PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    3rd Generation Cephalosporin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral third-generation cephalosporin
    Not effective for Pseudomonas aeruginosa infections
    Used commonly for enteric gram-negative meningitis and sepsis, serious bacteremias, pneumonia, intra-abdominal infections, bone and joint infections, urinary tract infections, and skin and skin structure infections

    COMMON BRAND NAMES

    Claforan

    HOW SUPPLIED

    Cefotaxime/Cefotaxime Sodium/Claforan Intramuscular Inj Pwd F/Sol: 1g, 2g, 10g, 500mg
    Cefotaxime/Cefotaxime Sodium/Claforan Intravenous Inj Pwd F/Sol: 1g, 2g, 10g, 500mg

    DOSAGE & INDICATIONS

    For the treatment of bacteremia and sepsis.
    Intravenous and Intramuscular dosage
    Adults

    2 g IV every 6 to 8 hours for severe infections and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day. Start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents weighing 50 kg or more

    2 g IV every 6 to 8 hours for severe infections and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.[29912] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP).[63245] 50 to 180 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose) is the FDA-approved dosage; use higher doses for more severe infections.[29912] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Neonates 32 weeks gestation and older and 8 days and older

    50 mg/kg/dose IV or IM every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.

    Neonates 32 weeks gestation and older and 0 to 7 days

    50 mg/kg/dose IV or IM every 12 hours.[29912] [63245] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

    For the treatment of bacterial meningitis and ventriculitis.
    Intravenous dosage
    Adults

    2 g IV every 4 to 6 hours. Recommended duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, and 21 days for gram negative bacilli.

    Children and Adolescents weighing 50 kg or more

    2 g IV every 4 to 6 hours. Recommended duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, and 21 days for gram negative bacilli.

    Infants, Children, and Adolescents weighing less than 50 kg

    225 to 300 mg/kg/day IV divided every 6 to 8 hours (Max: 2 g/dose) is recommended by the Infectious Diseases Society of America (IDSA). The FDA-approved dosage is 180 mg/kg/day IV divided every 4 to 6 hours (Max: 2 g/dose). Recommended duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, and 21 days for gram negative bacilli.

    Neonates 8 days and older

    50 mg/kg/dose IV every 6 to 8 hours is recommended by Infectious Diseases Society of America (IDSA). The FDA-approved dosage is 50 mg/kg/dose IV every 8 hours. Suggested duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, 21 days for gram negative bacilli, and at least 21 days for Listeria monocytogenes.

    Neonates 0 to 7 days

    50 mg/kg/dose IV every 8 to 12 hours is recommended by Infectious Diseases Society of America (IDSA). The FDA-approved dosage is 50 mg/kg/dose IV every 12 hours. Suggested duration of therapy is 7 days for N. meningitidis and H. influenzae, 10 to 14 days for S. pneumoniae, 14 to 21 days for S. agalactiae, 21 days for gram negative bacilli, and at least 21 days for Listeria monocytogenes.

    For the treatment of gonorrhea.
    For uncomplicated gonorrhea (e.g., cervicitis, urethritis, proctitis).
    Intramuscular dosage
    Adults

    500 mg IM as a single dose, in combination with azithromycin 1 g PO as a single dose, is recommended by the Centers for Disease Control (CDC) as an alternative to first-line agent, ceftriaxone. In males with proctitis, the FDA-approved dosage is 1 g IM as a single dose; however, the CDC does not recommend cefotaxime for proctitis.

    Children weighing 45 kg or more and Adolescents

    500 mg IM as a single dose, in combination with azithromycin 1 g PO as a single dose, is recommended by the Centers for Disease Control (CDC) as an alternative to first-line agent, ceftriaxone. In males with proctitis, the FDA-approved dosage is 1 g IM as a single dose; however, the CDC does not recommend cefotaxime for proctitis.

    For disseminated gonococcal infection† (e.g., sepsis, arthritis).
    Intravenous dosage
    Adults

    1 g IV every 8 hours plus azithromycin 1 g PO as a single dose is recommended as an alternative to ceftriaxone by the Centers for Disease Control (CDC). Cefotaxime should be continued for 24 to 48 hours after clinical improvement begins. Therapy may then be switched to an oral agent guided by antimicrobial susceptibility testing to complete at least 7 days of antibiotic therapy.

    Adolescents

    1 g IV every 8 hours plus azithromycin 1 g PO as a single dose is recommended as an alternative to ceftriaxone by the Centers for Disease Control (CDC). Cefotaxime should be continued for 24 to 48 hours after clinical improvement begins. Therapy may then be switched to an oral agent guided by antimicrobial susceptibility testing to complete at least 7 days of antibiotic therapy.

    For disseminated gonococcal infection† (e.g., sepsis, arthritis, meningitis) and scalp abscesses† in neonates.
    Intravenous and Intramuscular dosage
    Neonates

    25 mg/kg/dose IV or IM every 12 hours for 7 days, or for 10 to 14 days for meningitis, is recommended by the Centers for Disease Control (CDC) and American Academy of Pediatrics (AAP) as an alternative to ceftriaxone, particularly in neonates with hyperbilirubinemia.[59799] [63245]

    For surgical infection prophylaxis.
    Intravenous and Intramuscular dosage
    Adults

    1 g IV or IM as a single dose within 30 to 90 minutes prior to the surgical incision. For cesarean section, 1 g IV or IM as soon as the umbilical cord is clamped, then 1 g IV or IM every 6 hours for 2 more doses. Clinical practice guidelines suggest 1 g IV, or for obese patients, 2 g IV within 60 minutes prior to the surgical incision. Intraoperative redosing 3 hours from the first preoperative dose and duration of prophylaxis less than 24 hours are suggested by clinical practice guidelines. Cefotaxime is FDA-approved for surgical procedures that may be classified as contaminated or potentially contaminated (i.e., abdominal or vaginal hysterectomy, gastrointestinal and genitourinary tract surgery). However, clinical practice guidelines recommend cefotaxime only in combination with ampicillin for liver transplantation.

    Infants†, Children†, and Adolescents† undergoing liver transplantation

    50 mg/kg IV or IM as a single dose (Max: 1 g/dose; 2 g/dose in obese patients) within 60 minutes prior to the surgical incision, in combination with ampicillin. Repeat dose intraoperatively 3 hours after preoperative dose if surgery still in progress. The duration should not exceed 24 hours.

    For the treatment of urinary tract infection (UTI).
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 12 hours for uncomplicated infections; 1 to 2 g IV or IM every 8 hours for moderate to severe infections, and 2 g IV every 6 to 8 hours for severe infections. The maximum dosage is 12 g/day.

    Children and Adolescents weighing 50 kg or more

    1 g IV or IM every 12 hours for uncomplicated infections; 1 to 2 g IV or IM every 8 hours for moderate to severe infections, and 2 g IV every 6 to 8 hours for severe infections. The maximum dosage is 12 g/day.

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP). 50 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose) is the FDA-approved dosage; use higher doses for more severe infections. For initial dosing for UTI in febrile patients 2 months to 2 years, 150 mg/kg/day IV divided every 6 to 8 hours for 7 to 14 days is recommended by AAP.

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

    For the treatment of intraabdominal infections, including peritonitis.
    For the treatment of peritonitis in patients receiving peritoneal dialysis.
    Intraperitoneal dosage†
    Infants, Children, and Adolescents

    500 mg/L intraperitoneal (IP) loading dose followed by a maintenance dose of 250 mg/L of peritoneal dialysate. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.[53190]

    Intravenous or Intramuscular dosage
    Adults

    1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day. Guidelines suggest cefotaxime plus metronidazole for empiric treatment of mild to moderate community-acquired infections. For complicated intra-abdominal infections, treatment for 4 to 7 days is recommended.

    Children and Adolescents weighing 50 kg or more

    1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day. For complicated intra-abdominal infections, treatment for 4 to 7 days in combination with metronidazole is recommended.

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP). 50 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose) is the FDA-approved dosage; use higher doses for more severe infections. For initial dosing for complicated intra-abdominal infections, 150 to 200 mg/kg/day IV divided every 6 to 8 hours for 4 to 7 days in combination with metronidazole is recommended.

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

    For the treatment of skin and skin structure infections, including animal bite wounds and necrotizing infections.
    For the treatment of of necrotizing infections of the skin, fascia, and muscle.
    Intravenous dosage
    Adults

    2 g IV every 8 hours plus doxycycline for Vibrio vulnificus infections. Cefotaxime 2 g IV every 6 hours may also be considered empirically as part of broad spectrum therapy for mixed infections when administered with metronidazole or clindamycin. Surgical intervention is the primary therapeutic intervention. Antibiotic therapy should be administered until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours.

    Infants, Children, and Adolescents

    50 mg/kg/dose IV every 6 hours (Max: 2 g/dose), in combination with metronidazole or clindamycin, is recommended in clinical practice guidelines.

    For the treatment of animal bite wounds.
    Intravenous dosage
    Adults

    1 to 2 g IV every 6 to 8 hours with an anaerobic agent (clindamycin or metronidazole). In setting of a cat or dog bite, clinical practice guidelines also recommend pre-emptive antimicrobial therapy for 3 to 5 days for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 12 hours for uncomplicated infections; 1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.

    Children and Adolescents weighing 50 kg or more

    1 g IV or IM every 12 hours for uncomplicated infections; 1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP). 50 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose) is the FDA-approved dosage; use higher doses for more severe infections.

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

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

    1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.

    Children and Adolescents weighing 50 kg or more

    1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 8 g/day) is recommended by the American Academy of Pediatrics (AAP). 50 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose) is the FDA-approved dosage; use higher doses for more severe infections.

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

    For the treatment of gynecologic infections (e.g., endometritis, pelvic cellulitis, pelvic inflammatory disease (PID)).
    Intravenous or Intramuscular dosage
    Adults

    1 to 2 g IV or IM every 8 hours for moderate to severe infections and 2 g IV every 6 to 8 hours for severe infections. The maximum dosage is 12 g/day. The CDC suggests that cefotaxime may be effective for inpatient, intravenous treatment of PID; however, there is decreased anaerobic activity as compared to cefoxitin/cefotetan. Additionally, for outpatient PID therapy, cefotaxime may be administered with oral doxycycline with or without oral metronidazole for 14 days.

    Children and Adolescents weighing 50 kg or more

    1 to 2 g IV or IM every 8 hours for moderate to severe infections and 2 g IV every 6 to 8 hours for severe infections. The maximum dosage is 12 g/day. The CDC suggests that cefotaxime may be effective for inpatient, intravenous treatment of PID; however, there is decreased anaerobic activity as compared to cefoxitin/cefotetan. Additionally, for outpatient PID therapy, cefotaxime may be administered with oral doxycycline with or without oral metronidazole for 14 days.

    For the treatment of disseminated Lyme disease† (i.e., neuroborreliosis, carditis, recurrent/persistent arthritis).
    NOTE: Cefotaxime is recommended as an alternative to ceftriaxone for the treatment of early Lyme disease with acute neurological disease, for the initial treatment of hospitalized patients with Lyme carditis, and for late manifestations of Lyme disease.
    Intravenous and Intramuscular dosage
    Adults

    2 g IV or IM every 8 hours for 2 to 4 weeks.

    Infants, Children, and Adolescents

    150 to 200 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 6 g/day) for 2 to 4 weeks.

    For the empiric treatment of enteric infections†, including acute gastroenteritis† and infectious diarrhea† in HIV-infected patients.
    Intravenous dosage
    Adults

    1 g IV every 8 hours is recommended by guidelines as an alternative in HIV-infected patients as empiric therapy for bacterial enteric infections pending definitive diagnosis.

    Adolescents

    1 g IV every 8 hours is recommended by guidelines as an alternative in HIV-infected patients as empiric therapy for bacterial enteric infections pending definitive diagnosis.

    For the treatment of severe leptospirosis† due to Leptospira sp.†.
    Intravenous dosage
    Adults

    1 g IV every 6 hours for 7 days was as effective as IV penicillin G and doxycycline in an open-label, randomized comparative study.

    Adolescents

    1 g IV every 6 hours for 7 days was as effective as IV penicillin G and doxycycline in an open-label, randomized comparative study.

    For the treatment of acute bacterial sinusitis† in patients with severe infection requiring hospitalization.
    Intravenous dosage
    Adults

    2 g IV every 4 to 6 hours for 5 to 7 days is recommended as alternative therapy in patients with severe infection requiring hospitalization.

    Infants, Children, and Adolescents

    100 to 200 mg/kg/day IV divided every 6 hours (Max: 8 g/day) for 10 to 14 days is recommended as alternative therapy.

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

    1 g IV or IM every 12 hours for uncomplicated infections, 1 to 2 g IV or IM every 8 hours for moderate to severe infections, 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. Max: 12 g/day.[29912] For community-acquired empyema, guidelines recommend cefotaxime in combination with metronidazole for at least 2 weeks after drainage and defervescence.[61949]

    Children and Adolescents weighing 50 kg or more

    1 g IV or IM every 12 hours for uncomplicated infections, 1 to 2 g IV or IM every 8 hours for moderate to severe infections, 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. Max: 12 g/day.

    Infants, Children, and Adolescents weighing less than 50 kg

    150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose).[29912] [63245] Use higher doses for more severe infections.[29912]

    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 8 to 13 days

    50 mg/kg/dose IV or IM every 8 to 12 hours.

    Neonates younger than 32 weeks gestation and 0 to 7 days

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

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous dosage
    Adults

    1 to 2 g IV every 8 hours for at least 5 days as part of combination therapy for hospitalized patients.

    Adolescents

    150 mg/kg/day IV divided every 8 hours (Max: 6 g/day) for 5 to 10 days. Guidelines recommend empiric therapy with cefotaxime for hospitalized patients who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents high-level penicillin resistance, and for life-threatening infection. Consider combination therapy with a macrolide for suspected atypical pneumonia or with clindamycin or vancomycin for suspected infection due to S. aureus.[46963] In HIV-infected patients, cefotaxime is recommended as part of combination therapy for hospitalized patients.[34362]

    Infants and Children

    150 mg/kg/day IV divided every 8 hours (Max: 6 g/day) for 10 days. Guidelines recommend empiric therapy with cefotaxime for hospitalized patients who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents high-level penicillin resistance, and for life-threatening infection. Consider combination therapy with a macrolide for suspected atypical pneumonia or with clindamycin or vancomycin for suspected infection due to S. aureus.[46963]

    HIV-infected Infants and Children

    40 to 50 mg/kg/dose IV every 6 hours or 50 to 65 mg/kg/dose IV every 8 hours (Max: 8 to 10 g/day).

    For the treatment of salmonellosis† in HIV-infected patients.
    Intravenous dosage
    Adults

    1 g IV every 8 hours is recommended as an alternative therapy to a quinolone in the HIV guidelines. For patients with a CD4 count of 200 cells/mm3 or more, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with a CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long-term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with a CD4 count less than 200 cells/mm3 with severe diarrhea.[34362]

    Adolescents

    1 g IV every 8 hours is recommended as an alternative therapy to a quinolone in the HIV guidelines. For patients with a CD4 count of 200 cells/mm3 or more, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with a CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with a CD4 count less than 200 cells/mm3 with severe diarrhea.

    For the treatment of severe typhoid fever† due to multidrug-resistant or quinolone-resistant Salmonella typhii.
    Intravenous dosage
    Adults

    80 mg/kg/day IV divided every 8 to 12 hours (Max: 4 g/day) for 10 to 14 days.

    Infants, Children, and Adolescents

    80 mg/kg/day IV divided every 8 to 12 hours (Max: 4 g/day) for 10 to 14 days.

    For the treatment of infective endocarditis†.
    Intravenous dosage
    Adults

    2 g IV every 6 to 8 hours for septicemia and 2 g IV every 4 hours for life-threatening infections are recommended in the FDA-approved labeling. Guidelines recommend cefotaxime as an alternate therapy for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE) caused by HACEK microorganisms. In patients with penicillin-resistant streptococcal endocarditis with or without meningitis, high-dose cefotaxime is a reasonable option; if the isolate is cefotaxime-resistant, consider adding vancomycin and rifampin. Treat for 6 weeks for streptococcal PVE.

    Children and Adolescents

    200 mg/kg/day IV divided every 6 hours (Max: 12 g/day). Guidelines recommend cefotaxime as a preferred therapy for 4 weeks for endocarditis caused by HACEK group organisms or for at least 6 weeks in combination with an aminoglycoside for other gram-negative microorganisms.

    Infants

    150 to 180 mg/kg/day IV divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).

    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).

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    12 g/day IV/IM.

    Geriatric

    12 g/day IV/IM.

    Adolescents

    12 g/day IV/IM.

    Children

    Weighing 50 kg or more: 12 g/day IV/IM.
    Weighing less than 50 kg: 180 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 300 mg/kg/day (Max: 12 g/day) have been used off-label for meningitis.

    Infants

    180 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 300 mg/kg/day have been used off-label for meningitis.

    Neonates

    8 days and older: 150 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 200 mg/kg/day have been used off-label for meningitis.
    0 to 7 days: 100 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 150 mg/kg/day have been used off-label for meningitis.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Cefotaxime is metabolized by the liver to an active metabolite, desacetylcefotaxime. Dosage adjustments in patients with hepatic impairment without concomitant renal insufficiency are usually not necessary since cefotaxime has a high therapeutic index. However, specific guidelines for dosage adjustment in patients with hepatic impairment are not available.

    Renal Impairment

    Adults
    CrCl more than 20 mL/min: no dosage adjustment needed.
    CrCl 20 mL/min or less: reduce recommended dose by 50%.
     
    Pediatric patients
    The following dose adjustments are based on a usual recommended dose in children of 100 to 200 mg/kg/day IV/IM divided every 8 hours.
    CrCl more than 50 mL/min/1.73 m2: no dosage adjustment needed.
    CrCl 30 to 50 mL/min/1.73 m2: 35 to 70 mg/kg/dose IV/IM every 8 to 12 hours.
    CrCl 10 to 29 mL/min/1.73 m2: 35 to 70 mg/kg/dose IV/IM every 12 hours.
    CrCl less than 10 mL/min/1.73 m2: 35 to 70 mg/kg/dose IV/IM every 24 hours.
     
    Intermittent hemodialysis
    Approximately 50% of the serum concentration of cefotaxime is removed during a standard hemodialysis session. Some clinicians recommend that 0.5 to 2 g be given as single daily doses and that a supplemental dose of cefotaxime be given after each hemodialysis session. For pediatric patients, the recommended dose is 35 to 70 mg/kg/dose IV/IM every 24 hours, given after hemodialysis on dialysis days.
     
    Peritoneal dialysis
    For adult patients, give 1 g IV/IM every 24 hours. For pediatric patients, the recommended dose is 35 to 70 mg/kg/dose IV/IM every 24 hours.
     
    Continuous renal replacement therapy (CRRT)
    For adult patients, give 1 g IV/IM every 12 hours. For pediatric patients, the recommended dose is 35 to 70 mg/kg/dose IV/IM every 12 hours.

    ADMINISTRATION

    Injectable Administration

    Cefotaxime is administered intravenously or intramuscularly.
    One gram of cefotaxime in 14 mL of sterile water for injection is isotonic.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Infusion bottles, bulk packages, and frozen bags are for IV use only.
     
    IV Push
    Vials: reconstitute 500 mg, 1 g, or 2 g with 10 mL of sterile water for injection to give concentrations of 50, 95, or 180 mg/mL, respectively.
    Inject directly into a vein over 3—5 minutes or slowly into the tubing of a freely-flowing compatible IV solution.
     
    Intermittent or continuous IV infusion
    Vials: the reconstituted powder (see above) may be further diluted with 50—1000 mL of a compatible IV solution.
    Infusion bottles: reconstitute bottles containing 1 or 2 g with 50—100 mL of 0.9% Sodium Chloride injection or 5% Dextrose injection.
    Frozen bags: thaw at room temperature. Do not force thaw. No reconstitution necessary.
    Pharmacy bulk packages: reconstitute 10 grams with 47 or 97 mL of a compatible solution to give concentrations of 200 mg/mL or 100 mg/mL, respectively. Withdraw appropriate dose and dilute in a compatible IV solution.
    ADD-Vantage vials: for IV infusion only. Reconstitute only with 0.9% Sodium Chloride injection or 5% Dextrose injection in the appropriate 50 or 100 mL flexible diluent container.
    Infuse appropriate dose over 20—60 minutes.

    Intramuscular Administration

    Vials: reconstitute 500 mg, 1 g, or 2 g with 2, 3, 5 mL of sterile or bacteriostatic water for injection, respectively.
    Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).

    STORAGE

    Generic:
    - Protect from light
    - Store unreconstituted product at 59 to 86 degrees F
    Claforan:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from light
    - Store unreconstituted product at 68 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    A false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as cefotaxime, and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on cefotaxime treatment.
     
    Positive direct Coombs tests have been reported during treatment with cefotaxime. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs test of newborns whose mothers received cefotaxime before delivery, clinicians should keep in mind that a positive Coombs test may be due to the drug.

    Cephalosporin hypersensitivity, penicillin hypersensitivity

    Cefotaxime is contraindicated in patients with cephalosporin hypersensitivity or cephamycin hypersensitivity. Cefotaxime should be used cautiously in patients with hypersensitivity to penicillin. The structural similarity between cefotaxime 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 cefotaxime. Cross-reactivity to cephalosporins is approximately 3—7% with a documented history to penicillin.

    Corn hypersensitivity

    Cefotaxime solutions containing dextrose may be contraindicated in patients with known corn hypersensitivity or hypersensitivity to corn products.

    Renal disease, renal impairment

    Cefotaxime should be used with caution in patients with renal disease or renal impairment since the drug is eliminated via renal mechanisms. Dosages may need to be reduced in these patients.

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

    Almost all 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, cefotaxime 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.

    Coagulopathy, vitamin K deficiency

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

    Agranulocytosis, hematological disease, leukopenia, neutropenia, thrombocytopenia

    Use cefotaxime with caution in patients with hematological disease. Hematological abnormalities, such as leukopenia, neutropenia, thrombocytopenia, granulocytopenia, and more rarely, bone marrow failure, pancytopenia, or agranulocytosis, may occur during treatment with cefotaxime. Monitor blood counts for courses of therapy lasting longer than 10 days. Treatment discontinuation should be considered in cases of abnormal results.

    Infusion-related reactions

    Rapid administration (i.e., less than 60 seconds) of cefotaxime through a central venous catheter can result in infusion-related reactions that include potentially life-threatening arrhythmias. Avoid rapid bolus intravenous administration of cefotaxime.

    Pregnancy

    Cefotaxime is classified as FDA pregnancy risk category B. Cefotaxime crosses the placenta. Animal data reveal no teratogenic or fetotoxic effects; however, a slight decrease in fetal and neonatal weight was observed. There are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefotaxime has not been studied for use during labor and delivery. Treatment should be given only if clearly needed.

    Breast-feeding

    Cefotaxime is excreted in breast milk in small quantities. The manufacturer recommends that it should be used with caution during breast-feeding, considering the benefit to the mother. Rare potential complications in the nursing infant include alterations of gut flora that might result in diarrhea or other related complications (e.g., dehydration). Cefotaxime is generally considered compatible for use for breast-feeding women by the American Academy of Pediatrics. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Sexually transmitted disease

    While cefotaxime 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, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Geriatric

    Clinical trial and other reported clinical experience has not identified differences in responses between geriatric and younger adult patients, but greater sensitivity of some older individuals to cefotaxime cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) 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
    seizures / Delayed / 0-1.0
    agranulocytosis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    cholecystitis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

    Moderate

    eosinophilia / Delayed / 2.4-2.4
    colitis / Delayed / 1.4-1.4
    leukopenia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    vaginitis / Delayed / 0-1.0
    candidiasis / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    thrombocytopenia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    cholestasis / Delayed / Incidence not known
    cholelithiasis / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 4.3-4.3
    fever / Early / 2.4-2.4
    pruritus / Rapid / 2.4-2.4
    maculopapular rash / Early / 2.4-2.4
    nausea / Early / 1.4-1.4
    diarrhea / Early / 1.4-1.4
    vomiting / Early / 1.4-1.4
    headache / Early / 0-1.0
    urticaria / Rapid / Incidence not known
    dizziness / Early / Incidence not known
    malaise / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    Amikacin: (Minor) Cefotaxime'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) Cefotaxime'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.
    Amlodipine; Celecoxib: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Celecoxib: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Colchicine; Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion of cefotaxime, thereby causing higher, prolonged serum levels of the drug.
    Diclofenac: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Diclofenac; Misoprostol: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Diflunisal: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Diphenhydramine; Ibuprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Diphenhydramine; Naproxen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Esomeprazole; Naproxen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Etodolac: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Famotidine; Ibuprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Fenoprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Flurbiprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Gentamicin: (Minor) Cefotaxime'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.
    Hydrocodone; Ibuprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Ibuprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Ibuprofen; Oxycodone: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Ibuprofen; Pseudoephedrine: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Indomethacin: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Kanamycin: (Minor) Cefotaxime'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.
    Ketoprofen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Ketorolac: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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; Naproxen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    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.
    Meclofenamate Sodium: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Mefenamic Acid: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Meloxicam: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Nabumetone: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Naproxen: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Naproxen; Pseudoephedrine: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Naproxen; Sumatriptan: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Nonsteroidal antiinflammatory drugs: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    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.
    Oxaprozin: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Paromomycin: (Minor) Cefotaxime'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.
    Piroxicam: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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) Cefotaxime'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.
    Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion of cefotaxime, thereby causing higher, prolonged serum levels of the drug.
    Rofecoxib: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    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) Cefotaxime'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.
    Sulindac: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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) Cefotaxime'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.
    Tolmetin: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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.
    Valdecoxib: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), 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

    Cefotaxime is classified as FDA pregnancy risk category B. Cefotaxime crosses the placenta. Animal data reveal no teratogenic or fetotoxic effects; however, a slight decrease in fetal and neonatal weight was observed. There are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefotaxime has not been studied for use during labor and delivery. Treatment should be given only if clearly needed.

    Cefotaxime is excreted in breast milk in small quantities. The manufacturer recommends that it should be used with caution during breast-feeding, considering the benefit to the mother. Rare potential complications in the nursing infant include alterations of gut flora that might result in diarrhea or other related complications (e.g., dehydration). Cefotaxime is generally considered compatible for use for breast-feeding women by the American Academy of Pediatrics. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Cefotaxime, like other beta-lactam antibiotics, 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 the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of cefotaxime as well as other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefotaxime'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. Resistance to beta-lactam antibiotics can develop if there are changes in the PBPs, if cell wall permeability decreases, or if certain beta-lactamases are present. Cefotaxime retains activity against some beta-lactamase-producing isolates, including penicillinase and cephalosporinase; however, most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to the drug.

    PHARMACOKINETICS

    Cefotaxime is administered intravenously and intramuscularly. It is not absorbed from the GI tract. Approximately 13 to 38% of the circulating drug 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 crosses the placenta. Cefotaxime is metabolized primarily by the liver to desacetylcefotaxime, an active metabolite that displays 10% of the parent drug's antibacterial activity. Cefotaxime and its metabolites are excreted into the urine primarily via tubular secretion. A small percentage is excreted in breast milk. In patients with normal renal function, the elimination half-lives of cefotaxime and desacetylcefotaxime are 1 to 1.5 hours and 1.5 to 2 hours, respectively.

    Intramuscular Route

    Peak serum levels of cefotaxime occur within 30 minutes following an IM dose.