Ceftazidime – Fortaz ®

CEFTAZIDIME (FORTAZ ®)

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Stability / Miscellaneous

INDICATIONS AND USAGE
FORTAZ 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.; Streptococcuspneumoniae; and Staphylococcus aureus (methicillin-susceptible strains).

2. Skin and Skin­Structure Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteusmirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcusaureus (methicillin-susceptible strains); and Streptococcuspyogenes (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.

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 antibiotics have been used.

FORTAZ 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 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.

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 are listed in Table 3. The following dosage schedule is recommended.
Table 3. Recommended Dosage Schedule

* 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 may be given. An estimate of GFR should be made to determine the appropriate maintenance dosage. The recommended dosage is presented in Table 4.

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.
Table 4. Recommended Maintenance Dosages of FORTAZ in Renal Insufficiency

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 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.

Administration
FORTAZ 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 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 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 in the ADD-Vantage system is not recommended.
Table 5. Preparation of Solutions of FORTAZ

* 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 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 antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

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

Directions for Use of FORTAZ Frozen in Galaxy®
Plastic Containers

FORTAZ 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

1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.

HOW SUPPLIED
FORTAZ in the dry state should be stored between 15° and 30°C (59° and 86°F) and protected from light. FORTAZ 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 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.

GlaxoSmithKline
Research Triangle Park, NC 27709
January 2007 RL-2352