Maxipime

Mechanism of Action

Fourth-generation cephalosporin; has gram-negative coverage comparable to ceftazidime but better gram-positive coverage (comparable to ceftriaxone); is zwitterion and rapidly penetrates gram-negative cells; is best beta-lactam for IM administration; has poor capacity to cross blood-brain barrier and thus is not used for treatment of meningitis

Absorption

IM absorption rapid and complete

Peak plasma time: 0.5-1.5 hr (IV); 1-2 hr (IM)

Distribution

Penetrates into inflammatory fluid at concentrations ~80% of serum levels and into bronchial mucosa at concentrations ~60% of plasma levels; crosses blood-brain barrier

Protein bound: 16-19%

Vd: 16-20 L (adults)

Metabolism

Minimally metabolized in liver

Elimination

Half-life: 2 hr

Excretion: Urine (85% as unchanged drug)

Cefepime injection is used to treat certain infections caused by bacteria including pneumonia, and skin, urinary tract, and kidney infections. Cefepime injection is used in combination with metronidazole (Flagyl) to treat abdominal (stomach area) infections. Cefepime injection is also used to treat patients who have fever and are at high risk for infection because they have a low number of white blood cells. Cefepime injection is in a class of medications called cephalosporin antibiotics. It works by killing bacteria.

Antibiotics such as cefepime injection will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Common side effects of cefepime include:

• rash
• diarrhea
• nausea
• vomiting
• itching
• fever
• headache

This is not a complete list of cefepime side effects. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with maxipime . See the “Drug Precautions” section.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious side effects have been reported with cefepime including:

• hypersensitivity (severe allergic reaction). Signs of a hypersensitivity reaction, which include the following:
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • fainting
  • rash
• diarrhea. Diarrhea is a common problem caused by antibiotics, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, contact your doctor, as this may be a sign of an infection of the bowels.
• superinfection. maxipime should not be used for extended periods. Prolonged use can lead to the growth of dangerous organisms that are resistant or unresponsive to this medication. Take maxipime for the duration prescribed by your doctor.
• bleeding abnormalities. Your health care provider may want to monitor lab tests that show how well your blood is able to clot or that measure your tendency to bleed. Any abnormalities or irregularities that may occur may be more common in those with kidney dysfunction.
• nervous system disturbances. Some may experience nervous symptom abnormalities such as a seizure or disturbances of consciousness (confusion, hallucinations, stupor, coma) when the dose of cefepime exceeds the recommended dose, especially in the presence of kidney dysfunction.

Do not take maxipime if you:

• are allergic to maxipime or to any of its ingredients
• are allergic to similar antibiotics (penicillins, cephalosporins)

Before taking maxipime , tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to maxipime or to any of its ingredients
• are allergic to similar antibiotics (penicillins, cephalosporins)
• have gastrointestinal (stomach and bowel) problems, especially colitis
• have a history of seizure activity
• have kidney problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

If you take too much Maxipime call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Maxipime is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Intra-abdominal Infections

Treatment of complicated intra-abdominal infections caused by Escherichia coli, viridans streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter, or Bacteroides fragilis; used in conjunction with IV metronidazole.1 37 69 70 92 95

For initial empiric treatment of high-risk or severe community-acquired extrabiliary intra-abdominal infections in adults, IDSA recommends either monotherapy with a carbapenem (doripenem, imipenem, meropenem) or the fixed combination of piperacillin and tazobactam, or a combination regimen that includes either a cephalosporin (cefepime, ceftazidime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.70

Has been used alone for treatment of acute obstetric and gynecologic infections† (e.g., pelvic inflammatory disease [PID], pelvic surgical wound infection, postpartum endometritis),41 but safety and efficacy of cefepime monotherapy in these infections not established.1

Respiratory Tract Infections

Treatment of moderate to severe pneumonia (with or without concurrent bacteremia) caused by susceptible Streptococcus pneumoniae.1 5 8 14 15 92 95

Treatment of moderate to severe pneumonia caused by susceptible Ps. aeruginosa, K. pneumoniae, or Enterobacter.1 5 8 14 15 92 95

Treatment of community-acquired pneumonia (CAP)40 43 caused by S. pneumoniae, Haemophilus influenzae†, Moraxella catarrhalis†, and Staphylococcus aureus†.43 ATS and IDSA recommend cefepime for treatment of CAP only when Ps. aeruginosa is known or suspected to be involved.56 For empiric treatment of CAP in patients with risk factors for Ps. aeruginosa, IDSA and ATS recommend a combination regimen that includes an antipneumococcal, antipseudomonal β-lactam (cefepime, imipenem, meropenem, fixed combination of piperacillin and tazobactam) and ciprofloxacin or levofloxacin; one of these β-lactams, an aminoglycoside, and azithromycin; or one of these β-lactams, an aminoglycoside, and an antipneumococcal fluoroquinolone.56 If Ps. aeruginosa has been identified by appropriate microbiologic testing, these experts recommend treatment with a regimen that includes an antipseudomonal β-lactam (cefepime, ceftazidime, aztreonam, imipenem, meropenem, piperacillin, ticarcillin) and ciprofloxacin, levofloxacin, or an aminoglycoside.56

Treatment of nosocomial pneumonia.67 69 For empiric treatment in severely ill patients or in those with late-onset disease or risk factor for multidrug-resistant bacteria, used in conjunction with either an aminoglycoside (amikacin, gentamicin, tobramycin) or an antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin).69 In hospitals where methicillin-resistant (oxacillin-resistant) Staphylococcus is common or if there are risk factors for these strains, initial regimen also should include vancomycin or linezolid.67 69

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains only) or susceptible S. pyogenes (group A β-hemolytic streptococci).1 3 5 6 7 8 14 17 92 95

Urinary Tract Infections (UTIs)

Treatment of mild to moderate uncomplicated and complicated UTIs (including those associated with pyelonephritis and/or with concurrent bacteremia) caused by susceptible E. coli, K. pneumoniae, or Proteus mirabilis.1 3 5 6 8 9 16 92 95

Treatment of severe uncomplicated and complicated UTIs (including those associated with pyelonephritis and/or concurrent bacteremia) caused by susceptible E. coli or K. pneumoniae.1 6 7 14 45 92 95

Endocarditis

Empiric treatment of culture-negative endocarditis† in prosthetic valve recipients.94 AHA recommends multiple-drug regimen of vancomycin, gentamicin, cefepime, and rifampin for empiric treatment of culture-negative endocarditis with onset within 1 year of valve placement.94 Selection of the most appropriate anti-infective regimen is difficult and should be guided by epidemiologic features and clinical course of the infection.94 Consultation with an infectious diseases specialist recommended.94

Meningitis and Other CNS Infections

Treatment of meningitis† caused by susceptible gram-negative bacteria (e.g., H. influenzae, Neisseria meningitidis, E. coli, E. aerogenes, Ps. aeruginosa) or gram-positive bacteria (e.g., S. pneumoniae, S. aureus, S. epidermidis).46 75 77 79 83 84

Safety and efficacy not established.1 92 Manufacturers caution that patients in whom meningeal seeding from a distant infection site or in whom meningitis is suspected or documented should receive an alternative anti-infective with demonstrated clinical efficacy in this setting.1 92 Some clinicians state additional study needed regarding efficacy for treatment of meningitis, particularly for infections caused by penicillin- and/or cefotaxime-resistant S. pneumoniae.46 79 In addition, cefepime may not be a good choice for empiric treatment of meningitis if Acinetobacter may be involved.83

IDSA states cefepime is one of several alternatives for treatment of meningitis caused by H. influenzae or E. coli or treatment of meningitis caused by S. pneumonia susceptible to penicillins and third generation cephalosporins.75 For treatment of meningitis caused by Ps. aeruginosa, IDSA and other experts recommend a regimen that includes an antipseudomonal cephalosporin (cefepime or ceftazidime) or carbapenem (imipenem or meropenem) given with or without an aminoglycoside (amikacin, gentamicin, tobramycin).75 76 Use results of in vitro susceptibility tests to guide treatment.75

IDSA also recommends a regimen of cefepime and vancomycin as one of several options that can be used for empiric treatment of penetrating head trauma or postneurosurgical infections caused by S. aureus, coagulase-negative staphylococci (especially S. epidermidis), or aerobic gram-negative bacilli (including Ps. aeruginosa).75

Septicemia

Treatment of septicemia† caused by susceptible gram-negative bacteria.69

Select anti-infective for treatment of sepsis syndrome based on probable source of infection, causative organism, immune status of patient, and local patterns of bacterial resistance.69

For initial treatment of life-threatening sepsis in adults, some clinicians suggest that a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftriaxone, ceftazidime), the fixed combination of piperacillin and tazobactam, or a carbapenem (imipenem or meropenem) be used in conjunction with vancomycin; some also suggest including an aminoglycoside or fluoroquinolone during initial few days of treatment.69

Empiric Therapy in Febrile Neutropenic Patients

Empiric treatment of presumed bacterial infections in febrile neutropenic patients.1 26 34 35 36 58 59 62 69 92

Has been effective as monotherapy for empiric therapy in febrile neutropenic patients;34 35 36 58 59 62 used in conjunction with other anti-infectives in some patients.69 Manufacturers caution that safety and efficacy data limited to date and monotherapy may not be appropriate in patients at severe risk of infection (e.g., those with a history of recent bone marrow transplantation, hypotension on presentation, underlying hematologic malignancy, severe or prolonged neutropenia).1

Consult published protocols on treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of initial empiric regimen, when to change initial regimen, possible subsequent regimens, and duration of therapy in these patients.26 Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also advised.26 32 38

Administration

Administer by IV infusion1 3 5 6 12 14 92 95 or deep IM injection.1 3 5 6 12 14

Use IM route only for treatment of mild to moderate, uncomplicated or complicated UTIs caused by E. coli when this route is considered more appropriate.1 5

IV Infusion

If Y-type administration set used, discontinue other solution flowing through the tubing during cefepime infusion.1 92 95

Manufacturers recommend that aminoglycosides, ampicillin (>40 mg/mL), metronidazole, vancomycin, or aminophylline be administered separately from cefepime.1 92 95 (See Drug Compatibility under Compatibility.)

Reconstitute vials containing 500 mg, 1 g, or 2 g of cefepime with 5, 10, or 10 mL, respectively, of compatible IV solution to provide solutions containing approximately 100, 100, or 160 mg/mL, respectively.1 Then further dilute the appropriate dose of reconstituted solution in a compatible IV solution.1 (See Solution Compatibility under Compatibility.)

Reconstitute ADD-Vantage vials containing 1 or 2 g of cefepime with 50 or 100 mL of 0.9% sodium chloride or 5% dextrose injection according to the manufacturer’s directions.1

Reconstitute (activate) commercially available Duplex drug delivery system that contains 1 or 2 g of cefepime and 50 mL of 5% dextrose injection in separate chambers according to the manufacturer's directions.95 If refrigerated after reconstitution (see Storage under Stability), allow solution to reach room temperature prior to administration.95

Thaw commercially available premixed injection (frozen) at room temperature (25°C) or under refrigeration (5°C); do not thaw by immersion in a water bath or by exposure to microwave radiation.92 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.92 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact or leaks are found.92 Do not use in series connections with other plastic containers; such use could result in air embolism from residual air being drawn from primary container before administration of fluid from secondary container is complete.92

Administer by IV infusion over approximately 30 minutes.1 92 95

IM Injection

For IM injection, reconstitute vial containing 500 mg or 1 g of cefepime with 1.3 or 2.4 mL, respectively, of sterile water for injection, 0.9% sodium chloride, 5% dextrose, 0.5 or 1% lidocaine hydrochloride, or bacteriostatic water for injection (with parabens or benzyl alcohol) to provide a solution containing approximately 280 mg/mL.1

Dosage

Available as cefepime hydrochloride; dosage expressed in terms of cefepime, calculated on the anhydrous basis.1 92 95

Pediatric Patients

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours.1 92 95

Neonates ≤28 days of age†: AAP recommends 30 mg/kg every 12 hours; 50 mg/kg every 12 hours may be needed for Pseudomonas infections.64

Children beyond neonatal period: AAP recommends 100 mg/kg daily in 2 equally divided doses for treatment of mild to moderate infections and 100–150 mg/kg daily in 2 or 3 equally divided doses for treatment of severe infections.64

Do not use cefepime available in Duplex containers or the cefepime premixed injection (frozen) in pediatric patients who require less than the entire 1- or 2-g dose in the container.92 95

50 mg/kg every 12 hours for 4–7 days (in conjunction with IV metronidazole) recommended by IDSA.70 Longer treatment duration not associated with improved outcome and not recommended unless adequate source control difficult to achieve.70

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92 95

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92 95

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 7–10 days.1 92 95

150 mg/kg daily given in 3 equally divided doses in conjunction with vancomycin (40 mg/kg IV daily in 2 or 3 equally divided doses), gentamicin (3 mg/kg IV or IM daily in 3 equally divided doses), and rifampin (20 mg/kg orally or IV daily in 3 equally divided doses) recommended by AHA.94 Continue multiple-drug regimen for 6 weeks; discontinue gentamicin after first 2 weeks.94

Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 8 hours for 7 days or until neutropenia resolves.1 92 95

Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92 95

Adults

2 g every 12 hours for 7–10 days; use in conjunction with IV metronidazole.1 92 95

Some clinicians recommend 2 g every 8–12 hours for 4–7 days;70 longer treatment duration not associated with improved outcome and not recommended unless adequate source control difficult to achieve.70

1–2 g every 12 hours for 10 days.1 92 95

1–2 g every 8–12 hours recommended for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or healthcare-associated pneumonia.67 92

2 g every 12 hours for 10 days.1 92 95

0.5–1 g every 12 hours for 7–10 days.1 92 95

2 g every 12 hours for 10 days.1 92 95

6 g daily given in 3 equally divided doses in conjunction with vancomycin (30 mg/kg IV daily given in 2 equally divided doses), gentamicin (3 mg/kg IV or IM daily given in 3 equally divided doses), and rifampin (900 mg orally or IV daily in 3 equally divided doses) recommended by AHA.94 Continue multiple-drug regimen for 6 weeks; discontinue gentamicin after first 2 weeks.94

2 g every 8 hours for 7 days or until neutropenia resolves.1 34 35 36 92 95

Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92 95

Prescribing Limits

Pediatric Patients

Do not exceed recommended adult dosage.1 92 95

Special Populations

Hepatic Impairment

Dosage adjustments not required.1 92

Renal Impairment

Dosage adjustments necessary in patients with Clcr ≤60 mL/minute.1 92 95

Adults with Clcr ≤60 mL/minute (not undergoing hemodialysis): Give an initial dose using usually recommended adult dosage followed by maintenance dosage based on Clcr.1 92 95 (See Table 1 and Table 2.)

Adults undergoing hemodialysis: 1 g on the first day of treatment followed by 500 mg every 24 hours for treatment of infections or 1 g on the first day followed by 1 g every 24 hours for empiric therapy in febrile neutropenic patients.1 92 95 Administer the dose at the same time each day (given at completion of procedure on hemodialysis days).1 92 95

Adults undergoing CAPD: Give usually recommended dose once every 48 hours.1 6 10 12 92 95

Pediatric patients with renal impairment: Dosage adjustments required proportional to those recommended for adults.1 92

Contraindications

• Immediate hypersensitivity to cefepime, other cephalosporins, penicillins, or other β-lactams.1 92 95

• Solutions containing dextrose may be contraindicated in patients with known allergy or hypersensitivity to corn or corn products.92 95

Warnings/Precautions

Warnings

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy.1 92 95 Careful observation of the patient is essential.1 92 Institute appropriate therapy if superinfection occurs.1 92 95

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 92 95 96 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including cefepime, and may range in severity from mild diarrhea to fatal colitis.1 92 95 96 C. difficile produces toxins A and B which contribute to development of CDAD;1 92 95 96 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1 92 95

Consider CDAD if diarrhea develops and manage accordingly.1 92 95 96 Obtain a careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.1 92 95

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 95 96 Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1 92 95 96

Serious adverse events, including life-threatening or fatal encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, coma), myoclonus, and seizures reported rarely.1 85 86 87 88 91 92 95 Nonconvulsive status epilepticus, characterized by alteration of consciousness without convulsions that is associated with continuous epileptiform EEG activity, also reported.85 91 93 95

Most cases of cefepime-associated neurotoxicity occurred in patients with renal impairment who received dosages of the drug inappropriately high for their renal status;1 85 86 87 88 91 92 93 95 some cases occurred in patients who received dosage adjusted for renal function1 92 95 or in patients with normal renal function.87 88 93

Symptoms of neurotoxicity generally were reversible and resolved after cefepime was discontinued and/or after hemodialysis.1 92 93 95

If neurotoxicity associated with cefepime therapy occurs, consider discontinuing the drug or making dosage adjustment appropriate for patient's renal function.1 92 95 (See Renal Impairment under Dosage and Administration.)

In November 2007, FDA announced initiation of a cefepime safety review after a published meta-analysis described a higher risk of all-cause mortality in patients treated with cefepime compared with patients treated with comparator β-lactams.72 73 74

On June 17, 2009, FDA announced that, although the safety review is ongoing, it has determined that cefepime remains an appropriate therapy for its approved indications based on results of FDA’s additional meta-analyses.74 A trial-level meta-analysis indicated that all-cause mortality rates 30 days after treatment were 6.21% for cefepime-treated patients and 6% for comparator-treated patients.74 A patient-level meta-analysis indicated that all-cause mortality rates 30 days after treatment were 5.63% for cefepime-treated patients and 5.68% for comparator-treated patients.74 In addition, in a trial-level meta-analysis of 24 febrile neutropenia trials, there was no statistically significant increase in mortality in cefepime-treated patients compared with comparator-treated patients.74

Sensitivity Reactions

Possible hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.1 92 95

If an allergic reaction occurs, discontinue cefepime and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).1 92 95

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1 92 95

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1 92 Cautious use recommended in individuals hypersensitive to penicillins:1 92 95 avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.a

General Precautions

To reduce development of drug-resistant bacteria and maintain effectiveness of cefepime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1 92 95

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 92 95 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 92 95

Use with caution in patients with a history of GI disease, particularly colitis.1 92 95 (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Commercially available cefepime preparations contain l-arginine to adjust pH.1 92 95

At concentrations 33 times higher than the amount provided by the maximum recommended human cefepime dosage, arginine has altered glucose metabolism and transiently increased serum potassium concentrations.1 92 95 The effect of lower arginine concentrations not known.1 92 95

Like other dextrose-containing solutions, use commercially available Duplex drug delivery system containing cefepime and 5% dextrose injection with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.95

Specific Populations

Category B.1 92 95

Distributed into milk;1 6 92 95 use with caution.1 92 95

Safety and efficacy not established in neonates or infants <2 months of age.1 92 95

Safety and efficacy established for use in pediatric patients 2 months to 16 years of age for treatment of uncomplicated and complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, and pneumonia and for empiric therapy for febrile neutropenic patients.1 92 95 Use of cefepime in this age group supported by evidence from adequate and well-controlled adult studies and additional pharmacokinetic and safety data from pediatric studies.1 92 95

Not recommended for treatment of serious infections suspected or known to be caused by Haemophilus influenzae type b (Hib); manufacturers recommend use of an alternative anti-infective if the possibility of meningeal seeding from a distant infection site or meningitis is suspected or documented.1 92 95 (See Uses: Meningitis and Other CNS Infections.)

Do not use cefepime available in Duplex container or the commercially available cefepime premixed injection (frozen) in pediatric patients unless the entire 1- or 2-g dose in the container is required.92 95

Pharmacokinetic and adverse effect profiles similar to those reported in adults.1 92 95

Safety and efficacy in those ≥65 years of age similar to that in younger adults.1 92 95

Serious adverse effects (including life-threatening or fatal encephalopathy, myoclonus, and seizures) have occurred in geriatric patients who received cefepime dosage inappropriately high for their renal status.1 92 95

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.1 92 95 Select dosage with caution and assess renal function periodically because of age-related decreases in renal function.1 92 95 (See Renal Impairment under Dosage and Administration.)

Pharmacokinetics not affected.1 92

Possible decreased clearance and increased serum half-life.1 6 92 95

Serious adverse events, including life-threatening or fatal encephalopathy, may occur if inappropriately high dosage is used in patients with renal impairment.1 85 86 87 91 92 93 95 (See Neurotoxicity under Cautions.)

Dosage adjustments necessary in patients with Clcr ≤60 mL/minute.1 92 95 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Diarrhea,1 24 33 92 nausea,1 24 33 92 vomiting,1 23 33 92 rash,92 local reactions (e.g., phlebitis, pain, inflammation).1 92

Maxipime for Injection is a sterile white to pale yellow powder of cefepime in single-dose vials or ADD-Vantage vials for reconstitution and it is available in the following strengths:

Hypersensitivity Reactions

Before therapy with Maxipime for Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Maxipime occurs, discontinue the drug and institute appropriate supportive measures.

Neurotoxicity

Serious adverse reactions have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus [see Adverse Reactions (6.2)]. Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment. However, some cases of neurotoxicity occurred in patients receiving a dosage adjustment appropriate for their degree of renal impairment. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis. If neurotoxicity associated with cefepime therapy occurs, discontinue cefepime and institute appropriate supportive measures.

Clostridium difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Maxipime, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Development of Drug-Resistant Bacteria

Prescribing Maxipime in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antimicrobials, prolonged use of Maxipime may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.

Drug/Laboratory Test Interactions

Urinary Glucose

The administration of cefepime may result in a false-positive reaction for glucose in the urine when using some methods (e.g. Clinitest™ tablets) [see Drug Interactions (7.1)].

Coombs' Tests

Positive direct Coombs' tests have been reported during treatment with Maxipime. In patients who develop hemolytic anemia, discontinue the drug and institute appropriate therapy. Positive Coombs' test may be observed in newborns whose mothers have received cephalosporin antibiotics before parturition.

Prothrombin Time

Many cephalosporins, including cefepime, have been associated with a fall in prothrombin activity. 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.

Drug/Laboratory Test Interactions

The administration of cefepime may result in a false-positive reaction for glucose in the urine with certain methods. It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Aminoglycosides

Monitor renal function if aminoglycosides are to be administered with Maxipime because of the increased potential of nephrotoxicity and ototoxicity of aminoglycoside antibacterial drugs.

Diuretics

Nephrotoxicity has been reported following concomitant administration of other cephalosporins with potent diuretics such as furosemide. Monitor renal function when cefepime is concomitantly administered with potent diuretics.

Single-Dose Vial
NDC 0409-0219-11

Maxipime™

Cefepime for Injection, USP

1 gram/vial

Reconstitute before
Intramuscular Use. Dilute before
Intravenous Infusion.

Hospira

Rx only