cefepime (Rx)

>10%

Positive Coombs test result without hemolysis (16%)

1-10%

Rash (1-4%)

Elevated alanine aminotransferase (3%)

Hypophosphatemia (3%)

Diarrhea (<3%)

Eosinophilia (2%)

Erythema at injection site (2%)

Normal partial thromboplastin time (PTT) (2%)

Nausea or vomiting (<2%)

Fever (1%)

Headache (1%)

Pain (1%)

Pruritus (1%)

<1%

Agranulocytosis

Anaphylactic shock

Anaphylaxis

Coma

Encephalopathy

Hallucinations

Leukopenia

Myoclonus

Neuromuscular excitability

Neutropenia

Seizures

Thrombocytopenia

Postmarketing Reports

Neurotoxicity: Encephalopathy, aphasia, nonconvulsive status epilepticus

Other: Anaphylaxis (including anaphylactic shock), transient leukopenia

Contraindications

Documented hypersensitivity to cefepime, penicillins, or other beta-lactam antibiotics

Cautions

IM recommended only for mild-to-moderate complicated or uncomplicated UTI due to E coli

Prolonged use may cause superinfection

May increase international normalized ratio (INR) with prolonged treatment, especially in nutritionally deficient patients

Caution warranted with history of previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other drugs

Clostridium difficile-associated diarrhea (CDAD) may occur and should be considered in all patients who present with persistent diarrhea after use

Use with caution in patients with GI disease, particularly colitis

If CrCl <60 mL/min, adjust dosage to compensate for slower renal elimination rate

Neurotoxicity has been reported, including life-threatening or fatal occurrences such as aphasia, encephalopathy, myoclonus, seizures, and nonconvulsive status epilepticus

Nonconvulsive status epilepticus

• Risk of nonconvulsive status epilepticus may be increased if inadequate dosing adjustment is made with renal impairment
• Most cases occurred in patients with renal impairment who did not receive appropriate dosage adjustment; however, some occurred in patients receiving dosage adjustment appropriate for their degree of renal impairment
• Signs and symptoms of nonconvulsive status epilepticus may include altered mental status, confusion, and decreased responsiveness

Pregnancy

There are no cases of drug exposure during pregnancy reported from postmarketing experience or from clinical trials; available data from published 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

Animal data

• Cefepime was not associated with adverse developmental outcomes in rats, mice, or rabbits when administered parenterally during period of organogenesis; the doses used in these studies were 1.6 times (rats), approximately equal to (mice) and 0.3 times (rabbits) the maximum recommended clinical dose

Lactation

Drug is present in human milk at low concentration (0.5 mcg/mL); a nursing infant consuming approximately 1000 mL of human milk per day would receive approximately 0.5 mg of cefepime per day

There is no information regarding effects on milk production or on breastfed infant

Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for cefepime and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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)

IV Incompatibilities

Additive: Aminophylline, ampicillin(?), gentamicin, netilmicin, tobramycin

Y-site: Acyclovir, amphotericin B, amphotericin B cholesteryl sulfate, chlordiazepoxide, chlorpromazine, cimetidine, ciprofloxacin, cisplatin, dacarbazine, daunorubicin, diazepam, diphenhydramine, dobutamine, dopamine, doxorubicin, droperidol, enalaprilat, etoposide, etoposide phosphate, famotidine, filgrastim, floxuridine, ganciclovir, haloperidol, hydroxyzine, idarubicin, ifosfamide, magnesium sulfate, mannitol, mechlorethamine, meperidine, metoclopramide, mitomycin, mitoxantrone, morphine, nalbuphine, ofloxacin, ondansetron, plicamycin, prochlorperazine, promethazine, streptozocin, vancomycin, vinblastine, vincristine

IV Compatibilities

Solution compatible with most common solvents

Additive: Amikacin, clindamycin, heparin, metronidazole(?), potassium chloride, theophylline, vancomycin

Y-site (partial list): Ampicillin-sulbactam, calcium gluconate, carboplatin, dexamethasone sodium phosphate, fluconazole, fluorouracil, metronidazole, milrinone, propofol, sodium bicarbonate, trimethoprim-sulfamethoxazole (TMP-SMX)

IV Preparation

Reconstitute with 50-100 mL of NS, D5W, D10W, LR, D5/LR, or other compatible fluid

Thaw infusion solution at room temperature or in refrigerator, not in water bath or microwave oven

IV Administration

Infuse intermittently over 30 minutes

Do not administer other drugs through Y-site

IM Preparation

Add 2.4 mL of appropriate diluent (SWI, NS, D5W etc) to 1 g vial to yield solution containing approximately 280 mg/mL

IM Administration

Inject deeply

Give IM only in mild-to-moderate UTI due to E coli