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
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SPL UNCLASSIFIED SECTION

Susceptibility Test Methods

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. 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.

 DRUGS & SUPPLEMENTS

Ceftazidime

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Ceftazidime uses


SPL UNCLASSIFIED SECTION

Ceftazidime®

brand of

Ceftazidime for injection, USP                                                                   PRESCRIBING INFORMATION


PHARMACY BULK PACKAGE –

NOT FOR DIRECT INFUSION


                                                                                                                                                       

Rx only

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

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DESCRIPTION

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 structure:


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

Ceftazidime (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. Solutions of Ceftazidime range in color from light yellow to amber, depending on the diluent and volume used. The pH of freshly reconstituted solutions usually ranges from 5.0 to 7.5.

Ceftazidime is available in a 6 gram Pharmacy Bulk Package. The contents of this Pharmacy Bulk Package are intended for use by a pharmacy admixture service for addition to suitable parenteral fluids in the preparation of admixtures for intravenous infusion. FURTHER DILUTION IS REQUIRED BEFORE USE. The 6 gram pharmacy bulk package can be reconstituted with 26 mL of Sterile Water for Injection; after reconstitution, each 5 mL of the resulting solution contains approximately 1g of Ceftazidime.

Structural Formula Ceftazidime

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 mcg/mL 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 mcg/mL, 69 mcg/mL 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.

Table 1. Average Serum Concentrations of Ceftazidime

Ceftazidime

IV Dose


Serum Concentrations


0.5 hr


1 hr


2 hr


4 hr


8 hr


500 mg

1 g

2 g


42

60

129


25

39

75


12

23

42


6

11

13


2

3

5


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 g 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 mcg/mL 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.

Table 2. Ceftazidime Concentrations in Body Tissues and Fluids

 

 

Tissue or Fluid


Dose/Route


No. of

Patients


Time of Sample Postdose


Average Tissue or

Fluid Level

(mcg/mL or mcg/g)


Urine

 

Bile

Synovial fluid

Peritoneal fluid

Sputum

Cerebrospinal fluid

  (inflamed meninges)

Aqueous humor

Blister fluid

Lymphatic fluid

Bone

Heart muscle

Skin

Skeletal muscle

Myometrium


500 mg IM

2 g IV

2 g IV

2 g IV

2 g IV

1 g IV

2 g q8hr IV

2 g q8hr IV

2 g IV

1 g IV

1 g IV

2 g IV

2 g IV

2 g IV

2 g IV

2 g IV


6

6

3

13

8

8

5

6

13

7

7

8

35

22

35

31


0 to 2 hr

0 to 2 hr

90 min

2 hr

2 hr

1 hr

120 min

180 min

1 to 3 hr

2 to 3 hr

2 to 3 hr

0.67 hr

30 to 280 min

30 to 180 min

30 to 280 min

1 to 2 hr


2,100.0

12,000.0

36.4

25.6

48.6

9.0

9.8

9.4

11.0

19.7

23.4

31.1

12.7

6.6

9.4

18.7

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Microbiology

Mechanism of Action

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.

Mechanism of Resistance

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

- - - - - - - - - - - - - - - - - - - - - - - - - - - -
Table 3. Susceptibility Test Interpretive Criteria for Ceftazidime
§     Susceptibility interpretive criteria for Enterobacteriaceae are based on a dose of 1 gram q8h. For isolates with intermediate susceptibility, use a dose of 2 grams every 8 hours in patients with normal renal function.

*     For P. aeruginosa, susceptibility interpretive criteria are based on a dose of 2 grams IV every 8 hours in patients with normal renal function.

a     The current absence of data on resistant isolates precludes defining any category other than ‘Susceptible’. If isolates yield MIC results other than susceptible, they should be submitted to a reference laboratory for additional testing.

Susceptibility of staphylococci to Ceftazidime may be deduced from testing only penicillin and either cefoxitin or oxacillin.


Pathogen


Minimum Inhibitory Concentrations

(mcg/ml)


Disk Diffusion Zone Diameters (mm)


(S)

Susceptible


(I)

Intermediate


(R)

Resistant


(S)

Susceptible


(I)

Intermediate


(R)

Resistant


Enterobacteriaceae §


≤4


8


≥16


≥21


18 to 20


≤17


Haemophilus influenzae a


≤2


-


-


≥26


-


-


Pseudomonas aeruginosa*


≤8


-


≥16


≥18


-


≤17


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.

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SPL UNCLASSIFIED SECTION

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.

Table 4. Acceptable Quality Control Ranges for Ceftazidime

QC Strain


Minimum Inhibitory

Concentrations


Disk Diffusion Zone

diameters (mm)


Escherichia coli ATCC 25922


0.06 to 0.5


25 to 32


Staphylococcus aureus ATCC 25923


---------


16 to 20


Staphylococcus aureus ATCC 29213


4 to 16


---------


Haemophilus influenzae ATCC 49247


0.12 to 1


27 to 35


Neisseria gonorrhoeae ATCC 49226


0.03 to 0.12


35 to 43


Pseudomonas aeruginosa ATCC 27853


1 to 4


22 to 29

INDICATIONS AND USAGE

Ceftazidime (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 .

Ceftazidime (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 antibiotics have been used.

Ceftazidime may also be used concomitantly with other antibiotics, 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 antibiotics 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 Ceftazidime (ceftazidime) and other antibacterial drugs, Ceftazidime (ceftazidime) should be used only to treat or prevent 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

Ceftazidime is contraindicated in patients who have shown hypersensitivity to Ceftazidime or the cephalosporin group of antibiotics.

WARNINGS

BEFORE THERAPY WITH Ceftazidime 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 ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO Ceftazidime 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 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 antibiotic 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic 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, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia (see PRECAUTIONS ).

PRECAUTIONS

General

High and prolonged serum Ceftazidime concentrations can occur from usual dosages in patients with transient or persistent reduction of urinary output because of renal insufficiency.

The total daily dosage should be reduced when Ceftazidime is administered to patients with renal insufficiency. Elevated levels of Ceftazidime in these patients can lead to seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms.

As with other antibiotics, prolonged use of Ceftazidime (ceftazidime for injection, USP) may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient’s condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Inducible type I beta-lactamase resistance has been noted with some organisms (e.g., Enterobacter spp., Pseudomonas spp., and Serratia spp.). As with other extended-spectrum beta-lactam antibiotics, resistance can develop during therapy, leading to clinical failure in some cases. When treating infections caused by these organisms, periodic susceptibility testing should be performed when clinically appropriate. If patients fail to respond to monotherapy, an aminoglycoside or similar agent should be considered.

Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal and hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.

Ceftazidime should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Distal necrosis can occur after inadvertent intra-arterial administration of Ceftazidime.

Prescribing Ceftazidime (ceftazidime) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients

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

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 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Nephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibiotics or potent diuretics such as furosemide. Renal function should be carefully monitored, especially if higher dosages of the aminoglycosides are to be administered or if therapy is prolonged, because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. Nephrotoxicity and ototoxicity were not noted when Ceftazidime was given alone in clinical trials.

Chloramphenicol has been shown to be antagonistic to beta-lactam antibiotics, including Ceftazidime, based on in vitro studies and time kill curves with enteric gram-negative bacilli. Due to the possibility of antagonism in vivo , particularly when bactericidal activity is desired, this drug combination should be avoided.

In common with other antibiotics, Ceftazidime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Drug/Laboratory Test Interactions

The administration of Ceftazidime may result in a false-positive reaction for glucose in the urine when using CLINITEST® tablets, Benedict's solution, or Fehling's solution.

It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. However, a mouse micronucleus test and an Ames test were both negative for mutagenic effects.

Pregnancy

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 40 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Ceftazidime. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Ceftazidime is excreted in human milk in low concentrations. Caution should be exercised when Ceftazidime is administered to a nursing woman.

Pediatric Use

.

Geriatric Use

Of the 2,221 subjects who received Ceftazidime in 11 clinical studies, 824 (37%) were 65 and older while 391 (18%) were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater susceptibility of some older individuals to drug effects cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION ).

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.

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 antibiotics, 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 Ceftazidime (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 Ceftazidime (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 Ceftazidime 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 antibiotics:

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.

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


PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION


NOTE: The Pharmacy Bulk Package is intended for preparing IV admixtures only. Dosage recommendations for intramuscular or intravenous injection and intraperitoneal use are for informational purposes only.

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 Ceftazidime are listed in Table 5. The following dosage schedule is recommended. 

Table 5. Recommended Dosage Schedule

Dose


Frequency


Adults


Usual recommended dosage


1 gram IV or IM


q8-12hr


Uncomplicated urinary tract infections


250 mg IV or IM


q12hr


Bone and joint infections


2 grams IV


q12hr


Complicated urinary tract infections


500 mg IV or IM


q8-12hr


Uncomplicated pneumonia; mild skin and

skin-structure infections


500 mg to 1 gram

IV or IM


q8hr


Serious gynecologic and

intra-abdominal infections


2 grams IV


q8hr


Meningitis


2 grams IV


q8hr


Very severe life-threatening infections,

especially in immunocompromised patients


2 grams IV


q8hr


Lung infections caused by Pseudomonas

spp. in patients with cystic fibrosis with

normal renal functionAlthough clinical improvement has been shown, bacteriologic cures cannot be expected in patients with chronic respiratory disease and cystic fibrosis.


30 to 50 mg/kg IV

to a maximum

of 6 grams per day


q8hr

  


Neonates (0 – 4 weeks)


30 mg/kg IV


q12hr


Infants and children

(1 month – 12 years)

   


30 to 50 mg/kg IV

to a maximum

of 6 grams per dayThe higher dose should be reserved for immunocompromised pediatric patients or pediatric patients with cystic fibrosis or meningitis.


q8hr

   


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 6

Table 6. Recommended Maintenance Dosages of Ceftazidime (ceftazidime for injection, USP) in Renal Insufficiency

NOTE: IF THE DOSE RECOMMENDED IN TABLE 5 ABOVE IS LOWER THAN THAT RECOMMENDED FOR PATIENTS WITH RENAL INSUFFICIENCY AS OUTLINED IN TABLE 6 , THE LOWER DOSE SHOULD BE USED.


Creatinine

Clearance

(mL/min)


Recommended

Unit Dose of

Ceftazidime


Frequency

of Dosing


50 to 31

30 to 16

15 to 6

<5


1 gram

1 gram

500 mg

500 mg


q12hr

q24hr

q24hr

q48hr


When only serum creatinine is available, the following formula (Cockcroft’s equation)4 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 Ceftazidime 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.

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

Note: Generally Ceftazidime 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

Pharmacy Bulk Package is for use in a pharmacy admixture service only. Refer to Table 7. See above NOTE concerning the proper use of Pharmacy Bulk Packages.

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.

Intermittent IV infusion with a Y-type administration set can be accomplished with compatible solutions. However, during infusion of a solution containing Ceftazidime, it is desirable to discontinue the other solution.

All vials of Ceftazidime as supplied are under reduced pressure. When Ceftazidime is dissolved, carbon dioxide is released and a positive pressure develops.

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

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

Directions for Use of Pharmacy Bulk Packages:

Reconstitute with Sterile Water for Injection according to Table 7

Table 7. Preparation of Solutions of Ceftazidime

Diluent to Be Added


Approx. Avail. Volume


Approx. Avg. Concentration


26 mL

56 mL


30 mL

60 mL


1 gram/5 mL

1 gram/10 mL


Note: The Pharmacy Bulk Package is for use in a pharmacy admixture service only. Using aseptic technique, the closure should be penetrated only 1 time after reconstitution using a sterile dispensing set which 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. THE ENTIRE CONTENTS OF THE VIAL SHOULD BE DISPENSED WITHIN 4 HOURS OF INITIAL ENTRY.

A plastic bail attached to the Pharmacy Bulk Package provides a suitable hanging device while dispensing in the pharmacy.

Reconstitute with Sterile Water for Injection according to Table 7.

The vacuum may assist entry of the diluent. SHAKE WELL.

Insert a gas relief needle through the vial closure to relieve the internal pressure. Remove the gas relief needle before extracting any solution.

SPL UNCLASSIFIED SECTION

COMPATIBILITY AND STABILITY

IMPORTANT: The following chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that compounded admixtures should be administered as soon after preparation as is feasible.

Intravenous: Ceftazidime when reconstituted as directed with Sterile Water for Injection, should be used within 4 hours. Solutions in Sterile Water for Injection in the original container or in 0.9% Sodium Chloride Injection in VIAFLEX® small-volume containers that are frozen immediately after reconstitution are stable for 3 months when stored at -20°C. Do not force thaw by immersion in water baths or by microwave irradiation. Once thawed, solutions should not be refrozen. Thawed solutions may be stored for up to 24 hours at room temperature or for 7 days in a refrigerator. More concentrated solutions in Sterile Water for Injection in the original container that are frozen immediately after reconstitution are stable for 3 months when stored at -20°C. Once thawed, solutions should not be refrozen. Thawed solutions may be stored for up to 8 hours at room temperature or for 4 days in a refrigerator.

Ceftazidime (ceftazidime for injection, USP) is compatible with the more commonly used IV infusion fluids. Solutions at concentrations between 1 mg/mL 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.

Ceftazidime is less stable in Sodium Bicarbonate Injection than in other IV fluids. It is not recommended as a diluent. Solutions of Ceftazidime 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 U/mL or 50 U/mL, or potassium chloride 10 mEq/L 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, Ceftazidime (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

Ceftazidime in the dry state should be stored at 20° to 25°C (68° to 77°F) and protected from light. Ceftazidime (ceftazidime for injection, USP) is a dry, white to off-white powder supplied in vials as follows:

Pharmacy Bulk Package Bottles: equivalent to 6 grams of Ceftazidime.

6 gram (tray of 10) NDC 0409-5086-11 

Also available as:

Vials: equivalent to 1 gram and 2 grams of Ceftazidime.

1 gram (tray of 25) NDC 0409-5082-16

2 gram (tray of 10) NDC 0409-5084-11

ADD-Vantage® Vials: equivalent to 1 gram and 2 grams of Ceftazidime.

1 gram: NDC 0409-5092-16

2 gram: NDC 0409-5093-11

REFERENCES

1.Clinical and Laboratory Standards Institute. 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.   

Revised: 5/2016

 

 

                                                                                  EN-4285

Manufactured by Sandoz GmbH for

Hospira Worldwide, Inc., Lake Forest, IL 60045, USA                                                            

Made in Kundl, Austria.

46184541

Hospira logo

RL-1116

label NDC 0409-5086-11

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Ceftazidime pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Ceftazidime available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.

Price
Ceftazidime 1 gm vial10.46 USD
Ceftazidime 2 gm vial19.97 USD
Ceftazidime 6 gm vial97.05 USD
Ceftazidime-sodium carb powder6.27 USD
Fortaz 1 g/vial25.44 USD
Fortaz 1 gm add-vantage vial14.71 USD
Fortaz 1 gm vial14.23 USD
Fortaz 2 g/vial50.01 USD
Fortaz 2 gm add-vantage vial28.93 USD
Fortaz 2 gm vial28.45 USD
Fortaz 6 g/vial150.11 USD
Fortaz 6 gm vial82.8 USD
Fortaz-iso-osmot 2 gm/50 ml0.62 USD
Fortaz-iso-osmotic 1 gm/50 ml0.34 USD
Injectable; Infusion; Ceftazidime Pentahydrate 1 g;
Injectable; Infusion; Ceftazidime Pentahydrate 2 g
Injectable; Injection; Ceftazidime Pentahydrate 1 g
Injectable; Injection; Ceftazidime Pentahydrate 2 g
Injectable; Injection; Ceftazidime Pentahydrate 250 mg
Injectable; Injection; Ceftazidime Pentahydrate 500 mg
Injectable; Injection; Ceftazidime Pentahydrate 6 g
Tazicef 1 gram vial4.57 USD
Tazicef 2 gram vial10.66 USD
Tazicef 6 gram vial29.88 USD

Ceftazidime destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Ceftazidime Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Ceftazidime pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."TAZICEF (CEFTAZIDIME) INJECTION, POWDER, FOR SOLUTION [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."CEFTAZIDIME: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "ceftazidime". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Ceftazidime?

Depending on the reaction of the Ceftazidime after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ceftazidime not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Ceftazidime addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Ceftazidime, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Ceftazidime consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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