TAZICEF®
brand of
ceftazidime for injection, USP

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tazicef (ceftazidime) and other antibacterial drugs, Tazicef (ceftazidime) should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Ceftazidime is a semisynthetic, broad-spectrum, beta-lactam antibacterial drug 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 structure:

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

Tazicef (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 6-g Pharmacy Bulk Packages equivalent to 6 g of anhydrous ceftazidime.

The 6 grams Pharmacy Bulk Package bottle is a container of sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture program and are restricted to the preparation of admixtures for intravenous use. THE PHARMACY BULK PACKAGE IS NOT FOR DIRECT INFUSION, FURTHER DILUTION IS REQUIRED BEFORE USE (see DOSAGE AND ADMINISTRATION-Directions for Proper Use of Pharmacy Bulk Package).

Solutions of Tazicef 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 7.5.

CLINICAL PHARMACOLOGY

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.

INDICATIONS AND USAGE

Tazicef (ceftazidime for injection, USP) is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:

1.

Lower Respiratory Tract Infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin-resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains).

2.

Skin and Skin-Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A beta-hemolytic streptococci).

3.

Urinary Tract Infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli.

4.

Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains).

5.

Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains).

6.

Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli.

7.

Intra-abdominal Infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

8.

Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. Ceftazidime has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae.

Tazicef (ceftazidime for injection, USP) may be used alone in cases of confirmed or suspected sepsis. Ceftazidime has been used successfully in clinical trials as empiric therapy in cases where various concomitant therapies with other antibacterial drugs have been used.

Tazicef may also be used concomitantly with other antibacterial drugs, such as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening infections; and in the immunocompromised patient. When such concomitant treatment is appropriate, prescribing information in the labeling for the other antibacterial drugs should be followed. The dose depends on the severity of the infection and the patient's condition.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tazicef (ceftazidime) and other antibacterial drugs, Tazicef (ceftazidime) should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

Tazicef is contraindicated in patients who have shown hypersensitivity to ceftazidime or the cephalosporin group of antibacterial drugs.

WARNINGS

BEFORE THERAPY WITH TAZICEF IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFTAZIDIME, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBACTERIAL DRUGS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO TAZICEF OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftazidime, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Elevated levels of ceftazidime in patients with renal insufficiency can lead to seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia (see PRECAUTIONS ).

PRECAUTIONS

ADVERSE REACTIONS

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), nausea (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 Tazicef (ceftazidime for injection, USP) 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 Tazicef (ceftazidime for injection, USP) Products

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

General 

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

Hepatobiliary Tract

Hyperbilirubinemia, jaundice.

Renal and Genitourinary

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:

Adverse Reactions

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

Altered Laboratory Tests

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

To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. at 1-800-441-4100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Ceftazidime overdosage has occurred in patients with renal failure. Reactions have included seizure activity, encephalopathy, asterixis, neuromuscular excitability, and coma. Patients who receive an acute overdosage should be carefully observed and given supportive treatment. In the presence of renal insufficiency, hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body.

DOSAGE AND ADMINISTRATION

Dosage The usual adult dosage is 1 gram administered intravenously every 8 to 12 hours. The dosage and route should be determined by the susceptibility of the causative organisms, the severity of infection, and the condition and renal function of the patient.

The guidelines for dosage of Tazicef (ceftazidime for injection, USP) are listed in Table 3. The following dosage schedule is recommended. 

Impaired Hepatic Function

No adjustment in dosage is required for patients with hepatic dysfunction.

Impaired Renal Function

Ceftazidime is excreted by the kidneys, almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function (glomerular filtration rate [GFR] <50 mL/min), it is recommended that the dosage of ceftazidime be reduced to compensate for its slower excretion. In patients with suspected renal insufficiency, an initial loading dose of 1 gram of ceftazidime may be given. An estimate of GFR should be made to determine the appropriate maintenance dosage. The recommended dosage is presented in Table 4. 

When only serum creatinine is available, the following formula (Cockcroft's equation)1 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:

                                                                                 Weight (kg) x (140 - age)
Males: Creatinine clearance (mL/min) =                 ––––––––––––––––––––––––––
                                                                                 72 x serum creatinine (mg/dL)        

Females: 0.85 x male value 

In patients with severe infections who would normally receive 6 grams of Tazicef daily were it not for renal insufficiency, the unit dose given in the table above may be increased by 50% or the dosing frequency may be increased appropriately. Further dosing should be determined by therapeutic monitoring, severity of the infection, and susceptibility of the causative organism.

In pediatric patients as for adults, the creatinine clearance should be adjusted for body surface area or lean body mass, and the dosing frequency should be reduced in cases of renal insufficiency.

In patients undergoing hemodialysis, a loading dose of 1 gram is recommended, followed by 1 gram after each hemodialysis period.

Tazicef (ceftazidime for injection, USP) can also be used in patients undergoing intraperitoneal dialysis and continuous ambulatory peritoneal dialysis. In such patients, a loading dose of 1 gram of Tazicef may be given, followed by 500 mg every 24 hours. In addition to IV use, Tazicef can be incorporated in the dialysis fluid at a concentration of 250 mg for 2 L of dialysis fluid.

Note: Generally, Tazicef should be continued for 2 days after the signs and symptoms of infection have disappeared, but in complicated infections longer therapy may be required.

Administration

Intravenous Administration

The IV route is preferable for patients with bacterial septicemia, bacterial meningitis, peritonitis, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or pending.

Directions for Proper Use of a Pharmacy Bulk Package

Not for direct infusion. This Pharmacy Bulk Package is for use in a hospital pharmacy admixture service, only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time using a suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 hours from initial closure entry is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Package. DISCARD ANY UNUSED PORTION AFTER 4 HOURS. NOT FOR DIRECT INFUSION. THIS PHARMACY BULK PACKAGE IS NOT INTENDED TO BE DISPENSED AS A UNIT.

Freezing solutions of Tazicef is not recommended.

Tazicef (Pharmacy Bulk Package), when constituted as directed with Sterile Water for Injection, should have the contents withdrawn within 4 hours.

After constitution, add an appropriate quantity of the resulting solution to an IV container with one of the compatible IV fluids listed under the COMPATIBILITY AND STABILITY section.

All vials of Tazicef as supplied are under reduced pressure. When Tazicef is dissolved, carbon dioxide is released and a positive pressure develops. For ease of use please follow the recommended techniques of constitution described on the detachable Instructions for Constitution section of this insert.

Solutions of Tazicef, like those of most beta-lactam antibacterial drugs, should not be added to solutions of aminoglycoside antibacterial drugs because of potential interaction.

However, if concurrent therapy with Tazicef and an aminoglycoside is indicated, each of these antibacterial drugs can be administered separately to the same patient.

COMPATIBILITY AND STABILITY

Intravenous Tazicef (ceftazidime for injection, USP), when constituted as directed with Sterile Water for Injection, maintains satisfactory potency for 24 hours at room temperature or for 7 days under refrigeration.

Tazicef (ceftazidime for injection, USP) is compatible with the more commonly used IV infusion fluids. Solutions at concentrations between 1 and 40 mg/mL in 0.9% Sodium Chloride Injection; 1/6 M Sodium Lactate Injection; 5% Dextrose Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 10% Dextrose Injection; Ringer's Injection, USP; Lactated Ringer's Injection, USP; 10% Invert Sugar in Water for Injection; and NORMOSOL®-M in 5% Dextrose Injection may be stored for up to 24 hours at room temperature or for 7 days if refrigerated.

Tazicef is less stable in Sodium Bicarbonate Injection than in other IV fluids. It is not recommended as a diluent. Solutions of Tazicef in 5% Dextrose Injection and 0.9% Sodium Chloride Injection are stable for at least 6 hours at room temperature in plastic tubing, drip chambers, and volume control devices of common IV infusion sets.

Ceftazidime at a concentration of 4 mg/mL has been found compatible for 24 hours at room temperature or for 7 days under refrigeration in 0.9% Sodium Chloride Injection or 5% Dextrose Injection when admixed with: cefuroxime sodium (ZINACEF®) 3 mg/mL, heparin 10 or 50 U/mL, or potassium chloride 10 or 40 mEq/L.

Vancomycin solution exhibits a physical incompatibility when mixed with a number of drugs, including ceftazidime. The likelihood of precipitation with ceftazidime is dependent on the concentrations of vancomycin and ceftazidime present. It is therefore recommended, when both drugs are to be administered by intermittent IV infusion, that they be given separately, flushing the IV lines (with 1 of the compatible IV fluids) between the administration of these 2 agents.

Note: Parenteral drug products should be inspected visually for particulate matter before administration whenever solution and container permit.

As with other cephalosporins, Tazicef (ceftazidime for injection, USP) powder, as well as solutions, tend to darken depending on storage conditions; within the stated recommendations, however, product potency is not adversely affected.

HOW SUPPLIED

Tazicef in the dry state should be stored at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature] and protected from light. Tazicef (ceftazidime for injection, USP) is a dry, white to off-white powder supplied in pharmacy bulk vials as follows:

REFERENCES

1.

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.

ZINACEF is the registered trademark of Teligent, Inc.

CLINITEST and CLINISTIX are registered trademarks of Ames Division, Miles Laboratories, Inc.

Manufactured by Sandoz GmbH for
Hospira, Inc., Lake Forest, IL 60045, USA

LAB-1135-8.0

Revised: 3/2022

TEAR AWAY
Tazicef® (ceftazidime for injection, USP)
Instructions for Constitution

Pharmacy Bulk Package: 6 g

1. Insert the syringe needle through the vial closure and inject 26 mL of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
2. Shake to dissolve; a clear solution containing approximately 1 g of ceftazidime activity per 5 mL will be obtained in 1 to 2 minutes.
3. Insert a gas-relief needle through the vial closure to relieve the internal pressure. Remove the gas-relief needle before extracting any solution.

Note: To preserve product sterility, it is important that a gas-relief needle is not inserted through the vial closure before the product has dissolved.

Manufactured by Sandoz GmbH for
Hospira, Inc., Lake Forest, IL 60045, USA

LAB-1201-3.0

Revised: 12/2020