Cefazolin Sodium Drug Information

Important Administration Instructions If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram, 2 grams, or 3 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.

Dosage for the Treatment 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 are outlined in Table 1 below. 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 are outlined in Table 2 below.

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. 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. 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.

Dosage Recommendations in Adult 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.

Preparation for Use of 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.

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.

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.

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.

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. 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%). 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)

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, a fall in prothrombin activity, hepatic impairment including cholestasis, and pancytopenia.

The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin for Injection and Dextrose Injection is not recommended.

Pregnancy Risk Summary Available data from published prospective cohort studies, case series and case reports over several decades with cephalosporin use, including cefazolin, in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Cefazolin crosses the placenta. Animal reproduction studies with rats, mice and rabbits administered cefazolin during organogenesis at doses 1 to 3 times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes.

In rats subcutaneously administered cefazolin prior to delivery and throughout lactation, there were no adverse effects on offspring at a dose approximately 2 times the MRHD (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Human Data While available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.

There was no evidence of any adverse effects on embryofetal development due to cefazolin. In a peri-postnatal study in rats, cefazolin administered subcutaneously up to 1200 mg/kg/day (approximately 2 times the MRHD based on body surface area comparison) to pregnant dams prior to delivery and through lactation caused no adverse effects on offspring.

Pediatric Use Cefazolin for Injection and Dextrose Injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved, and for perioperative prophylaxis in pediatric patients aged 10 to 17 years old. Safety and effectiveness of Cefazolin for Injection and Dextrose Injection in premature infants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.

Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Cefazolin for Injection and Dextrose Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Cefazolin for Injection and Dextrose Injection that does not equal 1 gram or 2 grams is required and an alternative formulation of cefazolin should be considered. The safety and effectiveness of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis have been established in pediatric patients aged 10 to 17 years old. Use of Cefazolin for Injection and Dextrose Injection in these age groups is supported by evidence from adults with additional safety and pharmacokinetic data in pediatric patients aged 10 to 17 years old.

Safety and pharmacokinetics were evaluated in two multicenter, non-comparative studies (Study 1 and Study 2). These studies 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. The safety and effectiveness of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.

Hypersensitivity to Cefazolin or the Cephalosporin Class of Antibacterial Drugs, Penicillins, or Other Beta-lactams Cefazolin for Injection and Dextrose Injection 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.

Accidental overdosage resulting in seizures may occur in patients with renal impairment who receive doses greater than the recommended dosage of Cefazolin for Injection and Dextrose Injection. If seizures associated with accidental overdosage occur, discontinue Cefazolin for Injection and Dextrose Injection and give supportive treatment.