PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    2nd Generation Cephalosporin and Cephamycin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral/parenteral second-generation cephalosporin
    Used for severe upper and lower respiratory tract infections, skin infections, otitis media, and surgical prophylaxis
    Oral tablets and suspension are not bioequivalent and are not substitutable on a milligram-per-milligram basis

    COMMON BRAND NAMES

    Alti-Cefuroxime, Ceftin, Kefurox, Zinacef

    HOW SUPPLIED

    Alti-Cefuroxime/Ceftin/Cefuroxime/Cefuroxime Axetil Oral Tab: 250mg, 500mg
    Ceftin/Cefuroxime/Cefuroxime Axetil Oral Pwd F/Recon: 5mL, 125mg, 250mg
    Cefuroxime/Cefuroxime Sodium/Kefurox/Zinacef Intramuscular Inj Pwd F/Sol: 1.5g, 7.5g, 750mg
    Cefuroxime/Cefuroxime Sodium/Kefurox/Zinacef Intravenous Inj Pwd F/Sol: 1.5g, 7.5g, 750mg

    DOSAGE & INDICATIONS

    For the treatment of mild-to-moderate acute bacterial exacerbations of chronic bronchitis.
    Oral dosage (tablets)
    Adults

    250 to 500 mg PO every 12 hours for 10 days.

    Adolescents

    250 to 500 mg PO every 12 hours for 10 days.

    For the treatment of skin and skin structure infections, including impetigo.
    Oral dosage (tablets)
    Adults

    250 mg to 500 mg PO every 12 hours for 10 days.

    Adolescents

    250 mg to 500 mg PO every 12 hours for 10 days.

    Oral dosage (suspension)
    Infants 3 to 11 months, Children, and Adolescents

    15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days.

    Infants 1 to 2 months†

    15 mg/kg/dose PO every 12 hours for 10 days.

    Intravenous or Intramuscular dosage
    Adults

    0.75 to 1.5 g IV or IM every 8 hours in general. For life-threatening infections or infections due to less susceptible organisms, 1.5 g IV or IM every 6 hours may be required.

    Infants 3 to 11 months, Children, and Adolescents

    100 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day) is the general dosage recommended by the American Academy of Pediatrics (AAP). 50 to 100 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2.25 g/day) is the FDA-approved dosage.

    Infants 1 to 2 months†

    100 to 150 mg/kg/day IV or IM divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    For the treatment of urinary tract infection (UTI).
    Oral dosage (tablet)
    Adults

    250 mg PO every 12 hours for 7 to 10 days. The Infectious Diseases Society of America (IDSA) recommends beta-lactams used for 3 to 7 days as alternative therapy for cystitis when other agents cannot be used. For pyelonephritis, oral beta-lactams should be used after an initial intravenous dose of a long-acting antimicrobial (ceftriaxone or aminoglycoside) for 10 to 14 days. Beta-lactams generally have inferior efficacy than other agents.

    Adolescents

    250 mg PO every 12 hours for 7 to 10 days. The Infectious Diseases Society of America (IDSA) recommends beta-lactams used for 3 to 7 days as alternative therapy for cystitis when other agents cannot be used. For pyelonephritis, oral beta-lactams should be used after an initial intravenous dose of a long-acting antimicrobial (ceftriaxone or aminoglycoside) for 10 to 14 days. Beta-lactams generally have inferior efficacy than other agents.

    Intravenous or Intramuscular dosage
    Adults

    0.75 to 1.5 g IV or IM every 8 hours in general or 0.75 g IV or IM every 8 hours for uncomplicated UTIs.

    Infants 3 to 11 months, Children, and Adolescents

    100 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day) is the general dosage recommended by the American Academy of Pediatrics (AAP). 50 to 100 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2.25 g/day) is the FDA-approved dosage.

    Infants 1 to 2 months†

    100 to 150 mg/kg/day IV or IM divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    For the treatment of bone and joint infections.
    Intravenous or Intramuscular dosage
    Adults

    1.5 g IV or IM every 8 hours. For life-threatening infections or infections due to less susceptible organisms, 1.5 g IV or IM every 6 hours may be required.

    Infants 3 to 11 months, Children, and Adolescents

    150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day).

    Infants 1 to 2 months†

    100 to 150 mg/kg/day IV or IM divided every 8 hours.

    For the treatment of pharyngitis.
    Oral dosage (tablets)
    Adults

    250 mg PO every 12 hours for 10 days. Guidelines do not recommended cefuroxime for routine therapy for Group A Streptococcal pharyngitis therapy to prevent rheumatic fever.

    Adolescents

    250 mg PO every 12 hours for 10 days. Guidelines do not recommended cefuroxime for routine therapy for Group A Streptococcal pharyngitis therapy to prevent rheumatic fever.

    Oral dosage (suspension)
    Infants 3 to 11 months, Children, and Adolescents

    10 mg/kg/dose (Max: 250 mg/dose) PO every 12 hours for 10 days. Guidelines do not recommended cefuroxime for routine therapy for Group A Streptococcal pharyngitis therapy to prevent rheumatic fever.

    Infants 1 to 2 months†

    10 mg/kg/dose PO every 12 hours for 10 days. Guidelines do not recommended cefuroxime for routine therapy for Group A Streptococcal pharyngitis therapy to prevent rheumatic fever.

    For the treatment of gonorrhea.
    For uncomplicated gonococcal infection (e.g., vulvovaginitis, cervicitis, urethritis).
    Oral dosage (tablets)
    Adults

    Due to resistance, the CDC does not recommend cefuroxime for gonorrhea. The FDA-approved dosage is 1 g PO as a single dose.

    Adolescents

    Due to resistance, the CDC does not recommend cefuroxime for gonorrhea. The FDA-approved dosage is 1 g PO as a single dose.

    Intramuscular dosage
    Adults

    The CDC does not recommend IM cefuroxime. The FDA-approved dosage is 1.5 g IM as a single dose at 2 different sites in combination with probenecid.

    Adolescents

    The CDC does not recommend IM cefuroxime. The FDA-approved dosage is 1.5 g IM as a single dose at 2 different sites in combination with probenecid.

    For disseminated gonococcal infection due to N. gonorrhoeae.
    Intravenous or Intramuscular dosage
    Adults

    The CDC does not recommend cefuroxime for gonorrhea. The FDA-approved dosage is 750 mg IV or IM every 8 hours. In severe or complicated infections, a dosage of 1.5 g IV or IM every 8 hours is recommended.

    Adolescents

    The CDC does not recommend cefuroxime for gonorrhea. The FDA-approved dosage is 750 mg IV or IM every 8 hours. In severe or complicated infections, a dosage of 1.5 g IV or IM every 8 hours is recommended.

    For the treatment of early Lyme disease (erythema migrans).
    Oral dosage (tablets)
    Adults

    500 mg PO every 12 hours for 20 days.

    Adolescents

    500 mg PO every 12 hours for 20 days.

    Oral dosage (suspension)†
    Infants, Children, and Adolescents

    15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 14 days.

    For the treatment of acute otitis media.
    Oral dosage (tablets)
    Children (who can swallow whole tablets) and Adolescents†

    250 mg PO every 12 hours for 10 days. Cefuroxime is recommended by the American Academy of Pediatrics (AAP) as an alternative treatment to high-dose amoxicillin or high-dose amoxicillin; clavulanate. AAP recommends a 10-day course for any child with severe disease and for all patients younger than 2 years of age, regardless of severity. For children aged 2 to 5 years with mild to moderate disease, a 7-day course is acceptable. For children aged 6 years and older with mild to moderate disease, 5 to 7 days is acceptable.

    Oral dosage (suspension)
    Infants 3 to 11 months, Children, and Adolescents†

    15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days. Cefuroxime is recommended by the American Academy of Pediatrics (AAP) as an alternative treatment to high-dose amoxicillin or high-dose amoxicillin; clavulanate. AAP recommends a 10-day course for any child with severe disease and for all patients younger than 2 years of age, regardless of severity. For children aged 2 to 5 years with mild to moderate disease, a 7-day course is acceptable. For children aged 6 years and older with mild to moderate disease, 5 to 7 days is acceptable.

    Infants 1 to 2 months†

    15 mg/kg/dose PO every 12 hours. In general, cefuroxime is recommended by the AAP as an alternative treatment to amoxicillin for penicillin-allergic patients. AAP recommends a 10-day course for any child with severe disease and for all patients younger than 2 years of age, regardless of severity.

    For the treatment of bacteremia.
    Intravenous or Intramuscular dosage
    Adults

    1.5 g IV or IM every 8 hours. For life-threatening infections or infections due to less susceptible organisms, 1.5 g IV or IM every 6 hours may be required.

    Infants 3 to 11 months, Children, and Adolescents

    100 to 150 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 6 g/day).

    Infants 1 to 2 months†

    100 to 150 mg/kg/day IV or IM divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    For the treatment of meningitis.
    Intravenous or Intramuscular dosage
    Adults

    1.5 g IV or IM every 6 hours or 3 g IV or IM every 8 hours (Max: 9 g/day) is the FDA-approved dosage. However, guidelines recommend a third-generation cephalosporin for meningitis.

    Infants 3 to 11 months, Children, and Adolescents

    200 to 240 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 9 g/day) is the FDA-approved dosage. However, guidelines recommend a third-generation cephalosporin for meningitis.

    For surgical infection prophylaxis.
    for ophthalmic surgical infection prophylaxis†.
    Intraocular dosage
    Adults

    1 mg by intracameral injection is optional at the end of the procedure. Perioperative antisepsis with povidone-iodine is recommended. The necessity of continuing topical antimicrobials postoperatively has not been established.

    Intravenous or Intramuscular dosage
    Adults

    1.5 g IV or IM within 30 to 60 minutes prior to the surgical incision. For lengthy operations, additional doses of 750 mg IV or IM may be given during the procedure and postoperatively every 8 hours. For open heart surgery, 1.5 g IV every 12 hours for 6 g total dose. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Cefuroxime is FDA-approved for clean-contaminated or potentially contaminated procedures. Clinical practice guidelines recommend cefuroxime for cardiac or clean head and neck (with prosthesis) procedures and as an alternate therapy for urogynecology procedures. Cefuroxime is also recommended in combination with metronidazole for clean-contaminated head and neck procedures.

    Infants†, Children†, and Adolescents†

    50 mg/kg IV or IM as a single dose (Max: 1.5 g/dose) within 60 minutes prior to the surgical incision. Intraoperative redosing 4 hours from the first preoperative dose and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Clinical practice guidelines recommend cefuroxime for cardiac or clean head and neck (with prosthesis) procedures. Cefuroxime is also recommended in combination with metronidazole for clean-contaminated head and neck procedures.

    For the treatment of tonsillitis.
    Oral dosage (tablets)
    Adults

    250 mg PO every 12 hours for 10 days.

    Adolescents

    250 mg PO every 12 hours for 10 days.

    Oral dosage (suspension)
    Infants 3 to 11 months, Children, and Adolescents

    10 mg/kg/dose (Max: 250 mg/dose) PO every 12 hours for 10 days.

    Infants 1 to 2 months†

    10 mg/kg/dose PO every 12 hours for 10 days.

    For the treatment of sinusitis.
    Oral dosage (tablets)
    Adults

    250 mg PO every 12 hours for 10 days. The Infectious Diseases Society of America (IDSA) does not recommend cefuroxime for empiric use.

    Children (who can swallow tablets whole) and Adolescents

    250 mg PO every 12 hours for 10 days. The Infectious Diseases Society of America (IDSA) does not recommend cefuroxime for empiric use.

    Oral dosage (suspension)
    Infants 3 to 11 months, Children, and Adolescents

    15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 10 days. The Infectious Diseases Society of America (IDSA) does not recommend cefuroxime for empiric use.

    Infants 1 to 2 months†

    15 mg/kg/dose PO every 12 hours for 10 days. The Infectious Diseases Society of America (IDSA) does not recommend cefuroxime for empiric use.

    For the treatment of complicated intraabdominal infections†, including biliary tract infections† such as cholecystitis†.
    Intravenous dosage
    Adults

    1.5 g IV every 8 hours for 4 to 7 days. Guidelines suggest cefuroxime in combination with metronidazole as a preferred therapy for community-acquired, mild-to-moderate infections; for acute cholecystitis, cefuroxime monotherapy is recommended.

    Infants, Children, and Adolescents

    150 mg/kg/day IV divided every 6 to 8 hours (Max: 4.5 g/day) is recommended by the Infectious Diseases Society of America (IDSA). 100 to 150 mg/kg/day IV divided every 8 hours (Max: 6 g/day) is the general dosage recommended by the American Academy of Pediatrics (AAP). Treat for 4 to 7 days.

    Neonates 32 weeks gestation and older and 8 days and older

    50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    Neonates 32 weeks gestation and older and 0 to 7 days

    50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    Neonates younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    For the treatment of lower respiratory tract infections (LRTIs), including pneumonia, community-acquired pneumonia (CAP), and pleural empyema†.
    For the treatment of community-acquired pneumonia (CAP).
    Oral dosage†
    Adults

    500 mg PO every 12 hours for at least 5 days as part of combination therapy for outpatients with comorbidities. Guide treatment duration by clinical stability.[34362] [64669]

    Adolescents

    10 to 15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours for 5 to 7 days.[34362] [63245] Guidelines recommend cefuroxime as an alternative oral step-down therapy for patients with S. pneumoniae and penicillin allergy and as part of combination therapy for HIV-infected outpatients.[34362] [46963]

    Infants and Children

    10 to 15 mg/kg/dose (Max: 500 mg/dose) PO every 12 hours.[63245] Guidelines recommend cefuroxime as an alternative oral step-down therapy for infants and children 3 months of age and older with S. pneumoniae and penicillin allergy.[46963]

    For the treatment of nonspecific lower respiratory tract infections (LRTIs), pneumonia, and pleural empyema†.
    Intravenous or Intramuscular dosage
    Adults

    0.75 to 1.5 g IV or IM every 8 hours. For life-threatening infections or infections due to less susceptible organisms, 1.5 g IV or IM every 6 hours may be required.[49892] For community-acquired empyema, guidelines recommend cefuroxime in combination with metronidazole for at least 2 weeks after drainage and defervescence.[61949]

    Adolescents

    100 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day).[63245] Higher doses (i.e., 150 mg/kg/day) are generally recommended for pneumonia.[54904] FDA-approved labeling recommends 50 to 100 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 6 g/day).[49892]

    Infants and Children 3 months to 12 years

    100 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day).[63245] Higher doses (i.e., 150 mg/kg/day) are generally recommended for pneumonia.[54904] FDA-approved labeling recommends 50 to 100 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 6 g/day).[49892] Guidelines recommend cefuroxime as an alternative for bacterial pneumonia in HIV-infected patients.[34361]

    Infants 1 to 2 months†

    100 to 150 mg/kg/day IV or IM divided every 8 hours.[63245] Higher doses (i.e., 150 mg/kg/day) are generally recommended for pneumonia.[54904] Guidelines recommend cefuroxime as an alternative for bacterial pneumonia in HIV-infected patients.[34361]

    Neonates 32 weeks gestation and older and 8 days and older†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates 32 weeks gestation and older and 0 to 7 days†

    50 mg/kg/dose IV or IM every 12 hours.

    Neonates younger than 32 weeks gestation and 14 days and older†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days†

    50 mg/kg/dose IV or IM every 12 hours.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    9 g/day IV/IM; 1,000 mg/day PO.

    Geriatric

    9 g/day IV/IM; 1,000 mg/day PO.

    Adolescents

    240 mg/kg/day IV/IM (Max: 9 g/day); 1,000 mg/day PO.

    Children

    240 mg/kg/day IV/IM (Max: 9 g/day); 30 mg/kg/day PO (Max: 1,000 mg/day).

    Infants

    3 to 11 months: 240 mg/kg/day IV/IM; 30 mg/kg/day PO.
    1 to 2 months: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day IV/IM and 30 mg/kg/day PO have been used off-label.

    Neonates

    8 days and older: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day IV/IM have been used off-label.
    0 to 7 days: Safety and efficacy have not been established; however, doses up to 100 mg/kg/day IV/IM have been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; however, it appears no dosage adjustment is necessary.

    Renal Impairment

    Adult patients:
    Oral tablets
    The following are FDA-approved dose adjustments; however, some recommend the full dose regardless of the degree of renal impairment.[32569]
    CrCl 30 mL/minute or more: No dosage adjustment needed.
    CrCl 10 to 29 mL/minute: Reduce frequency to once every 24 hours.
    CrCl less than 10 mL/minute: Reduce frequency to once every 48 hours.[28573]
     
    IV/IM formulations [49892]
    CrCl more than 20 mL/minute: No dosage adjustment needed.
    CrCl 10 to 20 mL/minute: Give a loading dose of 0.75 to 1.5 g IV/IM, followed by 750 mg IV/IM every 12 hours.
    CrCl less than 10 mL/minute: Give a loading dose of 0.75 to 1.5 g IV/IM, followed by 750 mg IV/IM every 24 hours.
     
    Pediatrics:
    Oral suspension
    The following dose adjustments are based on a usual pediatric dose of 20 to 30 mg/kg/day PO divided every 12 hours.[28573] [32569]
    CrCl 10 mL/minute/1.73 m2 or higher: No dosage adjustment needed.
    CrCl less than 10 mL/minute/1.73 m2: 10 to 15 mg/kg/dose PO every 24 hours.
     
    IV/IM formulations
    The following dose adjustments are based on a usual pediatric dose of 75 to 150 mg/kg/day IV/IM divided every 8 hours.[32569]
    CrCl 30 mL/minute/1.73 m2 or higher: No dosage adjustment needed.
    CrCl 10 to 29 mL/minute/1.73 m2: 25 to 50 mg/kg/dose IV/IM every 12 hours.
    CrCl less than 10 mL/minute/1.73 m2: 25 to 50 mg/kg/dose IV/IM every 24 hours.[32569]
     
     
     
    Intermittent hemodialysis
    Adults
    Cefuroxime is significantly removed during a standard hemodialysis session. A supplemental IV/IM or oral dose should be given after each dialysis, or the dosing regimen should be timed so that the dose of cefuroxime is scheduled at the end of the dialysis session.[28573] [49892]
    Pediatrics
    10 to 15 mg/kg/dose PO every 24 hours OR 25 to 50 mg/kg/dose IV/IM every 24 hours after dialysis.[32569] [49892]
     
    Peritoneal dialysis
    Adults: Give a loading dose of 0.75 to 1.5 g IV/IM, followed by 750 mg IV/IM every 24 hours; oral dose adjustments not necessary.[32569]
    Pediatrics: 10 to 15 mg/kg/dose PO every 24 hours OR 25 to 50 mg/kg/dose IV/IM every 12 hours.[32569]
     
    Continuous renal replacement therapy
    Adults: 1 g IV/IM every 12 hours.[32569]
    Pediatrics: 25 to 50 mg/kg/dose IV/IM every 8 hours.[32569]

    ADMINISTRATION

    Oral Administration

    NOTE: Tablets and suspension are NOT bioequivalent and can not be substituted on a mg/mg basis.

    Oral Solid Formulations

    Tablets: May be administered without regard to meals. Tablets should be swallowed whole.

    Oral Liquid Formulations

    Oral Suspension: Must be administered with food. Shake well prior to each use. For accurate dosage, use a calibrated device, such as an oral syringe, calibrated spoon, or dosage cup.
    Taste and palatability of the suspension have been reported to be unpleasant, particularly compared with other oral cephalosporins.
    Reconstitution of oral suspension
    Review the reconstitution instructions for the particular product and package size, as the amount of water required for reconstitution may vary between manufacturers.
    Prior to reconstitution, tap the bottle several times to loosen the powder. Add the total amount of water, invert the bottle and vigorously rock the bottle from side to side so that water rises through the powder. Once the sound of the powder against the bottle disappears, turn the bottle upright and vigorously shake it in a diagonal direction.
    Some manufacturers recommend waiting one hour after reconstitution before administering to the patient. Check the manufacturer's instructions prior to administration.
    Storage after reconstitution: After mixing, store suspension in a refrigerator between 2 and 8 degrees C (36 and 46 degrees F). Discard any unused suspension after 10 days.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Reconstitution
    Vials: Reconstitute 750 mg or 1.5 g vial with 8.3 or 16 mL, respectively, of sterile water for injection to give a solution containing 90 mg/mL of cefuroxime.
    Pharmacy bulk package: Reconstitute 7.5 g vial with 77 mL of Sterile Water for Injection to give a solution containing 95 mg/mL of cefuroxime.
    Storage: Reconstituted solutions are stable for 24 hours at room temperature and for 48 hours (750 mg and 1.5 g vials) or 7 days (7.5 g pharmacy bulk vial) under refrigeration (5 degrees C).
    ADD-Vantage vials: Reconstitute only with 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 0.45% Sodium Chloride Injection in 50 mL or 100 mL flexible diluent container.
    Storage: Reconstituted ADD-Vantage vials are stable for 24 hours at room temperature and for 7 days under refrigeration. Joined vials not activated may be used within a 14 day period.
     
    Dilution
    For IV infusion, further dilute in compatible solution (i.e., 0.9% Sodium Chloride Injection, 5% Dextrose Injection) to a usual concentration of 15 to 30 mg/mL (range 1 to 30 mg/mL).
    Storage: Diluted solutions are stable for 24 hours at room temperature and for 7 days under refrigeration.
    Frozen bags: Solutions diluted in 0.9% Sodium Chloride Injection or 5% Dextrose Injection and added to Baxter VIAFLEX MINI-BAGS may be stored frozen for 6 months. Frozen solutions should be thawed at room temperature and not refrozen. Thawed solutions are stable for 24 hours at room temperature or 7 days under refrigeration.
     
    Thawing Frozen Pre-mixed Galaxy Bags
    Thaw at room temperature; do not force thaw. No reconstitution necessary.
    Storage: Thawed solution is stable for 24 hours at room temperature or 28 days in the refrigerator. Do not refreeze thawed antibiotics.
     
    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.
    Protect from light after removal of foil strip. If the foil strip is removed and the container will not be used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
    Once ready for activation, 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 24 hours if stored at room temperature or within 7 days if stored under refrigeration.
     
    IV Push
    Inject 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 15 to 60 minutes.

    Intramuscular Administration

    Reconstitution
    Reconstitute 750 mg vial with 3 mL of sterile water for injection to give a suspension containing 225 mg/mL of cefuroxime. Shake gently before administration and withdraw appropriate contents for each dose.
    Storage: After reconstitution, solution is stable for 24 hours at room temperature or 48 hours refrigerated (5 degrees C).[49892]
     
    Intramuscular Injection
    Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).[49892]

    STORAGE

    Generic:
    - Protect from light after removal of foil strip
    - Store unreconstituted product at room temperature (77 degrees F), excursions of 59 to 86 degrees F permitted
    - Use within 7 days after removal of foil strip
    Alti-Cefuroxime :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ceftin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Kefurox:
    - Protect from light
    - Reconstituted product is stable for up to 24 hours at room temperature and 48 hours under refrigeration
    - Store in carton until time of use
    - Store unreconstituted product at 68 to 77 degrees F
    - Store upright
    Zinacef:
    - Store at or below 68 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Antimicrobial resistance, viral infection

    Cefuroxime does not treat viral infection (e.g., common cold). Prescribing in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria (antimicrobial resistance). Patients should be told to complete the full course of treatment, even if they feel better earlier.

    Cephalosporin hypersensitivity, penicillin hypersensitivity

    Cefuroxime is contraindicated in patients with cephalosporin hypersensitivity or cephamycin hypersensitivity. Cefuroxime should be used cautiously in patients with hypersensitivity to penicillin. The structural similarity between cefuroxime and penicillin means that cross-reactivity can occur. Penicillins can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients who have experienced severe penicillin hypersensitivity should not receive cefuroxime. Cross-reactivity to cephalosporins is approximately 3—7% with a documented history to penicillin.

    Renal failure, renal impairment

    Caution is advised when administering cefuroxime to patients with renal impairment or renal failure. The drug is eliminated via renal mechanisms, therefore, patient with impaired renal function will clear it more slowly. To compensate for the prolonged elimination half-life, dosing frequency of the oral formulations should be reduced in patients with CrCl less than 30 mL/minute. Dosage/dosing frequency of the parenteral formulations should be reduced in patients with CrCl 20 mL/minute or less. The risk of reactions may be higher in patients with renal dysfunction.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Pregnancy

    Available data over several decades with cephalosporin use, including cefuroxime, during pregnancy in women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies during organogenesis with oral cefuroxime at 14 and 9 times the maximum recommended human dose (MRHD) based on body surface area, there were no adverse developmental outcomes.[28573]

    Breast-feeding

    Cefuroxime is excreted in human breast milk. The highest maternal milk concentration occurred in lactating women 8 hours after intramuscular administration of cefuroxime 750 mg. Allowing for infant milk consumption of 150 mL/kg/day, the estimated breast-fed infant dose would be less than 1% of the adult dose. No data are available on the effects of cefuroxime on the breast-fed infant or the effects of the drug on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cefuroxime and any potential adverse effects on the breast-fed infant from cefuroxime or the underlying maternal condition.[28573] Rare potential complications in the nursing infant include alterations of gut flora that might result in diarrhea or related complications (e.g., dehydration). Because the risk of serious reactions is relatively rare, the use of many cephalosporins is considered compatible with breast-feeding. Although the use of cefuroxime during breast-feeding has not been evaluated, previous American Academy of Pediatrics (AAP) recommendations and other experts consider other cephalosporins, such as cefazolin, cefprozil, and cefadroxil, as generally compatible with breast-feeding.[27500] [30584]

    Diabetes mellitus

    Patients with diabetes mellitus should be aware that cefuroxime therapy may interfere with certain glucose test products or assays. A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedict's or Fehling's solution or with CLINITEST tablets), but not with enzyme-based tests for glycosuria (e.g., CLINISTIX). As a false-negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving cefuroxime.

    Phenylketonuria

    Cefuroxime oral suspension should be used with caution in patients with phenylketonuria. The 125 mg/5 mL suspension contains 11.8 mg of phenylalanine per 5 mL. The 250 mg/5 mL suspension contains 25.2 mg of phenylalanine per 5 mL.

    Sexually transmitted disease

    While cefuroxime may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, and chlamydia at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Geriatric

    No overall differences in cefuroxime safety or effectiveness were observed between geriatric and younger adult subjects during clinical trials or in subsequent clinical experience. However, because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Cefuroxime is eliminated renally, and dosages should be adjusted if renal dysfunction is present. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    hemolytic anemia / Delayed / 0-1.0
    pancytopenia / Delayed / 0-1.0
    seizures / Delayed / 0-1.0
    interstitial nephritis / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    erythema multiforme / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    vasculitis / Delayed / 0-1.0
    serum sickness / Delayed / 0-1.0
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known

    Moderate

    eosinophilia / Delayed / 1.0-7.0
    vaginitis / Delayed / 0-5.4
    elevated hepatic enzymes / Delayed / 0-4.0
    phlebitis / Rapid / 1.7-1.7
    leukopenia / Delayed / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    hypoprothrombinemia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    candidiasis / Delayed / 0-1.0
    pseudomembranous colitis / Delayed / 0-1.0
    oral ulceration / Delayed / 0-1.0
    dysuria / Early / 0-1.0
    jaundice / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    erythema / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    dyspnea / Early / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    hyperbilirubinemia / Delayed / 0.2-0.2
    bleeding / Early / Incidence not known
    superinfection / Delayed / Incidence not known
    colitis / Delayed / Incidence not known

    Mild

    diarrhea / Early / 0.5-10.6
    nausea / Early / 0.2-7.0
    vomiting / Early / 3.0-7.0
    diaper dermatitis / Delayed / 3.0-3.0
    sinusitis / Delayed / 0-1.0
    infection / Delayed / 0-1.0
    anorexia / Delayed / 0-1.0
    abdominal pain / Early / 0-1.0
    flatulence / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    leukorrhea / Delayed / 0-1.0
    drowsiness / Early / 0-1.0
    restlessness / Early / 0-1.0
    headache / Early / 0-1.0
    dizziness / Early / 0-1.0
    fever / Early / 0-1.0
    rash / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    chills / Rapid / 0-1.0
    cough / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    muscle cramps / Delayed / 0-1.0
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    Amikacin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Aminoglycosides: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Antacids: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Aspirin, ASA; Omeprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Calcium Carbonate: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Risedronate: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Calcium Carbonate; Simethicone: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Cimetidine: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Dexlansoprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Esomeprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Esomeprazole; Naproxen: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Famotidine: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Famotidine; Ibuprofen: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Gentamicin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    H2-blockers: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Kanamycin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Lansoprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Lansoprazole; Naproxen: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Lanthanum Carbonate: (Major) To limit absorption problems, oral cefuroxime should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like cefuroxime, may also be bound by lanthanum carbonate. Separate the times of administration appropriately. Monitor the patient to ensure the appropriate response to cefuroxime is obtained.
    Loop diuretics: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Mycophenolate: (Minor) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Cefuroxime may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption.
    Nizatidine: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Omeprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Omeprazole; Sodium Bicarbonate: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Pantoprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Paromomycin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Plazomicin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Proton pump inhibitors: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Rabeprazole: (Major) Avoid the concomitant use of proton pump inhibitors (PPIs) and cefuroxime. Drugs that reduce gastric acidity, such as PPIs, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Ranitidine: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
    Sodium Bicarbonate: (Moderate) Antacids can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy. If an antacid must be used while a patient is taking cefuroxime, administer the oral dosage of cefuroxime at least 1 hour before or 2 hours after the antacid.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Streptomycin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Tobramycin: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including cephalosporins, may increase the INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Additionally, certain cephalosporins (cefotetan, cefoperazone, cefamandole) are associated with prolongation of the prothrombin time due to the methylthiotetrazole (MTT) side chain at the R2 position, which disturbs the synthesis of vitamin K-dependent clotting factors in the liver. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data over several decades with cephalosporin use, including cefuroxime, during pregnancy in women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies during organogenesis with oral cefuroxime at 14 and 9 times the maximum recommended human dose (MRHD) based on body surface area, there were no adverse developmental outcomes.[28573]

    Cefuroxime is excreted in human breast milk. The highest maternal milk concentration occurred in lactating women 8 hours after intramuscular administration of cefuroxime 750 mg. Allowing for infant milk consumption of 150 mL/kg/day, the estimated breast-fed infant dose would be less than 1% of the adult dose. No data are available on the effects of cefuroxime on the breast-fed infant or the effects of the drug on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cefuroxime and any potential adverse effects on the breast-fed infant from cefuroxime or the underlying maternal condition.[28573] Rare potential complications in the nursing infant include alterations of gut flora that might result in diarrhea or related complications (e.g., dehydration). Because the risk of serious reactions is relatively rare, the use of many cephalosporins is considered compatible with breast-feeding. Although the use of cefuroxime during breast-feeding has not been evaluated, previous American Academy of Pediatrics (AAP) recommendations and other experts consider other cephalosporins, such as cefazolin, cefprozil, and cefadroxil, as generally compatible with breast-feeding.[27500] [30584]

    MECHANISM OF ACTION

    Cefuroxime, a beta-lactam antibiotic, is mainly bactericidal. It 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 cell wall synthesis 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 cefuroxime as well as other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefuroxime'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. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.
     
    Beta-lactams, including cefuroxime, 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 cefuroxime are delineated by pathogen and dosage form. The MICs are defined for S. pneumoniae as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more for parenteral cefuroxime and as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more for oral cefuroxime. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more for both parenteral and oral cefuroxime. Oxacillin-susceptible staphylococci may be considered susceptible to cefuroxime. Similarly, for group A beta-hemolytic streptococci, penicillin susceptibility is a surrogate for cefuroxime. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacteriaceae. The CLSI defines MICs for Enterobacteriaceae as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more for parenteral cefuroxime (based on a dose of 1.5 g IV every 8 hours) and as susceptible at 4 mcg/mL or less, intermediate at 8 to 16 mcg/mL, and resistant at 32 mcg/mL or more for oral cefuroxime. The FDA defines MICs for Enterobacteriaceae as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more (based on a dose of 1.5 g IV every 8 hours).
     
    Resistance to cefuroxime is primarily through hydrolysis by beta-lactamases, alteration of PBPs, decreased permeability, and the presence of bacterial efflux pumps.

    PHARMACOKINETICS

    Cefuroxime is administered intravenously and intramuscularly as the sodium salt and orally as cefuroxime axetil. Approximately 50% of the circulating cefuroxime is protein-bound. It is distributed into most body tissues and fluids including gallbladder; liver; kidney; bone; uterus; ovary; sputum; bile; and peritoneal, pleural, and synovial fluids. It penetrates inflamed meninges and reaches therapeutic levels within the CSF. It does cross the placenta. Cefuroxime is largely excreted unchanged into the urine via glomerular filtration and tubular secretion. A small percentage is excreted in breast milk. The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Elimination half-life is 1 to 2 hours in patients with normal renal function. The axetil portion of cefuroxime axetil is metabolized to acetic acid and acetaldehyde.[28573] [49892]

    Oral Route

    Cefuroxime axetil is rapidly hydrolyzed in the intestinal mucosa, with approximately 37% of an oral dose reaching the systemic circulation as cefuroxime. Peak serum levels of cefuroxime after administration of cefuroxime axetil occur within 2 to 3 hours following an oral dose. Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults. The tablet and powder for oral suspension formulations are NOT substitutable on a milligram-per-milligram basis. The AUC for the suspension averaged 91% of that for the tablet, and the peak plasma concentration (Cmax) for the suspension averaged 71% of the peak plasma concentration of the tablets. Absorption of the tablet is greater when taken after food (absolute bioavailability of tablets increases from 37% to 52%); despite this difference in absorption, the clinical and bacteriologic responses were independent of administration technique and the tablets may be taken with or without food. All pharmacokinetic and clinical studies using the suspension formulation were conducted in the fed state; the suspension should thus be administered with food.[28573]

    Intravenous Route

    Following intravenous (IV) doses of 750 mg and 1.5 g of cefuroxime sodium to adults, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5 g doses every 8 hours to normal adult volunteers. The serum half-life after IV injection is approximately 80 minutes. Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations. IV doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.

    Intramuscular Route

    In adults, peak serum levels of cefuroxime sodium occur at roughly 45 minutes (range: 15 to 60 minutes) following intramuscular (IM) injection of a 750 mg dose; the mean peak serum concentration was 27 mcg/mL. The serum half-life after IM injection is approximately 80 minutes. Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations. Urinary concentrations following IM dosing averaged 1,300 mcg/mL during the first 8 hours.