Cefazolin Sodium Dailymed

2 Dosage And Administration

If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered. (2.1)

For intravenous use only administered over approximately 30 minutes. (2.1)

   Table 1: Recommended Dosing Schedule in Adult Patients with CLcr Greater Than or Equal To 55 mL/min. (2.1, 2.2 and 2.3)
  Site and 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)In rare instances, doses of up to 12 grams of cefazolin per day have been used.Â	  1 gram to 1.5 grams	  every 6 hours
  Perioperative prophylaxis	  1 gram to 2 grams	  ½ to 1 hour prior to start of surgery
	  500 mg to 1 g	  during surgery for lengthy procedures
	  500 mg to 1 g	  every 6 to 8 hours for 24 hours postoperatively

 Recommended Dosing Schedule in Pediatric Patients with CLcr Greater than or Equal to 70 mL/min. (2.1, 2.2, and 2.3)
 Site and Type of Infection	 Dose	 Frequency
 Moderate to severe infectionsFor the treatment indications (1.1 to 1.8) Â	25 to 50 mg per kg	divided into 3 or 4 equal doses
 Severe infectionsÂ	May increase to 100 mg per kg	divided into 3 or 4 equal doses
  Perioperative prophylaxis (10 to 17 years old)	 < 50 kg: 1 gram	½ to 1 hour prior to start of surgery
	 ≥ 50 kg: 2 grams
	 500 mg to 1 g	during surgery for lengthy procedures
	 500 mg to 1 g	 every 6 to 8 hours for 24 hours postoperatively

• Dosage adjustment is required for adult patients with CLcr that is less than 55 mL/min and pediatric patients with CLcr that is less than 70 mL/min. (2.4 and 8.6)
• See full prescribing information for preparation and administration instructions. (2.5)

2.1Important Administration Instructions

If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.

Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.

2.2 Dosage for theTreatment of Infections

D osage for the Treatment of Infections in Adults with Creatinine Clearance (CLcr) Equal to 55 mL/min or Greater  

The recommended adult dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table 1 below. Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.

   Table 1:  Recommended Dosage in Adult Patients with CLcr Equal to 55 mL/min or Greater If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.  .
  Site and 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)In rare instances, doses of up to 12 grams of cefazolin per day have been used.  Â	  1 gram to 1.5 grams	  every 6 hours

Dosage for the Treatment of Infections in Pediatric Patients with CLcr Equal to  70 mL/min or Greater 

The recommended pediatric dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table 2 below. Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.

If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered [see Use in Specific Populations (8.4)].

Table 2: Recommended Dosage in Pediatric Patients with  CLcr 70 mL/min or greater for Treatment of Infections [see Indications and Usage (1.1 to 1.8)] Â
 Type of Severity	 Recommended Total Daily Dosage
 Mild to moderate infections	 25 mg/kg to 50 mg/kg, divided into 3 or 4 equal dosesÂ
 Severe infections	 May increase to 100 mg/kg, divided into 3 or 4 equal doses

2.3 Dosage for Perioperative Prophylaxis

Dosage for Perioperative Prophylaxis in Adults with CLcr Equal to 55 mL/min or Greater

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended dosages are described in Table 3 below.

Table 3: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr to  55 mL/min or GreaterÂ
 Dose administered ½ hour  to 1 hour prior to the start of surgery	 Additional dose during lengthy operative procedures (e.g., 2 hours or more)	 Dose for 24 hours postoperatively
 1 g 2 g	 500 mg to 1 g	500 mg to 1 g every 6 hours to 8 hoursÂ

If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended and an alternative formulation of cefazolin should be considered.

It is important that (i) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the  time of initial surgical incision; and (ii) cefazolin be administered, if necessary, at appropriate  intervals during surgery to provide sufficient concentrations of the antibacterial drug at the anticipated moments of greatest exposure to infective organisms. 

The perioperative prophylactic administration of cefazolin 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 may be continued for 3 days to 5 days following the completion of surgery.

Dosage for  Perioperative  Prophyla xis in  Pediatric Patients Aged 10 to 17 Years Old with CLcr 70 mL/min or Greater

To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are described in Table 4 below.

Table 4: Recommended Dosage for Perioperative Prophylaxis in Pediatric Patients with CLcr 70 mL/min or greater Aged 10 to 17 years Old  Â
 Body weight (kg)	 Dose administered ½ to 1 hour prior to the start of surgery	 Additional dose during lengthy operative procedures (e.g., 2 hours or more)	Dose for 24 hours postoperativelyÂ
Less than 50 kg	 1 g	 500 mg to 1 g	500 mg to 1 g every 6 hours to 8 hoursÂ
Greater than or equal to 50 kg	 2 g

* If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.

It is important that (i) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the time of initial surgical incision; and (ii) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient concentrations of the antibacterial drug at the anticipated moments of greatest exposure to infective organisms.

The administration of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis should usually be discontinued within a 24-hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating the administration of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis may be continued for 3 days to 5 days following the completion of surgery.

2.4 Dosage RecommendationsinAdult and Pediatric Patients with Renal Impairment

Dosage Recommendations in Adult Patients with CLcr less than 55 mL/min

The dosage recommendation for Cefazolin for Injection and Dextrose Injection in adult patients with renal impairment (CLcr less than 55 mL/min)  is outlined in Table 5 below.

Table 5: Dosage Recommendation for  Adult Patients with CLcr less than 55 mL/minÂ
 Creatinine Clearance	 Dose	 Frequency
 35 to 54 mL/min	 Recommended dose	 every 8 hours or longer
 11 to 34 mL/min	 Half of recommended dose If the recommended dose in adult patients with creatinine clearance equal to 35 mL/min or greater is 1 gram, then this product is not recommended for use in patients with creatinine clearance less than 35 mL/min and an alternative formulation of cefazolin should be considered. Â	 every 12 hours
 10 mL/min or less	 Half of recommended doseÂ	 every 18 to 24 hours

Dosage Recommendations in  Pediatric  Patients with CLcr less than 70 mL/min

The dosage recommendation for Cefazolin for Injection and Dextrose Injection in pediatric patients with renal impairment (CLcr less than 70 mL/min)  is outlined in Table 6 below.

Table 6: Recommended Dosage in Pediatric Patients with CLcr less than 70 mL/minÂ
Creatinine Clearance	 Recommended Dosage
 40 to 70 mL/min	60% of the normal daily dose given in equally divided doses every 12 hoursÂ
 20 to 40 mL/min	25% of the normal daily dose given in equally divided doses every 12 hours
 5 to 20 mL/min	10% of the normal daily dose every 24 hours

*If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.

2.5 Preparation for Useof Cefazolin for Injection and Dextrose Injection in DUPLEX Container

This reconstituted solution of Cefazolin for Injection and Dextrose Injection is for intravenous use only.

Do not use plastic containers in series connections. Such use would result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Use only if solution is clear and container and seals are intact.

DUPLEX® Container Storage

• To avoid inadvertent activation, the DUPLEX® Container should remain in the folded position until activation is intended.

Patient Labeling and Drug Powder/Diluent Inspection

• Apply patient-specific label on foil side of container. Use care to avoid activation. Do not cover any portion of foil strip with patient label.
• Unlatch side tab and unfold DUPLEX® Container (see Diagram 1).

• Visually inspect diluent chamber for particulate matter.
• Use only if container and seals are intact.
• To inspect the drug powder for foreign matter or discoloration, peel foil strip from drug chamber (see Diagram 2).

• Protect from light after removal of foil strip.

Note: If foil strip is removed, the container should be re-folded and the side tab latched until ready to activate. The product must then be used within 7 days, but not beyond the labeled expiration date.

Reconstitution (Activation)

• Do not use directly after storage by refrigeration, allow the product to equilibrate to room temperature before patient use.
• Unfold the DUPLEX® Container and point the set port in a downward direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the diluent meniscus trapping all air above the fold. To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber (see Diagram 3).

• Agitate the liquid-powder mixture until the drug powder is completely dissolved.

Note: Following reconstitution (activation), product must be used within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.

Administration

• Visually inspect the reconstituted solution for particulate matter.
• Point the set port in a downwards direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the solution meniscus trapping all air above the fold. Squeeze the folded DUPLEX® Container until the seal between reconstituted drug solution and set port opens, releasing liquid to set port (see Diagram 4).

• Prior to attaching the IV set, check for minute leaks by squeezing container firmly. If leaks are found, discard container and solution as sterility may be compromised.
• Using aseptic technique, peel foil cover from the set port and attach sterile administration set (see Diagram 5).

• Refer to directions for use accompanying the administration set.

Important Administration Instructions

• Do not use in series connections.
• Do not introduce additives into the DUPLEX® Container.
• Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.

The following serious adverse reactions to Cefazolin for Injection and Dextrose Injection are described below and elsewhere in the labeling:

• Hypersensitivity reactions [see Warnings and Precautions (5.1)]
• Seizures in Patients with Renal Impairment [see Warnings and Precautions (5.2)]
• Clostridioides difficile-associated diarrhea [see  Warnings and Precautions (5.3)]

• Adult and Pediatric Patients: Most common adverse reactions: gastrointestinal (nausea, vomiting, diarrhea), and allergic reactions (anaphylaxis, urticaria, skin rash). (6)
• Pediatric Patients with Perioperative Prophylaxis: The most frequently reported adverse reactions (incidence ≥ 5%) were nausea, infusion site pain, and headache.

To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-800-854-6851 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

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. Reports of hepatitis have been received.

Renal: 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. 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.

Adverse Reactions in Pediatric Patients for Perioperative Prophylaxis

Two studies (Study 1: NCT 3231228 and Study 2: NCT 01904357) were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis in pediatric patients.

Study 1 was a multicenter, open-label, non-comparative, parallel group study to evaluate the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis in 61 pediatric patients 10 to 17 years of age. Thirty-three subjects with a weight of at least 25 kg but less than 60 kg received a single dose of 1 gram of cefazolin and 28 subjects with a weight of at least 60 kg received a single dose of 2 grams of cefazolin. The mean age of the safety population was 14 years and ranged from 10 to 17 years. There were no adverse reactions leading to study discontinuation or deaths reported during the study. The most frequently reported adverse reactions were nausea (14.8%), infusion site pain (6.6%), and headache (4.9%).  

Study 2 was a multicenter, non-comparative study that evaluated the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis in 12 pediatric patients 10 to 12 years of age. Subjects weighing at least 25 kg to less than 50 kg received a single dose of 1 gram of Cefazolin for Injection and Dextrose Injection and subjects weighing at least 50 kg to less than 85 kg received a single dose of 2 grams of Cefazolin for Injection and Dextrose Injection.

The safety findings in Study 2 in pediatric patients aged 10 to 12 years old  were similar to those observed in adult patients and the pediatric patients aged 10 to 17 years old in Study 1.

6.2Postmarketing Experience

The following adverse reactions have been identified during post approval use of cefazolin.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders: Serum sickness-like reaction

Renal and urinary disorders: Acute tubulointerstitial nephritis (ATIN)

Skin and subcutaneous tissue disorders: Acute generalized exanthematous pustulosis (AGEP)

6.3 Cephalosporin-class Adverse Reactions

In addition to the adverse reactions uled 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.