CEFTRIAXONE — ceftriaxone sodium injection, powder, for solution
A-S Medication Solutions
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftriaxone sodium and other antibacterial drugs, ceftriaxone for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Ceftriaxone for injection USP is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is (6R ,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-as -triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72 -(Z)-(O- methyloxime), disodium salt, sesquaterhydrate.
The chemical formula of ceftriaxone sodium is C18 H16 N8 Na2 O7 S3 · 3.5H2 O. It has a calculated molecular weight of 661.59 and the following structural formula:
Ceftriaxone for injection USP is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of ceftriaxone for injection solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.
Each vial contains ceftriaxone sodium equivalent to 250 mg, 500 mg, 1 gram or 2 grams of ceftriaxone activity. Ceftriaxone for injection USP contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 g dose and intramuscular (IM) administration of a single 0.5 (250 mg/mL or 350 mg/mL concentrations) or 1 g dose in healthy subjects are presented in Table 1.
ND = Not determined.
* IV doses were infused at a constant rate over 30 minutes.
|Dose / Route||Average Plasma Concentrations ( mcg / mL )|
|0 . 5 hr||1 hr||2 hr||4 hr||6 hr||8 hr||12 hr||16 hr||24 hr|
|0.5 g IV*||82||59||48||37||29||23||15||10||5|
|0.5 g IM|
|0.5 g IM|
|1 g IV*||151||111||88||67||53||43||28||18||9|
|1 g IM||40||68||76||68||56||44||29||ND||ND|
|2 g IV*||257||192||154||117||89||74||46||31||15|
Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM doses ranging from 0.5 to 2 g at 12- to 24-hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.
Ceftriaxone concentrations in urine are shown in Table 2.
ND = Not determined.
|Average Urinary Concentrations ( mcg / mL )|
|Dose / Route||0 to 2 hr||2 to 4 hr||4 to 8 hr||8 to 12 hr||12 to 24 hr||24 to 48 hr|
|0.5 g IV||526||366||142||87||70||15|
|0.5 g IM||115||425||308||127||96||28|
|1 g IV||995||855||293||147||132||32|
|1 g IM||504||628||418||237||ND||ND|
|2 g IV||2692||1976||757||274||198||40|
Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 g IV dose, average concentrations of ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/g in the gallbladder wall and 62.1 mcg/mL in the concurrent plasma.
Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of <25 mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta barrier.
The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table 3. Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table 3.
|50 mg / kg IV||75 mg / kg IV|
|Maximum Plasma Concentrations (mcg/mL)||216||275|
|Elimination Half-life (hr)||4.6||4.3|
|Plasma Clearance (mL/hr/kg)||49||60|
|Volume of Distribution (mL/kg)||338||373|
|CSF Concentration – inflamed meninges (mcg/mL)||5.6||6.4|
|Range (mcg/mL)||1.3 to 18.5||1.3 to 44|
|Time after dose (hr)||3.7 (± 1.6)||3.3 (± 1.4)|
Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (Table 4); therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 g per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis; in six of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced.
* Creatinine clearance
|Subject Group||Elimination Half – Life ( hr )||Plasma Clearance ( L / hr )||Volume of Distribution ( L )|
|Healthy Subjects||5.8 to 8.7||0.58 to 1.45||5.8 to 13.5|
|Elderly Subjects (mean age, 70.5 yr)||8.9||0.83||10.7|
|Patients with Renal Impairment|
|Hemodialysis Patients (0 to5 mL/min)*||14.7||0.65||13.7|
|Severe (5 to15 mL/min)||15.7||0.56||12.5|
|Moderate (16 to 30 mL/min)||11.4||0.72||11.8|
|Mild (31to 60 mL/min)||12.4||0.70||13.3|
|Patients with Liver Disease||8.8||1.1||13.6|
The elimination of ceftriaxone is not altered when ceftriaxone for injection is co-administered with probenecid.
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