Zyvox

What Is Zyvox?

Zyvox (linezolid) is an antibacterial drug used to treat susceptible Gram-positive infections (for example, Staphylococcus and Streptococcus spp.). Zyvox is available in other countries under the generic name linezolid.

What Are Side Effects of Zyvox?

Common side effects of Zyvox include:

• diarrhea,
• nausea,
• vomiting,
• headache,
• sleep problems (insomnia),
• constipation,
• dizziness,
• discolored tongue,
• unusual or unpleasant taste in the mouth,
• vaginal itching or discharge, or
• yeast infection in the mouth (oral thrush).

Severe side effects of Zyvox include:

• severe diarrhea or diarrhea that is watery or bloody,
• fungal infections,
• low platelet count (thrombocytopenia),
• myelosuppression,
• serotonin syndrome,
• nerve problems,
• skin swelling (angioedema),
• fever, chills, body aches, flu symptoms, sores in your mouth and throat,
• easy bruising or bleeding, pale skin, lightheadedness, shortness of breath, rapid heart rate, trouble concentrating,
• blurred vision, trouble seeing color,
• numbness, burning pain, or tingly feeling in your hands or feet,
• seizures (convulsions), or
• low blood sugar (headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery).

Dosage for Zyvox

Zyvox (linezolid) is available in an IV form (strength is 2mg per ml), in tablets (strengths of 400 and 600mg) and in an oral suspension (strength is 100mg per 5ml). Dose depends on the form of the drug used, the type of infection and if the drug is used to treat children or adults; the treating doctor should determine the dose. This drug is not to be used to treat Gram-negative bacterial infections. Zyvox has been used in the pediatric population with weight-adjusted dosing.

What Drugs, Substances, or Supplements Interact with Zyvox?

Zyvox may interact with MAO inhibitors, meperidine, diet pills, stimulants, cold or allergy medicines, ADHD medications, migraine or cluster headache medications, medications to treat Parkinson's disease or restless leg syndrome, antidepressants, or other medications used to treat depression, anxiety, and other psychiatric conditions. Tell your doctor all medications and supplements you use.

Zyvox During Pregnancy and Breastfeeding

Risk versus benefits should be considered before using Zyvox in pregnant or breastfeeding females.

Additional Information

Our Zyvox Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Zyvox Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Call your doctor at once if you have:

• vision problems, changes in color vision;
• severe stomach pain, diarrhea that is watery or bloody;
• a seizure;
• sweating, feeling anxious or shaky (may be signs of low blood sugar);
• lactic acidosis--unusual muscle pain, trouble breathing, stomach pain, vomiting, irregular heart rate, dizziness, feeling cold, or feeling very weak or tired; or
• low blood cell counts--fever, chills, tiredness, weakness, confusion, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.

Common side effects may include:

• nausea, vomiting, diarrhea;
• rash;
• anemia (low red blood cells); or
• headache, dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zyvox (Linezolid)

 

Zyvox Professional Information

SIDE EFFECTS

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% ofZYVOX-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 REACTIONS	Uncomplicated Skin and Skin Structure Infections		All 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)
Headache	8.8	8.4	5.7	4.4
Diarrhea	8.2	6.1	8.3	6.4
Nausea	5.1	4.5	6.6	4.6
Vomiting	2.0	1.5	4.3	2.3
Dizziness	2.6	3.0	1.8	1.5
Rash	1.1	1.1	2.3	2.6
Anemia	0.4	0	2.1	1.4
Taste alteration	1.8	2.0	1.0	0.3
Vaginal moniliasis	1.8	1.3	1.1	0.5
Oral moniliasis	0.5	0	1.7	1.0
Abnormal liver function tests	0.4	0.2	1.6	0.8
Fungal infection	1.5	0.2	0.3	0.2
Tongue discoloration	1.3	0	0.3	0
Localizedabdominal pain	1.3	0.6	1.2	0.8
Generalized abdominal pain	0.9	0.4	1.2	1.0
* Comparators included cefpodoxime proxetil 200 mgby mouth every 12 hours;ceftriaxone 1 gintravenously every 12 hours; dicloxacillin500 mgby mouth every 6hours; oxacillin 2 gintravenouslyevery6hours; vancomycin 1 gintravenously every 12 hours.

Of the patients treated for uSSSIs,3.5% ofZYVOX-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 thepediatricpatients treated foruSSSIs, 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 REACTIONS	Uncomplicated Skin and Skin Structure Infections*		All Other Indications†
	ZYVOX (n=248)	Cefadroxil (n=251)	ZYVOX (n=215)	Vancomycin (n=101)
Diarrhea	7.8	8.0	10.8	12.1
Vomiting	2.9	6.4	9.4	9.1
Headache	6.5	4.0	0.9	0
Anemia	0	0	5.6	7.1
Thrombocytopenia	0	0	4.7	2.0
Nausea	3.7	3.2	1.9	0
Generalized abdominal pain	2.4	2.8	0.9	2.0
Localized abdominal pain	2.4	2.8	0.5	1.0
Loose stools	1.6	0.8	2.3	3.0
Eosinophilia	0.4	0.8	1.9	1.0
Pruritus at non-application site	0.8	0.4	1.4	2.0
Vertigo	1.2	0.4	0	0
* Patients 5 through 11 years of agereceived ZYVOX10 mg/kg by mouth every 12hours or cefadroxil 15 mg/kg by mouth every 12hours.Patients 12 years or older received ZYVOX 600 mgby mouth every 12hours or cefadroxil 500 mgby 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 every6-24hours, depending on age and renal clearance.

Of thepediatric 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 [see WARNINGS AND PRECAUTIONS].

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 Assay	Uncomplicated Skin and Skin Structure Infections		All Other Indications
	ZYVOX 400 mg every 12 hours	Clarithromycin 250 mg every 12 hours	ZYVOX 600 mg every 12 hours	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; < 75% (<50% for neutrophils) of LLN and of baseline forvalues abnormal at baseline. † Comparators included cefpodoxime proxetil 200 mgby mouth every 12 hours; ceftriaxone 1 gintravenously every 12 hours; dicloxacillin 500 mgby 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 Assay	Uncomplicated Skin and Skin Structure Infections		All Other Indications
	ZYVOX 400 mg every 12 hours	Clarithromycin 250 mg every 12 hours	ZYVOX 600 mg every 12 hours	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; >2 x ULN and >2 x baseline for values abnormal at baseline. † Comparators included cefpodoxime proxetil 200 mgby mouth every 12 hours; ceftriaxone 1 gintravenously every 12 hours; dicloxacillin 500 mgby 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 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; < 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 agereceived ZYVOX10 mg/kg by mouth every12hoursor cefadroxil 15 mg/kg by mouth every 12hours. Patients 12 years or older received ZYVOX 600 mgby mouth every12hours or cefadroxil 500 mgby 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 6-24hours, 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 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 agereceived ZYVOX10 mg/kg by mouth every12hoursor cefadroxil 15 mg/kg by mouth every 12hours. Patients 12 years or older received ZYVOX 600 mgmouth every 12hours or cefadroxil 500 mgby 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 6-24hours, 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) [see WARNINGS AND PRECAUTIONS]; sideroblastic anemia.
• Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision [see WARNINGS AND PRECAUTIONS].
• Lactic acidosis [see WARNINGS AND PRECAUTIONS]. 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 opioids, and ZYVOX [see WARNINGS AND PRECAUTIONS].
• Convulsions [see WARNINGS AND PRECAUTIONS].
• Anaphylaxis, angioedema, bullous skin disorders including severecutaneous adverse reactions (SCAR) such as toxic epidermal necrolysis and Stevens-Johnson syndrome, and hypersensitivity vasculitis.
• Superficial tooth discoloration and tonguediscoloration 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 [see WARNINGS AND PRECAUTIONS].
• Hyponatremia and/or Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Monoamine Oxidase Inhibitors

Linezolid is a reversible, nonselective inhibitor of monoamine oxidase [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].

Adrenergic And Serotonergic Agents

Linezolid has the potential for interaction with adrenergic and serotonergic agents [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Zyvox (Linezolid)