CEFOXITIN SODIUM

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
1 and 2 g Vials (powder for solution)
Reconstitution
-Reconstitute each 1 g vial with 10 mL (resultant concentration: 95 mg/mL) and each 2 g vial with 10 or 20 mL (resultant concentration: 180 mg/mL or 95 mg/mL, respectively) using Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection.
-Storage: Reconstituted solutions are stable for 6 hours at room temperature or for 1 week under refrigeration (below 5 degrees C).
Dilution
-For Intermittent IV Injection: No further dilution is necessary.
-For Intermittent IV Infusion: Further dilute in compatible solution to a usual concentration of 10 to 40 mg/mL.
-Continuous IV Infusion: May further dilute in up to 1,000 mL of compatible solution.
-Storage: Diluted solutions are stable for an additional 18 hours at room temperature or 48 hours under refrigeration.

Pharmacy Bulk Vials (powder for solution)
Reconstitution
-Reconstitute each 10 g vial with 43 or 93 mL of a compatible solution (e.g., Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection) to give concentrations of 200 mg/mL or 100 mg/mL, respectively. Further dilution required; pharmacy bulk vials are not intended for administration via direct IV injection.
-Storage: Use reconstituted bulk vials within 4 hours of initial entry.
Dilution
-For Intermittent IV Infusion: Further dilute in a compatible solution to a usual concentration of 10 to 40 mg/mL.
-Continuous IV Infusion: May further dilute in up to 1,000 mL of compatible solution.
-Storage: Diluted solutions are stable for an additional 18 hours at room temperature or 48 hours under refrigeration.

Frozen Pre-mixed Bags
-Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation.
-Storage: The thawed solution remains stable for 24 hours at room temperature or 21 days under refrigeration. Do not refreeze.

DUPLEX Drug Delivery System
-Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber.
-Do not use in series connections to avoid an air embolism. If administration is controlled by a pumping device, discontinue pumping action before the container runs dry to avoid an air embolism.
-Do not introduce additives to the Duplex container.
-Protect from light after removal of foil strip. If the foil strip is removed and not used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
-Once ready for activation, do not use directly after refrigeration; allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. 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.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Storage: After reconstitution (activation), use within 12 hours if stored at room temperature or within 7 days if stored under refrigeration.

Intermittent IV Injection

-Inject appropriate dose directly into a vein over 3 to 5 minutes or slowly into the tubing of a freely-flowing compatible IV solution.

Intermittent IV Infusion
-Infuse over approximately 30 minutes.
-Duplex Drug Delivery System: Before attaching to IV set, fold the Duplex container, starting at the hanger tab end, just below the solution meniscus trapping all air above the fold. Squeeze the Duplex container until the seal between the reconstituted drug solution and the set port opens, releasing the liquid to the set port.

Intramuscular Administration
NOTE: Cefoxitin is not FDA-approved for intramuscular administration.
-Reconstitute vials to a final concentration of 400 mg/mL. Alternatively, for IM use only, 0.5% or 1% lidocaine (without epinephrine) may be used to minimize IM discomfort.
-Inject appropriate dose deeply into a large muscle (e.g., anterolateral thigh or deltoid [children and adolescents only]).

Cefoxitin is generally well tolerated. The most common adverse reaction is a local injection site reaction (thrombo-phlebitis) after intravenous administration.

Cefoxitin has been associated with elevations in serum creatinine and/or blood urea nitrogen (azotemia). Careful evaluation of the patient is warranted to determine whether an elevation in serum creatinine is associated with renal impairment or laboratory interaction. As with other cephalosporins, acute renal failure (unspecified) has been rarely reported with cefoxitin. Renal impairment and toxic nephropathy have been reported with cephalosporin antibiotics. Patients with preexisting renal dysfunction and patients taking other nephrotoxic drugs are more susceptible. In addition, high concentrations of cefoxitin (> 100 mcg/ml) may interfere with serum and urine creatinine measurement using the Jaffe reaction; creatinine concentrations may appear falsely elevated. Serum creatinine measurements should be collected at least 2 hours after cefoxitin administration.

Diarrhea has been reported with cefoxitin and has been reported in 1% to 19% of adults on cephalosporin therapy in general. Nausea and vomiting have been reported rarely. Transient elevated hepatic enzymes (AST, ALT, LDH, alkaline phosphatase) and jaundice have occurred with cefoxitin use. Elevated transaminases have been noted in 1% to 7% of patients receiving cephalosporins in general. Higher doses of cefoxitin have been associated with an increased rate of elevated AST in pediatric patients. Abdominal pain, colitis, elevated bilirubin (hyperbilirubinemia), and hepatic impairment, including cholestasis, have been reported with other cephalosporins.

Allergic reactions have been reported infrequently with cefoxitin; however, the development of eosinophilia appears to be more common in pediatric patients compared to adults. In general, approximately 1-3% of treatment courses result in some type of dermatologic allergic reaction. Allergic reactions include dyspnea, eosinophilia, fever, flushing, rash (unspecified), exfoliative dermatitis, toxic epidermal necrolysis, pruritus, urticaria, anaphylactoid reactions, interstitial nephritis, and angioedema. Interstitial nephritis has been reported in < 1% of patients receiving cephalosporins. Anaphylaxis has been reported rarely. Erythema multiforme, Stevens-Johnson syndrome, and serum sickness-like reactions have been reported with other cephalosporin antibiotics.

Hematologic adverse reactions have been reported infrequently with cefoxitin. Anemia (including hemolytic anemia), thrombocytopenia, bone marrow depression, eosinophilia, leukopenia (including granulocytopenia), and neutropenia have been reported. Higher doses of cefoxitin have been associated with an increased rate of eosinophilia in pediatric patients. Neutropenia has been reported in < 1% of patients, thrombocytopenia has occurred in <= 3% of patients, and hemolytic anemia has been reported in < 1% of patients receiving cephalosporins. A positive direct Coombs test may develop in some patients, especially those with azotemia. Agranulocytosis, aplastic anemia, bleeding (hemorrhage), pancytopenia, and prolonged prothrombin time have been reported during therapy with the cephalosporin class.

Several cephalosporin antibiotics have been associated with seizures, particularly in patients with renal impairment when the dosage was not reduced. Seizures have been reported in < 1% of patients receiving cephalosporins. If seizures occur during cefoxitin therapy, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Hypotension has been reported infrequently with cefoxitin therapy.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with cefoxitin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Vaginal candidiasis and vaginitis have been reported with cephalosporin use.

Cefoxitin may possibly cause an exacerbation of myasthenia gravis.

Cefoxitin is contraindicated in patients with cefoxitin hypersensitivity or hypersensitivity to other beta-lactams (carbapenem hypersensitivity, cephalosporin hypersensitivity, or penicillin hypersensitivity). Serious and occasionally fatal hypersensitivity reactions have been reported in patients being treated with beta-lactams, including cefoxitin. These reactions are more likely to occur in individuals with a history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before starting cefoxitin therapy, make careful inquiry concerning previous penicillin hypersensitivity, cephalosporin hypersensitivity, or other beta-lactam or allergen hypersensitivity. Cross-reactivity to cephalosporins is approximately 3% to 7% with a documented history to penicillin.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including cefoxitin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

All cephalosporins, including cefoxitin, may rarely cause hypothrombinemia and have the potential to cause bleeding. Cephalosporins that contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency) since these patients are at a higher risk for developing bleeding complications.

Use cefoxitin with caution in patients with renal disease, renal impairment, or renal failure because the drug is eliminated via renal mechanisms. Cephalosporins have been associated with seizures, especially in patients with renal impairment given unadjusted doses. Dosage reductions are recommended in these patients.

Monitor patients with myasthenia gravis carefully for a worsening of their condition. According to the FDA-approved labeling, cefoxitin use has been associated with a possible exacerbation of myasthenia gravis.

Administration of cefoxitin may result in laboratory test interference. A false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. Also, a positive direct Coombs' test may develop in some patients, particularly those with azotemia. High concentrations of cefoxitin (more than 100 mcg/mL) may interfere with serum and urine creatinine measurement using the Jaffe reaction and produce false increases of modest degree in reported creatinine concentrations. Collect serum samples for creatinine measurements at least 2 hours after cefoxitin administration. High urinary concentrations of cefoxitin may interfere with the measurement of urinary 17-hydroxycorticosteroids by the Porter-Silber reaction and produce false increases of modest degree in the reported concentrations.

Description: Cefoxitin is a parenteral cephamycin antibiotic. Although not technically a cephalosporin, because of cefoxitin's spectrum of activity, it is often classified as a second-generation cephalosporin. The drug has added stability against the beta-lactamases, providing better activity against certain gram-negative species compared to first-generation cephalosporins. When it was initially marketed, cefoxitin was the first cephalosporin-like antibiotic to exhibit activity against anaerobes. Many institutions have substituted cefotetan for cefoxitin because their spectra of activity is extremely similar and cefotetan can be dosed less frequently. In addition, cefoxitin has been found to be a potent inducer of beta-lactamases. One of the most common uses of cefoxitin is as surgical prophylaxis for gastrointestinal procedures. Other therapeutic uses of cefoxitin include intra-abdominal infection, gynecologic infection, soft-tissue and skin infections, and respiratory and urinary tract infections. Cefoxitin is FDA-approved for used in pediatric patients as young as 3 months of age.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Bacteroides fragilis, Bacteroides ovatus, Bacteroides sp., Bacteroides thetaiotaomicron, Clostridium perfringens, Clostridium sp., Eikenella corrodens, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella sp., Morganella morganii, Neisseria gonorrhoeae, Parabacteroides distasonis, Peptococcus niger, Peptostreptococcus sp., Prevotella bivia, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia sp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci)
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Fusobacterium sp., Peptococcus sp., Salmonella sp., Shigella sp.
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of bacteremia, bone and joint infections, lower respiratory tract infections (e.g., lung abscess, pneumonia), and urinary tract infection (UTI):
Intravenous or Intramuscular* dosage:
Neonates less than 32 weeks gestation and 0 to 7 days*: 35 mg/kg/dose IV or IM every 12 hours.
Neonates less than 32 weeks gestation and older than 7 days*: 35 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older*: 35 mg/kg/dose IV or IM every 8 hours.
Infants 1 to 2 months*: 80 to 160 mg/kg/day IV or IM divided every 6 to 8 hours.
Infants, Children, and Adolescents 3 months to 17 years: 80 to 160 mg/kg/day (Max: 12 g/day) IV or IM divided every 6 to 8 hours.

For surgical infection prophylaxis:
Intravenous dosage:
Infants 1 to 2 months*: 40 mg/kg/dose IV as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 2 hours from the first preoperative dose. May continue 40 mg/kg/dose IV every 6 hours for no more than 24 hours post-operatively if necessary. Guidelines recommend cefoxitin for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, and clean-contaminated urologic procedures.
Infants, Children, and Adolescents 3 months to 17 years: 30 to 40 mg/kg/dose (Max: 2 g/dose) IV as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 2 hours from the first preoperative dose. May continue 30 to 40 mg/kg/dose (Max: 2 g/dose) IV every 6 hours for no more than 24 hours post-operatively if necessary. Guidelines recommend cefoxitin for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, and clean-contaminated urologic procedures.

For the treatment of gynecologic infections, including endometritis, pelvic cellulitis, pelvic inflammatory disease (PID), and tubo-ovarian abscess*:
-for the general treatment of gynecologic infections:
Intravenous or Intramuscular* dosage:
Adolescents: 80 to 160 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 12 g/day).
-for the treatment of mild-to-moderate PID:
Intramuscular dosage*:
Adolescents: 2 g IM as a single dose plus probenecid given concurrently as a single dose plus oral doxycycline and metronidazole for 14 days. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.
-for the treatment of severe PID or tubo-ovarian abscess*:
Intravenous dosage:
Adolescents: 2 g IV every 6 hours in combination with doxycycline. Cefoxitin should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, and intraabdominal abscess:
-for the treatment of complicated community-acquired intraabdominal infections with adequate source control:
Intravenous or Intramuscular* dosage:
Neonates younger than 32 weeks gestation and 0 to 7 days*: 35 mg/kg/dose IV or IM every 12 hours for 7 to 10 days. In general, IV administration is preferred; IM administration in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.
Neonates younger than 32 weeks gestation and older than 7 days*: 35 mg/kg/dose IV or IM every 8 hours for 7 to 10 days.
Neonates 32 weeks gestation and older*: 35 mg/kg/dose IV or IM every 8 hours for 7 to 10 days.
Infants 1 to 2 months*: 80 to 160 mg/kg/day IV or IM divided every 6 to 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants, Children, and Adolescents 3 months to 17 years: 80 to 160 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 12 g/day) for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of uncomplicated intraabdominal infections:
Intravenous or Intramuscular* dosage:
Infants 1 to 2 months*: 80 to 160 mg/kg/day IV or IM divided every 6 to 8 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants, Children, and Adolescents 3 months to 17 years: 80 to 160 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 12 g/day). Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

For the treatment of skin and skin structure infections, including gas gangrene:
Intravenous or Intramuscular* dosage:
Neonates younger than 32 weeks gestation and 0 to 7 days*: 35 mg/kg/dose IV or IM every 12 hours. In general, IV administration is preferred; IM administration in very low birth weight neonates is not practical due to small muscle mass and unreliable absorption.
Neonates younger than 32 weeks gestation and older than 7 days*: 35 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older*: 35 mg/kg/dose IV or IM every 8 hours.
Infants 1 to 2 months*: 80 to 160 mg/kg/day IV or IM divided every 6 to 8 hours.
Infants, Children, and Adolescents 3 months to 17 years: 80 to 160 mg/kg/day IV or IM divided every 4 to 8 hours (Max: 12 g/day).

Maximum Dosage Limits:
-Neonates
0 to 7 days: Safety and efficacy have not been established; however, doses up to 70 mg/kg/day IV/IM for those less than 32 weeks gestation and 105 mg/kg/day IV/IM for those 32 weeks gestation and older have been used off-label.
older than 7 days: Safety and efficacy have not been established; however, doses up to 105 mg/kg/day IV/IM have been used off-label.
-Infants
1 to 2 months: Safety and efficacy have not been established; however, doses up to 160 mg/kg/day IV/IM have been used off-label.
3 to 11 months: 160 mg/kg/day IV/IM.
-Children
160 mg/kg/day IV/IM (Max: 12 g/day).
-Adolescents
160 mg/kg/day IV/IM (Max: 12 g/day).

Patients with Hepatic Impairment Dosing
Cefoxitin is primarily eliminated by the kidneys and is not metabolized by the liver. No dosage adjustments are required in patients with hepatic impairment.

Patients with Renal Impairment Dosing
The following dosage adjustments are based on a usual recommended dose in pediatric patients of 80 to 160 mg/kg/day divided every 6 hours :
CrCl more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 20 to 40 mg/kg/dose IV or IM every 8 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 20 to 40 mg/kg/dose IV or IM every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: 20 to 40 mg/kg/dose IV or IM every 24 hours.

Intermittent hemodialysis
Cefoxitin 20 to 40 mg/kg/dose IV or IM every 24 hours, given after hemodialysis on dialysis days.

Peritoneal hemodialysis
Cefoxitin 20 to 40 mg/kg/dose IV or IM every 24 hours.

Continuous renal replacement therapy (CRRT)
Cefoxitin 20 to 40 mg/kg/dose IV or IM every 8 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Cefoxitin, a beta-lactam cephamycin similar to penicillins and cephalosporins, inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of cefoxitin as well as the other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefoxitin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.

Beta-lactams, including cefoxitin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.

The susceptibility interpretive criteria for cefoxitin are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales and anaerobes. The MICs are defined for Enterobacterales by the FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however the MICs are defined by CLSI as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. The MICs are defined for anaerobes by the FDA as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more; however the MICs are defined by CLSI as susceptible at 16 mcg/mL or less, intermediate at 32 mcg/mL, and resistant at 64 mcg/mL or more. The MICs are defined for N. gonorrhoeae as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. Cefoxitin is tested as a surrogate for oxacillin for some species of Staphylococcus. The MICs are defined for S. aureus and S. lugdunesis as susceptible at 4 mcg/mL or less and resistant at 8 mcg/mL or more. The breakpoints for Enterobacterales, anaerobes, N. gonorrhoeae, and Staphylococcus sp. are based on a dosage regimen of 2 g every 6 hours. The MICs are defined for Aeromonas sp. and Vibrio sp. as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more.

Resistance to cephalosporins occurs as a result of decreased permeability, alterations of PBPs, and hydrolysis by beta-lactamases.

Pharmacokinetics: Cefoxitin is administered intravenously and intramuscularly. Approximately 73% of the circulating drug is protein-bound. It is distributed into most body tissues and fluids, including the gallbladder, kidney, bile, and peritoneal, pleural, and synovial fluids. Over a 6-hour period, 85% of the drug is excreted unchanged into the urine via glomerular filtration and tubular secretion. The elimination half-life is 40-60 minutes in adults with normal renal function. The coadministration of probenecid slows tubular excretion of cefoxitin.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
After a 1 gram intravenous dose in adults, serum concentrations of 110 mcg/ml at 5 minutes after the dose declined to < 1 mcg/ml at 4 hours.

Intramuscular Route
Cefoxitin is well absorbed after IM administration. After the initial distribution phase, absorption after IM administration is similar to that after IV administration. Peak concentrations are reached approximately 15-30 minutes after administration.


-Special Populations
Pediatrics
Neonates
Neonates and young infants (< 2 months of age) have a slower clearance, longer elimination half-life, and larger volume of distribution (Vd) compared to children and adults. In a pharmacokinetic study of 15 neonates and young infants, the mean clearance, Vd, and elimination half-life were 0.27 L/kg/hr, 0.5 L/kg, and 1.43 hours, respectively. The elimination half-life was inversely related to postnatal age. The gestational ages of the neonates ranged from 29 to 42 weeks, with all but 3 being > 35 weeks; postnatal ages at study entry were 10-53 days.

Infants and Children
Pharmacokinetics of cefoxitin in older infants and children are similar to those in adults. A mean elimination half-life of 42 minutes was reported in a study in infants and children (n = 32; 3 months to 12 years of age) which is similar to that reported in adults. Infants < 2 months of age have a slower clearance and longer elimination half-life.

Renal Impairment
Pharmacokinetic data are not available for children with renal impairment. However, cefoxitin is primarily eliminated renally and the elimination half-life increases significantly as renal function declines. In a pharmacokinetic study in adult patients with varying degrees of renal impairment, the following elimination half-lives were reported :
GFR 40-80 ml/min/1.73 m2: 1 +/- 0.2 hours (n = 7)
GFR 20-40 ml/min/1.73 m2: 2 +/- 0.6 hours (n = 7)
GFR 10-20 ml/min/1.73 m2: 7 +/- 2.3 hours (n = 4)
GFR 5-10 ml/min/1.73 m2: 13.7 +/- 2.8 hours (n = 7)
GFR < 5 ml/min/1.73 m2: 23.5 +/- 9 hours (n = 10)