Cefazolin for Injection: Indications, Dosage, Precautions, Adverse Effects
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Cefazolin for Injection - Product Information

Manufacture: Fresenius Kabi USA, LLC
Country: Canada
Condition: Bacterial Infection, Bone infection (Osteomyelitis), Endocarditis, Joint Infection, Respiratory Tract Infection, Upper (Upper Respiratory Tract Infection), Septicemia, Skin and Structure Infection, Urinary Tract Infection
Class: First generation cephalosporins
Form: Intramuscular (IM), Intravenous (IV), Powder
Ingredients: cefazolin

Action and Clinical Pharmacology

Cefazolin sodium is a cephalosporin antibiotic for parenteral administration. It exerts its bacterial effect by inhibiting bacterial cell wall synthesis.

Indications and Clinical Uses

Cefazolin for Injection, USP may be indicated in the treatment of the following infections when caused by susceptible strains of the listed organisms:

  • RESPIRATORY TRACT INFECTIONS caused by Streptococcus pneumoniae, Klebsiellapneumoniae, Hemophilus influenzae, Staphylococcus aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci.
  • URINARY TRACT INFECTIONS caused by Escherichia coli, Proteus mirabilis, Klebsiellapneumoniae and some strains of enterobacter and enterococci.
  • SKIN AND SOFT TISSUE INFECTIONS caused by Staphylococcus aureus (penicillin-sensitive and penicillin-resistant), group A beta-hemolytic streptococci and other strains of streptococci.
  • BONE AND JOINT INFECTIONS caused by Staphylococcus aureus.
  • SEPTICEMIA caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillin-sensitive and penicillin-resistant), Proteus mirabilis, Escherichia coli and Klebsiellapneumoniae.
  • ENDOCARDITIS caused by Staphylococcus aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci.

In order to determine the susceptibility of the causative organism to cefazolin sodium, appropriate culture and susceptibility studies should be performed. (See MICROBIOLOGY for disc susceptibility tests and dilution techniques.)

Most strains of Enterococci, indole positive Proteus (P. vulgaris), Enterobacter cloacae,Morganella morganii, Providencia rettgeri and methicillin-resistant staphylococci are resistant. Serratia, Pseudomonas, and Acinetobacter calcoaceticus (formerly Mima and Herellea species) are almost uniformly resistant to cefazolin. (See MICROBIOLOGY.)

Perioperative Prophylaxis

In patients undergoing potentially contaminated surgical procedures, and in patients in whom infection would pose a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty), the preoperative, intraoperative, and postoperative administration of cefazolin sodium may reduce the incidence of certain postoperative infections.

Should signs of infection occur, identification of the causative organisms should be made by culture in order that appropriate therapy may be instituted.

Contraindications

In patients with known allergy or hypersensitivity to the cephalosporin group of antibiotics, Cefazolin for Injection, USP is contraindicated.

Warnings

CEPHALOSPORIN DERIVATIVES SHOULD BE USED WITH CAUTION IN PENICILLIN-ALLERGIC PATIENTS. THERE ARE INSTANCES OF PATIENTS WHO HAVE HAD REACTIONS TO BOTH PENICILLINS AND CEPHALOSPORINS (INCLUDING FATAL ANAPHYLAXIS AFTER PARENTERAL USE). CLINICAL AND LABORATORY EVIDENCE OF PARTIAL CROSS-ALLERGENICITY FOR THESE TWO DRUG CLASSES EXISTS.

FOR ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS, CEFAZOLIN FOR INJECTION SHOULD BE ADMINISTERED CAUTIOUSLY AND THEN ONLY WHEN ABSOLUTELY NECESSARY. IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE IS REQUIRED FOR SERIOUS ANAPHYLACTOID REACTIONS. OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT INCLUDING INTUBATION, SHOULD ALSO BE EMPLOYED, AS NECESSARY.

There have been reports of pseudomembranous colitis with the use of cephalosporins. It is therefore important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use.

Precautions

The overgrowth of non- susceptible organisms may result from the prolonged use of Cefazolin for Injection, USP. It is essential that careful clinical observation be maintained. Appropriate measures should be taken if superinfection occurs during therapy.

In patients with a history of lower gastrointestinal disease, and in particular, colitis, cefazolin should be prescribed with caution.

Caution should be used in treating patients with pre-existing renal damage even though cefazolin has not shown evidence of nephrotoxicity.

In patients with low urinary output due to impaired renal function, cefazolin is not readily excreted and these patients should be administered reduced daily dosages of cefazolin (see DOSAGE AND ADMINISTRATION,Adult Dosage, Dosage in Patients with Reduced Renal Function). Blood levels of cefazolin in dialysis patients remain fairly high and should be monitored.

There have been reports during treatment with cefazolin of positive direct and indirect Coombs’ tests. These may also occur in neonates whose mothers received cephalosporins before delivery. The clinical significance of this effect has not been established.

False positive indications of urinary glucose may occur in cefazolin- treated patients where Clinitest* tablets solution are used, but not enzyme-based tests such as Clinistix* and Tes-Tape**.

* Registered trademark of Bayer Aktiengesellschaft

** Registered trademark of Eli Lilly Canada, Inc.

Drug Interactions

The renal tubular secretions of cefazolin may be decreased when probenecid is used concurrently, resulting in increased and prolonged cefazolin blood levels.

Pregnancy

The safety of cefazolin sodium for use during pregnancy has not been established.

Infants

The safety of cefazolin sodium for use in premature infants and in infants under one month of age has not been established.

Nursing Mothers

Very low concentrations of cefazolin sodium are found in the milk of nursing mothers. Caution should be used when cefazolin sodium is administered to a nursing woman.

Adverse Reactions

The following reactions have been reported.

Allergic

Anaphylaxis, eosinophilia, itching, drug fever, and skin rash.

Gastrointestinal

Diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia. During antibiotic treatment, symptoms of pseudomembranous colitis can appear. Nausea and vomiting have been reported rarely.

Hematologic

Neutropenia, anemia, leukopenia, thrombocythemia, positive direct and indirect antiglobulin (Coombs’) tests.

Hepatic and Renal

Transient increases in AST (SGOT), ALT (SGPT), BUN and alkaline phosphatase levels have been observed without clinical evidence of hepatic or renal impairment. Transient hepatitis and cholestatic jaundice have been reported rarely, as with some penicillins and some other cephalosporins.

Local Reactions

Phlebitis at the site of injection has rarely occurred, infrequently there may be pain and induration at the site of injection following intramuscular injection.

Other Reactions

Genital moniliasis, vaginitis, vulvar and anal pruritus.

Symptoms and Treatment of Overdosage

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Supportive therapy should be instituted according to symptoms in cases of suspected overdosage. There is presently a lack of experience with acute cefazolin overdosage.

Dosage and Administration

Cefazolin for Injection, USP may be administered either intramuscularly or intravenously after constitution. In both cases, total daily dosages are the same.

Treatment should be continued in beta-hemolytic streptococcal infections for at least 10 days to minimize possible complications associated with the disease.

Adult Dosage

ADULT DOSAGE GUIDE
Type of InfectionDoseFrequency
Pneumococcal pneumonia500 mgEvery 12 hours
Mild infections caused by susceptible Gram-
positive cocci
250 to 500 mgEvery 8 hours
Acute, uncomplicated urinary tract infections+1 gEvery 12 hours
Moderate to severe infections500 mg to 1 gEvery 6 to 8 hours

+ This dosage recommendation applies to intramuscular use. The efficacy of cefazolin sodium when administered intravenously at 12-hour intervals has not been established.

Cefazolin sodium has been administered in dosages of 6 grams per day in serious infections such as endocarditis.

Dosage in Patients with Reduced Renal Function

After an initial loading dose appropriate to the severity of the infections, the following reduced dosage schedule is recommended:

DOSAGE GUIDE FOR RENALLY IMPAIRED PATIENTS
Creatinine Clearance(mL/s)Serum Creatinine(μmol/L)Dosage
≥ 0.91≤ 140250 mg to 1 g every 6 - 12 hours
0.58 - 0.90141 - 273250 mg to 1 g every 8 - 12 hours
0.18 - 0.57274 - 406125 mg to 500 mg every 12 hours
≤ 0.17≥ 407125 mg to 500 mg every 18 hours

Perioperative Prophylactic Use

The following dosage regimens are recommended to prevent postoperative infection in contaminated or potentially contaminated surgery:

  1. One gram i.v. or i.m. administered ½ hour to 1 hour prior to the start of surgery so that at the time of the initial surgical incision, adequate antibiotic levels are present in the serum and tissues.
  2. 5 to 1 gram administered i.v. or i.m. during surgery for lengthy operative procedures (e.g., 2 hours or more). (Administration should be modified according to the duration of the operative procedure and the time of greatest exposure to infective organisms.)
  3. 5 gram to 1 gram i.v. or i.m. every 6 to 8 hours for 24 hours postoperatively. Following the completion of surgery in which the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin sodium may be continued for 3 to 5 days.

Pediatric Dosage

A total daily dosage of 25 to 50 mg per kg (approximately 10 to 20 mg per pound) of body weight, divided into three or four equal doses, is effective for most mild to moderately severe infections in children. Duration of therapy in most cases should be 5 to 10 days.

Treatment should be continued in beta-hemolytic streptococcal infections for at least 10 days to minimize possible complications associated with the disease.

For severe infections, the total daily dosage may be increased to 100 mg per kg (45 mg per pound) of body weight. Cefazolin administration to premature infants and in infants under one month is not recommended since the safety of cefazolin use in these patients has not been established.

Administration of 60 percent of the normal daily dose in divided doses every 12 hours may be used for children with mild to moderate renal impairment (CCr 0.67 - 1.17 mL/s). Children with moderate renal impairment (CCr 0.33 - 0.67 mL/s) should be given 25 percent of the normal daily dose in equally divided doses every 12 hours, and children with severe renal impairment (CCr 0.08 - 0.33 mL/s) should receive 10 percent of the normal daily dose every 24 hours. An initial loading dose precedes all recommended doses.

PEDIATRIC DOSAGE GUIDE – 25 mg/kg/day 
 Weight25 mg/kg/day – Divided into 3 doses25 mg/kg/day – Divided into 4 doses
 lb kgApprox. Single
Dose mg/q8h
Volume Needed
of 125 mg/mL
Solution
ApproxDose
mg/q6h . Single
Volume Needed
of 125 mg/mL
Solution
104.540 mg0.35 mL30 mg0.25 mL
209.075 mg0.60 mL55 mg0.45 mL
3013.6115 mg0.90 mL85 mg0.70 mL
4018.1150 mg1.20 mL115 mg0.90 mL
5022.7190 mg1.50 mL140 mg1.10 mL
125 mg/mL concentration may be obtained by constituting the 500 mg vial with 3.8 mL of diluent.
PEDIATRIC DOSAGE GUIDE – 50 mg/kg/day
Weight50 mg/kg/day – Divided into 3 doses50 mg/kg/day – Divided into 4 doses
lbkgApprox. Single
Dose mg/q8h
Volume Needed
of 225 mg/mL§
Solution
Approx. Single
Dose mg/q6h
Volume Needed of
225 mg/mL§
Solution
104.575 mg0.35 mL55 mg0.25 mL
209.0150 mg0.70 mL110 mg0.50 mL
3013.6225 mg1.00 mL170 mg0.75 mL
4018.1300 mg1.35 mL225 mg1.00 mL
5022.7375 mg1.70 mL285 mg1.25 mL
§ 225 mg/mL concentration may be obtained by constituting the 500 mg vial with 2.0 mL of diluent.

Administration

NOTE: See CONSTITUTION section for constitution and dilution directions.

For Intramuscular Use

Inject the constituted solution into a large muscle mass. Pain on injection with cefazolin is infrequent.

For Intravenous Use

The intravenous route is preferred for patients with septicemia, peritonitis, or other severe life-threatening infections.

Direct Intravenous (bolus) Injection

Inject the appropriately diluted constituted solution slowly over 3 to 5 minutes directly into vein or through tubing for patients receiving parenteral fluids. (See list of solutions for intravenous infusion in CONSTITUTION.)

Intermittent or Continuous Intravenous Infusion

The constituted solution can be administered along with primary intravenous fluid management programs in a volume control set or in a separate secondary i.v. bottle. (See list of solutions for intravenous infusion in CONSTITUTION.) It is desirable to discontinue the administration of other solutions during the infusion of cefazolin.

Cefazolin for Injection, USP, SmartPak Pharmacy Bulk Packages are for intravenous use only following constitution and transfer into syringes.

After transfer of the contents from the SmartPak Pharmacy Bulk Packages into syringes, cefazolin can be administered in intermittent or continuous infusion via a syringe pump.