The 10 gram vial should be reconstituted with 95 mL of an appropriate IV diluent in a suitable work area such as a laminar flow hood. The resulting solution will contain approximately 100 mg/mL of ceftriaxone. This closure may be penetrated only one time after reconstitution, using a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents.
The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial closure entry is permitted to complete fluid transfer operations. Unused portions of solution held longer than the recommended time periods should be discarded.
|Reconstituted Bulk Solutions Should Not Be Used For Direct Infusion.|
Transfer individual dose to appropriate intravenous solutions as soon as possible following reconstitution of the bulk package. The stability of the solution that has been transferred into a container varies according to diluent, concentration and temperature (see COMPATIBILITY AND STABILITY). Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired.
COMPATABILITY AND STABILITY: Ceftriaxone has been shown to be compatible with Flagyl® IV* (metronidazole hydrochloride). The concentration should not exceed 5 to 7.5 mg/mL metronidazole hydrochloride with ceftriaxone 10 mg/mL as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (D5W). No compatability studies have been conducted with the Flagyl® IV RTU® (metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.
*Registered trademark of G.D. Searle & Co.
Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for Injection vials or to further dilute a reconstituted vial for IV administration. Particulate formation can result.
Ceftriaxone for Injection solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, due to possible incompatibility (see WARNINGS).
Ceftriaxone for Injection sterile powder should be stored at 20 — 25°C (68 — 77°F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.
Ceftriaxone for Injection intravenous solutions, at concentrations of 10, 20, and 40 mg/mL, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:
|Diluent||Room Temp. (25°C)||Refrigerated (4°C)|
|Sterile Water||2 days||10 days|
|0.9% Sodium Chloride Solution||2 days||10 days|
|5% Dextrose Solution||2 days||10 days|
|10% Dextrose Solution||2 days||10 days|
|5% Dextrose + 0.9% Sodium Chloride Solution *||2 days||Incompatible|
|5% Dextrose + 0.45% Sodium Chloride Solution||2 days||Incompatible|
The following intravenous Ceftriaxone for Injection solutions are stable at room temperature (25 °C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).
After the indicated stability time periods, unused portions of solutions should be discarded.
NOTE : Parenteral drug products should be inspected visually for particulate matter before administration.
Ceftriaxone for Injection reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/mL and 40 mg/mL, and then stored in frozen state (- 20°C) in PVC or polyolefin containers, remains stable for 26 weeks.
Frozen solutions of Ceftriaxone for Injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.
Concretions consisting of the precipitated calcium salt of ceftriaxone have been found in the gallbladder bile of dogs and baboons treated with ceftriaxone.
These appeared as a gritty sediment in dogs that received 100 mg/kg/day for 4 weeks. A similar phenomenon has been observed in baboons but only after a protracted dosing period (6 months) at higher dose levels (335 mg/kg/day or more). The likelihood of this occurrence in humans is considered to be low, since ceftriaxone has a greater plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile and the calcium content of human gallbladder bile is relatively low.
Ceftriaxone for Injection, USP is available in Pharmacy Bulk Packages containing 10 g equivalent of ceftriaxone. Box of 1 (NDC 0143-9768-01).
NOTE: Ceftriaxone for Injection sterile powder should be stored at 20 — 25°C (68 — 77°F) [See USP Controlled Room Temperature] and protected from light.
Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media
In two adequate and well-controlled U.S. clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years. The clinical cure rates and statistical outcome appear in the table below:
|Clinical Efficacy in Evaluable Population|
|Study Day||Ceftriaxone Single Dose||Comparator –10 Days of Oral Therapy||95% Confidence Interval||Statistical Outcome|
|Study 1 – U.S.||amoxicillin/clavulanate||Ceftriaxone is lower than control at study day 14 and 28.|
|14||74% (220/296)||82% (247/302)||(-14.4%, -0.5%)|
|28||58% (167/288)||67% (200/297)||(-17.5%, -1.2%)|
|Study 2 – U.S.5||TMP-SMZ||Ceftriaxone is equivalent to control at study day 14 and 28.|
|14||54% (113/210)||60% (124/206)||(-16.4%, 3.6%)|
|28||35% (73/206)||45% (93/205)||(-19.9%, 0.0%)|
An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens. The results of this study are tabulated as follows:
Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen:
|Study Day 13-15||Study Day 30+2|
|Organism||No. Analyzed||No. Erad. (%)||No. Analyzed||No. Erad. (%)|
|Streptococcus pneumoniae||38||32 (84)||35||25 (71)|
|Haemophilus influenzae||33||28 (85)||31||22 (71)|
|Moraxella catarrhalis||15||12 (80)||15||9 (60)|
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