Generic Name: Cefepime Hydrochloride
Class: Fourth Generation Cephalosporins
Chemical Name: [6R - (6α,7β(Z)]] - 1 - [[7 - [[(2 - amino - 4 - thiazolyl)(methoxyimino)acetyl]amino] - 2 - carboxy - 8 - oxo - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - en - 3 - yl]methyl] -1-methylpyrrolidinium chloride monohydrochloride monohydrate
Molecular Formula: C19H25ClN6O5S2•HCl•H 2O
CAS Number: 123171-59-5
Introduction
Antibacterial; β-lactam antibiotic; fourth generation cephalosporin.1 2 6
Uses for Maxipime
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
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
Treatment of moderate to severe pneumonia caused by susceptible P. aeruginosa, K. pneumoniae, or Enterobacter.1 5 8 14 15 92
Treatment of community-acquired pneumonia (CAP)40 43 caused by S. pneumoniae, Haemophilus influenzae†, Moraxella catarrhalis†, and Staphylococcus aureus†.43 ATS and IDSA recommend use of 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 68 69 For empiric therapy 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 68 69
Skin and Skin Structure Infections
Treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible [methicillin-susceptible] strains only) or susceptible S. pyogenes (group A β-hemolytic streptococci).1 3 5 6 7 8 14 17 92
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
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
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 69 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 is 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 that can be used 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 consists of an antipseudomonal cephalosporin (cefepime or ceftazidime) or carbapenem (imipenem or meropenem) given with or without an aminoglycoside (amikacin, gentamicin, tobramycin).69 75 76 Treatment should be guided by results of in vitro susceptibility tests.75
IDSA also recommends a regimen of cefepime and vancomycin as one of several regimens 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, gram-stained smears of appropriate clinical specimens, immune status of the patient, and current patterns of bacterial resistance within the hospital and local community.69 Some clinicians suggest that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) are good choices for treatment of gram-negative sepsis.69
For initial treatment of life-threatening sepsis in adults, some clinicians suggest that a third or fourth generation cephalosporin (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime), fixed combination of piperacillin and tazobactam, or a carbapenem (imipenem or meropenem) be used in conjunction with vancomycin with or without an aminoglycoside (amikacin, gentamicin, tobramycin).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 an aminoglycoside in more seriously ill patients.69 Manufacturers caution that safety and efficacy data are 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, or severe or prolonged neutropenia).1
Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the 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 is advised.26 32 38
Maxipime Dosage and Administration
Administration
Administer by IV infusion or deep IM injection.1 2 3 5 6 12 14 92
IM route should be used only for treatment of mild to moderate, uncomplicated or complicated UTIs caused by E. coli when this route is considered more appropriate.1 2 5
IV Infusion
If a Y-type administration set is used, discontinue other solution flowing through the tubing during cefepime infusion.1 2 92
Manufacturers recommend that aminoglycosides, ampicillin (>40 mg/mL), metronidazole, vancomycin, or aminophylline be administered separately from cefepime.1 2 92 (See Drug Compatibility under Compatibility.)
Reconstitution and Dilution
Reconstitute vials for IV infusion with 0.9% sodium chloride, 5 or 10% dextrose, (1/6) M sodium lactate, 5% dextrose and 0.9% sodium chloride, lactated Ringer’s and 5% dextrose injection, Normosol-R, or Normosol-M in 5% dextrose injection.1
Reconstitute vials containing 500 mg, 1 g, or 2 g of cefepime with 5, 10, or 10 mL of one of these IV solutions, respectively, to provide solutions containing approximately 100, 100, or 160 mg/mL, respectively, and then dilute the appropriate dose in a compatible IV solution.1
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
Thaw the 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 The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.92
Rate of Administration
Administer by IV infusion over approximately 30 minutes.1 92
IM Injection
Reconstitution
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 2
Dosage
Available as cefepime hydrochloride; dosage expressed in terms of cefepime, calculated on the anhydrous basis.1 92
Pediatric Patients
General Pediatric Dosage
IV or IM
Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours.1 92
AAP recommends 100–150 mg/kg daily in 3 divided doses for treatment of mild to moderate infections and 150 mg/kg daily in 3 divided doses for treatment of severe infections in children >1 month of age.64
Respiratory Tract Infections
Pneumonia
IV
Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92
Skin and Skin Structure Infections
Uncomplicated Infections
IV
Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 10 days.1 92
Urinary Tract Infections (UTIs)
Uncomplicated or Complicated UTIs
IV or IM
Children 2 months to 16 years of age weighing <40 kg: 50 mg/kg every 12 hours for 7–10 days.1 92
Empiric Therapy in Febrile Neutropenic Patients
IV
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
Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92
Adults
Intra-abdominal Infections
Complicated Infections
IV
2 g every 12 hours for 7–10 days; use in conjunction with IV metronidazole.1 92
Respiratory Tract Infections
Moderate to Severe Pneumonia
IV
1–2 g every 12 hours for 10 days.1 92
1–2 g every 8–12 hours recommended for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or healthcare-associated pneumonia.67 92
Skin and Skin Structure Infections
Moderate to Severe Uncomplicated Infections
IV
2 g every 12 hours for 10 days.1 92
Urinary Tract Infections (UTIs)
Mild to Moderate Uncomplicated or Complicated UTIs
IV or IM
0.5–1 g every 12 hours for 7–10 days.1 92
Severe Uncomplicated or Complicated UTIs
IV
2 g every 12 hours for 10 days.1 92
Empiric Therapy in Febrile Neutropenic Patients
IV
2 g every 8 hours for 7 days or until neutropenia resolves.1 34 35 36 92
Frequently reevaluate need for continued anti-infective therapy if fever resolves but neutropenia remains for >7 days.1 92
Prescribing Limits
Pediatric Patients
Dosage should not exceed recommended adult dosage.1 92
Special Populations
Hepatic Impairment
Dosage adjustments not required.1 92
Renal Impairment
Dosage adjustments necessary in patients with Clcr ≤60 mL/minute.1 92
Adults with Clcr ≤60 mL/minute: Give an initial loading dose using the usually recommended adult dosage followed by maintenance dosage based on Clcr.1 92 (See Table 1 and Table 2.)
Table 1. Maintenance Dosage for Treatment of Infections in Adults with Renal Impairment192
Clcr (mL/minute)
|
Initial dose: 500 mg
|
Initial dose: 1 g
|
Initial dose: 2 g
|
|---|
30–60
|
500 mg every 24 h
|
1 g every 24 h
|
2 g every 24 h
|
11–29
|
500 mg every 24 h
|
500 mg every 24 h
|
1 g every 24 h
|
<11
|
250 mg every 24 h
|
250 mg every 24 h
|
500 mg every 24 h
|
Table 2. Maintenance Dosage for Empiric Therapy in Febrile Neutropenic Adults with Renal Impairment192
Clcr (mL/minute)
|
Initial Dose: 2 g
|
|---|
30–60
|
2 g every 12 h
|
11–29
|
2 g every 24 h
|
<11
|
1 g every 24 h
|
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 Administer the dose at the same time each day (given at completion of procedure on hemodialysis days).1 92
Adults undergoing CAPD: Give usually recommended dose once every 48 hours.1 2 6 10 12 92
Pediatric patients with renal impairment: Dosage adjustments required similar to those recommended for adults.1 92
Cautions for Maxipime
Contraindications
Immediate hypersensitivity to cefepime, other cephalosporins, penicillins, or other β-lactams.1 92
Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.92
Warnings/Precautions
Warnings
Superinfection/Clostridium difficile-associated Diarrhea and Colitis
Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy.1 92 Careful observation of the patient is essential.1 92 Institute appropriate therapy if superinfection occurs.1 92
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 92 C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including cefepime, and may range in severity from mild diarrhea to fatal colitis.1 92 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
Consider CDAD if diarrhea develops and manage accordingly.1 92 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1 92
If CDAD is suspected or confirmed may need to discontinue anti-infective therapy not directed against C. difficile.1 Some mild cases may respond to discontinuance alone.1 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.1 92
Neurotoxicity
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 92 91 Nonconvulsive status epilepticus, characterized by alteration of consciousness without convulsions that is associated with continuous epileptiform EEG activity, also reported.85 91
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 some cases occurred in patients who received dosage adjusted for renal function1 92 or in patients with normal renal function.87 88
Symptoms of neurotoxicity generally were reversible and resolved after cefepime was discontinued and/or after hemodialysis.1 92
If seizures occur, discontinue the drug.1 92 Use anticonvulsant therapy if clinically indicated.1 92
Increased Mortality
In November 2007, FDA announced that a safety review of cefepime was initiated 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 The published meta-analysis looked at all-cause mortality data from 57 randomized controlled trials that compared cefepime with other β-lactams for various indications.71 FDA began working with Bristol-Myers Squibb to further evaluate the findings presented in the published meta-analysis and additional safety data.72 73
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 FDA performed meta-analyses based on both trial- and patient-level data derived from all available cefepime comparative clinical trials.74 Results of the 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 FDA's 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 A review of deaths reported in 7 of these febrile neutropenia trials indicated that most patients appeared to have died from their underlying malignancies and/or comorbid conditions.74
As part of the continuing cefepime safety review, FDA and Bristol-Myers Squibb are in the process of using hospital drug utilization data to conduct additional separate analyses of cefepime-associated mortality.74 Results from these studies are unlikely to be available until at least summer 2010.74
Sensitivity Reactions
Hypersensitivity 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 a
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
Cross-hypersensitivity
Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.1 92 a
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 a 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
Selection and Use of Anti-infectives
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
When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 92 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 92
History of GI Disease
Use with caution in patients with a history of GI disease, particularly colitis.1 92 (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)
Arginine Content
Commercially available cefepime preparations contain l-arginine to adjust pH.1 92
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 The effect of lower arginine concentrations not known.1 92
Specific Populations
Pregnancy
Category B.1 92
Lactation
Distributed into milk;1 6 92 use with caution.1 92
Pediatric Use
Safety and efficacy not established in neonates or infants <2 months of age.1 92
Safety and efficacy have been 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 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
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 (See Uses: Meningitis and Other CNS Infections.)
The commercially available premixed injection (frozen) containing 1 or 2 g of cefepime should not be used in pediatric patients unless the entire 1- or 2-g dose is required.92
Pharmacokinetic and adverse effect profiles similar to those reported in adults.1 92
Geriatric Use
Safety and efficacy in those ≥65 years of age similar to that in younger adults.1 92
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
Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.1 92 Select dosage with caution and assess renal function periodically because of age-related decreases in renal function.1 92 (See Renal Impairment under Dosage and Administration.)
Hepatic Impairment
Pharmacokinetics not affected.1 92
Renal Impairment
Possible decreased clearance and increased serum half-life.1 6 92
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 (See Neurotoxicity under Cautions.)
Dosage adjustments necessary in patients with Clcr ≤60 mL/minute.1 2 92 (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
Interactions for Maxipime
Specific Drugs and Laboratory Tests
Drug or Test
|
Interaction
|
Comments
|
|---|
Aminoglycosides
|
Possible increased risk of nephrotoxicity and ototoxicity1 92
|
Closely monitor renal function if used concomitantly1 92
|
Tests for glucose
|
Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 92 a
|
Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1 92 a
|
Maxipime Pharmacokinetics
Absorption
Bioavailability
Not appreciably absorbed from GI tract; must be administered parenterally.1
Almost completely absorbed following IM administration;1 44 peak serum concentrations attained within 1.4–1.6 hours.1
Distribution
Extent
Widely distributed into tissues and fluids, including blister fluid,1 39 48 bronchial mucosa,1 sputum,1 bile,1 27 peritoneal fluid,1 27 appendix,1 gallbladder,1 27 and prostate.1
Distributed into CSF following IV administration in adults or pediatric patients.1 5 46 78 81 82 84 92
Distributed into milk.1 6
Plasma Protein Binding
20%.1
Elimination
Metabolism
Partially metabolized in vivo to N-methylpyrrolidine (NMP), which is rapidly converted to the N-oxide (NMP-N-oxide).1
Elimination Route
Eliminated principally unchanged in urine by glomerular filtration.1 47 49
In adults with normal renal function, 80–82% of a single dose excreted unchanged in urine;1 42 47 49 < 1% of the dose eliminated as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of the drug.1
Half-life
Adults with normal renal function: 2–2.3 hours.1 3 39 49
Children 2 months to 16 years of age: 1.5-1.9 hours.44
Neonates <2 months of age: 4.9 hours.80
Special Populations
Pharmacokinetics not affected by hepatic impairment.1
Patients with renal impairment: Clearance decreased and plasma half-life prolonged.1 42 Half-life averages 4.9, 10.5, 13.5 hours in those with Clcr 31–60, 11–30, or <10 mL/minute, respectively.42
Stability
Storage
Parenteral
Powder for Injection or Infusion
2–25° C; protect from light.1
Powder and reconstituted solutions may darken; does not indicate loss of potency.1
Reconstituted IV solutions containing 1–40 mg/mL are stable for 24 hours at 20–25°C or 7 days at 2–8°C.1
IV solutions in ADD-Vantage vials are stable for 24 hours at 20–25°C or 7 days at 2–8°C at concentrations of 10–40 mg/mL in 0.9% sodium chloride or 5% dextrose injection.1
Reconstituted IM solutions containing 280 mg/mL are stable for 24 hours at 20–25°C or 7 days at 2–8°C.1 2
Injection (Frozen) for IV Infusion
-20°C or lower.92 Thawed solutions are stable for 24 hours at room temperature (25°C) or 7 days under refrigeration (5°C).92
Do not refreeze after thawing.92
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution Compatibility
Compatible
|
|---|
Amino acids 4.25%, dextrose 25% with electrolytesHID
|
Dextrose 5% in Ringer’s injection, lactated1 HID
|
Dextrose 5% in sodium chloride 0.9%1 HID
|
Dextrose 5 or 10% in water1 HID
|
Normosol M in dextrose 5%1 HID
|
Normosol R1 HID
|
Normosol R in dextrose 5%
|
Sodium chloride 0.9%1 HID
|
Drug Compatibility
Admixture CompatibilityHID
Compatible
|
|---|
Amikacin sulfate
|
Clindamycin phosphate
|
Heparin sodium
|
Potassium chloride
|
Theophylline
|
Vancomycin HCl
|
Incompatible
|
|---|
Aminophylline
|
Gentamicin sulfate
|
Tobramycin sulfate
|
Variable
|
|---|
Ampicillin sodium
|
Metronidazole
|
Metronidazole HCl
|
Y-Site CompatibilityHID
Compatible
|
|---|
Amikacin sulfate
|
Ampicillin sodium–sulbactam sodium
|
Anidulafungin
|
Aztreonam
|
Bivalirudin
|
Bleomycin sulfate
|
Bumetanide
|
Buprenorphine HCl
|
Butorphanol tartrate
|
Calcium gluconate
|
Carboplatin
|
Carmustine
|
Co-trimoxazole
|
Cyclophosphamide
|
Cytarabine
|
Dactinomycin
|
Dexamethasone sodium phosphate
|
Dexmedetomidine HCl
|
Docetaxel
|
Doxorubicin HCl liposome injection
|
Fenoldopam mesylate
|
Fluconazole
|
Fludarabine phosphate
|
Fluorouracil
|
Furosemide
|
Gentamicin sulfate
|
Granisetron HCl
|
Hetastarch in lactated electrolyte injection (Hextend)
|
Hydrocortisone sodium phosphate
|
Hydrocortisone sodium succinate
|
Hydromorphone HCl
|
Imipenem–cilastatin sodium
|
Leucovorin calcium
|
Lorazepam
|
Melphalan
|
Mesna
|
Methotrexate sodium
|
Methylprednisolone sodium succinate
|
Metronidazole
|
Milrinone lactate
|
Paclitaxel
|
Piperacillin sodium–tazobactam sodium
|
Ranitidine HCl
|
Remifentanil HCI
|
Sargramostim
|
Sodium bicarbonate
|
Sufentanil citrate
|
Thiotepa
|
Ticarcillin disodium–clavulanate potassium
|
Tobramycin sulfate
|
Valproate sodium
|
Zidovudine
|
Incompatible
|
|---|
Acetylcysteine
|
Acyclovir sodium
|
Amphotericin B
|
Amphotericin B cholesteryl sulfate complex
|
Chlordiazepoxide HCl
|
Chlorpromazine HCl
|
Cimetidine HCl
|
Ciprofloxacin
|
Cisplatin
|
Dacarbazine
|
Daunorubicin HCl
|
Diazepam
|
Diphenhydramine HCl
|
Doxorubicin HCl
|
Droperidol
|
Enalaprilat
|
Erythromycin lactobionate
|
Etoposide
|
Etoposide phosphate
|
Famotidine
|
Filgrastim
|
Floxuridine
|
Gallium nitrate
|
Ganciclovir sodium
|
Haloperidol lactate
|
Hydroxyzine HCl
|
Idarubicin HCl
|
Ifosfamide
|
Lansoprazole
|
Magnesium sulfate
|
Mannitol
|
Mechlorethamine HCl
|
Meperidine HCl
|
Metoclopramide HCl
|
Midazolam HCI
|
Mitomycin
|
Mitoxantrone HCl
|
Nalbuphine HCl
|
Nicardipine HCI
|
Ofloxacin
|
Ondansetron HCl
|
Phenytoin sodium
|
Plicamycin
|
Prochlorperazine edisylate
|
Promethazine HCl
|
Streptozocin
|
Theophylline
|
Vinblastine sulfate
|
Vincr |
