Zyvox

Pregnancy category: C

Lactation: Unknown; use caution

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

IV Incompatibilities

Additive: Kanamycin, phenytoin, ceftriaxone, erythromycin lactobionate, TMP-SMX

Syringe: Ampicillin

Y-site: Ampho B, chlorpromazine, diazepam, pentamidine, phenytoin

IV Compatibilities

Additive: Aztreonam, cefazolin, ceftazidime, ciprofloxacin, gentamicin, levofloxacin, ofloxacin, piperacillin, tobramycin

Y-site: Acyclovir, alfentanil, amikacin, aminophylline, ampicillin, aztreonam, bretylium, buprenorphine, butorphanol, Ca-gluconate, cefazolin, cefoperazone, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, cimetidine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dexamethasone Na-phosphate, dexmetedomidine, digoxin, diphenhydramine, dobutamine, dopamine, doxorubicin, doxycycline, droperidol, enalaprilat, esmolol, etoposide PO4, famotidine, fenoldopam, fluconazole, fluorouracil, furosemide, ganciclovir, gemcitabine, gentamycin, granisetron, haloperidol, heparin, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, ifosfamide, imipenem-cilastatin, labetalol, leucovorin, lidocaine, lorazepam, magnesium sulfate, mannitol, meperidine, meropenem, mesna, methotrexate, methylprednisolone, metoclopramide, metronidazole, midazolam, minocycline, mitoxantrone, morphine sulfate, nalbuphine, nicardipine, naloxone, nitroglycerin, ofloxacin, ondansetron, paclitaxel, pentobarbital, piperacillin, KCl, prochlorperazine, promethazine, propranolol, ranitidine, remifentanil, Na-bicarbonate, sufentanil, theophylline, ticarcillin, tobramycin, vancomycin, vecuronium, verapamil, vincristine, zidovudine

IV Preparation

Injection is supplied as a single-use, ready-to-use infusion bag; inspect for particulate matter and minute leaks in bag

Infusion should be administered over 30-120 min

Use reconstituted suspension within 21 days

Storage

Store at 25°C (77°F)

Protect from light

Keep infusion bags in overwrap until ready to use

Protect infusion bags from freezing

Avoid eating or drinking large amounts of foods and beverages containing tyraminewhile using linezolid injection. Foods and beverages that have been pickled, smoked, or fermented usually contain tyramine. These foods and beverages include alcoholic beverages, especially beer, Chianti, and other red wines; alcohol-free beer; cheeses (especially strong, aged, or processed varieties); sauerkraut; yogurt; raisins; bananas; sour cream; pickled herring; liver (especially chicken liver); dried meats and sausage (including hard salami and pepperoni); canned figs; avocados; soy sauce; turkey; yeast extracts; papaya products (including certain meat tenderizers); fava beans; and broad bean pods.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Included as part of the "PRECAUTIONS" Section

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of linezolid in children.

Antibacterial; oxazolidinone.1 2 3 5 57

• Oxazolidinone anti-infective agent.1 2 3 5 57

• Binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents formation of a functional 70S initiation complex.1 2 3 57

• Bacteriostatic in vitro against susceptible enterococci and staphylococci; bactericidal against susceptible streptococci.1 2

• Active in vitro against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]),1 3 54 55 56 65 Streptococcus agalactiae (group B streptococci, GBS),1 3 65 S. pneumoniae,1 3 54 and S. pyogenes (group A β-hemolytic streptococci, GAS).1 3 65 Although clinical importance unknown, also active in vitro against S. epidermidis (including methicillin-resistant [oxacillin-resistant] strains),1 3 54 56 65 S. haemolyticus,1 3 65 viridans group streptococci,1 3 group G streptococci,65 Corynebacterium,65 and Pasteurella multocida.1 3 55

• Active in vitro against vancomycin-resistant Enterococcus faecium.1 3 53 54 56 Although clinical importance unknown, also active in vitro against E. faecium (vancomycin-susceptible strains) and E. faecalis (including vancomycin-resistant strains).1 53 54 56

• Active in vitro against Mycobacterium tuberculosis,59 60 61 63 including some multiple-drug resistant (MDR) and extensively drug-resistant (XDR) strains.60 61 Also has activity in vitro against some strains of M. chelonaei,62 M. fortuitum,62 M. gilvum,64 M. gordonae,64 M. kansasii,62 M. mucogenicum,64 and M. simiae.64

• Resistance to linezolid has been produced in vitro by serial passage of MRSA or enterococci (i.e., E. faecalis, E. faecium) in the presence of increasing concentrations of the drug8 9 57 and has emerged in patients receiving the drug for treatment of infections caused by MRSA1 7 or enterococci.1 53

• Linezolid resistance generally associated with point mutations in 23S rRNA.1 57 However, linezolid resistance in staphylococci mediated by the chloramphenicol-florfenicol (cfr) gene located on a plasmid has been reported and such resistance is transferable between staphylococci.1

• Cross-resistance between linezolid and other oxazolidinones (e.g., tedizolid) reported.1 45 52 Bacteria resistant to linezolid because of mutations in chromosomal genes encoding the 23S rRNA or ribosomal proteins (L3 and L4) generally cross-resistant to other oxazolidinones (e.g., tedizolid) and vice versa.1 44 52 In vitro data indicate presence of cfr gene in S. aureus that results in resistance to linezolid does not necessarily result in cross-resistance to tedizolid in the absence of chromosomal mutations.44 45 46 52

• Cross-resistance between linezolid and non-oxazolidinone anti-infectives unlikely.2 3 57

Linezolid is used to treat certain bacterial infections in many different parts of the body, including certain types of skin infections or pneumonia.

Linezolid belongs to the family of medicines called antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.

This medicine is available only with your doctor's prescription.

Hypersensitivity

Zyvox formulations are contraindicated for use in patients who have known hypersensitivity to linezolid or any of the other product components.

Monoamine 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.

Zyvox I.V. Injection, Zyvox Tablets, and Zyvox for Oral Suspension contain linezolid, 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 C16H20FN3O4. Its molecular weight is 337.35, and its chemical structure is represented below:

Zyvox I.V. Injection is supplied as a ready-to-use sterile isotonic solution for intravenous infusion. Each mL contains 2 mg of linezolid. Inactive ingredients are sodium citrate, citric acid, and dextrose in an aqueous vehicle for intravenous administration. The sodium (Na+) content is 0.38 mg/mL (5 mEq/300-mL bag; 3.3 mEq/200-mL bag; and 1.7 mEq/100-mL bag).

Zyvox Tablet for oral administration contains 600 mg linezolid as a film-coated compressed tablet. Inactive ingredients are corn starch, microcrystalline cellulose, hydroxypropylcellulose, sodium starch glycolate, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide, and carnauba wax. The sodium (Na+) content is 2.92 mg per 600-mg tablet (0.1 mEq/tablet).

Zyvox for Oral Suspension is supplied as an orange-flavored granule/powder for constitution into a suspension for oral administration. Following constitution, each 5 mL contains 100 mg of linezolid. Inactive ingredients are sucrose, citric acid, sodium citrate, microcrystalline cellulose and carboxymethylcellulose sodium, aspartame, xanthan gum, mannitol, sodium benzoate, colloidal silicon dioxide, sodium chloride, and flavors [see Patient Counseling Information (17)]. The sodium (Na+) content is 8.52 mg/5 mL (0.4 mEq/5 mL).

Patients should be counseled that antibacterial drugs including Zyvox should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Zyvox 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 Zyvox or other antibacterial drugs in the future.

Patients should be advised that:

• Zyvox may be taken with or without food.
• They should inform their physician if they have a history of hypertension.
• Large quantities of foods or beverages with high tyramine content should be avoided while taking Zyvox. 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.
• They should inform their physician if taking medications containing pseudoephedrine HCl or phenylpropanolamine HCl, such as cold remedies and decongestants.
• They should inform their physician if taking serotonin re-uptake inhibitors or other antidepressants.
• Phenylketonurics: Each 5 mL of the 100 mg/5 mL Zyvox for Oral Suspension contains 20 mg phenylalanine. The other Zyvox formulations do not contain phenylalanine. Contact your physician or pharmacist.
• They should inform their physician if they experience changes in vision.
• They should inform their physician if they have a history of seizures.
• Diarrhea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, 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 antibiotic. If this occurs, patients should contact their physician as soon as possible.
• Inform patient, particularly those with diabetes mellitus that 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.

LAB-0139-29.0

NDC 0009-5137-04
Contains 10 of NDC 0009-5137-01
QUANTITY: 1 (10 IV BAGS X 100 mL)

Zyvox® 200 mg/100 mL
(LINEZOLID) INJECTION

RX ONLY

STORE AT 25°C (77°F); EXCURSIONS PERMITTED TO 15-30°C (59-86°F) [SEE USP
CONTROLLED ROOM TEMPERATURE]. DO NOT FREEZE.

DISTRIBUTED BY
PHARMACIA &
UPJOHN DIVISION
OF PFIZER INC,
NY, NY 10017
MADE IN SINGAPORE

Pfizer Injectables

EXP 00/0000
LOT 00 00 00

FUU 0701 01-88-26-019D

UNIT DOSE

Pfizer
NDC 0009-5138-03

Zyvox®
(linezolid) tablets

600 mg

For in-institution use only

30 Tablets
Rx only