Ceftriaxone overdosage has been reported in patients with severe renal impairment. Reactions have included neurological outcomes, including encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus. In the event of overdosage, discontinue Ceftriaxone for Injection and Dextrose Injection therapy and provide general supportive treatment [see Dosage and Administration (2.1) and (Warnings and Precautions (5.3)].
In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.
Ceftriaxone for Injection and Dextrose Injection is a sterile, nonpyrogenic, single-dose, packaged combination of Ceftriaxone Sodium and Dextrose Injection (diluent) in the DUPLEX® sterile container. The DUPLEX® Container is a flexible dual chamber container.
The drug chamber is filled with ceftriaxone sodium, a sterile, semisynthetic, broad-spectrum cephalosporin antibacterial for intravenous 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 661.60 and the following structural formula:
Ceftriaxone sodium is supplied as a dry powder form equivalent to either 1 g or 2 g of ceftriaxone. Ceftriaxone sodium 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 sodium solutions ranges from light yellow to amber, depending on the length of storage and concentration.
Ceftriaxone sodium contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity.
The diluent chamber contains Dextrose Injection. The concentration of Hydrous Dextrose in Water for Injection USP has been adjusted to render the reconstituted drug product iso-osmotic. Dextrose USP has been added to adjust osmolality (approximately 1.87 g and 1.11 g to 1 g and 2 g dosages, respectively). Dextrose Injection is sterile, nonpyrogenic, and contains no bacteriostatic or antimicrobial agents.
Hydrous Dextrose USP has the following structural (molecular) formula:
The molecular weight of Hydrous Dextrose USP is 198.17.
After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is intended for single intravenous use. When reconstituted, the approximate osmolality for the reconstituted solution for Ceftriaxone for Injection and Dextrose Injection is 290 mOsmol/kg.
Not made with natural rubber latex, PVC or DEHP.
The DUPLEX® dual chamber container is made from a specially formulated material. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene ethylene copolymer that contains no plasticizers. The safety of the container system is supported by USP biological evaluation procedures.
Ceftriaxone is an antibacterial drug [see Microbiology (12.4)].
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 g dose in healthy subjects are presented in Table 2. Multiple IV 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.
TABLE 2: Ceftriaxone Plasma Concentrations After Single-Dose Administration
|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|
|1 g IV *||151||111||88||67||53||43||28||18||9|
|2 g IV *||257||192||154||117||89||74||46||31||15|
Over a 0.15 to 3 g dose range in healthy adult subjects, the mean elimination half-life ranged from 5.8 to 8.7 hours, plasma clearance ranged from 0.58 to 1.45 L/hour, and renal clearance ranged from 0.32 to 0.73 L/hour.
Ceftriaxone is reversibly bound to human plasma proteins and the binding of ceftriaxone decreases with increasing concentration from a value of 95% at plasma concentrations less than 25 mcg/mL to 85% at plasma concentration of 300 mcg/mL. Over a 0.15 to 3 g dose range in healthy adult subjects, the apparent volume of distribution ranged from 5.8 to 13.5 L.
Ceftriaxone crosses the blood placenta barrier.
Ceftriaxone penetrates the inflamed meninges of infants and pediatric patients. The average values of maximum plasma concentration, cerebrospinal fluid (CSF) concentrations, 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.
TABLE 3: Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients With Meningitis
|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 – 18.5||1.3 – 44|
|Time after dose (hr)||3.7 (±1.6)||3.3 (±1.4)|
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, and 78.2 mcg/g in the gallbladder wall compared to a corresponding concentration of 62.1 mcg/mL in plasma.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.