AHFS Class:

8:12.06.12 Third Generation Cephalosporins

Generic Name

• CefTAZidime

Ceftazidime is available as a powder in single-dose vials containing the equivalent of 500 mg, 1 g, and 2 g of ceftazidime as the pentahydrate and 6-g pharmacy bulk packages.³⁹⁰⁸; ³⁹¹⁰; ³⁹¹¹ The formulations contain sodium carbonate 118 mg per gram of ceftazidime to facilitate dissolution.³⁹⁰⁸; ³⁹¹⁰; ³⁹¹¹ Vials of ceftazidime are packaged with reduced pressure to account for carbon dioxide which is formed during reconstitution.³⁹⁰⁸; ³⁹¹⁰; ³⁹¹¹

For intramuscular injection, ceftazidime in single-dose vials may be reconstituted with sterile water for injection, bacteriostatic water for injection, or lidocaine hydrochloride 0.5 or 1%.³⁹⁰⁸; ³⁹¹¹ For intravenous administration, only sterile water for injection should be used for reconstitution.³⁹⁰⁸; ³⁹¹¹ To reconstitute single-dose vials, the recommended amount of diluent as shown in Table 1 should be added to the vial and the vial shaken to dissolve the contents.³⁹⁰⁸; ³⁹¹¹ Carbon dioxide will form during dissolution, but the solution will clear in about 1 to 2 minutes.³⁹⁰⁸; ³⁹¹¹ Any carbon dioxide bubbles that are withdrawn into the syringe should be expelled prior to injection.³⁹⁰⁸; ³⁹¹¹

For intravenous infusion, the reconstituted solution should be diluted further in a compatible infusion solution.³⁹⁰⁸; ³⁹¹¹

Table 1. Reconstitution of Ceftazidime³⁹⁰⁸; ³⁹¹¹

The use of a venting needle has been suggested for ease of use.¹¹³⁶ Spraying or leaking of the solution after needle withdrawal has been reported, especially with smaller vials.¹¹³⁷ The use of larger vials reduces the occurrence of such leakage.¹¹³⁷; ¹¹³⁸ Care must be taken if a multiple-additive set with a 2-way valve is used for reconstitution. The negative pressure in the product may cause inaccuracies in the volume of diluent added to the vial. In one test, almost 3 mL extra entered the vial during reconstitution.¹²⁴⁰ Vials have been vented prior to reconstitution but clamping the tubing from the supply bottle prior to adding the diluent to the vial when multiple-additive sets are used is recommended.¹²⁴¹

The 6-g pharmacy bulk package should be reconstituted with 26 mL of sterile water for injection to yield 30 mL of solution containing 1 g/5 mL (200 mg/mL) of ceftazidime.³⁹¹⁰ The diluent should be added to the vial and the vial shaken to dissolve the contents.³⁹¹⁰ The manufacturer states a venting needle should be inserted through the vial stopper to release the pressure in the vial only after the drug has completely dissolved.³⁹¹⁰ The reconstituted solution must be diluted further for intravenous infusion.³⁹¹⁰

Ceftazidime also is available as a powder in single-dose ADD-Vantage vials containing the equivalent of 1 or 2 g of ceftazidime with sodium carbonate 118 mg per gram of ceftazidime.³⁹⁰⁹ Ceftazidime in ADD-Vantage vials should be prepared with 50 or 100 mL of sodium chloride 0.9% or dextrose 5% or 50 mL of sodium chloride 0.45% in ADD-Vantage diluent bags.³⁹⁰⁹

pH

Reconstituted solutions have a pH of 5 to 8.³⁹⁰⁸

Osmolality

The osmolality of ceftazidime (Fortaz, Glaxo) 50 mg/mL was determined to be 321 mOsm/kg in dextrose 5% and 330 mOsm/kg in sodium chloride 0.9%.¹³⁷⁵

The following maximum ceftazidime concentrations were recommended to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients:¹¹⁸⁰

Sodium Content

Each gram of ceftazidime activity contains approximately 54 mg (2.3 mEq) of sodium in the formulation.³⁹⁰⁸; ³⁹¹⁰

Trade Name(s)

Fortaz, Tazicef

Ceftazidime may be administered by deep intramuscular injection, by direct intravenous injection over 3 to 5 minutes directly into a vein or through the tubing of a running compatible infusion solution, or by intermittent intravenous infusion.³⁹⁰⁸ The manufacturer recommends temporarily discontinuing other solutions being administered at the same site during ceftazidime infusion.³⁹⁰⁸ The drug may be instilled intraperitoneally in a concentration of 250 mg/2 L of compatible dialysis solution.³⁹⁰⁸ Intra-arterial administration should be avoided.³⁹⁰⁸

Solutions prepared from bulk pharmacy packages are intended only for intravenous infusion after dilution in a compatible solution.³⁹¹⁰ Solutions prepared from ADD-Vantage vials are intended for intravenous infusion only.³⁹⁰⁹

Intact vials should be stored at controlled room temperature and protected from light.³⁹⁰⁸; ³⁹⁰⁹; ³⁹¹⁰ Approximately 2% decomposition has been reported after 12 months of storage at 37°C with protection from light.¹¹³⁶

Ceftazidime is a white to off-white powder that forms a light yellow to amber solution upon reconstitution.³⁹⁰⁸ Both the dry material and solutions may darken depending on storage conditions; however, this discoloration is stated not to affect potency if stored within recommended conditions.³⁹⁰⁸

Stability of reconstituted and diluted ceftazidime solutions varies depending on the manufacturer; specific product labeling should be consulted.³⁹⁰⁸; ³⁹¹¹

Ceftazidime (Fortaz, Teligent) reconstituted as directed is stated to be stable for 12 hours at room temperature or 3 days refrigerated; solutions further diluted to concentrations from 1 to 40 mg/mL in a manufacturer-recommended solution are stated to be stable for 12 hours at room temperature or 3 days refrigerated.³⁹⁰⁸

Ceftazidime (Tazicef, Hospira) reconstituted as directed is stated to be stable for 24 hours at room temperature or 7 days refrigerated; solutions further diluted to concentrations from 1 to 40 mg/mL in a manufacturer-recommended solution are stated to be stable for 24 hours at room temperature or 7 days refrigerated.³⁹¹¹

Reconstituted solutions prepared from pharmacy bulk packages should be further diluted for infusion within 4 hours after initial entry into the vial.³⁹¹⁰ Unused portions of pharmacy bulk packages should be discarded after 4 hours of initial entry.³⁹¹⁰ Solutions further diluted to concentrations from 1 to 40 mg/mL in a manufacturer-recommended solution for infusion are stated to be stable for 24 hours at room temperature or 7 days refrigerated.³⁹¹⁰

One report of ceftazidime in concentrations of 1, 40, and 333 mg/mL in water indicated no loss after 24 hours at 4°C and 6 hours at 25°C. About a 4 to 6% loss was reported after 24 hours at 25°C.¹¹³⁶

Ceftazidime vials reconstituted with sterile water for injection to a concentration of 270 mg/mL were evaluated for stability at 4 temperatures. About 8 to 9% ceftazidime loss occurred in 7 days under refrigeration at 4°C and in 4 days at 10°C. At 20°C about 7 to 8% loss occurred in 24 hours, but at a higher room temperature of 30°C about 5% loss occurred in 6 hours and 12% loss occurred in 18 hours.²²⁸⁵

Ceftazidime solutions diluted to a concentration of 4 mg/mL in dextrose 5% or sodium chloride 0.9% are stated to be stable for at least 6 hours at room temperature in plastic tubing, drip chambers, and volume control devices of common intravenous infusion sets.³⁹⁰⁸

Freezing Solutions

Ceftazidime in single-dose vials reconstituted with sterile water for injection and immediately frozen in the original containers is stated to be stable for 3 months at -20°C.³⁹⁰⁸; ³⁹¹¹ Stability of thawed solutions varies depending on the manufacturer; thawed solutions of ceftazidime (Fortaz, Teligent) may be stored for up to 3 hours at room temperature or 3 days refrigerated while thawed solutions of ceftazidime (Tazicef, Hospira) may be stored for up to 8 hours at room temperature or 4 days refrigerated.³⁹⁰⁸; ³⁹¹¹ Thawed solutions should not be refrozen.³⁹⁰⁸; ³⁹¹¹

Ceftazidime (Tazicef, Hospira) reconstituted as directed and further diluted in sodium chloride 0.9% for infusion and immediately frozen is stated to be stable for 3 months at -20°C.³⁹¹¹ Frozen solutions should not be subject to force thawing by immersion in water baths or microwaving.³⁹¹¹ Thawed solutions may be stored for up to 24 hours at room temperature or 7 days refrigerated and should not be refrozen.³⁹¹¹

Ceftazidime (Fortaz, Glaxo) 1 g/50 mL in sodium chloride 0.9% was stored frozen at -20°C. About 7% loss occurred in 97 days. After thawing at room temperature, subsequent storage refrigerated for 4 days and at room temperature for 24 hours resulted in additional loss with only about 90% of the ceftazidime remaining.⁵⁰⁰

Less than a 2% ceftazidime (Fortaz, Glaxo) loss was reported from a solution containing 36.6 mg/mL in sterile water for injection in polyvinyl choride (PVC) and glass containers after 30 days at -20°C. Subsequent thawing and storage for 4 days at 5°C, followed by 24 hours at 37°C to simulate the use of a portable infusion pump, resulted in little additional ceftazidime loss.¹³⁹¹

Ceftazidime (Fortaz, Glaxo) 100 and 200 mg/mL in sterile water for injection in glass vials and polypropylene syringes (Becton Dickinson) was stored frozen at -20°C for 91 days followed by 8 hours at 22°C. Losses of about 5 and 10% occurred in the 100- and 200-mg/mL concentrations, respectively. Freezing at -20°C for 91 days followed by refrigeration at 4°C for 4 days resulted in losses of about 10 and 6% in the 100- and 200-mg/mL concentrations, respectively. Particle counts remained within USP limits throughout the study.¹⁵⁸⁰

Light Effects

Ceftazidime reconstituted with sterile water for injection to a concentration of 270 mg/mL exhibited no substantial difference in stability when stored protected from light or exposed to daylight.²²⁸⁵

Syringes

Ceftazidime (Fortaz, Glaxo) 100 and 200 mg/mL in sterile water for injection in polypropylene syringes (Becton Dickinson) and glass vials exhibited a 5% or less loss in 8 hours at 22°C and 96 hours at 4°C.¹⁵⁸⁰

Ceftazidime (Hospira) 1 mg/mL in sodium chloride 0.9% in plastic syringes was stored at room temperature, refrigerated, and frozen at -20°C. About 10% ceftazidime loss occurred in 3 days at room temperature and in 17 days refrigerated. No loss occurred in the frozen samples over 60 days.²⁷⁹³

Ambulatory Pumps

Ceftazidime (Fortaz, Glaxo) at a concentration of 60 mg/mL in water for injection was filled into PVC portable infusion pump reservoirs (Pharmacia Deltec). Storage at -20°C resulted in less than 3% loss in 14 days. The thawed reservoirs were then stored under refrigeration at 6°C. Losses totaled 10% after 5 days of refrigerated storage. Under simulated use conditions at 30°C, ceftazidime decomposes at a rate of about 10% in 18 hours. The authors concluded prefilling of reservoirs with ceftazidime solutions for home use was not advisable.²⁰⁰⁸

Central Venous Catheter

Ceftazidime (Fortaz, Glaxo Wellcome) 10 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.²³³⁵

Ceftazidime 10 mg/mL with heparin sodium 5000 units/mL as an antibiotic lock in polyurethane central hemodialysis catheters lost about 50% of the antibiotic over 72 hours at 37°C. The loss was attributed to sorption to the catheters. Nevertheless, the reduced antibiotic concentration (about 5 mg/mL) remained effective against common microorganisms in catheter-related bacteremia in hemodialysis patients.²⁵¹⁵; ²⁵¹⁶

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Peritoneal Dialysis Solutions

Ceftazidime may be added to a compatible peritoneal dialysis solution at a concentration of 250 mg of ceftazidime per 2 L of dialysis solution.³⁹⁰⁸; ³⁹¹¹

Ceftazidime (Glaxo) 125 mg/L and tobramycin sulfate (Lilly) 8 mg/L in Dianeal PD-2 with dextrose 2.5% (Baxter) were visually compatible and chemically stable. After 16 hours of storage at 25°C under fluorescent light, the loss of both drugs was less than 3%. Additional storage for 8 hours at 37°C, to simulate the maximum peritoneal dwell time, showed tobramycin sulfate concentrations of 96% and ceftazidime concentrations of 92 to 96%.¹⁶⁵²

Ceftazidime (Glaxo) 0.1 mg/mL in Dianeal PD-2 with dextrose 1.5% in PVC containers was physically and chemically stable for 24 hours at 25°C exposed to light, exhibiting about 9% loss; additional storage for 8 hours at 37°C resulted in additional loss of about 6%. Under refrigeration at 4°C protected from light, no loss occurred in 7 days. Additional storage for 16 hours at 25°C followed by 8 hours at 37°C resulted in about 6% loss.¹⁹⁸⁹

Ceftazidime (Glaxo) 0.1 mg/mL admixed with teicoplanin (Marion Merrell Dow) 0.025 mg/mL in Dianeal PD-2 with dextrose 1.5% in PVC containers did not result in a stable mixture. Large (but variable) teicoplanin losses generally in the 20% range were noted in as little as 2 hours at 25°C exposed to light. Ceftazidime losses of about 9% occurred in 16 hours. Refrigeration and protection from light of the peritoneal dialysis admixture reduced losses of both drugs to negligible levels. Even so, the authors did not recommend admixing these 2 drugs because of the high levels of teicoplanin loss at room temperature.¹⁹⁸⁹

Ceftazidime (Glaxo) 0.1 mg/mL in Dianeal PD-2 with dextrose 1.5% with or without heparin sodium 1 unit/mL in PVC bags was chemically stable for up to 6 days at 4°C (about 3 to 4% loss), 4 days at 25°C (about 9 to 10% loss), and less than 12 hours at body temperature of 37°C.⁸⁶⁶

The addition of vancomycin hydrochloride (Lederle) 0.05 mg/mL to this peritoneal dialysis solution demonstrated similar stability with the ceftazidime being the defining component. Ceftazidime was chemically stable for up to 6 days at 4°C (about 3% loss), 3 days at 25°C (about 9 to 10% loss), and 12 hours at body temperature of 37°C with the vancomycin exhibiting less loss throughout.⁸⁶⁶

Vancomycin hydrochloride (Lilly) 1 mg/mL admixed with ceftazidime (Lilly) 0.5 mg/mL in Dianeal PD-2 (Baxter) with 1.5% and also 4.25% dextrose were evaluated for compatibility and stability. Samples were stored under fluorescent light at 4 and 24°C for 24 hours and at 37°C for 12 hours. No precipitation or other change was observed by visual inspection in any sample. No loss of either drug occurred in the samples stored at 4°C and no loss of vancomycin hydrochloride and about 4 to 5% ceftazidime loss occurred in the samples stored at 24°C in 24 hours. Vancomycin hydrochloride losses of 3% or less and ceftazidime loss of about 6% were found in the samples stored at 37°C for 12 hours. No difference in stability was found between samples at either dextrose concentration.²²¹⁷

Ceftazidime (GlaxoWellcome) 0.125 mg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) was stable with 10% loss occurring in 7 days at refrigerator temperature and 3 days at room temperature.²⁵⁷³

Ceftazidime (Sandoz) 500 mg/L in Extraneal with icodextrin 7.5% (Baxter) peritoneal dialysis solution bags exhibited less than 10% loss in 14 days at 4°C and 2 days at 25°C; the drug was unstable at 37°C.³⁵³⁷ Ceftazidime (Sandoz) 500 mg/L with cefazolin sodium (Hospira) 500 mg/L in Extraneal with icodextrin 7.5% (Baxter) peritoneal dialysis solution bags exhibited less than 10% loss of either drug in 14 days at 4°C, 6% loss of ceftazidime and 2% loss of cefazolin in 2 days at 25°C, and no loss of ceftazidime and 2% loss of cefazolin in 6 hours at 37°C.³⁵³⁷

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions September 12, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.