Ceftazidime for Injection - Product Information
|Manufacture:||Fresenius Kabi USA, LLC|
|Condition:||Bacteremia, Bone infection (Osteomyelitis), Peritonitis, Pneumonia, Septicemia, Skin and Structure Infection, Urinary Tract Infection|
|Class:||Third generation cephalosporins|
|Form:||Intramuscular (IM), Intravenous (IV), Powder|
In vitro studies indicate that the bactericidal action of ceftazidime results from inhibition of bacterial cell wall synthesis.
Indications and Clinical Uses
Ceftazidime for Injection, USP may be indicated for the treatment of infections caused by susceptible strains of the designated organisms in the diseases listed below:
Pneumonia caused by Pseudomonas aeruginosa, H. influenzae (including ampicillin-resistant strains), Klebsiella sp., Enterobacter sp., Proteus mirabilis, E. coli, Serratia sp., Streptococcuspneumoniae, and Staphylococcus aureus (methicillin-susceptible strains).
Skin and skin-structure infections caused by Pseudomonas aeruginosa, Klebsiella sp., E. coli,Proteus mirabilis, Enterobacter sp., Staphylococcus aureus (methicillin-susceptible strains), and Streptococcus pyogenes.
Urinary tract infections caused by Pseudomonas aeruginosa, Enterobacter sp., Proteus sp. (indole-positive and negative), Klebsiella sp., and E. coli.
Bacteremia/Septicemia caused by Pseudomonas aeruginosa, Klebsiella sp., E. coli, Serratia sp., Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible strains) and Staphylococcus epidermidis.
Bone infections caused by Pseudomonas aeruginosa, Proteus mirabilis, Enterobacter sp., and Staphylococcus aureus (methicillin-susceptible strains).
Peritonitis caused by E. coli, Klebsiella sp., Peptostreptococcus sp. and Bacteroides sp. (most strains of B. fragilis are resistant).
Specimens for bacteriologic cultures should be obtained prior to therapy in order to isolate and identify causative organisms and to determine their susceptibilities to ceftazidime. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.
Due to the nature of the underlying conditions which usually predispose patients to pseudomonal infections of the lower respiratory and urinary tracts, a good clinical response accompanied by bacterial eradication may not be achieved despite evidence of in vitro sensitivity.
Ceftazidime for Injection, USP is contraindicated in patients who have shown hypersensitivity to ceftazidime or the cephalosporin group of antibiotics.
BEFORE THERAPY WITH CEFTAZIDIME FOR INJECTION, USP IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFTAZIDIME, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. CEFTAZIDIME FOR INJECTION SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. THIS PRODUCT SHOULD BE GIVEN WITH CAUTION TO PATIENTS WITH TYPE I HYPERSENSITIVITY REACTIONS TO PENICILLIN. IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG β-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 FOR INJECTION OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.
Clostridium difficile-associated disease
Clostridium difficile -associated disease (CDAD) has been reported with the use of many antibacterial agents, including Ceftazidime for Injection, USP. CDAD may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon, or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
Treatment with antibacterial agents may alter the normal flora of the colon and may permit overgrowth of Clostridium difficile. Clostridium difficile produces toxins A and B, which contribute to the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can be refractory to antimicrobial therapy.
If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not directed against Clostridium difficile. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial agent clinically effective against Clostridium difficile. Surgical evaluation should be instituted as clinically indicated, as surgical intervention may be required in certain severe cases (see ADVERSE REACTIONS).
CEFTAZIDIME FOR INJECTION, USP SHOULD NOT BE USED IN PATIENTS WITH A HISTORY OF CEPHALOSPORIN-ASSOCIATED HEMOLYTIC ANEMIA SINCE THE RECURRENCE OF HEMOLYSIS IS MUCH MORE SEVERE.
An immune mediate hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials, including Ceftazidime for Injection, USP. Severe cases of hemolytic anemia, including fatalities, have been reported in both adults and children. If a patient develops anemia anytime during, or within 2 - 3 weeks subsequent to the administration of Ceftazidime for Injection, USP, the diagnosis of a cephalosporin-associated anemia should be considered and the drug discontinued until the etiology is determined.
Patients may benefit from periodic monitoring for signs and symptoms of hemolytic anemia, including measurement of hematological parameters or drug-induced antibody testing, where appropriate (see ADVERSE REACTIONS).
Ceftazidime for Injection, USP dosage should be reduced in patients with impaired renal function (see DOSAGE AND ADMINISTRATION). High and prolonged serum antibiotic concentrations can occur from normal 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 such patients to avoid the clinical consequences, e.g., seizures, encephalopathy, asterixis, and neuromuscular excitability due to elevated levels of antibiotics (see DOSAGE AND ADMINISTRATION). Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organism.
Chloramphenicol in combination with cephalosporins, including ceftazidime, has been shown to be antagonistic in vitro. Due to the possibility of antagonism in vivo, this combination should be avoided.
As with other antibiotics, prolonged use of Ceftazidime for Injection may result in the overgrowth of non-susceptible organisms including species originally sensitive to the drug. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken. Resistance has developed during therapy with ceftazidime by Staphylococcus aureus, Enterobacteriaceae, Acinetobacter species, and Pseudomonas species.
Ceftazidime for Injection should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
Nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics or potent diuretics, such as furosemide. Although transient elevations of BUN and serum creatinine have been observed in clinical studies, there is no evidence that ceftazidime, when administered alone, is significantly nephrotoxic.
The safety of Ceftazidime for Injection, USP in the treatment of infections during pregnancy has not been established. If the administration of ceftazidime to pregnant patients is considered necessary, its use requires that the potential benefits be weighed against the possible hazards to the fetus.
Ceftazidime is excreted in human milk in low concentrations (3.8 - 5.2 mg/mL). Caution should be exercised when Ceftazidime for Injection, USP is administered to a nursing woman.
Safety in infants 1 month of age or younger has not been established.
The elimination of ceftazidime may be reduced due to impairment of renal function.
Laboratory Test Changes
A false-positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution or with Clinitest tablets. As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen, and/or serum creatinine, hepatic enzymes [aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT)/serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH) and alkaline phosphatases] were observed occasionally. Transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia and lymphocytosis were very rarely seen.
The most common adverse reactions associated with the administration of Ceftazidime for Injection, USP in clinical trials are listed below:
Local effects: reported in < 2% of patients, were phlebitis, thrombophlebitis, pain and inflammation at the site of injection or infusion.
Hypersensitivity reactions: reported in 2% of patients, were pruritus, urticaria, rash, and fever. Immediate reactions, generally manifested by rash and/or pruritus, occurred in 1 in 285 patients. Angioedema and anaphylaxis (0.2% of patients; bronchospasm and/or hypotension) have been reported very rarely (see WARNINGS).
Gastrointestinal symptoms: reported in < 2% of patients, were diarrhea, colitis, nausea, vomiting, and abdominal pain. Pseudomembranous colitis has been reported (see WARNINGS).
Central nervous system reactions: (less than 1%) included headache, dizziness, and paresthesia. Seizures have been reported with several cephalosporins including ceftazidime (see PRECAUTIONS).
Less frequent adverse events: (< 1%) were candidiasis (including oral thrush) and vaginitis.
Hepatic: < 4% of patients experienced transient elevations of hepatic values, these included: SGOT, SGPT, LDH, and alkaline phosphatase.
Renal: transient elevations of blood urea, blood urea nitrogen, and/or serum creatinine were noted in <1% of patients.
Hematopoietic effects: were noted and included eosinophilia (3.4%), positive Coombs' test without hemolysis (5.1%). Transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, and lymphocytosis were seen in < 1% of patients.
Hematologic: Cases of hemolytic anemia have been reported (see WARNINGS).
Symptoms and Treatment of Overdosage
For management of a suspected drug overdose, contact your regional Poison Control Centre.
Signs and Symptoms
Overdosage has occurred in patients with renal failure. Reactions have included seizure activity, encephalopathy, asterixis, and neuromuscular excitability. 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. It is reported that the administration of large doses of parenteral cephalosporins may cause dizziness, paresthesias, and headaches. Seizures may occur following overdosage with some cephalosporins, particularly in patients with renal impairment in whom accumulation is likely to occur.
Laboratory abnormalities that may occur after an overdose include elevations in creatinine, BUN, liver enzymes and bilirubin, a positive Coombs' test, thrombocytosis, thrombocytopenia, eosinophilia, leukopenia, and prolongation of the prothrombin time.
If seizures occur, the drug should be discontinued promptly and anticonvulsant therapy may be administered if clinically indicated. The patient's airway should be protected and ventilation and perfusion supported. The patient's vital signs, blood gases, serum electrolytes, etc. should be meticulously monitored and maintained, within acceptable limits.
In cases of severe overdosage, especially in a patient with renal failure, combined hemodialysis and hemoperfusion may be considered if response to more conservative therapy fails. However, no clinical data supporting such therapy of Ceftazidime for Injection, USP overdosage are available.
Dosage and Administration
Ceftazidime for Injection, USP may be administered intravenously or intramuscularly after reconstitution. Dosage and route of administration should be determined by the severity of infection, susceptibility of the causative organisms, and condition and renal function of the patient.
The usual recommended daily dose of Ceftazidime for Injection, USP is 1 g to 6 g in divided doses; 250 mg to 2 g every 8 to 12 hours (see Table 1).
|Type of infection||Dosage||Frequency and Route|
|Uncomplicated urinary tract infections||250 mg||q12h IM or IV|
|Skin and skin structure infections and uncomplicated pneumonia||500 mg - 1 g||q8h IM or IV|
|Bone infections||2 g||q12h IV|
|Life-threatening infections (those commonly needing antibiotics in higher doses e.g., peritonitis or septicemia) or infections due to less susceptible organisms||2 g||q12h IV|
A normal course of treatment should continue until 48 - 72 hours after the patient defervesces or after bacterial eradication has been obtained, usually 10 - 14 days, except for bone infections where treatment can continue for 6 weeks. In the treatment of beta-hemolytic streptococcal infections, Ceftazidime for Injection, USP should be administered for at least 10 days.
Adults With Impaired Renal Function
A reduced dosage must be employed and the serum levels closely monitored. After an initial dose of 1 g, a maintenance dosage schedule should be followed (see Table 2 below). The maintenance dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organism.
When only serum creatinine is available, the following formula (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.
|Recommended Dose of
Ceftazidime for Injection
|50 - 31 1||1 g||q12h|
|30 - 16 1||1 g||q24h|
|15 - 6 5||500 mg||q24h|
|≤ 5 5||500 mg||q48h|
In patients with severe infections who would normally receive 6 g of ceftazidime daily were it not for renal insufficiency, the dose given in the above table may be increased by 50% or the dosing frequency increased appropriately. Continued dosage should be determined by therapeutic monitoring, severity of the infection, and susceptibility of the causative organism.
In patients undergoing hemodialysis, a loading dose of 0.5 - 1 g of ceftazidime is recommended, followed by 0.5 - 1 g after each hemodialysis period.
Ceftazidime for Injection, USP can also be used in patients undergoing intraperitoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). In such patients, a loading dose of 1 g of ceftazidime may be given, followed by 500 mg every 24 hours. In addition to intravenous use, ceftazidime can be incorporated in the dialysis fluid at a concentration of 250 mg/2 L of dialysis fluid.
Children with Impaired Renal Function
In children, as in 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.
Impaired Hepatic Function
No adjustment in dosage is required for patients with hepatic dysfunction provided renal function is not impaired.
Infants and Children*
The following dosage schedule (not to exceed the maximum adult dose) is recommended, although renal status and seriousness of infection must be considered:
|1 month - 2 months||12.5 - 25 mg/kg||q12h IV|
|2 months - 12 years||10 - 33 mg/kg||q8h IV|
* Safety and efficacy have not been established in infants less than 1 month of age.
Due to the nature of the underlying conditions which usually predispose patients to Pseudomonas infections of the lower respiratory and urinary tracts, a good clinical response accompanied by bacterial eradication may not be achieved despite evidence of in vitro sensitivity.
Ceftazidime for Injection, USP should be injected well within the body of a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh.
The intravenous route is preferable for patients with septicemia, peritonitis, or other severe or life-threatening infections.
Intermittent Intravenous Administration
The reconstituted solution may be slowly injected into the vein over a period of 3 to 5 minutes or given through the tubing of an administration set. During the infusion of the solution containing ceftazidime, the administration of other solutions should be discontinued temporarily.
Continuous Intravenous Infusion
Ceftazidime for Injection, USP may also be administered over a longer period of time.
|NOTE:||If therapy with Ceftazidime for Injection is carried out in combination with an aminoglycoside antibiotic, either, each of these antibiotics should be administered at different sites, or ceftazidime and aminoglycosides may be administered sequentially by intermittent intravenous infusion. After the administration of one of the two drugs, the tubing is carefully and thoroughly flushed with an approved solution for reconstitution and then the other drug solution is administered. An aminoglycoside should not be mixed with Ceftazidime for Injection in the same container.|