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.
FORTAZ is contraindicated in patients who have shown hypersensitivity to ceftazidime or the cephalosporin group of antibacterial drugs.
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.
HematologicRare 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 ProductsIn 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.
GeneralAnaphylaxis; allergic reactions, which, in rare instances, were severe (e.g., cardiopulmonary arrest); urticaria; pain at injection site.
Hepatobiliary TractHyperbilirubinemia, jaundice.
Renal And GenitourinaryRenal impairment.
Cephalosporin-Class Adverse ReactionsIn 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 ReactionsColitis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage.
Altered Laboratory TestsProlonged 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.
FORTAZ is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:
FORTAZ 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.
FORTAZ 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 FORTAZ and other antibacterial drugs, FORTAZ 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.
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 FORTAZ. 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.
FORTAZ in the dry state should be stored between 15°C and 30°C (59°F and 86°F) and protected from light. FORTAZ is a dry, white to off-white powder supplied in vials as follows:
(The above TwistVial™ vials are to be used only with compatible diluent containers.)
FORTAZ frozen as a premixed solution of ceftazidime sodium should not be stored above -20°C. FORTAZ is supplied frozen in 50-mL, single-dose, plastic containers as follows:
*Equivalent to anhydrous ceftazidime.
REFERENCES
5. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.
Distributed by Teligent Pharma, Inc. Buena, NJ 08310. Manufactured by GlaxoSmithKline Verona, Italy 37135. Revised: Jul 2017
BEFORE THERAPY WITH FORTAZ 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 HAVE BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO FORTAZ 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 FORTAZ, 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 GeneralHigh 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 (see DOSAGE AND ADMINISTRATION). Elevated levels of ceftazidime in these patients can lead to seizures, nonconvulsive status epilepticus, 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 antibacterial drugs, prolonged use of FORTAZ 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 antibacterial drugs, 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.
FORTAZ 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 FORTAZ 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.
Drug/Laboratory Test InteractionsThe 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 (such as CLINISTIX®) be used.
Carcinogenesis, Mutagenesis, Impairment Of FertilityLong-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 EffectsPregnancy 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 FORTAZ. 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 MothersCeftazidime is excreted in human milk in low concentrations. Caution should be exercised when FORTAZ is administered to a nursing woman.
Pediatric UseSee DOSAGE AND ADMINISTRATION.
Geriatric UseOf 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).
The usual adult dosage is 1 gram administered intravenously or intramuscularly 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 FORTAZ are listed in Table 5. The following dosage schedule is recommended.
Table 5. Recommended Dosage Schedule
| Dose | Frequency | |
| Adults | ||
| Usual recommended dosage | 1 gram intravenous or intramuscular | every 8 to 12 hours |
| Uncomplicated urinary tract infections | 250 mg intravenous or intramuscular | every 12 hours |
| Bone and joint infections | 2 grams intravenous | every 12 hours |
| Complicated urinary tract infections | 500 mg intravenous or intramuscular | every 8 to 12 hours |
| Uncomplicated pneumonia; mild skin and skin- structure infections | 500 mg to 1 gram intravenous or intramuscular | every 8 hours |
| Serious gynecologic and intra-abdominal infections | 2 grams intravenous | every 8 hours |
| Meningitis | 2 grams intravenous | every 8 hours |
| Very severe life-threatening infections, especially in immunocompromised patients | 2 grams intravenous | every 8 hours |
| Lung infections caused by Pseudomonas spp. in patients with cystic fibrosis with normal renal function * | 30 to 50 mg/kg intravenous to a maximum of 6 grams per day | every 8 hours |
| Neonates (0-4 weeks) | 30 mg/kg intravenous | every 12 hours |
| Infants and children (1 month-12 years) |
30 to 50 mg/kg intravenous to a maximum of 6 grams per day† | every 8 hours |
| *Although clinical improvement has been shown, bacteriologic cures cannot be expected in patients with chronic respiratory disease and cystic fibrosis. †The higher dose should be reserved for immunocompromised pediatric patients or pediatric patients with cystic fibrosis or meningitis. |
No adjustment in dosage is required for patients with hepatic dysfunction.
Impaired Renal FunctionCeftazidime 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 FORTAZ 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 FORTAZ in Renal Insufficiency
| Note: if the dose recommended in table 5 above is lower thanThat 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 FORTAZ | Frequency of Dosing |
| 50-31 | 1 gram | every 12 hours |
| 30-16 | 1 gram | every 24 hours |
| 15-6 | 500 mg | every 24 hours |
| less than 5 | 500 mg | every 48 hours |
When only serum creatinine is available, the following formula (Cockcroft’s equation)5 may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function:
| Males: Creatinine clearance (mL/min) = | Weight (kg) x (140 - age) 72 x serum creatinine (mg/dL) |
| Females: 0.85 x male value | |
In patients with severe infections who would normally receive 6 grams of FORTAZ 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.
FORTAZ can also be used in patients undergoing intraperitoneal dialysis and continuous ambulatory peritoneal dialysis. In such patients, a loading dose of 1 gram of FORTAZ may be given, followed by 500 mg every 24 hours. In addition to IV use, FORTAZ can be incorporated in the dialysis fluid at a concentration of 250 mg for 2 L of dialysis fluid.
Note: Generally, FORTAZ should be continued for 2 days after the signs and symptoms of infection have disappeared, but in complicated infections longer therapy may be required.
AdministrationFORTAZ may be given intravenously or by deep IM injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh. Intra-arterial administration should be avoided (see PRECAUTIONS).
Intramuscular AdministrationFor IM administration, FORTAZ should be constituted with one of the following diluents: Sterile Water for Injection, Bacteriostatic Water for Injection, or 0.5% or 1% Lidocaine Hydrochloride Injection. Refer to Table 7.
Intravenous AdministrationThe 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.
For direct intermittent IV administration, constitute FORTAZ as directed in Table 7 with Sterile Water for Injection. Slowly inject directly into the vein over a period of 3 to 5 minutes or give through the tubing of an administration set while the patient is also receiving one of the compatible IV fluids (see Compatibility And Stability).
For IV infusion, constitute the 500-mg, 1-gram, or 2-gram vial and 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.
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.
TwistVial™ vials are to be constituted only with 50 or 100 mL of 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 0.45% Sodium Chloride Injection in compatible flexible diluent containers (see Instructions for Constitution). TwistVial™ vials that have been joined to compatible diluent containers and activated to dissolve the drug are stable for 12 hours at room temperature or for 3 days under refrigeration. Joined vials that have not been activated may be used within a 14-day period; this period corresponds to that for use of compatible diluent containers following removal of the outer packaging (overwrap).
Freezing solutions of FORTAZ is not recommended.
Table 7. Preparation of Solutions of FORTAZ
| Size | Amount of Diluent to be Added (mL) |
Approximate Available Volume (mL) |
Approximate Ceftazidime Concentration (mg/mL) |
| Intramuscular | |||
| 500-mg vial | 1.5 | 1.8 | 280 |
| 1-gram vial | 3 | 3.6 | 280 |
| Intravenous | |||
| 500-mg vial | 5.3 | 5.7 * | 100 |
| 1-gram vial | 10 | 10.8† | 100 |
| 2-gram vial | 10 | 11.5‡ | 170 |
| * To obtain a dose of 500 mg, withdraw 5 mL from the vial following reconstitution. †To obtain a dose of 1 g, withdraw 10 mL from the vial following reconstitution. ‡To obtain a dose of 2 g, withdraw 11.5 mL from the vial following reconstitution. |
|||
All vials of FORTAZ as supplied are under reduced pressure. When FORTAZ 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 FORTAZ, 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 FORTAZ and an aminoglycoside is indicated, each of these antibacterial drugs can be administered separately to the same patient.
Directions For Use Of FORTAZ Frozen In Galaxy® Plastic ContainersFORTAZ supplied as a frozen, sterile, iso-osmotic, nonpyrogenic solution in plastic containers is to be administered after thawing either as a continuous or intermittent IV infusion. The thawed solution is stable for 8 hours at room temperature or for 3 days if stored under refrigeration. Do not refreeze.
Thaw container at room temperature (25°C) or under refrigeration (5°C). Do not force thaw by immersion in water baths or by microwave irradiation. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Mix after solution has reached room temperature. Check for minute leaks by squeezing bag firmly. Discard bag if leaks are found as sterility may be impaired. Do not add supplementary medication. Do not use unless solution is clear and seal is intact.
Use sterile equipment.
CautionDo not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation For AdministrationFORTAZ, when constituted as directed with Sterile Water for Injection, Bacteriostatic Water for Injection, or 0.5% or 1% Lidocaine Hydrochloride Injection, maintains satisfactory potency for 12 hours at room temperature or for 3 days under refrigeration. Solutions in Sterile Water for Injection that are frozen immediately after constitution in the original container 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 3 hours at room temperature or for 3 days in a refrigerator.
IntravenousFORTAZ, when constituted as directed with Sterile Water for Injection, maintains satisfactory potency for 12 hours at room temperature or for 3 days under refrigeration. Solutions in 0.9 % Sodium Chloride Injection in VIAFLEX® small-volume containers that are frozen immediately after constitution 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 12 hours at room temperature or for 3 days in a refrigerator. More concentrated solutions in Sterile Water for Injection in the original container that are frozen immediately after constitution 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 3 days in a refrigerator.
FORTAZ 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 12 hours at room temperature or for 3 days if refrigerated.
The 1- and 2-g FORTAZ TwistVial™ vials, when diluted in 50 or 100 mL of 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 0.45% Sodium Chloride Injection, may be stored for up to 12 hours at room temperature or for 3 days under refrigeration.
FORTAZ is less stable in Sodium Bicarbonate Injection than in other IV fluids. It is not recommended as a diluent. Solutions of FORTAZ 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 12 hours at room temperature or for 3 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, FORTAZ powder, as well as solutions, tend to darken depending on storage conditions; within the stated recommendations, however, product potency is not adversely affected.
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.
HematologicRare 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 ProductsIn 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.
GeneralAnaphylaxis; allergic reactions, which, in rare instances, were severe (e.g., cardiopulmonary arrest); urticaria; pain at injection site.
Hepatobiliary TractHyperbilirubinemia, jaundice.
Renal And GenitourinaryRenal impairment.
Cephalosporin-Class Adverse ReactionsIn 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 ReactionsColitis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage.
Altered Laboratory TestsProlonged 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.
DRUG INTERACTIONSNephrotoxicity has been reported following concomitant administration of cephalosporins with aminoglycoside antibacterial drugs 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 antibacterial drugs. Nephrotoxicity and ototoxicity were not noted when ceftazidime was given alone in clinical trials.
Chloramphenicol has been shown to be antagonistic to beta-lactam antibacterial drugs, 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 antibacterial drugs, ceftazidime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
