AHFS Class:

8:12.06.12 Third Generation Cephalosporins

Generic Name

• CefTRIAXone Sodium (TEST MONOGRAPH ONLY!!)

Ceftriaxone sodium is available as a powder in single-dose vials containing the equivalent of 250 mg, 500 mg, 1 g, and 2 g of ceftriaxone³⁷⁴⁹ and pharmacy bulk containers containing the equivalent of 10 g and 100 g of ceftriaxone.³⁷⁵⁰; ³⁷⁵⁵

For intramuscular use, reconstitute the vials with a compatible diluent in the amounts indicated to yield a 250- or 350-mg/mL solution:³⁷⁴⁹

^a This vial size not recommended for 350-mg/mL concentration because withdrawal of the entire contents may not be possible.

More dilute solutions for intramuscular injection may be prepared if required.³⁷⁴⁹

For intermittent intravenous infusion, reconstitute the vials with a compatible diluent in the amounts indicated to yield a 100-mg/mL solution:³⁷⁴⁹

After reconstitution, withdraw the entire vial contents and further dilute in a compatible infusion solution to the desired concentration.³⁷⁴⁹ Concentrations between 10 and 40 mg/mL are recommended, but lower concentrations may be used.³⁷⁴⁹

The 10-g bulk pharmacy container should be reconstituted with 95 mL of a compatible diluent to yield a 100-mg/mL solution.³⁷⁵⁰ The 100-g bulk pharmacy container should be reconstituted with 950 mL of sterile water for injection to yield a 100-mg/mL solution.³⁷⁵⁵ Bulk pharmacy containers are intended for preparation of solutions for intravenous infusion only and must be diluted further before use.³⁷⁵⁰; ³⁷⁵⁵ The 100-g bulk pharmacy container should be used only to prepare doses for patients who require a 1-g dose.³⁷⁵⁵

For intravenous infusion, ceftriaxone sodium also is available in ADD-Vantage vials containing the equivalent of 1 or 2 g of ceftriaxone as a powder.³⁷⁵¹ ADD-Vantage vials should be prepared with 50 or 100 mL of dextrose 5% or sodium chloride 0.9% in ADD-Vantage diluent bags.³⁷⁵¹

For intravenous infusion, ceftriaxone sodium also is available in dual-chamber single-use flexible containers containing the equivalent of 1 or 2 g of ceftriaxone as a powder.³⁷⁵² The diluent chamber for the 1- or 2-g dose contains approximately 50 mL of dextrose 3.74 or 2.22%, respectively.³⁷⁵² The manufacturer states that these containers should be used only when the full dose supplied in the container (i.e., 1 or 2 g) is needed.³⁷⁵²

Ceftriaxone sodium also is available as a frozen premixed infusion solution in single-dose Galaxy containers containing the equivalent of 1 or 2 g of ceftriaxone in 50-mL bags with dextrose 1.9 or 1.2 g, respectively, in water.³⁷⁵³ Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH.³⁷⁵³

pH

The pH of a 10-mg/mL aqueous solution of the drug is approximately 6.7.³⁷⁴⁹; ³⁷⁵⁰; ³⁷⁵¹; ³⁷⁵² The frozen premixed infusion solutions have a pH range of 6 to 8.³⁷⁵³

Osmolality

The frozen premixed infusion solutions are iso-osmotic.³⁷⁵³

The osmolality of ceftriaxone sodium (Roche) 50 mg/mL was determined to be 351 mOsm/kg in dextrose 5% and 364 mOsm/kg in sodium chloride 0.9%.¹³⁷⁵

Ceftriaxone sodium in dual-chamber flexible containers is iso-osmotic with an osmolality of 290 mOsm/kg when activated with the dextrose diluent.³⁷⁵²

Sodium Content

Ceftriaxone sodium contains approximately 3.6 mEq (83 mg) of sodium per gram of ceftriaxone activity.³⁷⁴⁹; ³⁷⁵¹; ³⁷⁵²; ³⁷⁵³

Trade Name(s)

Rocephin

Ceftriaxone sodium is administered by intramuscular injection³⁷⁴⁹ or by intermittent intravenous infusion over 30 minutes in patients other than neonates; in neonates, administration over 60 minutes is recommended.³⁷⁴⁹; ³⁷⁵¹; ³⁷⁵²; ³⁷⁵³ Ceftriaxone sodium activated in dual-chamber flexible containers or reconstituted from ADD-Vantage vials are intended for intravenous infusion only.³⁷⁵¹; ³⁷⁵²

Frozen premixed infusion solution is intended for intravenous infusion only.³⁷⁵³

Bulk pharmacy containers are intended for preparation of solutions for intravenous infusion only.³⁷⁵⁰; ³⁷⁵⁵

Intact vials of ceftriaxone sodium should be stored at controlled room temperature and protected from light.³⁷⁴⁹; ³⁷⁵⁰; ³⁷⁵¹ After reconstitution, normal exposure to light is permitted.³⁷⁴⁹; ³⁷⁵⁰; ³⁷⁵¹ Solutions may vary from light yellow to amber, depending on length of storage, diluent, and concentration.³⁷⁴⁹; ³⁷⁵⁰; ³⁷⁵¹

Reconstituted solutions of ceftriaxone sodium for intramuscular injection are stable, exhibiting less than a 10% potency loss for the time periods indicated:³⁷⁴⁹

Reconstituted solutions prepared from pharmacy bulk containers should be further diluted for infusion not more than 4 hours after initial entry into the vial.³⁷⁵⁰ Pharmacy bulk containers should be discarded within 4 hours of initial entry.³⁷⁵⁰

Unactivated dual-chamber flexible plastic containers should be stored at a controlled room temperature.³⁷⁵² Once the foil strip has been removed from the drug chamber, the product must be protected from light and used within 7 days, but not beyond the labeled expiration date.³⁷⁵² Once reconstituted (activated), the drug should be used within 24 hours if stored at room temperature or 7 days if stored under refrigeration.³⁷⁵²

Ceftriaxone sodium is incompatible with calcium-containing solutions, including Ringer’s injection and Ringer’s injection, lactated.³⁷⁴⁹; ³⁷⁵⁰ Precipitation has been observed to form rapidly.²²²² Ceftriaxone sodium must not be administered simultaneously with calcium-containing intravenous solutions, including parenteral nutrition, via Y-site.³⁷⁴⁹; ³⁷⁵⁰ In patients other than neonates, ceftriaxone sodium and calcium-containing intravenous solutions may be administered sequentially if the infusion lines are thoroughly flushed with a compatible solution between the separate infusions.³⁷⁴⁹ Because fatalities have been reported in neonates who received ceftriaxone sodium intravenously concomitantly with calcium-containing solutions, ceftriaxone sodium must not be used in neonates younger than 28 days of age if they are receiving or expected to receive calcium-containing intravenous solutions.³⁷⁴⁹

pH Effects

The pH of maximum stability for ceftriaxone sodium has been variously reported as 2.5 to 4.5¹⁰⁸⁰ and 7.2.¹²⁴⁴

Freezing Solutions

The manufacturer indicates that ceftriaxone sodium 10 to 40 mg/mL in dextrose 5% or sodium chloride 0.9%, when frozen at -20°C in polyvinyl chloride (PVC) or polyolefin containers, is stable for 26 weeks.³⁷⁴⁹; ³⁷⁵⁰ Thawing should be performed at room temperature; thawed solutions should not be refrozen.³⁷⁴⁹; ³⁷⁵⁰

The frozen premixed infusion solution in single-dose Galaxy containers should be stored at -20°C.³⁷⁵³ Solutions should be thawed at room temperature (25°C) or under refrigeration (5°C); solutions should not be subject to force thawing by immersion in water baths or microwaving.³⁷⁵³ Thawed solutions are stable for 48 hours at room temperature or 21 days at 5°C.³⁷⁵³ Thawed solutions should not be refrozen.³⁷⁵³

Ceftriaxone sodium (Roche) 250 and 450 mg/mL in dextrose 5%, 250 mg/mL in bacteriostatic water for injection, and 450 mg/mL in lidocaine hydrochloride 1% (Lyphomed) were evaluated for stability and pharmaceutical integrity during frozen storage at -15°C. The solutions were packaged in 10-mL polypropylene syringes with attached needles (Becton Dickinson) and frozen for 8 weeks. Some syringes were stored further at 4°C for 10 days for at 20°C for 3 days. Ceftriaxone sodium losses of 5% or less were found after 8 weeks of frozen storage. However, particulate matter levels were unacceptable in most samples. While additional storage at 4°C for 10 days did not cause unacceptable drug loss, storage at 20°C for 3 days resulted in 12% drug loss.¹⁸²⁴

Ceftriaxone sodium (Roche) 2 g/100 mL of dextrose 5% in polyolefin containers was found to remain stable for 14 weeks frozen at -20°C with no loss of drug occurring. Subsequent thawing in a microwave oven and storage at about 4°C resulted in 10% drug loss in 44 to 56 days, depending on the power level used for thawing.²⁷²⁴

Ceftriaxone sodium activated in dual-chamber flexible containers or reconstituted from ADD-Vantage vials should not be frozen.³⁷⁵¹; ³⁷⁵²

Syringes

Bailey et al. reported the stability of ceftriaxone sodium (Roche) 10 and 40 mg/mL in dextrose 5% and sodium chloride 0.9% packaged in polypropylene syringes. The solutions were visually compatible and lost 5% or less ceftriaxone in 48 hours at 4 and 20°C and 10 days stored frozen at -10°C.^17,20

Plumridge et al. reported on the stability of ceftriaxone sodium (Roche) 100 mg/mL in sterile water for injection packaged in polypropylene syringes (Terumo). About 9 to 10% loss of ceftriaxone occurred in 5 days at 20°C and 40 days at 4°C. However, the room temperature samples underwent color intensification that the authors found unacceptable after about 72 hours. Little or no loss occurred during 180 days of frozen storage at -20°C.¹⁹⁹⁰

O’Connell et al. evaluated the stability of reconstituted ceftriaxone sodium 100 mg/mL packaged in 10-mL polypropylene syringes. Stored under refrigeration at 8°C, about 5% loss occurred in 10 days and 8% in 13 days.¹⁹⁹⁹

Elastomeric Reservoir Pumps

Ceftriaxone sodium (Roche) 10 mg/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). No binding was found after storage for 2 weeks at 35°C with gentle agitation.²⁰¹⁴

Plasticizer Leaching

Ceftriaxone sodium frozen premixed infusion solution is in contact with polyethylene contained in the Galaxy plastic container and can leach out certain chemical components of the plastic in very small amounts within the expiration period.³⁷⁵³ The suitability of the plastic has been confirmed according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.³⁷⁵³

Central Venous Catheter

Ceftriaxone sodium (Roche) 5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. 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

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Peritoneal Dialysis Solutions

Ceftriaxone sodium (Roche) 1 mg/mL in Dianeal PD-1 with dextrose 1.5 and 4.25% was stable, retaining at least 90% for 14 days at 4°C, 24 hours at 23°C, or 6 hours at 37°C.¹⁵⁹²

Aminoglycosides

Ceftriaxone sodium is stated to be incompatible with aminoglycosides in admixtures.³⁷⁴⁹ If concomitant therapy with these drugs is necessary, sequential administration with thorough flushing of the infusion lines with a compatible solution between the separate infusions is recommended.³⁷⁴⁹

Metronidazole

The admixture of ceftriaxone sodium 10 mg/mL and metronidazole (Flagyl, Searle) at concentrations not exceeding 5 to 7.5 mg/mL in sodium chloride 0.9% or dextrose 5% is stated to be stable for 24 hours at room temperature.³⁷⁴⁹ Precipitation occurs if the admixture is refrigerated.³⁷⁴⁹ Precipitation occurs at metronidazole concentrations greater than 8 mg/mL.³⁷⁴⁹

Protamine Sulfate

Immediate precipitation has been observed when protamine sulfate is mixed with ceftriaxone sodium.³⁷⁴⁸ Protamine sulfate is stated to be incompatible with some antibiotics, including cephalosporins.³⁷⁴⁷

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

ASHP^® Injectable Drug Information^TM. Selected Revisions March 31, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.