Cefepime is a parenteral cephalosporin with pharmacokinetics and spectrum of activity similar to ceftazidime, a 'third-generation' cephalosporin. Because cefepime may be active against some organisms resistant to ceftazidime, some consider cefepime a 'fourth-generation' cephalosporin. Cefepime is comparable to ceftazidime in its coverage of Pseudomonas aeruginosa, and it may be more active than ceftazidime against Enterobacter sp. due to enhanced stability against beta-lactamases. Clinical uses of cefepime are similar to those of the third-generation cephalosporins. Cefepime was approved in January 1996. It was approved for the treatment of febrile neutropenia in June 1997 and for complicated intra-abdominal infections in January 1998. In early 2007, the safety of cefepime relative to other beta-lactam antibiotics was questioned. A meta-analysis evaluating the efficacy and safety of cefepime reported a higher all-cause mortality in patients treated with cefepime compared to other beta-lactams. The FDA has conducted additional analyses and determined that the data do not indicate a higher rate of death in cefepime-treated patients. While the FDA has concluded that cefepime remains an appropriate therapy for its approved indications, they will continue to review its safety.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Add 5 mL of compatible IV diluent to each 500 mg vial or 10 mL of diluent to each 1 g or 2 g vial. The resultant solution will be 100 mg/mL for the 500 mg and 1 g vials and 160 mg/mL for the 2 g vial. Further dilution is required.
-Compatible diluents include Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride Injection, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol.
-Storage: Reconstituted solutions are stable for up to 24 hours at room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
Dilution
-Dilute reconstituted solution with a compatible IV solution to provide a solution with a final concentration between 1 mg/mL and 40 mg/mL.
-Compatible solutions include 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 10% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer's and 5% Dextrose Injection, or Normosol-R and Normosol-M in 5% Dextrose Injection.
-Storage: Diluted solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
ADD-Vantage Vials
-Constitute with 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
-Storage: Solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
Frozen Pre-mixed Bags
-Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation.
-Storage: The thawed solution is stable for 7 days under refrigeration (5 degrees C, 41 degrees F) or for 24 hours at room temperature. Do not refreeze.
DUPLEX Drug Delivery System
-Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber.
-Protect from light after removal of foil strip. If the foil strip is removed and not used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
-Once ready for activation, do not use directly after refrigeration; allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
-To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Storage: After reconstitution (activation), use within 12 hours if stored at room temperature or within 5 days if stored under refrigeration.
Intermittent IV Infusion
-Administer IV over a period of 30 minutes.
-DUPLEX Drug Delivery System: Prior to attaching to IV set, fold the Duplex container, starting at the hanger tab end, just below the solution meniscus trapping all air above the fold. Squeeze the Duplex container until the seal between the reconstituted drug solution and the set port opens, releasing the liquid to the set port. Do not use in series connections.
Intravenous (IV) Push*
NOTE: Cefepime is not approved by the FDA for IV push administration.
Powder Vials for Injection
Reconstitution
-A study included 368 adult hospitalized patients who received cefepime IV push (median 8 doses).
--Doses of 1 g were reconstituted with 10 mL of 0.9% Sodium Chloride Injection and doses of 2 g were reconstituted with 20 mL of 0.9% Sodium Chloride Injection.
-A study included 535 adult patients who received cefepime by IV push in the emergency department.
--Doses of 1 and 2 g were reconstituted with 0.9% Sodium Chloride Injection to a total volume of 10 mL.
-A study included 1,110 adult patients who received cephalosporins, including cefepime, by IV push in the emergency department.
--Doses of 1 g were reconstituted with 10 mL of Sterile Water for Injection and doses of 2 g were reconstituted with 20 mL of Sterile Water for Injection.
-Stability:
--Solutions of 1 and 2 g reconstituted with 10 mL of a compatible solution are stable in the vial for up to 24 hours at room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
-In a study, cefepime concentrations of 100 and 200 mg/mL in Sterile Water for Injection, 0.9% Sodium Chloride Injection, and 5% Dextrose Injection were stable in polypropylene syringes for 1 day at room temperature (22 to 24 degrees C), for 7 to 14 days at 4 degrees C, and up to 90 days at -20 degrees C. Concentrations were maintained at more than 90% of the initial concentration.
Intermittent IV Push
-Doses have been administered IVP at a rate of 2 to 5 minutes.
Intramuscular Administration
Powder Vials for Injection
Reconstitution:
-Reconstitute with 1 of the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride Injection, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol.
-Add 1.3 mL of diluent to each 500 mg vial, or 2.4 mL of diluent to each 1 g vial.
-The final concentration after constitution will be 280 mg/mL.
-Storage: Reconstituted solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
Intramuscular Injection:
-Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). To reduce injection site pain, mix cefepime with 1% lidocaine WITHOUT epinephrine.
In clinical trials using multiple doses of cefepime, 4137 patients were treated with the recommended dosages of cefepime (500 mg to 2 g intravenous every 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. Sixty-four (1.5%) patients discontinued medication due to adverse events thought by the investigators to be possibly, probably, or almost certainly related to drug toxicity. Thirty-three (51%) of the 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued treatment due to drug-related adverse events was very similar at daily doses of 500 mg, 1 g, and 2 g every 12 hours (0.8%, 1.1%, and 2%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses. A similar safety profile was seen in clinical trials of pediatric patients.
Fever and headache were both reported during cefepime trials. The incidence of both were lower (> 0.1% to < 1%) with lower doses, but increased to 1% with doses of 2 g IV every 8 hours.
Elevated hepatic enzymes, including ALT (2.8%) and AST (2.4%), have been reported in cefepime clinical trials. Hepatic dysfunction including cholestasis has been reported for cephalosporin-class antibiotics, but were not reported for cefepime during clinical trials. Changes occurring in < 1% but > 0.1% of patients included increased alkaline phosphatase and total bilirubin.
As with some other drugs in this class, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and non-convulsive status epilepticus have been reported with cefepime. Although most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of encephalopathy occurred in patients receiving a dosage adjustment for their renal function. In the majority of cases, symptoms of neurotoxicity resolved after discontinuation of cefepime and/or after hemodialysis. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. Precautions should be taken to adjust daily dosage in patients with renal insufficiency. Seizures are a rare (< 1%), but serious complication of cephalosporin and penicillin therapy in general. Cefepime has caused seizures in pre- and post-marketing studies. The epileptogenic properties of both penicillins and cephalosporins are thought to be related to their beta-lactam ring although penicillins are more commonly associated with seizures. High doses and renal impairment are associated risk factors for the development of seizures with penicillins and cephalosporins.
As with other cephalosporins, anaphylactoid reactions including anaphylactic shock have been reported with cefepime. Rash (unspecified) (1.1-4%), pruritus (> 0.1% to 1%), urticaria (> 0.1% to < 1%), and erythema (> 0.1% to < 1%) have also occurred in clinical trials. Angioedema has also been reported. In addition to the adverse reactions listed observed in patients treated with cefepime, the following adverse reactions have been reported for cephalosporin-class antibiotics: Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis (TEN).
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with cefepime. Colitis, including pseudomembranous colitis, was reported at an incidence of more than 0.1% to less than 1%. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Other infectious complications occurring at an incidence of more than 0.1% to less than 1% include oral candidiasis and vaginitis.
Injection site reaction, including phlebitis (1.3%) and pain/inflammation (0.6%), has been reported in 3% of patients during cefepime clinical trials.
Nausea, vomiting, and diarrhea were all reported during cefepime clinical trials. The incidence of these adverse reactions was > 0.1% to < 1% with lower doses, but increased with doses of 2 g IV every 8 hours. In these patients, nausea was reported at 2%, vomiting was reported at 1%, and diarrhea was reported at 3%.
Hematologic adverse events reported during cefepime clinical trials include positive Coombs' test without hemolysis (16.2%), eosinophilia (1.7%), abnormal PTT (1.6%), and abnormal PT (1.4%). Other laboratory abnormalities occurring at a rate of > 0.1% to < 1% include anemia and decreased hematocrit, neutrophils, platelets, and WBC. Cefepime has also been associated with a fall in prothrombin activity (hypoprothrombinemia) with risk factors including renal/hepatic impairment, poor nutritional state, and a protracted antibiotic course. Prothrombin time should be monitored in at risk patients and vitamin K administered as indicated. As with other cephalosporins, transient leukopenia, neutropenia, agranulocytosis, and thrombocytopenia have been reported. Extended therapy with cefepime may be associated with the development of neutropenia. A comparative case review study evaluated the occurrence of neutropenia in patients receiving long-term (6-weeks) cefepime therapy or other antimicrobial agent for osteomyelitis. Thirteen courses of cefepime was administered to 12 patients and 121 courses of other IV antimicrobials was given to 120 patients. Eight (62%) courses of cefepime resulted in neutropenia compared to none for the other antimicrobials. Other adverse events associated with the cephalosporin class include aplastic anemia, hemolytic anemia, bleeding/hemorrhage, and pancytopenia.
Adverse events reported in > 0.1% to < 1% of patients in cefepime clinical trials include increased BUN (azotemia) and creatinine. Renal dysfunction and toxic nephropathy have been associated with the cephalosporin class of antibiotics.
Abnormal laboratory values reported during cefepime clinical trials include hypophosphatemia (2.8%), hypercalcemia (> 0.1% to < 1%), hyperphosphatemia (> 0.1% to < 1%), hyperkalemia (> 0.1% to < 1%), and hypocalcemia (> 0.1% to < 1%). Hypocalcemia was more commonly reported in elderly patients; however, clinical consequences from changes in either calcium or phosphorus were not reported.
Cefepime is contraindicated in patients with cephalosporin hypersensitivity or cephamycin hypersensitivity. Cefepime should be used cautiously in patients with hypersensitivity to penicillin. The structural similarity between cefepime 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 cefepime. Cross-reactivity to cephalosporins is approximately 3% to 7% with a documented history to penicillin.
Cefepime is eliminated via renal mechanisms and should be used with caution in patients with renal impairment (creatinine clearance 60 mL/minute or less) or renal failure; dosage adjustments are required for patients with renal impairment. Serious adverse events have occurred in patients with renal insufficiency given unadjusted doses of cefepime, including life-threatening or fatal encephalopathy, seizures, and non-convulsive status epilepticus. Although most reported cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules, some cases of neurotoxicity have occurred in patients receiving an appropriate dosage adjustment for their renal function. In the majority of cases, symptoms of neurotoxicity resolved after discontinuation of cefepime and/or after hemodialysis. If neurotoxicity associated with drug therapy occurs, consider discontinuing therapy or making necessary dosage adjustments in patients with renal insufficiency. While data are unavailable for pediatric patients with impaired renal function, changes in dosing regimen similar to those for adults are recommended.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including cefepime, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Many cephalosporins, including cefepime, have been rarely associated with a fall in prothrombin activity (hypoprothrombinemia). Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk, and exogenous vitamin K administered as indicated. Cephalosporins that contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been particularly associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency, severe hepatic disease) because these patients may be at a higher risk for these complications.
Cefepime is eliminated renally. Geriatric patients are more likely to have decreased renal function; therefore, care should be taken in dose selection, and renal function should be monitored. Cefepime dosages should be adjusted if renal dysfunction is present. Overall, at the usual recommended adult dose, the clinical efficacy and safety in elderly patients were comparable to safety and efficacy in non-elderly adults. 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.
Cefepime may cause laboratory test interference. Positive direct Coombs' tests have been reported during treatment with cefepime. 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 cefepime before delivery, clinicians should keep in mind that a positive Coombs' test may be due to the drug. Discontinue cefepime and institute appropriate therapy in patients who develop hemolytic anemia. Also, a false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as cefepime, 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 cefepime treatment.
Available data from observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no cases of cefepime exposure during pregnancy reported from postmarketing experience or clinical trials; however, cefepime crosses the placenta. Cefepime was not embryocidal and did not cause fetal malformations when administered to animals during organogenesis at doses up to 1.6-times the maximum recommended clinical dose based on body surface area.
Cefepime is excreted in human milk at low concentrations. A nursing infant consuming approximately 1,000 mL/day of human milk would receive approximately 0.5 mg/day of cefepime. In a pharmacokinetic study in 9 healthy lactating women, the mean breast milk concentrations of cefepime were approximately 0.5 mcg/mL during the first 8 hours after a single 1,000 mg IV dose. Concentrations declined and became undetectable at 12 to 24 hours after the dose. The mean cumulative breast milk excretion of cefepime over 24 hours was 0.01% of the administered dose. There is no information regarding the effects of cefepime on milk production or on the breast-fed infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cefepime and any potential adverse effects on the breast-fed child from cefepime or the underlying maternal condition.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of antibacterial drugs, this drug should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter calcoaceticus, Acinetobacter lwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Pantoea agglomerans, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Aeromonas hydrophila, Gardnerella vaginalis, Neisseria gonorrhoeae, Neisseria meningitidis, Salmonella sp., Serratia liquefaciens, Shigella sp., Streptococcus bovis, Yersinia enterocolitica
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For empiric monotherapy of febrile neutropenia:
NOTE: Data are insufficient to support the efficacy of cefepime monotherapy in patients at high risk for severe infection (including patients with a history of recent bone marrow transplant, hypotension at presentation, underlying hematologic malignancy, or severe or prolonged neutropenia).
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 days or until resolution of neutropenia. For patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be reevaluated.
Infants 2 months and older, Children, and Adolescents: 50 mg/kg/dose IV every 8 hours (Max: 2 g/dose) for 7 days or until resolution of neutropenia. For patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be reevaluated.
For the treatment of moderate to severe uncomplicated skin and skin structure infections and diabetic foot ulcer*:
-for the treatment of moderate to severe uncomplicated skin and skin structure infections:
Intravenous dosage:
Adults: 2 g IV every 12 hours for 10 days.
Infants, Children, and Adolescents 2 months to 17 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 days.
Infants 1 month*: 50 mg/kg/dose IV every 12 hours.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates younger than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours.
-for the treatment of diabetic foot ulcer*:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure or infections with no complicating features or with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
For the treatment of pneumonia, including community-acquired pneumonia (CAP), nosocomial pneumonia, and cases associated with concurrent bacteremia, and pleural empyema*:
-for the treatment of nonspecific pneumonia and pleural empyema*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 to 12 hours for 10 days. For infections caused by P. aeruginosa, 2 g IV every 8 hours for 10 days. For hospital-acquired or postprocedural empyema, guidelines recommend cefepime in combination with metronidazole and vancomycin for at least 2 weeks after drainage and defervescence.
Infants, Children, and Adolescents 2 months to 17 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 days. For infections caused by P. aeruginosa, 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.
Infants 1 month*: 50 mg/kg/dose IV every 12 hours. For infections caused by P. aeruginosa, 50 mg/kg/dose IV every 8 hours.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates younger than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 7 days.
Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 7 days.
-for the treatment of nosocomial pneumonia:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 days.
For the treatment of uncomplicated and complicated urinary tract infection (UTI), including pyelonephritis:
-for the treatment of mild to moderate UTI, including pyelonephritis:
Intravenous or Intramuscular dosage:
Adults: 0.5 to 1 g IV or IM every 12 hours for 7 to 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents 2 months to 17 years: 50 mg/kg/dose (Max: 1 g/dose) IV or IM every 12 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Infants younger than 2 months*: 50 mg/kg/dose IV or IM every 12 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is less than 4 mg/L. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
-for the treatment of severe UTI, including pyelonephritis:
Intravenous dosage:
Adults: 2 g IV every 12 hours for 7 to 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents 2 months to 17 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Infants younger than 2 months*: 50 mg/kg/dose IV every 12 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is less than 4 mg/L. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, biliary tract infections (cholecystitis and cholangitis), and peritoneal dialysis-related peritonitis*:
-for the general treatment of complicated intraabdominal infections:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours as part of combination therapy for 7 to 10 days.
Adolescent 17 years: 2 g IV every 8 to 12 hours as part of combination therapy for 7 to 10 days.
Infants*, Children*, and Adolescents* 1 month to 16 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. FDA-labeling for other populations suggests a duration of 7 to 10 days.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. FDA-labeling for other populations suggests a duration of 7 to 10 days.
Neonates less than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours. FDA-labeling for other populations suggests a duration of 7 to 10 days.
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Adolescent 17 years: 1 to 2 g IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants*, Children*, and Adolescents* 1 month to 16 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Neonates 36 weeks gestation and older*: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates less than 36 weeks gestation*: 30 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days.
-for the treatment of uncomplicated intraabdominal infections*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Adolescent 17 years: 1 to 2 g IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants, Children, and Adolescents 1 month to 16 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Adults: 1 g intraperitoneally every 24 hours for 21 to 28 days.
Infants, Children, and Adolescents: 15 mg/kg intraperitoneally every 24 hours for 14 to 21 days.
Continuous Intraperitoneal dosage*:
Adults: 250 to 500 mg/L intraperitoneal loading dose, followed by 100 to 125 mg/L in each dialysate exchange. Treat for 21 to 28 days.
Infants, Children, and Adolescents: 500 mg/L intraperitoneal loading dose, followed by 125 mg/L in each dialysate exchange. Treat for 14 to 21 days.
For the treatment of meningitis* and ventriculitis*:
-for the treatment of meningitis* or ventriculitis* due to H. influenzae:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 days.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 7 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for 7 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for 7 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
-for the treatment of pneumococcal meningitis* or ventriculitis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 10 to 14 days.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 14 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for 10 to 14 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for 10 to 14 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
-for the treatment of meningitis* or ventriculitis* due to gram-negative organisms:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 10 to 21 days.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for 10 to 21 days. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
Neonates younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer. Although cefepime is included as a treatment option in guidelines for treatment of bacterial meningitis, the FDA-approved labeling recommends alternate therapy in children with meningitis or in those whom meningeal seeding from a distant site has occurred.
For the treatment of infective endocarditis*:
-for the treatment of native valve endocarditis due to HACEK microorganisms*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 4 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours for 4 weeks.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for 4 weeks. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates less than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for 4 weeks.
-for the treatment of prosthetic valve endocarditis due to HACEK microorganisms*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 6 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours for 4 to 6 weeks.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for 4 to 6 weeks. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates less than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for 4 to 6 weeks.
-for the treatment of native or prosthetic valve endocarditis due to enteric gram-negative microorganisms*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 6 weeks as part of combination therapy.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours for at least 6 weeks as part of combination therapy.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours for at least 6 weeks as part of combination therapy. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.
Neonates less than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours for at least 6 weeks as part of combination therapy.
-for the treatment of nosocomial or early culture-negative prosthetic valve endocarditis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours. Consult with an infectious diseases specialist; combination therapy is dependent on most likely pathogens.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. Consult with an infectious diseases specialist; combination therapy is dependent on most likely pathogens.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. Consult with an infectious diseases specialist; combination therapy is dependent on most likely pathogens.
Neonates less than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours. Consult with an infectious diseases specialist; combination therapy is dependent on most likely pathogens.
For the treatment of sepsis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV 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 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. 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 younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours.
For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, infectious bursitis*, and orthopedic device-related infection*:
-for the treatment of unspecified osteomyelitis*:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours for 4 to 6 weeks.
Infants, Children, and Adolescents 3 months to 17 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Infants 1 to 2 months: 50 mg/kg/dose IV every 8 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
-for the treatment of native vertebral osteomyelitis*:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours for 6 weeks. May consider addition of ciprofloxacin or aminoglycoside for P. aeruginosa infections.
-for the treatment of infectious arthritis*:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.
Infants, Children, and Adolescents 3 months to 17 years: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Infants 1 to 2 months: 50 mg/kg/dose IV every 8 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 36 weeks gestation and older: 50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 36 weeks gestation: 30 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
-for the treatment of infectious bursitis*:
Intravenous dosage:
Adults: 2 g IV every 8 to 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Children and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
-for the treatment of prosthetic joint infections*:
Intravenous dosage:
Adults: 2 g IV every 12 hours for 4 to 6 weeks, which may be followed by long-term suppressive therapy. May consider addition of an aminoglycoside for P. aeruginosa infections; if aminoglycoside is in spacer and organism is aminoglycoside-susceptible, then double coverage is provided with IV or oral monotherapy.
Maximum Dosage Limits:
-Adults
6 g/day IV or 2 g/day IM.
-Geriatric
6 g/day IV or 2 g/day IM.
-Adolescents
150 mg/kg/day IV (Max: 6 g/day) or 100 mg/kg/day IM (Max: 2 g/day).
-Children
150 mg/kg/day IV (Max: 6 g/day) or 100 mg/kg/day IM (Max: 2 g/day).
-Infants
2 to 11 months: 150 mg/kg/day IV or 100 mg/kg/day IM.
1 month: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day IV or 100 mg/kg/day IM have been used off-label.
-Neonates
Neonates 36 weeks gestation and older: Safety and efficacy have not been established; however, doses up to 100 mg/kg/day IV have been used off-label.
Neonates less than 36 weeks gestation: Safety and efficacy have not been established; however, doses up to 60 mg/kg/day IV have been used off-label.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Adult patients receiving a usual dose of 500 mg IV/IM every 12 hours (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 11 to 60 mL/minute: 500 mg IV/IM every 24 hours.
CrCl less than 11 mL/minute: 500 mg IV/IM once, then 250 mg IV/IM every 24 hours.
Adult patients receiving a usual dose of 1 g IV/IM every 12 hours (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 1 g IV/IM every 24 hours.
CrCl 11 to 29 mL/minute: 1 g IV/IM once, then 500 mg IV/IM every 24 hours.
CrCl less than 11 mL/minute: 1 g IV/IM once, then 250 mg IV/IM every 24 hours.
Adult patients receiving a usual dose of 2 g IV every 12 hours (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 2 g IV every 24 hours.
CrCl 11 to 29 mL/minute: 2 g IV once, then 1 g IV every 24 hours.
CrCl less than 11 mL/minute: 2 g IV once, then 500 mg IV every 24 hours.
Adult patients receiving a usual dose of 2 g IV every 8 hours (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 2 g IV every 12 hours.
CrCl 11 to 29 mL/minute: 2 g IV every 24 hours.
CrCl less than 11 mL/minute: 2 g IV once, then 1 g IV every 24 hours.
Adult patients (alternative)*
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 10 to 50 mL/minute: Administer 50% to 100% of the usual dose every 24 hours.
CrCl less than 10 mL/minute: Administer 25% to 50% of the usual dose every 24 hours.
Pediatric patients (non-neonatal)
Specific data in pediatric patients with impaired renal function are not available. Because cefepime pharmacokinetics are similar in adults and non-neonatal pediatric patients, changes in the dosage regimen proportional to those in adults are recommended for pediatric patients. The below recommendations for maintenance dose adjustments in pediatric patients are consistent with recommendations for adult patients with renal impairment.
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours with a Max of 1 g/dose (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV once, then 25 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV once, then 12.5 mg/kg/dose (Max: 250 mg/dose) IV every 24 hours.
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours with a Max of 2 g/dose (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 12.5 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours.
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 8 hours (FDA-labeling)
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
Pediatric patients (alternative)*
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
GFR 10 to 50 mL/minute/1.73 m2: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 50 mg/kg/dose (Max: 2 g/dose) IV every 48 hours.
Intermittent hemodialysis
NOTE: Approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. Administer doses at the same time each day and after the completion of hemodialysis on hemodialysis days.
Adult patients receiving a usual dose of 500 mg IV/IM every 12 hours, 1 g IV/IM every 12 hours, or 2 g IV every 12 hours (FDA-labeling)
1g IV/IM once, then 500 mg IV/IM every 24 hours.
Adult patients receiving a usual dose of 2 g IV every 8 hours (FDA-labeling)
1 g IV every 24 hours.
Adult patients (alternative)*
Administer 25% to 50% of the usual dose every 24 hours. A dose 2 g IV after each dialysis session has also been suggested.
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours (FDA-labeling)
25 mg/kg/dose (Max: 1 g/dose) IV on day 1, then 12.5 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours thereafter.
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 8 hours (FDA-labeling)
25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
Pediatric patients (alternative)*
50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
Peritoneal dialysis
Adult and Pediatric patients (FDA-approved labeling)
For continuous ambulatory peritoneal dialysis (CAPD), FDA-labeling suggests administering recommended doses of cefepime as indicated for the infection and extend the dosing interval to every 48 hours.
Adult patients (alternative)*
Administer 25% to 50% of the usual dose every 24 hours.
Pediatric patients (alternative)*
50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.
Adult patients
Doses of 1 to 2 g IV every 12 hours or a 2 g IV loading dose then 1 g IV every 8 to 12 hours have generally been suggested for CRRT. General recommendations for patients receiving CVVH suggest 1 to 2 g IV every 12 hours. A 2 g loading dose may be used. General recommendations for patients receiving CVVHD and CVVHDF suggest 2 g IV every 12 hours or 1 g IV every 8 hours. A 2 g loading dose may be used. In patients with pathogens with a MIC of 4 mcg/mL or higher, a dose of 2 g IV every 8 hours might be needed. More specific recommendations based on ultrafiltrate rates (UFRs) suggest 1 g IV every 8 hours in patients receiving CVVH, CVVHD, or CVVHDF with a UFR of 1 L/hour and 1 g IV every 6 hours or 2 g IV every 8 hours with a UFR of 2 L/hour or higher. Alternatively, a 2 g IV loading dose then 4 g given as a continuous IV infusion can be considered for patients receiving CVVH or CVVHD with a UFR of 3 L/hour or higher. Pharmacokinetic modeling suggests these doses are sufficient to reach target attainment; however, in patients with more resistant pathogens, there is a higher chance for suboptimal concentrations.
Pediatric patients
25 to 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours. Pediatric recommendations are based on limited study data, mainly derived from adult patients, and extrapolation of CRRT clearance based on cefepime pharmacokinetic parameters.
Hybrid hemodialysis*
NOTE: Hybrid hemodialysis modalities include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.
Adult patients
In a Monte Carlo simulation study using population pharmacokinetic data, dosing was studied using 4 different PIRRT setting simulations over 8 to 10 hours/day. A dose of 2 g IV as a loading dose then 1 g IV every 6 hours achieved at least a 90% probability of target attainment for an 8-hour PIRRT session. An alternative regimen that meets the goal is 2 g IV pre-PIRRT, then 3 g IV post-PIRRT.
Pediatric patients
Cefepime dosing data are not available in pediatric patients receiving hybrid hemodialysis. Based on adult data, dosage adjustments may be necessary.
*non-FDA-approved indication
Amikacin: (Minor) Cefepime'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) Cefepime'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.
Bumetanide: (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.
Desogestrel; Ethinyl Estradiol: (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.
Dienogest; Estradiol valerate: (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.
Drospirenone: (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.
Drospirenone; Estetrol: (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.
Drospirenone; Estradiol: (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.
Drospirenone; Ethinyl Estradiol: (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.
Drospirenone; Ethinyl Estradiol; Levomefolate: (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.
Elagolix; Estradiol; Norethindrone acetate: (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.
Estradiol; Levonorgestrel: (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.
Estradiol; Norethindrone: (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.
Estradiol; Norgestimate: (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.
Ethacrynic Acid: (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.
Ethinyl Estradiol; Norelgestromin: (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.
Ethinyl Estradiol; Norethindrone Acetate: (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.
Ethinyl Estradiol; Norgestrel: (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.
Ethynodiol Diacetate; Ethinyl Estradiol: (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.
Etonogestrel; Ethinyl Estradiol: (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.
Furosemide: (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.
Gentamicin: (Minor) Cefepime'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.
Leuprolide; Norethindrone: (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.
Levonorgestrel: (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.
Levonorgestrel; Ethinyl Estradiol: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (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.
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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (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.
Norethindrone: (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.
Norethindrone; Ethinyl Estradiol: (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.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (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.
Norgestimate; Ethinyl Estradiol: (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.
Norgestrel: (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.
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.
Paromomycin: (Minor) Cefepime'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) Cefepime'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.
Relugolix; Estradiol; Norethindrone acetate: (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.
Segesterone Acetate; Ethinyl Estradiol: (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.
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) Cefepime'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) Cefepime'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.
Torsemide: (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.
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.
Cefepime, a beta-lactam antibiotic, is mainly bactericidal. Like other cephalosporins and penicillins, cefepime 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 cefepime, 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, cefepime'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 the 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 cefepime, 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 cefepime are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales. The MICs for Enterobacterales are defined by the FDA as susceptible at 2 mcg/mL or less, intermediate at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more; for isolates with an intermediate susceptibility, the recommended dose is 2 g IV every 8 hours in patients with normal renal function. The MICs for Enterobacterales are defined by CLSI as susceptible at 2 mcg/mL or less, susceptible-dose dependent (SDD) at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more; the breakpoint for susceptible is based on a dose of 1 g IV every 12 hours, and the breakpoint for SDD is based on dosage regimens that result in higher cefepime exposure (up to the approved maximum dosage regimen). The CLSI and the FDA differ on MIC interpretation for P. aeruginosa. The MICs for P. aeruginosa are defined by the FDA as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more; the recommended dose is 2 g IV every 8 hours in patients with normal renal function. The MICs for P. aeruginosa are defined by CLSI as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more; the breakpoints are based on a dose of 1 g IV every 8 hours or 2 g IV every 12 hours. The MICs are defined for Acinetobacter sp. and non-Enterobacterales as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. The MICs are defined for Aeromonas sp. and Vibrio sp.as susceptible at 2 mcg/mL or less, intermediate at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more based on a dosage regimen of 1 g IV every 12 hours. The MICs are defined for S. pneumoniae for meningitis isolates as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for S. pneumoniae for non-meningitis isolates, Abiotrophia sp., Granulicatella sp., and Corynebacterium sp. as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Streptococcus sp. Viridans group susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for beta-hemolytic streptococci and N. gonorrhoeae as susceptible at 0.5 mcg/mL or less. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 2 mcg/mL or less. The MICs are defined for E. rhusiopathiae as susceptible at 1 mcg/mL or less. Methicillin-susceptible staphylococci may be considered susceptible to cefepime.
Compared with third-generation cephalosporins, cefepime possesses an increased ability to penetrate the bacterial cell's outer membrane and a lower rate of hydrolysis by bacterial beta-lactamases. Cefepime exists as a zwitterion and it is thought that this property enhances its ability to penetrate porin channels in the cell walls of gram-negative bacteria. Cefepime has a low affinity for chromosomally-encoded beta-lactamases and is highly resistant to hydrolysis by most beta-lactamases.
Cefepime is administered intravenously and intramuscularly. The average steady-state Vd in adults is 18 L. In general, pediatric patients have slightly faster clearance and larger Vd than adults. The Vd of cefepime in pediatric patients is approximately 0.37 L/kg. Approximately 20% of the circulating drug is protein-bound. It is distributed into most body tissues and fluids. In a pediatric pharmacokinetic trial, CSF concentrations peaked 30 minutes after the dose and were lowest immediately before the next dose; however, there was relatively little variation in CSF concentrations over the 8-hour dosing interval.
Cefepime is metabolized to N-methylpyrrolidine (NMP), which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged cefepime accounts for approximately 85% of the administered dose in adults. Less than 1% of the administered dose is recovered from urine as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of cefepime. The elimination half-life in children with normal renal function is approximately 1.7 hours compared to 2 hours in adults.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
Cefepime pharmacokinetics are linear over the dose range of 250 mg to 2 g IV. The mean peak serum concentrations (Cmax) are 39.1 mcg/mL with a 500 mg IV dose, 81.7 mcg/L with a 1 g IV dose, and 163.9 mcg/mL with a 2 g IV dose in healthy adult males. There is no evidence of accumulation in healthy adult male volunteers receiving clinically relevant doses for a period of 9 days.
Intramuscular Route
Cefepime pharmacokinetics are linear over the dose range of 500 mg to 2 g IM. The mean peak serum concentrations (Cmax) are 13.9 mcg/mL with a 500 mg IV dose, 29.6 mcg/L with a 1 g IV dose, and 57.5 mcg/mL with a 2 g IV dose in healthy adult males. Cmax occurs approximately 1.5 hours after IM administration in adults. In pediatric patients who received a 50 mg/kg/dose IV and IM, the absolute bioavailability of the IM dose was 82.3%.
-Special Populations
Hepatic Impairment
No differences in the pharmacokinetics of cefepime were reported in adults with hepatic impairment who received a single 1 g dose (n = 11).
Renal Impairment
In adults with renal impairment, the elimination half-life of cefepime is prolonged. The average half-life in adults requiring hemodialysis was 13.5 +/- 2.7 hours and in patients requiring continuous peritoneal dialysis was 19 +/- 2 hours. Cefepime total body clearance decreased proportionally with creatinine clearance in patients with renal impairment. Cefepime is removed by hemodialysis; approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period.
Pediatrics
Infants, Children, and Adolescents
The combined results from 3 clinical studies in children (total n = 88; 2 months to 16 years) found mean values for clearance, Vd, and elimination half-life to be 3.1 mL/kg/minute, 0.37 L/kg, and 1.7 hours, respectively. In patients with bacterial meningitis, mean cerebrospinal fluid (CSF) concentrations ranged from 3.3 +/- 2.8 mcg/mL to 5.7 +/- 7.3 mcg/mL over the dosing interval, compared to mean plasma concentrations ranging from 4.9 +/- 5.9 mcg/mL to 67.1 +/- 57.2 mcg/mL.
Neonates
In a clinical study in 55 neonates (gestational age, 30.5 weeks +/- 5.3; postnatal age, 14.7 days +/- 14.5; weight, 1.91 kg +/- 1.04), mean values for clearance, Vd, and elimination half-life were 1.15 mL/kg/minute, 0.43 L/kg, and 4.9 hours, respectively. The volume of distribution was larger in neonates with a postconceptional age younger than 30 weeks compared to those with a postconceptional age older than 30 weeks (0.51 vs. 0.39 L/kg, respectively). Clearance in neonates is approximately 40% lower than that of older pediatric patients, and there was not a significant relationship between gestational age at birth and cefepime clearance (r = 0.14, p more than 0.1). The authors concluded that a dose of 30 mg/kg/dose IV every 12 hours for neonates younger than 14 days regardless of postconceptual age should achieve concentrations at or above those achieved by doses of 50 mg/kg/dose IV every 8 hours in older populations.
Geriatric
Cefepime pharmacokinetics have been investigated in the elderly (65 years of age and older) whose mean creatinine clearance was 74 +/-15 mL/minute. There appeared to be a decrease in cefepime total body clearance as a function of creatinine clearance.
Other
Lactating Patients
The pharmacokinetics of cefepime are similar between lactating and non-lactating patients.