Cefepime: Difference between revisions
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If [[CDAD]] is suspected or confirmed, ongoing antibiotic 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. | If [[CDAD]] is suspected or confirmed, ongoing antibiotic 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. | ||
|clinicalTrials=Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. | |||
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 these 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued study drug because of 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 2.0%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses. The following adverse events were thought to be probably related to cefepime during evaluation of the drug in clinical trials conducted in North America (n=3125 cefepime-treated patients). | |||
[[file:Cefepime Adverse Effects1.png|none|450px]] | |||
At the higher dose of 2 g every 8 hours, the incidence of probably-related adverse events was higher among the 795 patients who received this dose of cefepime. They consisted of [[rash]] (4%), [[diarrhea]] (3%), [[nausea]] (2%), [[vomiting]] (1%), [[pruritus]] (1%), [[fever]] (1%), and [[headache]] (1%). The following adverse laboratory changes, irrespective of relationship to therapy with Cefepime, were seen during clinical trials conducted in North America. | |||
[[file:Cefepime Adverse Effects2.png|none|450px]] | |||
A similar safety profile was seen in clinical trials of pediatric patients. | |||
|postmarketing=In addition to the events reported during North American clinical trials with cefepime, the following adverse experiences have been reported during worldwide postmarketing experience. | |||
As with some other drugs in this class, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures have been reported. 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. (See also WARNINGS.) 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 or other conditions that may compromise renal function to reduce antibiotic concentrations that can lead or contribute to these and other serious adverse events, including renal failure. As with other cephalosporins, anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia have been reported. | |||
======Cephalosporin-Class Adverse Reactions====== | |||
In addition to the adverse reactions listed above that have been observed in patients treated with cefepime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis, and pancytopenia. | |||
|administration======For Intravenous Infusion===== | |administration======For Intravenous Infusion===== | ||
Constitute the 500 mg, 1 g, or 2 g vial, and add an appropriate quantity of the resulting solution to an intravenous container with one of the compatible intravenous fluids listed in the compatibility and stability subsection. The resulting solution should be administered over approximately 30 minutes. | Constitute the 500 mg, 1 g, or 2 g vial, and add an appropriate quantity of the resulting solution to an intravenous container with one of the compatible intravenous fluids listed in the compatibility and stability subsection. The resulting solution should be administered over approximately 30 minutes. | ||
Revision as of 21:18, 13 January 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
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Overview
Cefepime is a antibiotic (cephalosporin) that is FDA approved for the treatment of pneumonia, febrile neutropenia, uncomplicated UTI, uncomplicated skin infection and complicated intraabdominal infections. Common adverse reactions include rash, hypophosphatemia, diarrhea, Direct Coombs test positive, ALT/SGPT level raised, AST/SGOT level raised.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cefepime in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cefepime in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Same dosification as exposed in the table on FDA - Adult Indications and Dosage.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cefepime in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cefepime in pediatric patients.
Contraindications
Cefepime for injection is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibiotics, penicillins or other beta-lactam antibiotics.
Warnings
Before therapy with cefepime 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 drugs. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to cefepime for injection occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures including oxygen, corticosteroids, intravenous fluids, intravenous antihistamines, pressor amines, and airway management, as clinically indicated.
In patients with creatinine clearance less than or equal to 60 mL/min, the dose of cefepime for injection (cefepime hydrochloride) should be adjusted to compensate for the slower rate of renal elimination. Because high and prolonged serum antibiotic concentrations can occur from usual dosages in patients with renal impairment or other conditions that may compromise renal function, the maintenance dosage should be reduced when cefepime is administered to such patients. Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms. During postmarketing surveillance, serious adverse events have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures. Most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules. However, some cases of encephalopathy occurred in patients receiving a dosage adjustment for their renal function. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefepime for injection, 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 antibiotic 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 antibiotic 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.
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
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 these 64 patients who discontinued therapy did so because of rash. The percentage of cefepime-treated patients who discontinued study drug because of 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 2.0%, respectively). However, the incidence of discontinuation due to rash increased with the higher recommended doses. The following adverse events were thought to be probably related to cefepime during evaluation of the drug in clinical trials conducted in North America (n=3125 cefepime-treated patients).
At the higher dose of 2 g every 8 hours, the incidence of probably-related adverse events was higher among the 795 patients who received this dose of cefepime. They consisted of rash (4%), diarrhea (3%), nausea (2%), vomiting (1%), pruritus (1%), fever (1%), and headache (1%). The following adverse laboratory changes, irrespective of relationship to therapy with Cefepime, were seen during clinical trials conducted in North America.
A similar safety profile was seen in clinical trials of pediatric patients.
Postmarketing Experience
In addition to the events reported during North American clinical trials with cefepime, the following adverse experiences have been reported during worldwide postmarketing experience.
As with some other drugs in this class, encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures have been reported. 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. (See also WARNINGS.) 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 or other conditions that may compromise renal function to reduce antibiotic concentrations that can lead or contribute to these and other serious adverse events, including renal failure. As with other cephalosporins, anaphylaxis including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia have been reported.
Cephalosporin-Class Adverse Reactions
In addition to the adverse reactions listed above that have been observed in patients treated with cefepime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis, and pancytopenia.
Drug Interactions
There is limited information regarding Cefepime Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Cefepime in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cefepime in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Cefepime during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Cefepime in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Cefepime in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Cefepime in geriatric settings.
Gender
There is no FDA guidance on the use of Cefepime with respect to specific gender populations.
Race
There is no FDA guidance on the use of Cefepime with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Cefepime in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Cefepime in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Cefepime in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Cefepime in patients who are immunocompromised.
Administration and Monitoring
Administration
For Intravenous Infusion
Constitute the 500 mg, 1 g, or 2 g vial, and add an appropriate quantity of the resulting solution to an intravenous container with one of the compatible intravenous fluids listed in the compatibility and stability subsection. The resulting solution should be administered over approximately 30 minutes. Intermittent intravenous infusion with a Y-type administration set can be accomplished with compatible solutions. However, during infusion of a solution containing cefepime, it is desirable to discontinue the other solution.
Intramuscular Administration
For intramuscular administration, cefepime for injection (cefepime hydrochloride) should be constituted with one of the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride, 5% Dextrose Injection, 0.5% or 1.0% Lidocaine Hydrochloride, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol.
Monitoring
There is limited information regarding Cefepime Monitoring in the drug label.
IV Compatibility
Cefepime for injection is compatible at concentrations between 1 mg/mL and 40 mg/mL with the following intravenous infusion fluids: 0.9% Sodium Chloride Injection, 5% and 10% Dextrose Injection, M/6 Sodium Lactate Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringers and 5% Dextrose Injection, Normosol-R™, and Normosol-M™ in 5% Dextrose Injection. These solutions may be stored up to 24 hours at controlled room temperature 20° to 25° C (68° to 77° F) or 7 days in a refrigerator 2° to 8° C (36° to 46° F).
Cefepime for injection admixture compatibility information is summarized in the following table: none|450px
Solutions of cefepime for injection, like those of most beta-lactam antibiotics, should not be added to solutions of ampicillin at a concentration greater than 40 mg/mL, and should not be added to metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate or aminophylline because of potential interaction. However, if concurrent therapy with cefepime for injection is indicated, each of these antibiotics can be administered separately.
IM Administration
Cefepime for injection (cefepime hydrochloride) constituted as directed is stable for 24 hours at controlled room temperature 20° to 25° C (68° to 77° F) or for 7 days in a refrigerator 2° to 8° C (36° to 46° F) with the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol, or 0.5% or 1% Lidocaine Hydrochloride.
Overdosage
There is limited information regarding Cefepime overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Cefepime Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Cefepime Mechanism of Action in the drug label.
Structure
There is limited information regarding Cefepime Structure in the drug label.
Pharmacodynamics
There is limited information regarding Cefepime Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Cefepime Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Cefepime Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Cefepime Clinical Studies in the drug label.
How Supplied
There is limited information regarding Cefepime How Supplied in the drug label.
Storage
There is limited information regarding Cefepime Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Cefepime |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Cefepime |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Cefepime Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Cefepime interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Cefepime Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Cefepime Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [4]
Overview
Cefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents. Cefepime hydrochloride was first marketed in 1994 and is currently marketed under various trade names including Maxipime (Elan Pharma), Maxcef, Cepimax, Cepimex, and Axepim.
Category
Cephalosporin, Fourth-Generation
US Brand Names
MAXIPIME®
FDA Package Insert
Description | Clinical Pharmacology | Microbiology | Indications and Usage | Contraindications | Warnings | Precautions | Adverse Reactions | Overdosage | Clinical Studies | Dosage and Administration | Compatibility, Reconstitution, and Stability | Directions For Use | How Supplied | Labels and Packages