CEFAZOLIN- cefazolin injection, powder, for solution 
General Injectables & Vaccines, Inc

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use CEFAZOLIN FOR INJECTION USP safely and effectively. See full prescribing information for CEFAZOLIN FOR INJECTION USP.

CEFAZOLIN INJECTION USP, for intravenous or intramuscular use
Initial U.S. Approval:  1973

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 bacteria.

INDICATIONS AND USAGE

Cefazolin for Injection USP is a cephalosporin antibacterial indicated in the treatment of the following infections caused by susceptible isolates of the designated microorganisms:  Respiratory tract infections (1.1); urinary tract infections (1.2); skin and skin structure infections (1.3); biliary tract infections (1.4); bone and joint infections (1.5); genital infections (1.6); septicemia (1.7); endocarditis (1.8) and perioperative prophylaxis (1.9). (1)

DOSAGE FORMS AND STRENGTHS

  • 500 mg per vial and 1 g per vial (3)

CONTRAINDICATIONS

  • Hypersensitivity to cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams (4.1)

WARNINGS AND PRECAUTIONS

  • Hypersensitivity reactions:  Cross-hypersensitivity may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue the drug. (5.1)
  • Use in patients with renal impairment:  Dose adjustment required for patients with CrCl less than 55 mL/min. (5.2)
  • Clostridium difficile-associated diarrhea:  May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. (5.3)

ADVERSE REACTIONS

  • Most common adverse reactions:  gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). (6)

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

  • Probenecid:  may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood concentrations. (7)

Revised: 4/2014

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Respiratory Tract Infections

1.2 Urinary Tract Infections

1.3 Skin and Skin Structure Infections

1.4 Biliary Tract Infections

1.5 Bone and Joint Infections

1.6 Genital Infections

1.7 Septicemia

1.8 Endocarditis

1.9 Perioperative Prophylaxis

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

4.1 Hypersensitivity to Cefazolin or the Cephalosporin Class of Antibacterial Drugs, Penicillins, or Other Beta-lactams

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams

5.2 Use In Patients with Renal Impairment

5.3 Clostridium difficile-associated Diarrhea

5.5 Risk of Development of Drug-resistant Bacteria

5.6 Drug/Laboratory Test Interactions

5.7 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Cephalosporin-class Adverse Reactions

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Patients with Renal Impairment

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

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.

Cefazolin for Injection USP is indicated for the treatment of the following infections when caused by susceptible bacteria.

1.1 Respiratory Tract Infections

Respiratory tract infections due to Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes.

Injectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.

Cefazolin is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.

1.2 Urinary Tract Infections

Urinary tract infections due to Escherichia coli, and Proteus mirabilis.

1.3 Skin and Skin Structure Infections

Skin and skin structure infections due to S. aureus, S. pyogenes, and Streptococcus agalactiae.

1.4 Biliary Tract Infections

Biliary infections due to E. coli, various isolates of streptococci, P. mirabilis, and S. aureus.

1.5 Bone and Joint Infections

Bone and joint infections due to S. aureus.

1.6 Genital Infections

Genital infections due to E. coli, and P. mirabilis.

1.7 Septicemia

Septicemia due to S. pneumoniae, S. aureus, P. mirabilis, and E. coli.

1.8 Endocarditis

Endocarditis due to S. aureus and S. pyogenes.

1.9 Perioperative Prophylaxis

The prophylactic administration of cefazolin 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 cefazolin 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).

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.

3 DOSAGE FORMS AND STRENGTHS

Single-use container:

  • 500 mg Cefazolin for Injection USP
  • 1 g Cefazolin for Injection USP

4 CONTRAINDICATIONS

4.1 Hypersensitivity to Cefazolin or the Cephalosporin Class of Antibacterial Drugs, Penicillins, or Other Beta-lactams

Cefazolin for Injection USP is contraindicated in patients who have a history of immediate hypersensitivity reactions (e.g., anaphylaxis, serious skin reactions) to cefazolin or the cephalosporin class of antibacterial drugs, penicillins, or other beta-lactams [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with Cefazolin for Injection USP is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs 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 USP occurs, discontinue the drug.

5.2 Use In Patients with Renal Impairment

As with other beta-lactam antibacterial drugs, seizures may occur if inappropriately high doses are administered to patients with impaired renal function (creatinine clearance less than 55 mL/min.) [see Dosage and Administration (2.3)].

5.3 Clostridium difficile-associated Diarrhea

Clostridium-difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefazolin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.5 Risk of Development of Drug-resistant Bacteria

Prescribing Cefazolin for Injection USP in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antimicrobials, prolonged use of Cefazolin for Injection USP may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.

5.6 Drug/Laboratory Test Interactions

Urinary Glucose

The administration of cefazolin may result in a false-positive reaction with glucose in the urine when using CLINITEST tablets. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (e.g., CLINISTIX) be used.

Coombs' Test

Positive direct Coombs' tests have been reported during treatment with cefazolin. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibacterial drugs before parturition, it should be recognized that a positive Coombs' test may be due to the drug.

5.7 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance

As with other dextrose-containing solutions, Cefazolin for Injection USP should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

6 ADVERSE REACTIONS

The following serious adverse reactions of cefazolin are described below and elsewhere in the labeling:

  • Hypersensitivity reactions [see Warnings and Precautions (5.1)].
  • Clostridium difficile-associated diarrhea [see Warnings and Precautions (5.3)].

6.1 Clinical Trials Experience

The following adverse reactions were reported from clinical trials:

Gastrointestinal:  Diarrhea, oral candidiasis (oral thrush), mouth ulcers, vomiting, nausea, stomach cramps, epigastric pain, heartburn, flatus, anorexia and pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.3)].

Allergic:  Anaphylaxis, eosinophilia, urticaria, itching, drug fever, skin rash, Stevens-Johnson syndrome.

Hematologic:  Neutropenia, leukopenia, thrombocytopenia, thrombocythemia.

Hepatic:  Transient rise in SGOT, SGPT, and alkaline phosphatase levels has been observed. As with other cephalosporins, reports of hepatitis have been received.

Renal:  As with other cephalosporins, reports of increased BUN and creatinine levels, as well as renal failure, have been received.

Local Reactions:  Instances of phlebitis have been reported at site of injection. Pain at the site of injection after intramuscular administration has occurred infrequently. Some induration has occurred.

Other Reactions:  Pruritus (including genital, vulvar and anal pruritus, genital moniliasis, and vaginitis). Dizziness, fainting, lightheadedness, confusion, weakness, tiredness, hypotension, somnolence and headache.

6.2 Cephalosporin-class Adverse Reactions

In addition to the adverse reactions listed above that have been observed in patients treated with cefazolin, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterials:  Stevens-Johnson syndrome, erythema, multiforme, toxic epidermal necrolysis, renal impairment, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic impairment including cholestasis, and pancytopenia.

7 DRUG INTERACTIONS

Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Reproduction studies have been performed in rats, mice and rabbits at doses of 2000, 4000, and 240 mg/kg/day or 1 to 3 times the maximum recommended human dose on a body surface area basis. There was no evidence of impaired fertility or harm to the fetus due to cefazolin.

8.2 Labor and Delivery

When cefazolin has been administered prior to caesarean section, drug concentrations 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.

8.3 Nursing Mothers

Cefazolin is present in very low concentrations in the milk of nursing mothers. Caution should be exercised when Cefazolin for Injection USP is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness for use in premature infants and neonates have not been established. See Dosage and Administration (2.4) for recommended dosage in pediatric patients older than 1 month.

8.5 Geriatric Use

Of the 920 subjects who received cefazolin 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 Dosage and Administration (2.3) and Warnings and Precautions (5.2)].

8.6 Patients with Renal Impairment

When Cefazolin for Injection USP is administered to patients with low urinary output because of impaired renal function (creatinine clearance less than 55 mL/min.), lower daily dosage is required [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)].

11 DESCRIPTION

Cefazolin for Injection USP is a sterile white to yellowish powder containing Cefazolin Sodium USP supplied in vials equivalent to 500 mg or to 1 gram of cefazolin for parenteral administration.

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.

Cefazolin Sodium USP has the following structural formula:

Formula1

The sodium content is 24 mg (1.05 mEq) per 500 mg of cefazolin sodium and 48 mg (2.1 mEq) per 1 gram of cefazolin sodium.

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

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 to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 g dose.

The serum half-life for cefazolin is approximately 1.8 hours following IV administration and approximately 2 hours following IM 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 produced a steady serum concentration at the third hour of approximately 28 mcg/mL.

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

Bile concentrations in patients with 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 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. Cefazolin 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.

12.4 Microbiology

SAMPLE PACKAGE LABEL

Label1.jpg

CEFAZOLIN 
cefazolin injection, powder, for solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:52584-024(NDC:0781-3450)
Route of AdministrationINTRAMUSCULAR, INTRAVENOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
CEFAZOLIN (UNII: IHS69L0Y4T) (CEFAZOLIN - UNII:IHS69L0Y4T) CEFAZOLIN500 mg
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:52584-024-701 in 1 BAG04/12/201206/30/2017
11 in 1 VIAL; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA06283104/12/201206/30/2017
Labeler - General Injectables & Vaccines, Inc (108250663)

Revised: 8/2019
 
General Injectables & Vaccines, Inc