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CefOXitin


General


Pronunciation

(se FOKS i tin)


Brand Names: U.S.

  • Mefoxin [DSC]

Indications


Use: Labeled Indications

Bone and joint infections: Treatment of bone and joint infections caused by Staphylococcus aureus (including penicillinase-producing strains).

Gynecological infections: Treatment of endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia coli, Neisseria gonorrhoeae (including penicillinase-producing strains), Bacteroides species including Bacteroides fragilis, Clostridium species, P. niger, Peptostreptococcus species, and Streptococcus agalactiae.

Intra-abdominal infections: Treatment of peritonitis and intra-abdominal infections or abscess, caused by E. coli, Klebsiella species, Bacteroides species (including B. fragilis), and Clostridium species.

Lower respiratory tract infections: Treatment of pneumonia and lung abscess, caused by Streptococcus 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.

Perioperative prophylaxis: Prophylaxis of infection in patients undergoing uncontaminated GI surgery, abdominal or vaginal hysterectomy, or cesarean section.

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).

Limitations of use: Cefoxitin does not have activity against Chlamydia trachomatis. When cefoxitin is used to treat pelvic inflammatory disease, add appropriate antichlamydial coverage.


Contraindications


Hypersensitivity to cefoxitin, any component of the formulation, or other cephalosporins


Dosing and Administration


Dosing: Adult

Susceptible infections: IV: 1 to 2 g every 6 to 8 hours (IM injection is painful); up to 12 g daily

Bite wounds (animal) (off-label use): IV: 1 g every 6 to 8 hours (IDSA [Stevens 2014])

Gas gangrene: IV: 2 g every 4 hours or 3 g every 6 hours (maximum daily dosage: 12 g daily)

Intra-abdominal infection, complicated, community acquired, mild-to-moderate (Solomkin 2010): IV: 2 g every 6 hours for 4 to 7 days (provided source controlled)

Moderately severe or severe infections: IV: 1 g every 4 hours or 2 g every 6 to 8 hours (maximum daily dosage: 8 g daily)

Mycobacterium abscessus, not MTB or MAI (off-label use; Griffith 2007): IV: 12 g daily in divided doses with concomitant amikacin for ≥14 days

Pelvic inflammatory disease (CDC [Workowski 2015]):

Inpatients: IV: 2 g every 6 hours plus doxycycline for at least 24 to 48 hours after clinical improvement, followed by oral doxycycline to complete 14 days

Outpatients: IM: 2 g as a single dose plus oral probenecid, followed by oral doxycycline (with or without concomitant metronidazole) for 14 days

Surgical (perioperative) prophylaxis:

Manufacturers labeling (procedures other than Cesarian section): IV: 2 g 30 to 60 minutes prior to surgical incision, followed by 2 g every 6 hours for no more than 24 hours after surgery depending on the procedure

Cesarean section: IV: 2 g as soon as umbilical cord is clamped as a single dose or 2 g as soon as umbilical cord is clamped followed by 2 g at 4 and 8 hours after the initial dose.

Alternative recommendations: 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 (Bratzler 2013).

Uncomplicated cutaneous, urinary tract, lung infections: IV: 1 g every 6 " “8 hours (maximum daily dosage: 4 g daily)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Note: 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

Infants >3 months, Children, and Adolescents:

Manufacturers labeling: IV: 80 to 160 mg/kg/day divided every 4 to 6 hours (maximum daily dose: 12 g daily)

Alternative recommendations (Red Book [AAP] 2012):

Mild-to-moderate infection: IV: Infants >3 months and Children: 80 mg/kg/day in divided doses every 6 to 8 hours (maximum daily dose: 4000 mg daily)

Severe infection: IV: Infants >3 months and Children: 160 mg/kg/day in divided doses every 4 to 6 hours (maximum daily dose: 12 g daily)

Infants >3 months and Children:

Surgical (perioperative) prophylaxis:

Manufacturer's labeling: IV: 30 to 40 mg/kg 30 to 60 minutes prior to surgical incision followed by 30 to 40 mg/kg/dose every 6 hours for no more than 24 hours after surgery depending on the procedure

Alternative recommendations: Children ≥1 year: IV: 40 mg/kg within 60 minutes prior to surgical incision (maximum: 2000 mg per dose). Doses may be repeated in 2 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013).

Adolescents:

Surgical (perioperative) prophylaxis: Refer to adult dosing.


Dosing: Renal Impairment

IV:

CrCl 30 to 50 mL/minute: 1 to 2 g every 8 to 12 hours

CrCl 10 to 29 mL/minute: 1 to 2 g every 12 to 24 hours

CrCl 5 to 9 mL/minute: 0.5 to 1 g every 12 to 24 hours

CrCl <5 mL/minute: 0.5 to 1 g every 24 to 48 hours

Hemodialysis: Loading dose: 1 to 2 g after each hemodialysis; maintenance dose as noted above based on creatinine clearance


Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer 's labeling.


Reconstitution

Reconstitute vials with SWFI, bacteriostatic water for injection, NS, or D5W. For IV infusion, solutions may be further diluted in NS, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, D5LR, mannitol 5% or 10%, or sodium bicarbonate 5%.


Administration

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


Dietary Considerations

Some products may contain sodium.


Storage

Prior to reconstitution store between 2 ‚ °C and 25 ‚ °C (36 ‚ °F and 77 ‚ °F). Avoid exposure to temperatures >50 ‚ °C (122 ‚ °F). Cefoxitin tends to darken depending on storage conditions; however, product potency is not adversely affected.

Reconstituted solutions of 1 g per 10 mL in sterile water for injection, bacteriostatic water for injection, sodium chloride 0.9% injection, or dextrose 5% injection are stable for 6 hours at room temperature or for 7 days under refrigeration (<5 ‚ °C [43 ‚ °F]).

DUPLEX container: Store unactivated container at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F); do not freeze. Following activation, solution is stable for 12 hours at room temperature and 7 days refrigerated.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Mefoxin: 1 g (50 mL [DSC]); 2 g (50 mL [DSC])

Solution Reconstituted, Injection:

Generic: 10 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 10 g (1 ea)

Solution Reconstituted, Intravenous:

Generic: 1 g (1 ea); 2 g (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 1 g (1 ea); 2 g (1 ea)


Compatibility

Stable in D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, NS, mannitol 5% or 10%, sodium bicarbonate 5%; variable stability (consult detailed reference) in peritoneal dialysis solution.

Y-site administration: Incompatible with filgrastim, hetastarch in lactate electrolyte injection (Hextend), pentamidine.


Drug Interactions

Aminoglycosides: Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Cephalosporins. 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. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy


Monitoring Parameters

Monitor renal function periodically when used in combination with other nephrotoxic drugs; prothrombin time. Observe for signs and symptoms of anaphylaxis during first dose.


Lab Test Interferences


Test Interactions

Positive direct Coombs, false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest ‚ ®, Fehling's solution), false-positive serum or urine creatinine with Jaffe reaction


Adverse Reactions


1% to 10%: Gastrointestinal: Diarrhea

<1% (Limited to important or life-threatening): 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


Warnings/Precautions


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.

- Elderly: 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.


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Cefoxitin crosses the placenta and reaches the cord serum and amniotic fluid.

Peak serum concentrations of cefoxitin during pregnancy may be similar to or decreased compared to nonpregnant values. Maternal half-life may be shorter at term. Pregnancy-induced hypertension increases trough concentrations in the immediate postpartum period. Cefoxitin is one of the antibiotics recommended for prophylactic use prior to cesarean delivery.


Actions


Pharmacology

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)


Excretion

Urine (85% as unchanged drug)


Time to Peak

Serum: IM: Within 20-30 minutes


Half-Life Elimination

Neonates and Infants (PNA: 10-53 days): 1.4 hours (Regazzi 1983); Adults: 41-59 minutes; prolonged with renal impairment


Protein Binding

65% to 79%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), bruising, bleeding, urinary retention, change in amount of urine passed, severe loss of strength and energy, chills, pharyngitis, seizures, injection site irritation, vaginitis, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (rare) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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