Zyvoxam 600 mg

Large quantities of foods or beverages with high tyramine content should be avoided while taking ZYVOXAM. Quantities of tyramine consumed should be less than 100 mg per meal. 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 (0 to 15 mg tyramine per 28 g); fermented or air-dried meats (0.1 to 8 mg tyramine per 28 g); sauerkraut (8 mg tyramine per 224 g); soy sauce (5 mg tyramine per 1 teaspoon); tap beers (4 mg tyramine per 360 mL); red wines (0 to 6 mg tyramine per 240 mL). The tyramine content of any protein-rich food may be increased if stored for long periods or improperly refrigerated.

Linezolid is not an inducer of cytochrome P450 (CYP) in rats. It is not detectably metabolized by human cytochrome P450 and it does not inhibit the activities of clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4). Therefore, no CYP450-induced drug interactions are expected with linezolid. Concurrent administration of linezolid does not substantially alter the pharmacokinetic characteristics of (S)-warfarin, which is extensively metabolized by CYP2C9. Drugs such as warfarin and phenytoin, which are CYP2C9 substrates, may be given with linezolid without changes in dosage regimen.

There are no reported drug-laboratory test interactions.

The pharmacokinetics of linezolid or gentamicin are not altered when administered together.

A significant pressor response has been observed in normal adult subjects receiving linezolid and tyramine doses of more than 100 mg. Therefore, patients receiving linezolid need to avoid consuming large amounts of foods or beverages with high tyramine content (see Warnings and Precautions, Drug Interactions).

A reversible enhancement of the pressor response of either pseudoephedrine HCl (PSE) or phenylpropanolamine HCl (PPA) is observed when linezolid is administered to healthy normotensive subjects (see Warnings and Precautions, Drug Interactions). A similar study has not been conducted in hypertensive patients. The interaction studies conducted in normotensive subjects evaluated the blood pressure and heart rate effects of placebo, PPA or PSE alone, linezolid alone, and the combination of steady-state linezolid (600 mg q12h for 3 days) with two doses of PPA (25 mg) or PSE (60 mg) given 4 hours apart. Heart rate was not affected by any of the treatments. Blood pressure was increased with both combination treatments. Maximum blood pressure levels were seen 2 to 3 hours after the second dose of PPA or PSE, and returned to baseline 2 to 3 hours after peak.

Linezolid is a mild reversible inhibitor of MAO-A and MAO B. Studies in healthy volunteers have examined the effect of linezolid on the pharmacodynamic responses to tyramine, sympathomimetic amines, and dextromethorphan.

Interactions with herbal products have not been established.

A study to assess the potential interaction of linezolid with a serotonin reuptake inhibitor (dextromethorphan) was conducted in healthy volunteers. No significant differences were found in the pharmacodynamic measures of temperature, digit symbol substitution, nurse rated sedation, blood pressure, or pulse when subjects were administered dextromethorphan with or without linezolid. The effects of other serotonin reuptake inhibitors have not been studied. Very rare spontaneous reports of serotonin syndrome with co-administration of linezolid and serotonergic agents have been reported (see Warnings and Precautions, Drug Interactions).

The pharmacokinetics of linezolid or aztreonam are not altered when administered together.

No studies have been conducted with antacids and chelating agents. Based on the chemical structure, concurrent administration with these agents is not expected to affect absorption of linezolid.

ZYVOXAM Injection is supplied as a ready-to-use sterile isotonic solution for intravenous infusion. As with all parenteral drug products, intravenous solutions should be inspected visually for clarity, particulate matter, precipitate and leakage prior to administration, whenever solution and container permit. Solutions showing haziness, particulate matter, precipitate or leakage should not be used.

ZYVOXAM Injection may exhibit a yellow color that can intensify over time without adversely affecting potency. Discard unused portions.

Physical incompatibilities resulted when ZYVOXAM Injection was combined with the following drugs during simulated Y-site administration: amphotericin B, chlorpromazine HCl, diazepam, pentamidine isethionate, erythromycin lactobionate, phenytoin sodium, and trimethoprim-sulfamethoxazole. Additionally, chemical incompatibility resulted when ZYVOXAM Injection was combined with ceftriaxone sodium.

Patients with infection due to MRSA should be treated with ZYVOXAM 600 mg q12h.

In controlled clinical trials, the protocol-defined duration of treatment for all infections ranged from 7 to 28 days. Total treatment duration was determined by the treating physician based on site and severity of the infection, and on the patient's clinical response.

No dose adjustment is necessary when switching from intravenous to oral administration. Patients whose therapy is started with ZYVOXAM Injection may be switched to ZYVOXAM Tablets at the discretion of the physician, when clinically indicated.

ZYVOXAM may be taken with or without food.

5% Dextrose Injection, USP; 0.9% Sodium Chloride Injection, USP; and Lactated Ringer's Injection, USP.

ZYVOXAM Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. Do not use this intravenous infusion bag in series connections. Additives should not be introduced into this solution. If ZYVOXAM Injection is to be given concomitantly with another drug, each drug should be given separately in accordance with the recommended dosage and route of administration for each product.

If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of ZYVOXAM Injection with an infusion solution compatible with ZYVOXAM Injection and with any other drug(s) administered via this common line (see Compatible I.V. Solutions under Dosage and Administration).

If a dose is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule resumed. Doses should not be doubled.

In controlled clinical trials the pattern of drug related adverse reactions by body system with an incidence less than 1.0% but greater than 0.1% were similar to comparators.

Serious adverse reactions in controlled clinical trials considered possibly or probably related to ZYVOXAM treatment with an incidence less than 0.1% were, hypertension, kidney failure, liver function test abnormality, pancreatitis, thrombocytopenia, transient ischemic attacks and vomiting.

In Study 113, serious drug-related events were reported for seven patients in the linezolid treatment group: congestive heart failure, peripheral vascular disease; biliary pain and cholestatic jaundice; C. difficile colitis; gastrointestinal bleeding; anemia; and hypokalemia.

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

The safety of ZYVOXAM (linezolid) Tablets and Injection were evaluated in 2046 patients enrolled in seven phase III comparator-controlled clinical trials, who were treated for up to 28 days. In these studies, 85% of the adverse events reported with ZYVOXAM were described as mild to moderate in intensity. The most common adverse events in patients treated with ZYVOXAM 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%).

Other adverse events reported in phase II and phase III studies included oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Myelosuppression (anemia including pure red blood cell aplasia, leukopenia, pancytopenia, and thrombocytopenia) has been reported during postmarketing use of ZYVOXAM (see Warnings and Precautions).

Peripheral neuropathy, and optic neuropathy sometimes progressing to loss of vision, have been reported in patients treated with linezolid. These reports have primarily been in patients treated for longer than the maximum recommended duration of 28 days (see Warnings and Precautions).

Lactic acidosis (see Warnings and Precautions, General), convulsions (see Warnings and Precautions, Neurologic), angioedema and anaphylaxis have been reported.

Very rare reports of bullous skin disorders such as those described as Stevens Johnson syndrome have been received.

Very rare spontaneous reports of serotonin syndrome with co-administration of linezolid and serotonergic agents have been reported (see Warnings and Precautions, Drug Interactions).

These events have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ZYVOXAM, 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.

Frequencies of Abnormal Values for Selected Chemistry Assays at EOT^a [Study 113, linezolid in the treatment of adult diabetic patients with clinically documented complicated skin and skin structure infections (“diabetic foot infections”)]

Each white, oval, film-coated, compressed tablet, printed with “ZYVOXAM 600mg” in red, contains: linezolid 600 mg. Nonmedicinal ingredients: ammonium hydroxide, carnauba wax, cornstarch, ethanol, ethyl acetate, hydroxypropylcellulose, hypromellose, iron oxide black, iron oxide red, magnesium stearate, microcrystalline cellulose, polyethylene glycol, propylene glycol, shellac, sodium starch glycolate, titanium dioxide and 2-ethoxyethanol. Bottles of 20.

Each mL of sterile, isotonic solution for i.v. infusion, contains: linezolid 2 mg. Nonmedicinal ingredients: citric acid, dextrose, hydrochloric acid, sodium citrate, sodium hydroxide and water for injection. Latex- and PVC-free (bags and ports). Single use, ready-to-use flexible plastic infusion bags of 300 mL (600 mg), in a foil laminate overwrap.

See also Drug Interactions, Drug-Drug Interactions.

Dose- and time-dependent myelosuppression, as evidenced by bone marrow hypocellularity, decreased hematopoiesis, and decreased levels of circulating erythrocytes, leukocytes, and platelets, has been seen in animal studies. The hematopoietic effects occurred at doses of 40 and 80 mg/kg/day in dogs and rats, respectively (at exposures approximately 0.6 times in the dog and equal in the rat to the expected human exposure based on AUC). Hematopoietic effects were reversible, although in some studies reversal was incomplete within the duration of the recovery period.

ZYVOXAM is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.

Optic neuropathy has been reported in patients treated with ZYVOXAM, primarily those treated for longer than the maximum recommended duration of 28 days. When outcome was known, recovery was reported in some cases following ZYVOXAM withdrawal. In cases of optic neuropathy that progressed to loss of vision, patients were treated for longer than the maximum recommended duration. Visual blurring has been reported in some patients treated with ZYVOXAM for less than 28 days.

Visual function should be monitored in all patients taking ZYVOXAM for longer than the maximum recommended duration and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOXAM. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmologic evaluation is recommended. If optic neuropathy occurs, the continued use of ZYVOXAM in these patients should be weighed against the potential risks.

Although it may be possible to extrapolate adult efficacy to pediatric patients, the appropriate dose and safety of ZYVOXAM have not been established in this population. Drug clearance of ZYVOXAM is increased in pediatric patients compared to adults, resulting in a shorter half-life (see Action and Clinical Pharmacology, Special Populations and Conditions, Pediatrics). Pediatric dosing regimens that provide a pharmacokinetic profile similar to adults have not been determined.

There are no adequate and well-controlled studies in pregnant women. ZYVOXAM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Of the 2046 patients treated with ZYVOXAM in phase III 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.

Myelosuppression (anemia including pure red blood cell aplasia, leucopenia, 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. Complete blood counts should be monitored at least weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, patients who are at increased risk for bleeding, those with pre-existing myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or decreased hemoglobin levels or platelet counts or function, or those with a chronic infection who have received previous or concomitant antibiotic therapy. Discontinuation of therapy with linezolid should be considered in patients who develop or have worsening myelosuppression.

The use of antibiotics may promote the overgrowth of nonsusceptible organisms. Should superinfection occur during therapy, appropriate measures should be taken.

ZYVOXAM (linezolid) Tablets and Injection have not been studied in patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism.

Large quantities of foods or beverages with high tyramine content should be avoided while taking ZYVOXAM (see Drug Interactions, Drug-Food Interactions for foods or beverages with high tyramine content).

The safety and efficacy of ZYVOXAM given for longer than 28 days have not been evaluated in controlled clinical trials.

Lactic acidosis has been reported with the use of ZYVOXAM. Patients who develop recurrent nausea or vomiting, unexplained acidosis, or a low bicarbonate level while receiving ZYVOXAM should receive immediate medical attention.

Peripheral neuropathy has been reported primarily in patients treated for longer than the maximum recommended duration of 28 days with ZYVOXAM. When outcome was known, recovery was reported in only some cases following ZYVOXAM withdrawal.

If symptoms of peripheral neuropathy such as numbness, tingling, prickling sensations or burning pain occur, the continued use of ZYVOXAM should be weighed against the potential risk.

Convulsions have been reported to occur rarely in patients when treated with ZYVOXAM. In most of these cases, a history of seizures or risk factors for seizures was reported.

Some individuals receiving ZYVOXAM may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Commonly used drugs such as phenylpropanolamine and pseudoephedrine have been specifically studied. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.

Complete blood counts should be monitored at least weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than two weeks, patients who are at increased risk for bleeding, those with pre-existing myelosuppression, those receiving concomitant drugs that produce bone marrow suppression, or decreased hemoglobin levels or platelet counts or function, or those with a chronic infection who have received previous or concomitant antibiotic therapy (see Warnings and Precautions, Hematologic, Myelosuppression).

Visual function should be monitored in all patients taking ZYVOXAM for longer than the maximum recommended duration and in all patients reporting new visual symptoms regardless of length of therapy with ZYVOXAM. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmologic evaluation is recommended (see Warnings and Precautions, Ophthalmologic).

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including linezolid, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of any antibacterial agent.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by C. difficile is a primary cause of “antibiotic-associated colitis”.

After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against C. difficile.

Very rare spontaneous reports of serotonin syndrome with co-administration of linezolid and serotonergic agents have been reported. Since there is limited experience with concomitant administration of linezolid and serotonergic agents, physicians should be alert to the possibility of signs and symptoms of serotonin syndrome (e.g., hyperpyrexia, and cognitive dysfunction) in patients receiving such concomitant therapy (see Drug Interactions, Drug-Drug Interactions, Serotonergic Agents).

Patients should be advised that:

• They should inform their physician if they have a history of hypertension.

  
  

• They should inform their physician if taking medications containing sympathomimetic agents such as pseudoephedrine HCl, often found in cold remedies and decongestants.

  
  

• They should inform their physician if taking serotonin re-uptake inhibitors or other antidepressants.

  
  

• They should inform their physician if they experience changes in vision during therapy with linezolid.

  
  

• They should inform their physician if they experience numbness, tingling, prickling sensations or burning pain during therapy with linezolid.

  
  

• They should inform their physician if they have a history of seizures or convulsions.

ZYVOXAM and its metabolites are excreted in the milk of lactating rats. Concentrations in milk were similar to those in maternal plasma. It is not known whether linezolid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ZYVOXAM is administered to a nursing woman.

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 L in healthy adult volunteers.

Linezolid concentrations have been determined in various fluids from a limited number of subjects in Phase I volunteer studies following multiple dosing of linezolid. The ratio of linezolid in saliva relative to plasma was 1.2 to 1 and for sweat relative to plasma was 0.55 to 1. The ratio for epithelial lining fluid was 4.5 to 1, and for alveolar cells of the lung was 0.15 to 1, when measured at steady-state C_max. In a small study of subjects with ventricular-peritoneal shunts and essentially non-inflamed meninges, the ratio of linezolid in cerebrospinal fluid to plasma at C_max was 0.7 to 1 after multiple dosing of linezolid.

Linezolid is rapidly and extensively absorbed after oral dosing. As shown in Figure 1, 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-∞ values is similar under both conditions.

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 renal clearance of linezolid is low (average 40 mL/min) and 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 doses of linezolid, which appears to be due to lower renal and nonrenal clearance of linezolid at higher concentrations. However, the difference in clearance was small and was not reflected in the apparent elimination half-life.

The average minimum plasma concentrations (C_min) at steady state for oral administration of 400 or 600 mg linezolid every 12 hours were 3.08 and 6.15 µg/mL, respectively, and the corresponding average maximum concentrations (C_max) were 11.0 and 21.2 µg /mL, respectively. These results indicate that for these dose regimens, the C_min values are near or above the highest MIC₉₀ (4 µg/mL) for target microorganisms.

Females have a slightly lower volume of distribution of linezolid than males. Plasma concentrations are higher in females than in males, which is partly due to body weight differences. After a 600 mg dose, mean oral clearance is approximately 38% lower in females than in males. However, there are no significant gender differences in mean apparent elimination-rate constant or half-life. Thus, drug exposure in females is not expected to substantially increase beyond levels known to be well tolerated. Therefore, dose adjustment by gender is not necessary.

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 B is mediated by a non-enzymatic chemical oxidation mechanism in vitro. Linezolid is not an inducer of cytochrome P450 (CYP) in rats, and it has been demonstrated from in vitro studies that linezolid is not detectably metabolized by human cytochrome P450 and it does not inhibit the activities of clinically significant human CYP isoforms (1A2, 2C9, 2C19, 2D6, 2E1, 3A4).

The lack of effect of linezolid to induce CYP2C9 was shown in a healthy volunteer study using warfarin as a metabolism probe.

Mean (Standard Deviation) AUCs and Elimination Half-lives of Linezolid and Metabolites A and B in Patients with Varying Degrees of Renal Insufficiency After a Single 600-mg Oral Dose of Linezolid

Pediatrics Currently, there are limited data on the pharmacokinetics of linezolid during multiple dosing in pediatric patients of all ages. No data have been collected in infants younger than 3 months of age. Pharmacokinetic information indicates that pediatric patients dosed with 10 mg/kg IV have a similar Cmax but a higher average clearance when corrected by body weight, and shorter apparent elimination half-life than adults receiving 625 mg of linezolid. Pediatric dosing regimens that provide a pharmacokinetic profile similar to adults have not been determined. Studies using doses higher than 10 mg/kg or dosing more frequently than every 12 hours have not been conducted in pediatric patients. Geriatrics The pharmacokinetics of linezolid are not significantly altered in elderly patients Hepatic Insufficiency The pharmacokinetics of linezolid are not altered in patients (n=7) with mild-to-moderate hepatic insufficiency (Child-Pugh class A or B). On the basis of the available information, no dose adjustment is recommended for patients with mild-to-moderate hepatic insufficiency. The pharmacokinetics of linezolid in patients with severe hepatic insufficiency have not been evaluated. Mechanism of Action Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, with in vitro activity against aerobic gram-positive bacteria, certain gram-negative bacteria, and anaerobic microorganisms. Linezolid inhibits bacterial protein synthesis through a unique mechanism of action. Linezolid binds to sites on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. The mechanism of action of linezolid (oxazolidinones) differs from that of other antibiotic classes (e.g., aminoglycosides, beta-lactams, folic acid antagonists, glycopeptides, lincosamides, quinolones, rifamycins, streptogramins, tetracyclines, chloramphenicol). Therefore, cross-resistance between linezolid and the mentioned classes of antibiotics is unlikely. Linezolid is active against selected gram positive bacteria that are susceptible or resistant to these antibiotics. In vitro tests have shown that resistance to linezolid develops slowly via multiple-step mutations in the 23S ribosomal RNA and occurs at a frequency of 1×10-9 to 1×10-11. Figure 1 - ZYVOXAM Plasma Concentrations of Linezolid at Steady-state Following Oral Dosing of 600 mg Every 12 Hours (Mean±Standard Deviation, n=16) Race The total clearance of linezolid is not influenced by race. Therefore, dose adjustment is not necessary for different races. Contraindications ZYVOXAM (linezolid) Tablets and Injection are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components. Your Shopping Cart You currently have no items in your cart. Customer Support Call Toll Free: 1-888-254-3038 Live Chat Help: 90 Day Risk Free Refund Buy with confidence, your satisfaction is guaranteed Salinas Firm Initiates A Voluntary Recall Because Of Possible Health Risk Taylor Farms Retail, Inc. is initiating a voluntary recall of Organic Baby Spinach with the potential to be... Pacific Coast Fruit Company Recalls Single Side Serving Processed Salads for Potential Listeria monocytogenes Contamination Pacific Coast Fruit Company, Portland, Oregon is voluntarily recalling multiple types of bagged processed salads based... Now Hiring Are you an energetic, self starter, looking to succeed? Call us today @ 1-888-254-3038 and set up an interview. * Standard shipping is $8.88; many vendors offer Free Shipping Specials on select products. * We utilize average wholesale price from our US mail order pharmacy as the comparison for competitive purposes. * If your shopping cart contains one or more prescription (Rx) items, then a prescription is required, written by your doctor, on all new prescription orders by the pharmacy prior to dispensing the product. You can place your order now and the pharmacy staff at The Drug Company will work with you to obtain your prescription (Rx) at a later date. We also offer a prescription transfer service, please call to learn more. All Rights Reserved. Designated trademarks and brands are the property of their respective owners. Use of this website constitutes acceptance of the COMPANY™ Information about Terms of Service, Returns, Privacy is available from our Site Map.