"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
FORTAZ (ceftazidime) is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:
- 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).
- 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).
- 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.
- Bacterial Septicemia caused by Pseudomonas aeruginosa, Klebsiella spp., Haemophilus influenzae, Escherichia coli, Serratia spp., Streptococcus pneumoniae, and Staphylococcus aureus (methicillin-susceptible strains).
- Bone and Joint Infections caused by Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus (methicillin-susceptible strains).
- Gynecologic Infections, including endometritis, pelvic cellulitis, and other infections of the female genital tract caused by Escherichia coli.
- 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).
- 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.
FORTAZ (ceftazidime) 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.
FORTAZ (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 FORTAZ (ceftazidime) and other antibacterial drugs, FORTAZ (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.
DOSAGE AND ADMINISTRATION
Dosage: 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 (ceftazidime) are listed in Table 3. The following dosage schedule is recommended.
Table 3. Recommended Dosage Schedule
|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-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,||2 grams IV||q8hr|
|especially in immunocompromised patients|
|Lung infections caused by Pseudomonas spp. in||30-50 mg/kg IV to a||q8hr|
|patients with cystic fibrosis with normal renal function*||maximum of 6 grams per day|
|Neonates (0-4 weeks)||30 mg/kg IV||q12hr|
|Infants and children(1 month-12 years)||30-50 mg/kg IV to a maximum of 6 grams per day†||q8hr|
| * 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.
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 FORTAZ (ceftazidime) may be given. An estimate of GFR should be made to determine the appropriate maintenance dosage. The recommended dosage is presented in Table 4.
Table 4. Recommended Maintenance Dosages of FORTAZ (ceftazidime) in Renal
NOTE: IF THE DOSE RECOMMENDED IN TABLE 3 ABOVE IS LOWER THAN THAT RECOMMENDED FOR PATIENTS WITH RENAL INSUFFICIENCY AS OUTLINED IN TABLE 4, THE LOWER DOSE SHOULD BE USED.
|Creatinine Clearance (mL/min)||Recommended Unit Dose of FORTAZ||Frequency of Dosing|
|< 5||500 mg||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:
|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 (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 patients undergoing hemodialysis, a loading dose of 1 gram is recommended, followed by 1 gram after each hemodialysis period.
FORTAZ (ceftazidime) can also be used in patients undergoing intraperitonealdialysis and continuous ambulatory peritoneal dialysis. In such patients, a loading dose of 1 gram of FORTAZ (ceftazidime) may be given, followed by 500 mg every 24 hours. In addition to IV use, FORTAZ (ceftazidime) can be incorporated in the dialysis fluid at a concentration of 250 mg for 2 L of dialysis fluid. Note: Generally FORTAZ (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: FORTAZ (ceftazidime) 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 Administration: For IM administration, FORTAZ (ceftazidime) 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 5.
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.
For direct intermittent IV administration, constitute FORTAZ (ceftazidime) as directed in Table 5 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 1- or 2-gram infusion pack with 100 mL of Sterile Water for Injection or one of the compatible IV fluids listed under the COMPATIBILITY AND STABILITY section. Alternatively, 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.
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.
ADD-Vantage 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 Abbott ADD-Vantage flexible diluent containers (see Instructions for Constitution). ADD-Vantage vials that have been joined to Abbott ADD-Vantage diluent containers and activated to dissolve the drug are stable for 24 hours at room temperature or for 7 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 Abbott ADD-Vantage containers following removal of the outer packaging (overwrap).
Freezing solutions of FORTAZ (ceftazidime) in the ADD-Vantage system is not recommended.
Table 5. Preparation of Solutions of FORTAZ (ceftazidime)
|Size||Amount of Diluentto be Added (mL)||Approximate Available Volume (mL)||Approximate Ceftazidime Concentration (mg/mL)|
|Pharmacy bulk package|
| * To obtain a dose of 500 mg, withdraw 5.0
mL from the vial following reconstitution.
† To obtain a dose of 1 g, withdraw 10.0 mL from the vial following reconstitution.
‡ To obtain a dose of 2 g, withdraw 11.5 mL from the vial following reconstitution.
§ Note: Addition should be in 2 stages (see Instructions for Constitution).
All vials of FORTAZ (ceftazidime) as supplied are under reduced pressure. When FORTAZ (ceftazidime) 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 (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 FORTAZ (ceftazidime) and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.
Directions for Use of FORTAZ (ceftazidime) Frozen in Galaxy® Plastic Containers: FORTAZ (ceftazidime) 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 24 hours at room temperature or for 7 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.
Caution: Do 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 Administration:
- Suspend container from eyelet support.
- Remove protector from outlet port at bottom of container.
- Attach administration set. Refer to complete directions accompanying set.
Compatibility And Stability
Intramuscular: FORTAZ (ceftazidime) , 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 24 hours at room temperature or for 7 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 8 hours at room temperature or for 4 days in a refrigerator.
Intravenous: FORTAZ (ceftazidime) , when constituted as directed with Sterile Water for Injection, maintains satisfactory potency for 24 hours at room temperature or for 7 days under refrigeration. Solutions in Sterile Water for Injection in the infusion vial or in 0.9% Sodium Chloride Injection in VIAFLEX® small-volume containers that are frozen immediately after constitution are stable for 6 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 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 4 days in a refrigerator.
FORTAZ (ceftazidime) is compatible with the more commonly used IV infusion fluids. Solutions at concentrations between 1 and 40 mg/mL in 0.9% Sodium Chloride Injection; 1/6 M Sodium Lactate Injection; 5% Dextrose Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 10% Dextrose Injection; Ringer's Injection, USP; Lactated Ringer's Injection, USP; 10% Invert Sugar in Water for Injection; and NORMOSOL®-M in 5% Dextrose Injection may be stored for up to 24 hours at room temperature or for 7 days if refrigerated.
The 1- and 2-g FORTAZ (ceftazidime) ADD-Vantage 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 24 hours at room temperature or for 7 days under refrigeration.
FORTAZ (ceftazidime) is less stable in Sodium Bicarbonate Injection than in other IV fluids. It is not recommended as a diluent. Solutions of FORTAZ (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 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 (ceftazidime) powder, as well as solutions, tend to darken depending on storage conditions; within the stated recommendations, however, product potency is not adversely affected.
(ceftazidime for injection)
Instructions for Constitution
Vials: 500 mg IM/IV, 1 g IM/IV, 2 g IV
- Insert the syringe needle through the vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
- Shake to dissolve; a clear solution will be obtained in 1 to 2 minutes.
- Invert the vial. Ensuring that the syringe plunger is fully depressed, insert the needle through the vial closure and withdraw the total volume of solution into the syringe (the pressure in the vial may aid withdrawal). Ensure that the needle remains within the solution and does not enter the headspace. The withdrawn solution may contain some bubbles of carbon dioxide.
Note: As with the administration of all parenteral products, accumulated gases should be expressed from the syringe immediately before injection of FORTAZ (ceftazidime) .
Infusion Pack: 1 g, 2 g
- Insert the syringe needle through the vial closure and inject 10 mL of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
- Shake to dissolve; a clear solution will be obtained in 1 to 2 minutes.
- Insert a gas-relief needle through the vial closure to relieve the internal pressure. With the gas-relief needle in position, add the remaining 90 mL of diluent. Remove the gas-relief needle and syringe needle; shake the vial and set up for infusion in the normal way.
Note: To preserve product sterility, it is important that a gas-relief needle is not inserted through the vial closure before the product has dissolved.
ADD-Vantage® Vials: 1 g, 2 g
To Open Diluent Container:
Peel the corner of the ADD-Vantage diluent overwrap and remove flexible diluent container. Some opacity of the plastic flexible container due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.
To Assemble Vial and Flexible Diluent Container (Use Aseptic Technique):
1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
a. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (see Figure 1), then pull straight up to remove the cap (see Figure 2).
Note: Once the breakaway cap has been removed, do not access vial with syringe.
b. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover (see Figure 3). 2. Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately one-half turn (180°) after the first audible click (see Figure 4). The clicking sound does not assure a seal; the vial must be turned as far as it will go.
Note: Once vial is seated, do not attempt to remove (see Figure 4).
3. Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
4. Label appropriately.
To Prepare Admixture:
1. Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
2. With the other hand, push the drug vial down into the container, telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container (see Figure 5).
3. Pull the inner cap from the drug vial (see Figure 6). Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.
4. Mix container contents thoroughly and use within the specified time.
Preparation for Administration (Use Aseptic Technique):
- Confirm the activation and admixture of vial contents.
- Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
- Close flow control clamp of administration set.
- Remove cover from outlet port at bottom of container.
- Insert piercing pin of administration set into port with a twisting motion
until the pin is firmly seated.
Note: See full directions on administration set carton.
- Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
- Squeeze and release drip chamber to establish proper fluid level in chamber.
- Open flow control clamp and clear air from set. Close clamp.
- Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
- Regulate rate of administration with flow control clamp.
WARNING: Do not use flexible container in series connections.
Pharmacy Bulk Package: 6 g
- Insert the syringe needle through the vial closure and inject 26 mL of diluent. The vacuum may assist entry of the diluent. Remove the syringe needle.
- Shake to dissolve; a clear solution containing approximately 1 g of ceftazidime activity per 5 mL will be obtained in 1 to 2 minutes.
- Insert a gas-relief needle through the vial closure to relieve the internal pressure. Remove the gas-relief needle before extracting any solution.
Note: To preserve product sterility, it is important that a gas-relief needle is not inserted through the vial closure before the product has dissolved.
FORTAZ (ceftazidime) in the dry state should be stored between 15° and 30°C (59° and 86°F) and protected from light. FORTAZ (ceftazidime) is a dry, white to off-white powder supplied in vials and infusion packs as follows:
NDC 0173-0377-10 500-mg* Vial (Tray of 10)
NDC 0173-0378-10 1-g* Vial (Tray of 10)
NDC 0173-0379-34 2-g* Vial (Tray of 10)
NDC 0173-0380-32 1-g* Infusion Pack (Tray of 10)
NDC 0173-0381-32 2-g* Infusion Pack (Tray of 10)
NDC 0173-0382-37 6-g* Pharmacy Bulk Package (Tray of 6)
NDC 0173-0434-00 1-g ADD-Vantage® Vial (Tray of 25)
NDC 0173-0435-00 2-g ADD-Vantage® Vial (Tray of 10)
(The above ADD-Vantage vials are to be used only with Abbott ADD-Vantage diluent containers.)
FORTAZ frozen as a premixed solution of ceftazidime sodium should not be stored above -20°C. FORTAZ (ceftazidime) is supplied frozen in 50-mL, single-dose, plastic containers as follows:
NDC 0173-0412-00 1-g* Plastic Container (Carton of 24)
NDC 0173-0413-00 2-g* Plastic Container (Carton of 24)
*Equivalent to anhydrous ceftazidime.
4. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.
FORTAZ® (ceftazidime for injection): GlaxoSmithKline., Research Triangle
Park, NC 27709
FORTAZ® (ceftazidime injection): Manufactured for GlaxoSmithKline Research., Triangle Park, NC 27709 by Baxter Healthcare Corporation Deerfield, IL 60015
FORTAZ (ceftazidime) and ZINACEF are registered trademarks of GlaxoSmithKline. ADD-Vantage is a registered trademark of Abbott Laboratories. CLINITEST and CLINISTIX are registered trademarks of Ames Division, Miles Laboratories,Inc. GALAXY and VIAFLEX are registered trademarks of Baxter International Inc. January 2007
FDA rev date: 7/9/2007
Last reviewed on RxList: 7/19/2007
This monograph has been modified to include the generic and brand name in many instances.
Additional Fortaz Information
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