Storage, Stability, CompatibilityThe sterile powder for reconstitution should be stored at, orbelow 25°C and protected from light.
After reconstituting with either 0.9% sodium chloride or D5W, ceftriaxone solutions (at concentrations of approximately 100 mg/ml) are stable for 3 days at room temperature and for 10 days when refrigerated. Solutions of concentrations of 250 mg/ml are stable for 24 hours at room temperature and 3 days when refrigerated. At concentrations of 10-40 mg/ml solutions frozen at -20°C are stable for 26 weeks. The manufacturer does not recommend admixing any other anti-infective drugs with ceftriaxone sodium.
Pharmacology - CEFTRIAXONE SODIUMCeftriaxone is a third generation injectable cephalosporin agent. For more information, refer to the monograph: Cephalosporins, General Information.
Uses, IndicationsCeftriaxone is used to treat serious infections, particularly against susceptible
Enterobacteriaceae that are not susceptible to other less expensive agents or when aminoglycosides are not indicated (due to their potential toxicity). Its long half life, good CNS penetration, and activity against Borrelia burgdorferi also has made it a potential choice for treating Lyme's disease.
Pharmacokinetics - CEFTRIAXONE SODIUMCeftriaxone is not absorbed after oral administration and must be given parenterally. It is widely distributed throughout the body; CSF levels are higher when meninges are inflamed. Ceftriaxone crosses the placenta and enters maternal milk in low concentrations; nodocumented adverse effects to offspring have been noted. Ceftriaxone is excreted by both renal andnon-renal mechanisms and in humans, elimination half-lives are approximately 6-11 hours. Dosageadjustments generally are not required for patients with renal insufficiency (unless severely uremic)or with hepatic impairment.
Contraindications, Precautions, Reproductive SafetyOnly prior allergic reaction tocephalosporins contraindicates ceftriaxone's use. In humans documented hypersensitive topenicillin, up to 16% may also be allergic to cephalosporins. The veterinary significance of this isunclear.
Although bleeding times have only been reported rarely in humans, ceftriaxone should be usedwith caution in patients with vitamin K utilization or synthesis abnormalities (e.g., severe hepaticdisease).
No teratogenic effects were demonstrated in studies in pregnant mice and rats given up to 20 timeslabeled doses of ceftriaxone.
Adverse Effects, WarningsBecause veterinary usage of ceftriaxone is very limited, an accurateadverse effect profile has not been determined. The following adverse effects have been reported inhumans and may or may not apply to veterinary patients: hematologic effects, includingeosinophilia (6%), thrombocytosis (5%), leukopenia (2%) and more rarely, anemia, neutropenia, lymphopenia and thrombocytopenia. Approximately 2-4% of humans get diarrhea. Very highdosages (100 mg/kg/day) in dogs have caused a "sludge" in bile. Hypersensitivity reactions(usually a rash) have been noted. Increased serum concentrations of liver enzymes, BUN, creatinine, and urine casts have been described in about 1-3% of patients. When given IM, pain may be notedat the injection site.
Overdosage, Acute ToxicityLimited information available; overdoses should be monitored andtreated symptomatically and supportively if required.
Drug InteractionsSynergism against some Enterobacteriaceae (e.g., Pseudomonas aeruginosa)may be attained if using cefoperazone with an aminoglycoside (e.g., gentamicin, amikacin).
Organisms with a high degree of resistance to both ceftriaxone and the aminoglycoside are unlikelyto be affected when the two drugs are used together.
Probenecid does not have an effect on ceftriaxone elimination.
Laboratory Considerations - When using Kirby-Bauer disk diffusion procedures for testingsusceptibility, a specific 30 micrograms ceftriaxone disk should be used. A cephalosporin-classdisk containing cephalothin should not be used to test for ceftriaxone susceptibility. An inhibitionzone of 18 mm or more indicates susceptibility; 14-17 mm, intermediate; and 13 mm or less, resistant.
When using a dilution susceptibility procedure, an organism with a MIC of 16 micrograms/ml orless is considered susceptible and 64 micrograms/ml or greater is considered resistant. With eithermethod, infections caused by organisms with intermediate susceptibility may be effectively treated ifthe infection is limited to tissues where the drug is concentrated or if a higher than normal dose isused.
Ceftriaxone, like most other cephalosporins, may cause a false-positive urine glucose determination when using the cupric sulfate solution test (e.g., Clinitest®).
Ceftriaxone in very high concentrations (50 micrograms/ml or greater) may cause falsely elevated serum creatinine levels when manual methods of testing are used. Automated methods do not appear to be affected.