Ceftazidime

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• aminoglycosides such as amikacin (Amikin), gentamicin (Garamycin), and tobramycin (Nebcin)
• furosemide (Lasix)
• probenecid (Probalan, Benemid)
• methotrexate (Trexall, Rheumatrex)
• birth control pills
• chloramphenicol (Chloromycetin, Mychel-S)

This is not a complete list of ceftazidime drug interactions. Ask your doctor or pharmacist for more information.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of ceftazidime, there are no specific foods that you must exclude from your diet when receiving this medication.

• Tazicef

© Ceptaz Patient Information is supplied by Cerner Multum, Inc. and Ceptaz Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Do not use this medication if you are allergic to ceftazidime, or to similar antibiotics, such as Ceclor, Ceftin, Cefzil, Duricef, Keflex, Omnicef, Spectracef, Suprax, and others.

Before using this medication, tell your doctor if you have liver or kidney disease, diabetes, heart failure, cancer, a stomach or intestinal disorder, if you are malnourished, or if you are allergic to penicillin.

Ceftazidime can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while using ceftazidime.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Ceftazidime will not treat a viral infection such as the common cold or flu.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or has blood in it, call your doctor. Do not use any medicine to stop the diarrhea unless your doctor has told you to.

This medication can cause unusual results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using ceftazidime.

Ceftazidime is generally well tolerated. The incidence of adverse reactions associated with the administration of ceftazidime was low in clinical trials. The most common were local reactions following IV injection and allergic and gastrointestinal reactions. Other adverse reactions were encountered infrequently. No disulfiram-like reactions were reported.

The following adverse effects from clinical trials were considered to be either related to ceftazidime therapy or were of uncertain etiology:

Local Effects, reported in fewer than 2% of patients, were phlebitis and inflammation at the site of injection (1 in 69 patients).

Hypersensitivity Reactions, reported in 2% of patients, were pruritus, rash, and fever. Immediate reactions, generally manifested by rash and/or pruritus, occurred in 1 in 285 patients. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have also been reported with cephalosporin antibacterial drugs, including ceftazidime. Angioedema and anaphylaxis (bronchospasm and/or hypotension) have been reported very rarely.

Gastrointestinal Symptoms, reported in fewer than 2% of patients, were diarrhea (1 in 78), nausa (1 in 156), vomiting (1 in 500), and abdominal pain (1 in 416). The onset of pseudomembranous colitis symptoms may occur during or after treatment (see WARNINGS).

Central Nervous System Reactions(fewer than 1%) included headache, dizziness, and paresthesia. Seizures have been reported with several cephalosporins, including ceftazidime. In addition, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in renally impaired patients treated with unadjusted dosing regimens of ceftazidime (see PRECAUTIONS: General).

Less Frequent Adverse Events (fewer than 1%) were candidiasis (including oral thrush) and vaginitis.

Hematologic

Rare cases of hemolytic anemia have been reported.

Laboratory Test Changes noted during clinical trials with FORTAZ were transient and included: eosinophilia (1 in 13), positive Coombs test without hemolysis (1 in 23), thrombocytosis (1 in 45), and slight elevations in one or more of the hepatic enzymes, aspartate aminotransferase (AST, SGOT) (1 in 16), alanine aminotransferase (ALT, SGPT) (1 in 15), LDH (1 in 18), GGT (1 in 19), and alkaline phosphatase (1 in 23). As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen, and/or serum creatinine were observed occasionally. Transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia, and lymphocytosis were seen very rarely.

Postmarketing Experience With FORTAZ Products

In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with FORTAZ and were reported spontaneously. For some of these events, data are insufficient to allow an estimate of incidence or to establish causation.

Anaphylaxis; allergic reactions, which, in rare instances, were severe (e.g., cardiopulmonary arrest); urticaria; pain at injection site.

Hyperbilirubinemia, jaundice.

Renal impairment.

Cephalosporin-Class Adverse Reactions

In addition to the adverse reactions listed above that have been observed in patients treated with ceftazidime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterial drugs:

Colitis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage.

Prolonged prothrombin time, false-positive test for urinary glucose, pancytopenia.

To report SUSPECTED ADVERSE REACTIONS, contact Teligent Pharma, Inc. at 1-856697-1441, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Read the entire FDA prescribing information for Fortaz (Ceftazidime)

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If you need to store ceftazidime at home, talk with your doctor, nurse, or pharmacist about how to store it.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take ceftazidime or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to ceftazidime. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibiotic for parenteral administration. It is the pentahydrate of pyridinium, 1-[[7-[[(2-amino-4-thiazolyl)[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-, hydroxide, inner salt, [6R-[6α,7β(Z)]]. It has the following structural formula:

The molecular formula is C22H32N6O12S2, representing a molecular weight of 636.6.

Ceftazidime for injection, USP is a sterile, dry-powdered mixture of Ceftazidime pentahydrate and sodium carbonate. The sodium carbonate at a concentration of 118 mg/g of Ceftazidime activity has been admixed to facilitate dissolution. The total sodium content of the mixture is approximately 54 mg (2.3 mEq)/g of Ceftazidime activity.

Ceftazidime for injection, USP in sterile crystalline form is supplied in vials equivalent to 1 g or 2 g of anhydrous Ceftazidime. Ceftazidime for injection, USP is a white to cream-colored crystalline powder. Solutions of Ceftazidime for injection, USP range in color from light yellow to amber, depending on the diluent and volume used. The pH of freshly constituted solutions usually ranges from 5 to 8.

After IV administration of 500 mg and 1 g doses of Ceftazidime over 5 minutes to normal adult male volunteers, mean peak serum concentrations of 45 and 90 mcg/ mL, respectively, were achieved. After IV infusion of 500 mg, 1 g, and 2 g doses of Ceftazidime over 20 to 30 minutes to normal adult male volunteers, mean peak serum concentrations of 42, 69, and 170 mcg/mL, respectively, were achieved. The average serum concentrations following IV infusion of 500 mg, 1 g, and 2 g doses to these volunteers over an 8-hour interval are given in Table 1.

The absorption and elimination of Ceftazidime were directly proportional to the size of the dose. The half-life following IV administration was approximately 1.9 hours. Less than 10% of Ceftazidime was protein bound. The degree of protein binding was independent of concentration. There was no evidence of accumulation of Ceftazidime in the serum in individuals with normal renal function following multiple IV doses of 1 and 2 g every 8 hours for 10 days.

Following intramuscular (IM) administration of 500 mg and 1 g doses of Ceftazidime to normal adult volunteers, the mean peak serum concentrations were 17 and 39 mcg/mL, respectively, at approximately 1 hour. Serum concentrations remained above 4 mcg/mL for 6 and 8 hours after the IM administration of 500 mg and 1 g doses, respectively. The half-life of Ceftazidime in these volunteers was approximately 2 hours.

The presence of hepatic dysfunction had no effect on the pharmacokinetics of Ceftazidime in individuals administered 2 g intravenously every 8 hours for 5 days. Therefore, a dosage adjustment from the normal recommended dosage is not required for patients with hepatic dysfunction, provided renal function is not impaired.

Approximately 80% to 90% of an IM or IV dose of Ceftazidime is excreted unchanged by the kidneys over a 24-hour period. After the IV administration of single 500 mg or 1 g doses, approximately 50% of the dose appeared in the urine in the first 2 hours. An additional 20% was excreted between 2 and 4 hours after dosing, and approximately another 12% of the dose appeared in the urine between 4 and 8 hours later. The elimination of Ceftazidime by the kidneys resulted in high therapeutic concentrations in the urine.

The mean renal clearance of Ceftazidime was approximately 100 mL/min. The calculated plasma clearance of approximately 115 mL/min indicated nearly complete elimination of Ceftazidime by the renal route. Administration of probenecid before dosing had no effect on the elimination kinetics of Ceftazidime. This suggested that Ceftazidime is eliminated by glomerular filtration and is not actively secreted by renal tubular mechanisms.

Since Ceftazidime is eliminated almost solely by the kidneys, its serum half-life is significantly prolonged in patients with impaired renal function. Consequently, dosage adjustments in such patients as described in the DOSAGE AND ADMINISTRATION section are suggested.

Therapeutic concentrations of Ceftazidime are achieved in the following body tissues and fluids.

Microbiology

Ceftazidime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftazidime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Resistance to Ceftazidime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Interaction with Other Antimicrobials

In an in vitro study, antagonistic effects have been observed with the combination of chloramphenicol and Ceftazidime.

Ceftazidime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Gram-negative bacteria

• Citrobacter species
• Enterobacter species
• Escherichia coli
• Klebsiella species
• Haemophilus influenzae
• Neisseria meningitidis
• Proteus mirabilis
• Proteus vulgaris
• Pseudomonas aeruginosa
• Serratia species

Gram-positive bacteria

• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes
• Streptococcus agalactiae

Anaerobic bacteria

• Bacteroides species (Note: many isolates of Bacteroides species are resistant)

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Ceftazidime. However, the efficacy of Ceftazidime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-negative bacteria

• Acinetobacter species
• Citrobacter diversus
• Citrobacter freundii
• Providencia species (including Providencia rettgeri)
• Salmonella species
• Shigella species
• Haemophilus parainfluenzae
• Morganella morganii
• Neisseria gonorrhoeae
• Yersinia enterocolitica

Gram-positive bacteria

• Staphylococcus epidermidis

Anaerobic bacteria

• Clostridium species (Not including Clostridium difficile)
• Peptostreptococcus species

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2. The MIC values should be interpreted according to criteria provided in Table 3.

Diffusion techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method2,3. This procedure uses paper disks impregnated with 30 mcg Ceftazidime to test the susceptibility of microorganisms to Ceftazidime. The disk diffusion interpretive criteria are provided in Table 3.

A report of "Susceptible" indicates that the antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of “Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test1,2,3,4. Standard Ceftazidime powder should provide the following range of MIC values noted in Table 4. For the diffusion technique using the 30 mcg disk, the criteria in Table 4 should be achieved.

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fourth Informational Supplement, CLSI document M100-S24. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2014.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition, CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
4. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - Eighth Edition. CLSI document M11-A8. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA, 2012.
5. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.

SAGENT™

Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in Brazil
©2014 Sagent Pharmaceuticals, Inc.

Brands listed are the trademarks of their respective owners.

Revised: December 2014

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TEAR AWAY

Ceftazidime FOR INJECTION, USP

Instructions for Constitution

Vials: 1 g IM/IV, 2 g IV

1. Insert the syringe needle through the vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve; a clear solution will be obtained in 1 to 2 minutes.
3. Invert the vial. Ensuring that the syringe plunger is fully depressed, insert the needle through the vial closure and withdraw the total volume of solution into the syringe (the pressure in the vial may aid withdrawal). Ensure that the needle remains within the solution and does not enter the headspace. The withdrawn solution may contain some bubbles of carbon dioxide.

Note: As with the administration of all parenteral products, accumulated gases should be expressed from the syringe immediately before injection of Ceftazidime for injection.

SAGENT™

Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in Brazil
©2014 Sagent Pharmaceuticals, Inc.

Revised: December 2014

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-127-20

1 g per vial

Ceftazidime FOR INJECTION, USP

Rx only

For Intravenous or Intramuscular Use

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-128-50

2 g per vial

Ceftazidime FOR INJECTION, USP

Rx only

For Intravenous Use

• Tazidime

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs), which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Distribution

Widely throughout the body including bone, bile, skin, CSF (higher concentrations achieved when meninges are inflamed), endometrium, heart, pleural and lymphatic fluids

Excretion

Urine (80% to 90% as unchanged drug)

Time to Peak

Serum: IM: ~1 hour

Half-Life Elimination

1 to 2 hours, prolonged with renal impairment

Protein Binding

<10%

Malignant (necrotizing) otitis externa: 2 g IV every 8 hours

Therapy may be required for 2 to 6 weeks, depending on the nature and severity of the infection.

Otitis media in hospitalized intubated patients: 2 g IV every 8 hours

1 to 2 g IV every 8 hours for 10 to 14 days, depending on the nature and severity of the infection

Peritoneal dialysis patients (ceftazidime sodium):
Intermittent: 1 g/2 L dialysate intraperitoneally once daily
Continuous: 1 g /2 L dialysate intraperitoneally, followed by 250 to 500 mg/2 L dialysate

Lung infections caused by Pseudomonas: 30 to 50 mg/kg IV every 8 hours to a maximum of 6 g/day, in patients with normal renal function

One uncontrolled study of pregnant women between 19 and 21 weeks gestation has suggested that ceftazidime serum concentrations are approximately 50% those expected in nonpregnant women.

Ceftazidime has been assigned to pregnancy category B by the FDA. Animal studies have failed to reveal any evidence of teratogenicity. There are no controlled data in human pregnancy. Ceftazidime should only be given during pregnancy when need has been clearly established.

Ceftazidime is excreted into human milk in small amounts. Ceftazidime is considered compatible with breast-feeding by the American Academy of Pediatrics. The manufacturer recommends that caution be used when administering ceftazidime to nursing women.