Dosing and uses of Maxipime (cefepime)
Adult dosage forms and strengths
infusion solution
- 1g/50mL
- 2g/100mL
powder for injection
- 1g
- 2g
Pneumonia
Treatment of moderate-to-severe pneumonia
1-2 g IV q8-12hr for 7-10 days (if not caused by Pseudomonas) or for up to 21 days (if caused by Pseudomonas)
Febrile Neutropenia
Empiric therapy in febrile neutropenic patients
2 g IV q8hr for 7 days or until neutropenia resolves
Urinary Tract Infections
Treatment of uncomplicated and complicated urinary tract infections (UTIs), including pyelonephritis
0.5-1 g IV or IM q12hr for 7-10 days
Severe UTIs due to Escherichia coli or Klebsiella pneumoniae: 2 g IV q12hr for 10 days
Skin/Skin Structure Infections
Treatment of uncomplicated skin and skin structure infections
2 g IV q12hr for 10 days
Intra-abdominal Infections
Treatment of complicated intra-abdominal infections; use in combination with metronidazole
2 g IV q12hr for 7-10 days
Dosing Modifications
Adjust recommended maintenance dosages according to CrCL
Recommended maintenance dosage 500 mg q12hr
- CrCl >60 mL/min: 500 mg q12hr
- CrCl 30-60 mL/min: 500 mg q24hr
- CrCl 11-29 mL/min: 500 q24hr
- CrCl <11 mL/min: 250 q24hr
- Continuous ambulatory peritoneal dialysis (CAPD): 500 mg q48hr
- Hemodialysis: 1 g on day 1, then 500-1000 mg q24hr thereafter (on hemodialysis days, administer after hemodialysis)
Recommended maintenance dosage 1 g q12hr
- CrCl >60 mL/min: 1 g q12hr
- CrCl 30-60 mL/min: 1 g q24hr
- CrCl 11-29 mL/min: 500 mg q24hr
- CrCl <11 mL/min: 250 mg q24hr
- CAPD: 1 g q48hr
- Hemodialysis: 1 g on day 1, then 500 mg q24hr thereafter (on hemodialysis days, administer after hemodialysis)
Recommended maintenance dosage 2 g q12hr
- CrCl >60 mL/min: 2 g q12hr
- CrCl 30-60 mL/min: 2 g q24hr
- CrCl 11-29 mL/min: 1 g q24hr
- CrCl <11 mL/min: 500 mg q24hr
- CAPD: 2 g q48hr
- Hemodialysis: 1 g on day 1, then 500 mg q24hr thereafter (on hemodialysis days, administer after hemodialysis)
Recommended maintenance dosage 2 g q8hr
- CrCl >60 mL/min: 2 g q8hr
- CrCl 30-60 mL/min: 2 g q12hr
- CrCl 11-29 mL/min: 2 g q24hr
- CrCl <11 mL/min: 1 g q24hr
- CAPD: 2 g q48hr
- Hemodialysis: 1 g q24hr (on hemodialysis days, administer after hemodialysis)
Dosing Considerations
Susceptible organisms
- Bacteroides spp, Enterobacter spp, Escherichia coli, Haemophilus influenzae, Klebsiella spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus aureus, Streptococcus pyogenes
Pediatric dosage forms and strengths
infusion solution
- 1g/50mL
- 2g/100mL
powder for injection
- 1g
- 2g
Febrile Neutropenia
Empiric therapy in febrile neutropenic patients
>2 months, <40 kg: 50 mg/kg IV q8hr for 7 days or until neutropenia resolves; not to exceed 2 g q8hr
Pneumonia
Treatment of moderate-to-severe pneumonia
50 mg/kg IV q12hr for 10 days; not to exceed 2 g q12hr
Skin/Skin Structure Infections
Treatment of uncomplicated skin and skin structure infections
50 mg/kg IV q12hr for 10 days; not to exceed 2 g q12hr
Urinary Tract Infections
Treatment of uncomplicated and complicated UTIs, including pyelonephritis
50 mg/kg IV/IM q12hr for 7-10 days; not to exceed 2 g q12hr
Maxipime (cefepime) adverse (side) effects
>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
Warnings
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 and lactation
Pregnancy category: B
Lactation: Drug enters breast milk; use with caution
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.
Pharmacology of Maxipime (cefepime)
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)
Administration
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
