1.9 1.0
Taste alteration 1.8 2.0 0.9 0.2
Vaginal moniliasis 1.6 1.3 1.0 0.4
Fungal infection 1.5 0.2 0.1 <0.1
Abnormal liver function tests 0.4 0 1.3 0.5
Vomiting 0.9 0.4 1.2 0.4
Tongue discoloration 1.1 0 0.2 0
Dizziness 1.1 1.5 0.4 0.3
Oral moniliasis 0.4 0 1.1 0.4

Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.

The most commonly reported drug-related adverse events leading to discontinuation in patients treated with ZYVOX were nausea, headache, diarrhea, and vomiting.

 

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 these studies, 83% and 99%, respectively, of the adverse events reported with ZYVOX were described as mild to moderate in intensity. 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. Table 8 shows the incidence of adverse events reported in at least 2% of pediatric patients treated with ZYVOX in these trials.

Table 8. Incidence (%) of Adverse Events Reported in ≥2% of Pediatric Patients Treated with ZYVOX in Comparator-Controlled Clinical Trials
Uncomplicated Skin and Skin Structure Infections * All Other Indications †
Event ZYVOX
(n=248)
Cefadroxil
(n = 251)
ZYVOX
(n = 215)
Vancomycin
(n=101)
Fever 2.9 3.6 14.1 14.1
Diarrhea 7.8 8.0 10.8 12.1
Vomiting 2.9 6.4 9.4 9.1
Sepsis 0 0 8.0 7.1
Rash 1.6 1.2 7.0 15.2
Headache 6.5 4.0 0.9 0
Anemia 0 0 5.6 7.1
Thrombocytopenia 0 0 4.7 2.0
Upper respiratory infection 3.7 5.2 4.2 1.0
Nausea 3.7 3.2 1.9 0
Dyspnea 0 0 3.3 1.0
Reaction at site of injection or of vascular catheter 0 0 3.3 5.1
Trauma 3.3 4.8 2.8 2.0
Pharyngitis 2.9 1.6 0.5 1.0
Convulsion 0 0 2.8 2.0
Hypokalemia 0 0 2.8 3.0
Pneumonia 0 0 2.8 2.0
Thrombocythemia 0 0 2.8 2.0
Cough 2.4 4.0 0.9 0
Generalized abdominal pain 2.4 2.8 0.9 2.0
Localized abdominal pain 2.4 2.8 0.5 1.0
Apnea 0 0 2.3 2.0
Gastrointestinal bleeding 0 0 2.3 1.0
Generalized edema 0 0 2.3 1.0
Loose stools 1.6 0.8 2.3 3.0
Localized pain 2.0 1.6 0.9 0
Skin disorder 2.0 0 0.9 1.0

Patients 5 through 11 years of age received ZYVOX 10 mg/kg PO q12h or cefadroxil 15 mg/kg PO q12h. Patients 12 years or older received ZYVOX 600 mg PO q12h or cefadroxil 500 mg PO q12h.

Patients from birth through 11 years of age received ZYVOX 10 mg/kg IV/PO q8h or vancomycin 10 to 15 mg/kg IV q6–24h, depending on age and renal clearance.

Table 9 shows the incidence of drug-related adverse events 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 9. Incidence (%) of Drug-related Adverse Events Occurring in >1% of Pediatric Patients (and >1 Patient) in Either Treatment Group in Comparator-Controlled Clinical Trials
Event Uncomplicated Skin and Skin Structure Infections * All Other Indications †
ZYVOX
(n=248)
Cefadroxil
(n=251)
ZYVOX
(n=215)
Vancomycin
(n=101)
% of patients with ≥1 drug-related adverse event 19.2 14.1 18.8 34.3
% of patients discontinuing due to a drug-related adverse event 1.6 2.4 0.9 6.1
Diarrhea 5.7 5.2 3.8 6.1
Nausea 3.3 2.0 1.4 0
Headache 2.4 0.8 0 0
Loose stools 1.2 0.8 1.9 0
Thrombocytopenia 0 0 1.9 0
Vomiting 1.2 2.4 1.9 1.0
Generalized abdominal pain 1.6 1.2 0 0
Localized abdominal pain 1.6 1.2 0 0
Anemia 0 0 1.4 1.0
Eosinophilia 0.4 0.4 1.4 0
Rash 0.4 1.2 1.4 7.1
Vertigo 1.2 0.4 0 0
Oral moniliasis 0 0 0.9 4.0
Fever 0 0 0.5 3.0
Pruritus at non-application site 0.4 0 0 2.0
Anaphylaxis 0 0 0 10.1 ‡

Patients 5 through 11 years of age received ZYVOX 10 mg/kg PO q12h or cefadroxil 15 mg/kg PO q12h. Patients 12 years or older received ZYVOX 600 mg PO q12h or cefadroxil 500 mg PO q12h.

Patients from birth through 11 years of age received ZYVOX 10 mg/kg IV/PO q8h or vancomycin 10 to 15 mg/kg IV q6–24h, depending on age and renal clearance.

These reports were of 'red-man syndrome', which were coded as anaphylaxis.

 

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 (see WARNINGS).

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 10, 11, 12, and 13.

Table 10. Percent of Adult Patients who Experienced at Least One Substantially Abnormal * Hematology Laboratory Value in Comparator-Controlled Clinical Trials with ZYVOX
Laboratory Assay Uncomplicated Skin and Skin Structure Infections All Other Indications
ZYVOX
400 mg q12h
Clarithromycin
250 mg q12h
ZYVOX
600 mg q12h
All Other Comparators †
Hemoglobin (g/dL) 0.9 0.0 7.1 6.6
Platelet count (x 103/mm3) 0.7 0.8 3.0 1.8
WBC (x 103/mm3) 0.2 0.6 2.2 1.3
Neutrophils (x 103/mm3) 0.0 0.2 1.1 1.2

<75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline;

Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.

Table 11. Percent of Adult Patients who Experienced at Least One Substantially Abnormal * Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with ZYVOX
Laboratory Assay Uncomplicated Skin and Skin Structure Infections All Other Indications
ZYVOX
400 mg q12h
Clarithromycin
250 mg q12h
ZYVOX
600 mg q12h
All Other
Comparators †
AST (U/L) 1.7 1.3 5.0 6.8
ALT (U/L) 1.7 1.7 9.6 9.3
LDH (U/L) 0.2 0.2 1.8 1.5
Alkaline phosphatase (U/L) 0.2 0.2 3.5 3.1
Lipase (U/L) 2.8 2.6 4.3 4.2
Amylase (U/L) 0.2 0.2 2.4 2.0
Total bilirubin (mg/dL) 0.2 0.0 0.9 1.1
BUN (mg/dL) 0.2 0.0 2.1 1.5
Creatinine (mg/dL) 0.2 0.0 0.2 0.6

>2 x Upper Limit of Normal (ULN) for values normal at baseline;

Comparators included cefpodoxime proxetil 200 mg PO q12h; ceftriaxone 1 g IV q12h; dicloxacillin 500 mg PO q6h; oxacillin 2 g IV q6h; vancomycin 1 g IV q12h.

Table 12. Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal * Hematology Laboratory Value in Comparator-Controlled Clinical Trials with ZYVOX
Laboratory Assay Uncomplicated Skin and Skin Structure Infections † All Other Indications ‡
ZYVOX Cefadroxil ZYVOX Vancomycin
Hemoglobin (g/dL) 0.0 0.0 15.7 12.4
Platelet count (x 103/mm3) 0.0 0.4 12.9 13.4
WBC (x 103/mm3) 0.8 0.8 12.4 10.3
Neutrophils (x 103/mm3) 1.2 0.8 5.9 4.3

<75% (<50% for neutrophils) of Lower Limit of Normal (LLN) for values normal at baseline;

Patients 5 through 11 years of age received ZYVOX 10 mg/kg PO q12h or cefadroxil 15 mg/kg PO q12h. Patients 12 years or older received ZYVOX 600 mg PO q12h or cefadroxil 500 mg PO q12h.

Patients from birth through 11 years of age received ZYVOX 10 mg/kg IV/PO q8h or vancomycin 10 to 15 mg/kg IV q6–24h, depending on age and renal clearance.

Table 13. Percent of Pediatric Patients who Experienced at Least One Substantially Abnormal * Serum Chemistry Laboratory Value in Comparator-Controlled Clinical Trials with ZYVOX
Laboratory Assay Uncomplicated Skin and Skin Structure Infections † All Other Indications ‡
ZYVOX Cefadroxil ZYVOX Vancomycin
ALT (U/L) 0.0 0.0 10.1 12.5
Lipase (U/L) 0.4 1.2 --- ---
Amylase (U/L) --- --- 0.6 1.3
Total bilirubin (mg/dL) --- --- 6.3 5.2
Creatinine (mg/dL) 0.4 0.0 2.4 1.0

>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 PO q12h or cefadroxil 15 mg/kg PO q12h. Patients 12 years or older received ZYVOX 600 mg PO q12h or cefadroxil 500 mg PO q12h.

Patients from birth through 11 years of age received ZYVOX 10 mg/kg IV/PO q8h or vancomycin 10 to 15 mg/kg IV q6–24h, depending on age and renal clearance.

 

Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported during postmarketing use of ZYVOX (see WARNINGS). Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision, have been reported in patients treated with ZYVOX. Lactic acidosis has been reported with the use of ZYVOX (see PRECAUTIONS, General). 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 (see PRECAUTIONS, General). Convulsions have been reported with the use of ZYVOX (see PRECAUTIONS, General). Anaphylaxis, angioedema, and bullous skin disorders such as those described as Stevens Johnson syndrome have been reported. 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, has been reported (see WARNINGS). These events have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ZYVOX, or a combination of these factors. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made and causal relationship cannot be precisely established.

 



REPORTS OF SUSPECTED ZYVOX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Zyvox. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zyvox side effects / adverse reactions in 45 year old female

Reported by a physician from Japan on 2011-10-03

Patient: 45 year old female weighing 38.0 kg (83.6 pounds)

Reactions: Gastrointestinal Haemorrhage, Lactic Acidosis, Shock

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Zyvox
    Indication: Liver Abscess

Zyvox
    Dosage: 600 mg, 2x/day
    Indication: Sepsis
    Start date: 2011-08-07
    End date: 2011-08-09

Other drugs received by patient: Aminic; Dipotassium Phosphate; Pantol; Bisolvon; Midazolam; Arginine Hydrochloride; Humulin R; Norepinephrine; Sodium Bicarbonate; Multivitamin Additive; Manganese Chloride; Magnesium Sulfate; Rehabix K2; Zosyn; Dobutamine Hydrochloride; Aspara K



Possible Zyvox side effects / adverse reactions in 22 year old female

Reported by a physician from Switzerland on 2011-10-03

Patient: 22 year old female

Reactions: Abdominal Pain, Chest Discomfort, Dyspnoea, Pruritus, Vomiting, Nausea, Urticaria, Anaphylactic Reaction, Tachycardia, Headache, Rash, Paraesthesia, Infusion Site Pain

Adverse event resulted in: hospitalization

Suspect drug(s):
Invanz
    Dosage: unk
    Indication: Osteomyelitis
    Start date: 2011-05-12
    End date: 2011-05-13

Garamycin
    Dosage: unk
    Start date: 2011-09-08

Targocid
    Dosage: unk
    Indication: Osteomyelitis
    Start date: 2011-05-12
    End date: 2011-06-13

Zyvox
    Dosage: unk
    Administration route: Oral
    Indication: Osteomyelitis
    Start date: 2011-05-07
    End date: 2011-05-07

Ciproflaxacin
    Dosage: unk
    Administration route: Oral
    Indication: Osteomyelitis
    Start date: 2011-05-07
    End date: 2011-05-07

Targocid
    Dosage: unk
    Start date: 2011-09-08

Garamycin
    Dosage: unk
    Indication: Osteomyelitis
    Start date: 2011-05-10
    End date: 2011-05-11

Ciproflaxacin
    Dosage: unk
    Start date: 2011-05-09

Garamycin
    Dosage: unk
    Start date: 2011-05-14
    End date: 2011-06-13

Zyvox
    Dosage: unk
    Start date: 2011-05-09
    End date: 2011-05-10

Other drugs received by patient: Clindamycin HCL; Augmentin '125'; Cubicin; Clindamycin HCL



Possible Zyvox side effects / adverse reactions in 20 year old female

Reported by a physician from Japan on 2011-10-03

Patient: 20 year old female weighing 13.0 kg (28.6 pounds)

Reactions: Arterial Haemorrhage, Cardiac Failure, Drug Ineffective FOR Unapproved Indication, Sepsis, Lactic Acidosis

Adverse event resulted in: life threatening event

Suspect drug(s):
Zyvox
    Dosage: 600 mg, 2x/day
    Indication: Staphylococcal Osteomyelitis
    Start date: 2011-05-17
    End date: 2011-06-09

Zyvox
    Dosage: 200 mg, 2x/day
    Start date: 2011-06-10

Other drugs received by patient: Clonazepam; Zosyn; Topiramate



See index of all Zyvox side effect reports >>

Drug label data at the top of this Page last updated: 2013-04-03

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