Label: Refrigerate.
Stability data:
|
| Drug |
Stability
Refrigerated |
Stability
Room Temp. |
Vial/Powder |
Notes |
| Cefazolin Powder |
10 days if stored under refrigeration (5°C or 41°F). |
Before reconstitution, store at 20° to 25°C (68° to 77°F).
24 hours |
Powder |
Parenteral drug products should be SHAKEN WELL when reconstituted, and inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solutions should be discarded.
Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.
Prior to administration parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.
As with other cephalosporins, reconstituted Cefazolin for Injection, USP tends to darken depending on storage conditions, within the stated recommendations. However, product potency is not adversely affected.
Protect from light. |
| Cefazolin Solution |
Store in a freezer capable of maintaining a temperature of -20°C (-4°F).
The thawed solution is stable for 30 days under refrigeration (5°C/41°F) |
The thawed solution is stable for 48 hours at 25°C/77°F |
Solution |
Thaw frozen container at room temperature (25°C/ 77°F) or under refrigeration (5°C/41°F). (DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.)
Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.
As with other cephalosporins, cefazolin tends to darken depending on storage conditions; within the stated recommendations, however, product potency is not adversely affected.
Handle frozen product containers with care. Product containers may be fragile in the frozen state. |
Microbiology
In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis. Cefazolin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in INDICATIONS AND USAGE.
Gram-Positive Aerobes
Staphylococcus aureus (including ß-lactamase-producing strains)
Staphylococcus epidermidis
Streptococcus pyogenes,Streptococcus agalactiae, and other strains of streptococci
Streptococcus pneumoniae
Methicillin-resistant staphylococci are uniformly resistant to cefazolin, and many strains of enterococci are resistant.
Gram-Negative Aerobes
Escherichia coli
Proteus mirabilis
Most strains of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri,Serratia spp., and Pseudomonas spp. are resistant to cefazolin
INDICATIONS AND USAGE
ANCEF is indicated in the treatment of the following infections due to susceptible organisms:
Respiratory Tract Infections
Due to S. pneumoniae, S aureus (including ß-lactamase-producing strains) and S. pyogenes.
Injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.
ANCEF is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of ANCEF in the subsequent prevention of rheumatic fever are not available.
Urinary Tract Infections
Due to E. coli, P mirabilis.
Skin and Skin Structure Infections
Due to S. aureus (including ß-lactamase-producing strains), S. pyogenes, and other strains of streptococci.
Biliary Tract Infections
Due to E. coli, various strains of streptococci, P. mirabilis, and S. aureus.
Bone and Joint Infections
Due to S. aureus.
Genital Infections
(i.e., prostatitis, epididymitis) due to E. coli, P. mirabilis.
Septicemia
Due to S. pneumoniae, S. aureus (including ß-lactamase-producing strains), P. mirabilis, E. coli.
Endocarditis
Due to S. aureus (including ß-lactamase-producing strains) and S. pyogenes.
Appropriate culture and susceptibility studies should be performed to determine susceptibility of the causative organism to ANCEF.
Perioperative Prophylaxis
The prophylactic administration of ANCEF preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice, or common duct bile stones).
The perioperative use of ANCEF 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 ANCEF 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 ANCEF 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 ANCEF and other antibacterial drugs, ANCEF 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.
CONTRAINDICATIONS
ANCEF IS CONTRAINDICATED IN PATIENTS WITH KNOWN ALLERGY TO THE CEPHALOSPORIN GROUP OF ANTIBIOTICS.
WARNINGS
BEFORE THERAPY WITH ANCEF 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 ANCEF 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 is a primary cause of “antibiotic-associated colitis”.
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 colitis
Dosage Adjustment for Patients With Reduced Renal Function
ANCEF may be used in patients with reduced renal function with the following dosage adjustments: Patients with a creatinine clearance of 55 mL/min. or greater or a serum creatinine of 1.5 mg % or less can be given full doses. Patients with creatinine clearance rates of 35 to 54 mL/min. or serum creatinine of 1.6 to 3.0 mg % can also be given full doses but dosage should be restricted to at least 8 hour intervals. Patients with creatinine clearance rates of 11 to 34 mL/min. or serum creatinine of 3.1 to 4.5 mg % should be given 1/2 the usual dose every 12 hours. Patients with creatinine clearance rates of 10 mL/min. or less or serum creatinine of 4.6 mg % or greater should be given 1/2 the usual dose every 18 to 24 hours. All reduced dosage recommendations apply after an initial loading dose appropriate to the severity of the infection.
DOSAGE AND ADMINISTRATION
Usual Adult Dosage
| Type of Infection |
Dose |
Frequency |
| Moderate to severe infections |
500 mg to 1 gram |
every 6 to 8 hrs. |
| 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 ANCEF per day have been used.
Renal dosing: >55/q6-8h || 35-54/q8h || 11-34/ 50% usual dose q12h || <10 ml/min/ 50% to full dose q24-48h. || Hemodialysis: 0.5-1g after dialysis
Perioperative Prophylactic Use
To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are:
a. 1 gram IV or IM administered 1/2 hour to 1 hour prior to the start of surgery.
b. For lengthy operative procedures (e.g., 2 hours or more), 500 mg to 1 gram IV or IM during surgery (administration modified depending on the duration of the operative procedure).
c. 500 mg to 1 gram IV or IM every 6 to 8 hours for 24 hours postoperatively.
It is important that (1) the preoperative dose be given just (1/2 to 1 hour) prior 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) ANCEF 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 ANCEF may be continued for 3 to 5 days following the completion of surgery.
Pediatric Dosage
In pediatric patients, a total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections. Total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight for severe infections. Since safety for use in premature infants and in neonates has not been established, the use of ANCEF in these patients is not recommended.
| Pediatric Dosage Guide |
| Weight |
25 mg/kg/day
Divided into 3 Doses |
25 mg/kg/day
Divided into 4 Doses |
| Lbs |
Kg |
Approximate Single Dose mg/q8h |
Vol. (mL) needed with dilution of 125 mg/mL |
Approximate Single Dose mg/q6h |
Vol. (mL) needed with dilution of 125 mg/mL |
| 10 |
4.5 |
40 mg |
0.35 mL |
30 mg |
0.25 mL |
| 20 |
9.0 |
75 mg |
0.60 mL |
55 mg |
0.45 mL |
| 30 |
13.6 |
115 mg |
0.90 mL |
85 mg |
0.70 mL |
| 40 |
18.1 |
150 mg |
1.20 mL |
115 mg |
0.90 mL |
| 50 |
22.7 |
190 mg |
1.50 mL |
140 mg |
1.10 mL |
| Weight |
50 mg/kg/day
Divided into 3 Doses |
50 mg/kg/day
Divided into 4 Doses |
| Lbs |
Kg |
Approximate Single Dose mg/q8h |
Vol. (mL) needed with dilution of 225 mg/mL |
Approximate Single Dose mg/q6h |
Vol. (mL) needed with dilution of 225 mg/mL |
| 10 |
4.5 |
75 mg |
0.35 mL |
55 mg |
0.25 mL |
| 20 |
9.0 |
150 mg |
0.70 mL |
110 mg |
0.50 mL |
| 30 |
13.6 |
225 mg |
1.00 mL |
170 mg |
0.75 mL |
| 40 |
18.1 |
300 mg |
1.35 mL |
225 mg |
1.00 mL |
| 50 |
22.7 |
375 mg |
1.70 mL |
285 mg |
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
Parenteral drug products should be SHAKEN WELL when reconstituted, and inspected visually for particulate matter prior to administration. If particulate matter is evident in reconstituted fluids, the drug solutions should be discarded.
---- Storage/Stability ----
When reconstituted or diluted according to the instructions below, ANCEF 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
For IM injection, IV direct (bolus) injection or IV infusion, reconstitute with Sterile Water for Injection according to the following table. SHAKE WELL.
| Vial Size |
Amount of Diluent |
Approximate
Concentration |
Approximate
Available Volume |
| 1 gram |
2.5 mL |
330 mg/mL |
3.0 mL |
Pharmacy Bulk Vials
Add Sterile Water for Injection, Bacteriostatic Water for Injection, or Sodium Chloride Injection according to the table below. SHAKE WELL. Use promptly. (Discard vial within 4 hours after initial entry.)
| 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 |
“Piggyback” Vials
Reconstitute with 50 to 100 mL of Sodium Chloride Injection or other IV solution listed under ADMINISTRATION. When adding diluent to vial, allow air to escape by using a small vent needle or by pumping the syringe. SHAKE WELL. Administer with primary IV fluids, as a single dose.
ADMINISTRATION
Intramuscular Administration
Reconstitute vials with Sterile Water for Injection according to the dilution table above. Shake well until dissolved. ANCEF should be injected into a large muscle mass. Pain on injection is infrequent with ANCEF.
Intravenous Administration
Direct (bolus) injection: Following reconstitution according to the above table, further dilute vials with approximately 5 mL Sterile Water for Injection. Inject the solution slowly over 3 to 5 minutes, directly or through tubing for patients receiving parenteral fluids (see list below).
Intermittent or continuous infusion: Dilute reconstituted ANCEF in 50 to 100 mL of 1 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
ANCEF is a registered trademark of GlaxoSmithKline.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2005, GlaxoSmithKline. All rights reserved.
April 2005 AF:L60 |
