Cefazolin Sodium (Page 6 of 8)

10 OVERDOSAGE

Accidental overdosage resulting in seizures may occur in patients with renal impairment who receive doses greater than the recommended dosage of Cefazolin for Injection and Dextrose Injection [see Warnings and Precautions (5.2)]. If seizures associated with accidental overdosage occur, discontinue Cefazolin for Injection and Dextrose Injection and give supportive treatment.

11 DESCRIPTION

Cefazolin for Injection USP and Dextrose Injection USP is a sterile, nonpyrogenic, single-dose, packaged combination of Cefazolin Sodium USP (lyophilized) and sterile iso-osmotic diluent in the DUPLEX® sterile container. The DUPLEX® Container is a flexible dual chamber container.

After reconstitution the approximate osmolality for Cefazolin for Injection USP and Dextrose Injection USP is 290 mOsmol/kg.

The drug chamber is filled with sterile lyophilized Cefazolin Sodium USP, a semi-synthetic cephalosporin and has the following IUPAC nomenclature: Sodium (6R,7R)-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo-7-[2-(1H -tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate. Its empirical formula is C14 H13 N8 NaO4 S3 and its molecular weight is 476.48.

Cefazolin Sodium USP has the following structural formula:

Diagram of Cefazolin Molecular Structure
(click image for full-size original)

The sodium content is 48 mg/g of cefazolin sodium.

The diluent chamber contains Dextrose Injection USP, an iso-osmotic diluent using Hydrous Dextrose USP in Water for Injection USP. Dextrose Injection USP is sterile, nonpyrogenic, and contains no bacteriostatic or antimicrobial agents. Its empirical formula is C6 H12 O6 •H2 O and its molecular weight is 198.17.

Hydrous Dextrose USP has the following structural (molecular) formula:

Diagram of Dextrose Molecular Structure

Cefazolin Sodium USP is supplied as a lyophilized form equivalent to either 1 g or 2 g of cefazolin. Dextrose hydrous USP has been added to the diluent to adjust osmolality (approximately 2 g [4.0% w/v] and 1.5 g [3.0% w/v] for the 1 g and 2 g dosages, respectively).

After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is intended for single intravenous use.

Reconstituted solutions of Cefazolin for Injection and Dextrose Injection range in color from pale yellow to amber.

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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Cefazolin is an antibacterial drug [see Microbiology (12.4)].

12.2 Pharmacodynamics

The pharmacokinetic/pharmacodynamic relationship for cefazolin has not been evaluated in patients.

12.3 Pharmacokinetics

Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 gram dose.

The serum half-life for cefazolin is approximately 1.8 hours following IV administration.

In a study of constant intravenous infusion with dosages of 3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg the next 2 hours (approximately 100 mg) in healthy volunteers, cefazolin serum concentrations at the third hour were approximately 28 mcg/mL.

Plasma pharmacokinetic parameters of cefazolin in healthy volunteers (N=12) following a single 15-minute IV infusion of 2 grams of Cefazolin for Injection and Dextrose Injection are summarized in Table 7.

*
Tmax reported as median (range)
Table 7: Mean (Standard Deviation) Plasma Pharmacokinetic Parameters of Cefazolin in Healthy Volunteers
N

Cmax

(mcg/mL)

Tmax * (h)

AUC0-inf (mcg*h/mL)

t1/2 (h)

CL (L/h)

Vz (L)

Single 2 grams Dose as a 15-Minute IV Infusion 12 280.9 (45.9) 0.25 (0.25-0.33) 509.9 (89.3) 2.01 (0.28) 4.03 (0.68) 11.50 (1.53)

N= number of subjects observed; Cmax = maximum plasma concentration; Tmax = time to maximum plasma concentration; AUC0-inf = area under the plasma concentration-time curve extrapolated to infinity; t1/2 = apparent plasma terminal elimination half-life; CL = total clearance; Vz = volume of distribution

Studies in patients hospitalized with infections indicate that cefazolin mean peak serum concentrations were approximately equivalent to those seen in healthy volunteers.

Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to five times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (less than 1.0 mcg/mL).

In synovial fluid, the cefazolin concentration becomes comparable to that reached in serum at about 4 hours after drug administration.

Studies of cord blood show prompt transfer of cefazolin across the placenta. Cefazolin is present in very low concentrations in the milk of nursing mothers.

Cefazolin is excreted unchanged in the urine. In the first 6 hours, approximately 60% of the drug is excreted in the urine and this increases to 70% to 80% within 24 hours.

Specific Populations

Pediatric Patients for Perioperative Prophylaxis

A simulation based on pharmacokinetic data from healthy adults (n=24), pediatric patients aged 10 to 17 years (n=26: Study 1 [see Adverse Reactions (6.1)]), and pediatric patients aged 10 to 12 years (n=12: Study 2 [see Adverse Reactions (6.1)] indicate that the administration of a 1 gram cefazolin dose for pediatric patients weighing less than 50 kg and a 2 grams cefazolin dose for those weighing 50 kg or greater will provide comparable exposures between pediatric patients aged 10 to 17 years and healthy adults receiving 2 grams Cefazolin for Injection and Dextrose Injection [see Dosage and Administration (2.2 and 2.3) and Use in Specific Populations (8.4)].

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.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.