CEFAZOLIN- cefazolin_injection, powder, for solution

After intramuscular administration of Cefazolin for Injection to normal volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour and 3 mcg/mL at 8 hours following a 500‑mg dose, and 64 mcg/mL at 1 hour and 7 mcg/mL at 8 hours following a 1‑gram dose. Studies have shown that following intravenous administration of Cefazolin for Injection 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 for Injection is approximately 1.8 hours following I.V. administration and approximately 2 hours following I.M. administration. In a study (using normal volunteers) 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), Cefazolin for Injection produced a steady serum level at the third hour of approximately 28 mcg/mL. Studies in patients hospitalized with infections indicate that Cefazolin for Injection produces mean peak serum levels approximately equivalent to those seen in normal volunteers. Bile levels in patients without obstructive biliary disease can reach or exceed serum levels by up to 5 times; however, in patients with obstructive biliary disease, bile levels of Cefazolin for Injection are considerably lower than serum levels (less than 1 mcg/mL). In synovial fluid, the level of Cefazolin for Injection becomes comparable to that reached in serum at about 4 hours after drug administration. Studies of cord blood show prompt transfer of Cefazolin for Injection across the placenta. Cefazolin for Injection is present in very low concentrations in the milk of nursing mothers. Cefazolin for Injection 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. Cefazolin for Injection achieves peak urine concentrations of approximately 2,400 mcg/mL and 4,000 mcg/mL respectively following 500‑mg and 1‑gram intramuscular doses. In patients undergoing peritoneal dialysis (2 L/hr.), Cefazolin for Injection produced mean serum levels of approximately 10 and 30 mcg/mL after 24 hours’ instillation of a dialyzing solution containing 50 mg/L and 150 mg/L, respectively. Mean peak levels were 29 mcg/mL (range 13 to 44 mcg/mL) with 50 mg/L (3 patients), and 72 mcg/mL (range 26 to 142 mcg/mL) with 150 mg/L (6 patients). Intraperitoneal administration of Cefazolin for Injection is usually well tolerated. Controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring CBC, SGOT, SGPT, bilirubin, alkaline phosphatase, BUN, creatinine, and urinalysis, indicated no clinically significant changes attributed to Cefazolin for Injection. Microbiology Mechanism of Action Cefazolin is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Resistance Predominant mechanisms of bacterial resistance to cephalosporins include the presence of extended-spectrum beta-lactamases and enzymatic hydrolysis. Antimicrobial Activity Cefazolin has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE (1) Gram-Positive Bacteria Staphylococcus aureus Staphylococcus epidermidis Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Methicillin-resistant staphylococci are uniformly resistant to cefazolin. Gram-Negative Bacteria Escherichia coli Proteus mirabilis Most isolates of indole positive Proteus ( Proteus vulgaris Enterobacter Morganella morganii, Providencia rettgeri, Serratia Pseudomonas Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

Cefazolin for Injection, USP is indicated for the treatment of the following serious infections due to susceptible organisms: Respiratory Tract Infections: S. pneumoniae, Klebsiella , H. influenzae, S. aureus Injectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefazolin for Injection, USP is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of Cefazolin for Injection, USP in the subsequent prevention of rheumatic fever are not available at present. Urinary Tract Infections: E. coli, P. mirabilis, Klebsiella Skin and Skin Structure Infections: S. aureus Biliary Tract Infections: E. coli P. mirabilis Klebsiella S. aureus Bone and Joint Infections: S. aureus Genital Infections: E. coli P. mirabilis Klebsiella Septicemia: S. pneumoniae S. aureus P. mirabilis E. coli Klebsiella Endocarditis: S. aureus Perioperative Prophylaxis: The perioperative use of Cefazolin for Injection, USP may also be effective in surgical patients in whom infection at the operative site would present a serious risk (e.g., during open‑heart surgery and prosthetic arthroplasty). The prophylactic administration of Cefazolin for Injection, USP should usually be discontinued within a 24‑hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of Cefazolin for Injection, USP may be continued for 3 to 5 days following the completion of surgery. If there are signs of infection, specimens for cultures should be obtained for the identification of the causative organism so that appropriate therapy may be instituted. (See DOSAGE AND ADMINISTRATION.) To reduce the development of drug‑resistant bacteria and maintain the effectiveness of Cefazolin for Injection, USP and other antibacterial drugs, Cefazolin for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Usual Adult Dosage: Type of Infection Dose Frequency Moderate to severe infections 500 mg to 1 gram every 6 to 8 hours Mild infections caused by susceptible gram-positive cocci 250 mg to 500 mg every 8 hours Acute, uncomplicated urinary tract infections 1 gram every 12 hours Pneumococcal pneumonia 500 mg every 12 hours Severe, life-threatening infections (e.g., endocarditis, septicemia)* 1 gram to 1.5 grams every 6 hours * In rare instances, doses of up to 12 grams of Cefazolin for Injection per day have been used. Perioperative Prophylactic Use a. b. c. It is important that (1) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibiotic levels are present in the serum and tissues at the time of initial surgical incision; and (2) Cefazolin for Injection be administered, if necessary, at appropriate intervals during surgery to provide sufficient levels of the antibiotic at the anticipated moments of greatest exposure to infective organisms. In surgery where the occurrence of infection may be particularly devastating (e.g., open‑heart surgery and prosthetic arthroplasty), the prophylactic administration of Cefazolin for Injection may be continued for 3 to 5 days following the completion of surgery. Dosage Adjustment for Patients With Reduced Renal Function: 1 2 1 2 Pediatric Dosage: Weight 25 mg/kg/day Divided into 3 Doses 25 mg/kg/day Divided into 4 Doses Lbs Kg Approximate Single Dose mg/q 8 h Vol. (mL) needed with dilution of 125 mg/mL Approximate Single Dose mg/q 6 h Vol. (mL) needed with dilution of 125 mg/mL 10 20 30 40 50 4.5 9 13.6 18.1 22.7 40 mg 75 mg 115 mg 150 mg 190 mg 0.35 mL 0.6 mL 0.9 mL 1.2 mL 1.5 mL 30 mg 55 mg 85 mg 115 mg 140 mg 0.25 mL 0.45 mL 0.7 mL 0.9 mL 1.1 mL Weight 50 mg/kg/day Divided into 3 Doses 50 mg/kg/day Divided into 4 Doses Lbs Kg Approximate Single Dose mg/q 8 h Vol. (mL) needed with dilution of 225 mg/mL Approximate Single Dose mg/q 6 h Vol. (mL) needed with dilution of 225 mg/mL 10 20 30 40 50 4.5 9 13.6 18.1 22.7 75 mg 150 mg 225 mg 300 mg 375 mg 0.35 mL 0.7 mL 1 mL 1.35 mL 1.7 mL 55 mg 110 mg 170 mg 225 mg 285 mg 0.25 mL 0.5 mL 0.75 mL 1 mL 1.25 mL In pediatric patients with mild to moderate renal impairment (creatinine clearance of 70 to 40 mL/min.), 60 percent of the normal daily dose given in equally divided doses every 12 hours should be sufficient. In patients with moderate impairment (creatinine clearance of 40 to 20 mL/min.), 25 percent of the normal daily dose given in equally divided doses every 12 hours should be adequate. Pediatric patients with severe renal impairment (creatinine clearance of 20 to 5 mL/min.) may be given 10 percent of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose. RECONSTITUTION Preparation of Parenteral Solution: When reconstituted or diluted according to the instructions below, Cefazolin for Injection is stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5°C or 41°F). Reconstituted solutions may range in color from pale yellow to yellow without a change in potency. Single-Dose Vials: Vial Size Amount of Diluent Approximate Concentration Approximate Available Volume 500 mg 2 mL 225 mg/mL 2.2 mL 1 gram 2.5 mL 330 mg/mL 3 mL Pharmacy Bulk Vials: Vial Size Amount of Diluent Approximate Concentration Approximate Available Volume 10 grams 45 mL 1 gram/5 mL 51 mL 96 mL 1 gram/10 mL 102 mL 20 grams 87 mL 1 gram/5 mL 99 mL ADMINISTRATION Intramuscular Administration: Intravenous Administration: Intermittent or continuous infusion: Dilute reconstituted Cefazolin for Injection in 50 to 100 mL of one of the following solutions: Sodium Chloride Injection, USP 5% or 10% Dextrose Injection, USP 5% Dextrose in Lactated Ringer’s Injection, USP 5% Dextrose and 0.9% Sodium Chloride Injection, USP 5% Dextrose and 0.45% Sodium Chloride Injection, USP 5% Dextrose and 0.2% Sodium Chloride Injection, USP Lactated Ringer’s Injection, USP Invert Sugar 5% or 10% in Sterile Water for Injection Ringer’s Injection, USP 5% Sodium Bicarbonate Injection, USP

The following reactions have been reported: Gastrointestinal: Allergic: Hematologic: Hepatic: Renal: Local Reactions: Other Reactions: To report SUSPECTED ADVERSE REACTIONS, contact WG Critical Care, LLC at 1-866-562-4708 or FDA at 1-800-FDA-1088 or www.fda.gov .

CEFAZOLIN FOR INJECTION IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.

Pregnancy
Teratogenic Effects:
Nursing Mothers
Cefazolin for Injection is present in very low concentrations in the milk of nursing mothers. Caution should be exercised when Cefazolin for Injection is administered to a nursing woman.
Pediatric Use
Safety and effectiveness for use in premature infants and neonates have not been established. See DOSAGE AND ADMINISTRATION for recommended dosage in pediatric patients older than 1 month.
Geriatric Use
Of the 920 subjects who received Cefazolin for Injection in clinical studies, 313 (34%) were 65 years and over, while 138 (15%) were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels. A false positive reaction for glucose in the urine may occur with Benedict’s solution, Fehling’s solution or with CLINITEST registered registered Positive direct and indirect antiglobulin (Coombs) tests have occurred; these may also occur in neonates whose mothers received cephalosporins before delivery.

WARNINGS
BEFORE THERAPY WITH CEFAZOLIN FOR INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEFAZOLIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. IF THIS PRODUCT IS GIVEN TO PENICILLIN‑SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS‑HYPERSENSITIVITY AMONG BETA‑LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY. IF AN ALLERGIC REACTION TO CEFAZOLIN FOR INJECTION OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES, INCLUDING OXYGEN, IV FLUIDS, IV ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY INDICATED. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefazolin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an oral antibacterial drug clinically effective against C. difficile
Carcinogenesis/Mutagenesis
Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Cefazolin for Injection have not been performed.
Labor and Delivery
When cefazolin has been administered prior to caesarean section, drug levels in cord blood have been approximately one quarter to one third of maternal drug levels. The drug appears to have no adverse effect on the fetus.

WG Critical Care, LLC

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