Usual dosage range: IV: 1 to 2 g every 6 to 8 hours.
Bite wound (animal) (off-label use): IV: 1 g every 6 to 8 hours (Ref).
Gonococcal infection, uncomplicated (infection of the cervix, rectum, or urethra) (alternative agent) (off-label use):
Note: Use cefoxitin only if ceftriaxone is unavailable given a lack of contemporary efficacy data (Ref).
IM: 2 g as a single dose plus oral probenecid; give in combination with treatment for chlamydia if it has not been excluded (Ref). When treatment failure is suspected (eg, detection of N. gonorrhoeae after treatment without additional sexual exposure), consult an infectious diseases specialist. Report failures to the CDC through state and local health departments (Ref).
Mycobacterial (nontuberculous, rapidly growing) infection (off-label use):
Patients without cystic fibrosis: 2 to 4 g two to three times daily or 200 mg/kg/day in 3 divided doses (maximum daily dosage: 12 g/day) as part of an appropriate combination regimen (Ref).
Patients with cystic fibrosis: 200 mg/kg/day in 3 divided doses (maximum daily dosage: 12 g/day) as part of an appropriate combination regimen (Ref).
Duration of therapy: The optimal duration of therapy is unknown, but generally the duration of parenteral therapy is ≤12 weeks depending on severity of infection, tolerability, and other patient-specific factors, followed by long-term oral maintenance therapy; consult an infectious diseases specialist for specific recommendations (Ref).
Pelvic inflammatory disease:
Inpatients: IV: 2 g every 6 hours in combination with doxycycline. Total duration of therapy (which may include oral step-down therapy) is 14 days; oral therapy can usually be initiated within 24 to 48 hours of clinical improvement (Ref).
Outpatients: IM: 2 g as a single dose plus oral probenecid, followed by oral doxycycline and metronidazole for 14 days (Ref).
Surgical (perioperative) prophylaxis: IV: 2 g within 60 minutes prior to surgical incision. Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Single doses of IV or IM cefoxitin (eg, used for perioperative prophylaxis or outpatient treatment of pelvic inflammatory disease) do not require dosage adjustment for any degree of kidney dysfunction or in patients receiving kidney replacement therapies (Ref).
Altered kidney function:
CrCl |
If the usual recommended dose is 1 to 2 g every 8 hours |
If the usual recommended dose is 1 to 2 g every 6 hours |
If the usual recommended dose is 200 mg/kg per day in 3 divided doses (maximum 12 g/day)b |
---|---|---|---|
a Humbert 1979; expert opinion; manufacturer's labeling. | |||
b No data available. Recommendations based on expert opinion only. | |||
CrCl >50 mL/minute |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
CrCl 30 to 50 mL/minute |
1 to 2 g every 12 hours |
1 to 2 g every 8 hours |
150 mg/kg per day in 3 divided doses (maximum 9 g per day) |
CrCl 10 to 29 mL/minute |
1 to 2 g every 24 hours |
1 to 2 g every 12 hours |
100 mg/kg per day in 2 divided doses (maximum 6 g per day) |
CrCl <10 mL/minute |
1 g once, followed by 500 mg to 1 g every 24 hours |
1 g every 24 hours |
50 mg/kg per day in 1 or 2 divided doses (maximum 3 g per day) |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: Limited data for use of cefoxitin in ARC exist. For treatment of severe infections, consider alternative antimicrobial agents as the maximum daily dose (12 g per day) may still not achieve pharmacodynamic targets (Ref). If necessary, consider 2 g every 4 hours. Prolonged (continuous or extended) infusions may be necessary to optimize PK/PD target attainment (Ref).
Hemodialysis, intermittent (thrice weekly): Substantially dialyzable (exact % unknown) (Ref): IV: Dose as for CrCl <10 mL/minute. When scheduled dose falls on a hemodialysis day, administer after dialysis (Ref).
Peritoneal dialysis: Not significantly dialyzable: IV: Dose as for CrCl <10 mL/minute (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.
IV: Limited data exist for the use of cefoxitin in CRRT. Consider alternative antibiotic with more robust data for use. If necessary, dose as for CrCl 30 to 50 mL/minute.(Ref)
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.
IV: Limited data exist for use of cefoxitin in PIRRT. Consider alternative antibiotic with more robust data for use.
If necessary:
PIRRT days: Dose as for CrCl 10 to 29 mL/minute, with one of the doses administered after the PIRRT session finishes (Ref).
Non-PIRRT days: Dose as for CrCl <10 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Cefoxitin: Pediatric drug information")
General dosing: Infants, Children, and Adolescents: Limited data available in infants <3 months of age: IM, IV: 80 to 160 mg/kg/day divided every 4 to 8 hours; maximum daily dose: 12 g/day (Ref).
Intra-abdominal infection: Note: Cefoxitin is not recommended for the empiric treatment of intra-abdominal infection due to increasing resistance of anaerobic bacteria (ie, Bacteroides fragilis group); other options are preferred (Ref).
Infants, Children, and Adolescents: Limited data available in infants <3 months of age: IV: 80 to 160 mg/kg/day divided every 4 to 8 hours; maximum dose: 2,000 mg/dose. Use doses on the higher end of the range (ie, 160 mg/kg/day) for severe, complicated, or undrained infections (Ref). Treatment duration should be 4 to 7 days unless source control inadequate; in some circumstances (ie, acute or gangrenous appendicitis without perforation) therapy should be limited to ≤24 hours (Ref).
Mycobacterial (nontuberculous) infection (eg, Mycobacterium abscessus), pulmonary infection in patients with or without cystic fibrosis: Limited data available:
Infants, Children, and Adolescents: IV: 150 mg/kg/day divided every 6 to 8 hours; maximum daily dose: 12 g/day. The duration of parenteral therapy is generally 4 to 12 weeks depending on clinical response, followed by transition to oral and/or inhaled therapy; total antibiotic treatment duration is ≥12 months after culture conversion (Ref).
Pelvic inflammatory disease:
Children ≥45 kg and Adolescents:
Mild to moderate (outpatient management): IM: 2,000 mg as a single dose, in combination with a single dose of probenecid, followed by 14 days of oral therapy with doxycycline and metronidazole (Ref).
Severe (inpatient management): IV: 2,000 mg every 6 hours in combination with doxycycline; once patient has clinically improved (typically within 24 to 48 hours), may transition to oral therapy with doxycycline and metronidazole to complete a total of 14 days of therapy (Ref).
Peritonitis (peritoneal dialysis), prophylaxis in patients undergoing GI or genitourinary procedures: Limited data available:
Infants, Children, and Adolescents: IV: 30 to 40 mg/kg administered 30 to 60 minutes before procedure; maximum dose: 2,000 mg/dose (Ref).
Surgical prophylaxis:
Infants, Children, and Adolescents: Limited data available in infants <3 months of age: IV: 40 mg/kg within 60 minutes prior to surgery; may repeat dose in 2 hours for prolonged procedure or excessive blood loss; maximum dose: 2,000 mg/dose (Ref).
Infants, Children, and Adolescents: The manufacturer's labeling suggests dosing modification consistent with the adult recommendations. Some clinicians have used the following guidelines (Ref); Note: Renally adjusted dose recommendations are based on doses of 20 to 40 mg/kg/dose every 6 hours.
GFR >50 mL/minute/1.73 m2: No adjustment required.
GFR 30 to 50 mL/minute/1.73 m2: 20 to 40 mg/kg/dose every 8 hours.
GFR 10 to 29 mL/minute/1.73 m2: 20 to 40 mg/kg/dose every 12 hours.
GFR <10 mL/minute/1.73 m2: 20 to 40 mg/kg/dose every 24 hours.
Intermittent hemodialysis: Moderately dialyzable (20% to 50%): 20 to 40 mg/kg/dose every 24 hours.
Peritoneal dialysis (PD): 20 to 40 mg/kg/dose every 24 hours.
Continuous renal replacement therapy (CRRT): 20 to 40 mg/kg/dose every 8 hours.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Gastrointestinal: Diarrhea
<1%: Anaphylaxis, angioedema, bone marrow depression, dyspnea, eosinophilia, exacerbation of myasthenia gravis, exfoliative dermatitis, fever, hemolytic anemia, hypotension, increased blood urea nitrogen, increased serum creatinine, increased serum transaminases, interstitial nephritis, jaundice, leukopenia, nausea, nephrotoxicity (increased; with aminoglycosides), phlebitis, prolonged prothrombin time, pruritus, pseudomembranous colitis, skin rash, thrombocytopenia, thrombophlebitis, toxic epidermal necrolysis, urticaria, vomiting
Hypersensitivity to cefoxitin, any component of the formulation, or other cephalosporins
Concerns related to adverse effects:
• Hypersensitivity: Use with caution in patients with a history of penicillin allergy, especially IgE-mediated hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria). If a hypersensitivity reaction occurs, discontinue immediately.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• GI disease: Use with caution in patients with a history of gastrointestinal disease, particularly colitis.
• Renal impairment: Use with caution in patients with renal impairment; modify dosage in severe impairment.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
Special populations:
• Children: In pediatric patients ≥3 months of age, higher doses have been associated with an increased incidence of eosinophilia and elevated AST.
• Older adult: 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. Elderly patients are more likely to have decreased renal function; use care in dose selection and monitor renal function.
Other warnings/precautions:
• Discontinuation of therapy: For group A beta-hemolytic streptococcal infections, antimicrobial therapy should be given for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection [preservative free]:
Generic: 10 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 2 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea)
Yes
Solution (reconstituted) (cefOXitin Sodium Intravenous)
1 g (per each): $3.60 - $11.94
2 g (per each): $7.20 - $23.94
10 g (per each): $60.00 - $112.25
Solution (reconstituted) (cefOXitin Sodium-Dextrose Intravenous)
1GM 4%(50ML) (per each): $22.63
2GM 2.2%(50ML) (per each): $40.25
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 1 g (1 ea); 2 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 10 g (1 ea)
IM: Inject deep IM into large muscle mass. Note: IM injection is painful and this route of administration is not described in the prescribing information.
IV: Can be administered IVP over 3 to 5 minutes or by IV intermittent infusion over 10 to 60 minutes
Parenteral:
IV Push: Administer over 3 to 5 minutes.
Intermittent IV infusion: Administer over 15 to 60 minutes (Ref).
IM: Inject into a large muscle mass (Ref).
Bacteremia/sepsis: Treatment of bacteremia/sepsis caused by Streptococcus pneumoniae , Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli , Klebsiella species, and Bacteroides species including B. fragilis.
Bone and joint infections: Treatment of bone and joint infections caused by S. aureus (including penicillinase-producing strains).
Gynecological infections: Treatment of endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by E. coli, Neisseria gonorrhoeae (including penicillinase-producing strains), Bacteroides species including Bacteroides fragilis, Clostridium species, P. niger, Peptostreptococcus species, and Streptococcus agalactiae.
Limitations of use: Cefoxitin does not have activity against Chlamydia trachomatis. When cefoxitin is used to treat pelvic inflammatory disease, add appropriate antichlamydial coverage.
Lower respiratory tract infections: Treatment of pneumonia and lung abscess, caused by S. pneumoniae, other streptococci (excluding enterococci; eg, Enterococcus faecalis [formerly Streptococcus faecalis]), S. aureus (including penicillinase-producing strains), E. coli, Klebsiella species, Haemophilus influenzae, and Bacteroides species.
Septicemia: Treatment of septicemia caused by S. pneumoniae, S. aureus (including penicillinase-producing strains), E. coli, Klebsiella species, and Bacteroides species including B. fragilis.
Skin and skin structure infections: Treatment of skin and skin structure infections caused by S. aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pyogenes and other streptococci (excluding enterococci [eg, E. faecalis] [formerly S. faecalis]), E. coli, Proteus mirabilis, Klebsiella species, Bacteroides species including B. fragilis, Clostridium species, P. niger, and Peptostreptococcus species.
Urinary tract infections: Treatment of UTIs caused by E. coli, Klebsiella species, P. mirabilis, Morganella morganii, Proteus vulgaris, and Providencia species (including Providencia rettgeri).
Bite wounds (animal); Gonococcal infection, uncomplicated; Mycobacterial (nontuberculous, rapidly growing) infection
CefOXitin may be confused with ceFAZolin, cefotaxime, cefoTEtan, cefTAZidime, cefTRIAXone, Cytoxan
Mefoxin may be confused with Lanoxin
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Furosemide: May enhance the nephrotoxic effect of Cephalosporins. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Cefoxitin crosses the placenta and reaches the cord serum and amniotic fluid.
An increased risk of major birth defects or other adverse fetal or maternal outcomes has generally not been observed following use of cephalosporin antibiotics, including cefoxitin, during pregnancy.
Cefoxitin is one of the antibiotics recommended for prophylactic use prior to cesarean delivery (ACOG 199 2018).
Cefoxitin is present in breast milk.
The estimated dose to a breastfed infant would be <0.1% of the maternal dose. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, cephalosporins are generally considered acceptable for use in breastfeeding women (Ito 2000). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Some products may contain sodium.
Monitor renal function periodically when used in combination with other nephrotoxic drugs; prothrombin time. Observe for signs and symptoms of anaphylaxis during first dose. CBC with prolonged use (ATS/ERS/ESCMID/IDSA [Daley 2020]).
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Widely to body tissues and fluids including ascitic, pleural, synovial, bile; poorly penetrates into CSF even with inflammation of the meninges (Landesman 1981).
Vd:
Neonates and Infants <2 months of age (PNA: 10 to 53 days): 0.5 ± 0.21 L/kg (Regazzi 1983).
Protein binding: 65% to 79%.
Half-life elimination:
Neonates and Infants <2 months of age (PNA: 10 to 53 days): 1.4 hours (Regazzi 1983).
Infants ≥3 months of age and Children: 42.4 ± 5.3 minutes (Feldman 1980).
Adults: 41 to 59 minutes; prolonged with renal impairment.
Time to peak, serum: IM: Within 20 to 30 minutes.
Excretion: Urine (85% as unchanged drug).
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC): Goal: ≥40% to 50% (fT) > MIC (bacteriostatic), ≥60% to 70% (fT) > MIC (bactericidal) (Abdul-Aziz 2020; Craig 1996; Craig 1998; Turnidge 1998).
Expected drug exposure in normal renal function:
Pediatric patients: Cmax (peak):
Single dose (30 mg/kg): IV: Neonates and Infants <2 months of age (PNA: 10 to 53 days): 69.8 ± 31.9 mg/L (Regazzi 1983).
Steady state (37.5 mg/kg/dose every 6 hours): IV: Infants ≥3 months and Children: 81.9 ± 33 mg/L (Feldman 1980).
Adults: Cmax (peak): Single dose (2 g): IV: 118.9 to 158.6 mg/L (Carver 1989; Isla 2012).
Postantibiotic effect: Generally <1 hour; varies by organism (Craig 1991; Craig 1998). For Bacteroides spp.: Variable, ranging from 0 to 15 hours (Aldridge 2002; Siverhus 1988).
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