Cefuroxime Sodium

Samson Medical Technologies, L.L.C.

Cefuroxime for Injection, USP

FULL PRESCRIBING INFORMATION: CONTENTS*

• REFERENCES

FULL PRESCRIBING INFORMATION

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefuroxime and other antibacterial drugs, Cefuroxime for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Cefuroxime is a semisynthetic, broad-spectrum, cephalosporin antibiotic for parenteral administration. It is the sodium salt of (6R,7R)-3-carbamoyloxymethyl-7-[Z-2-methoxyimino-2- (fur-2-yl)acetamido]ceph-3-em-4-carboxylate, and it has the following chemical structure:

The empirical formula is C₁₆H₁₅N₄NaO₈S, representing a molecular weight of 446.4.

Cefuroxime for Injection contains approximately 54.2 mg (2.4 mEq) of sodium per gram of cefuroxime activity.

Cefuroxime for Injection in sterile crystalline form is supplied in Pharmacy Bulk Packages equivalent to 75 g or 225 g of cefuroxime as cefuroxime sodium. Solutions of cefuroxime range in color from light yellow to amber, depending on the concentration and diluent used. The pH of freshly constituted solutions usually ranges from 6 to 8.5.

A Pharmacy Bulk Package is a container of a sterile preparation for intravenous use that contains many single doses. The contents are intended for use in a pharmacy admixture service and are restricted to the preparation of admixtures for intravenous infusion. BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 95 mg/mL OR 100 mg/mL AND TRANSFER INTO STERILE SYRINGES.

Following intravenous doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following intravenous administration of 1.5-g doses every 8 hours to normal volunteers. The serum half-life after intravenous injections is approximately 80 minutes.

Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.

Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL respectively during the first 8-hour period.

The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.

Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.

Table 1. Concentrations of Cefuroxime Achieved in Cerebrospinal Fluid During Multiple Dosing of Patients with Meningitis

Cefuroxime is approximately 50% bound to serum protein.

Microbiology: Cefuroxime has in vitro activity against a wide range of gram-positive and gram-negative organisms, and it is highly stable in the presence of beta-lactamases of certain gram-negative bacteria. The bactericidal action of cefuroxime results from inhibition of cell-wall synthesis.

Cefuroxime is usually active against the following organisms in vitro.

Aerobes, Gram-positive: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Streptococcus pyogenes (and other streptococci).

NOTE: Most strains of enterococci, e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to cefuroxime. Methicillin-resistant staphylococci and Listeria monocytogenes are resistant to cefuroxime.

Aerobes, Gram-negative: Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella (Branhamella) catarrhalis (including ampicillin- and cephalothin-resistant strains), Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase- and non-penicillinase-producing strains), Neisseria meningitidis, Proteus mirabilis, Providencia rettgeri (formerly Proteus rettgeri), Salmonella spp., and Shigella spp.

NOTE: Some strains of Morganella morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in vitro tests to be resistant to cefuroxime and other cephalosporins. Pseudomonas and Campylobacter spp., Legionella spp., Acinetobacter calcoaceticus, and most strains of Serratia spp. and Proteus vulgaris are resistant to most first- and second-generation cephalosporins.

Anaerobes: Gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus spp.), gram-positive bacilli (including Clostridium spp.), and gram-negative bacilli (including Bacteroides and Fusobacterium spp.).

NOTE: Clostridium difficile and most strains of Bacteroides fragilis are resistant to cefuroxime.

Susceptibility Tests: Diffusion Techniques: Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such standard procedure¹ that has been recommended for use with disks to test susceptibility of organisms to cefuroxime uses the 30-mcg cefuroxime disk. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for cefuroxime.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels.  A report of "Moderately Susceptible" suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissues and fluids in which high antibiotic levels are attained. A report of "Intermediate" suggests an equivocable or indeterminate result. A report of "Resistant" indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.

      Reports from the laboratory giving results of the standard single-disk susceptibility test for organisms other than Haemophilus spp. and Neisseria gonorrhoeae with a 30-mcg cefuroxime disk should be interpreted according to the following criteria:

Results for Haemophilus spp. should be interpreted according to the following criteria:

Results for Neisseria gonorrhoeae should be interpreted according to the following criteria:

 Organisms should be tested with the cefuroxime disk since cefuroxime has been shown by in vitro tests to be active against certain strains found resistant when other beta-lactam disks are used.  The cefuroxime disk should not be used for testing susceptibility to other cephalosporins.

   Standardized procedures require the use of laboratory control organisms. The 30-mcg cefuroxime disk should give the following zone diameters.

1. Testing for organisms other than Haemophilus spp. and Neisseria gonorrhoeae:

2. Testing for Haemophilus spp.:

3. Testing for Neisseria gonorrhoeae

Dilution Techniques: Use a standardized dilution method¹ (broth, agar, microdilution) or equivalent with cefuroxime powder. The MIC values obtained for bacterial isolates other than Haemophilus spp. and Neisseria gonorrhoeae should be interpreted according to the following criteria:

MIC values obtained for Haemophilus spp. should be interpreted according to the following criteria:

MIC values obtained for Neisseria gonorrhoeae should be interpreted according to the following criteria:

   As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard cefuroxime powder should provide the following MIC values.

1. For organisms other than Haemophilus spp. and Neisseria gonorrhoeae:

2. For Haemophilus spp.:

3. For Neisseria gonorrhoeae:

Cefuroxime for Injection is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:

1. Lower Respiratory Tract Infections, including pneumonia, caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella spp., Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes, and Escherichia coli.

2. Urinary Tract Infections caused by Escherichia coli and Klebsiella spp.

3. Skin and Skin-Structure Infections caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes, Escherichia coli, Klebsiella spp., and Enterobacter spp.

4. Septicemia caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp.

5. Meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Neisseria meningitidis, and Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains).

6. Gonorrhea: Uncomplicated and disseminated gonococcal infections due to Neisseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains) in both males and females.

7. Bone and Joint Infections caused by Staphylococcus aureus (penicillinase- and non- penicillinase-producing strains).

   Clinical microbiological studies in skin and skin-structure infections frequently reveal the growth of susceptible strains of both aerobic and anaerobic organisms. Cefuroxime for Injection has been used successfully in these mixed infections in which several organisms have been isolated. 

   In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, Cefuroxime for Injection may be used concomitantly with an aminoglycoside (see PRECAUTIONS). The recommended doses of both antibiotics may be given depending on the severity of the infection and the patient’s condition.

   To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefuroxime for Injection and other antibacterial drugs, Cefuroxime for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.  In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Prevention: The preoperative prophylactic administration of cefuroxime may prevent the growth of susceptible disease-causing bacteria and thereby may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures (e.g., vaginal hysterectomy) that are classified as clean-contaminated or potentially contaminated procedures. Effective prophylactic use of antibiotics in surgery depends on the time of administration.  Cefuroxime should usually be given one-half to 1 hour before the operation to allow sufficient time to achieve effective antibiotic concentrations in the wound tissues during the procedure. The dose should be repeated intraoperatively if the surgical procedure is lengthy.

   Prophylactic administration is usually not required after the surgical procedure ends and should be stopped within 24 hours. In the majority of surgical procedures, continuing prophylactic administration of any antibiotic does not reduce the incidence of subsequent infections but will increase the possibility of adverse reactions and the development of bacterial resistance.

   The perioperative use of cefuroxime has also been effective during open-heart surgery for surgical patients in whom infections at the operative site would present a serious risk. For these patients it is recommended that therapy with cefuroxime be continued for at least 48 hours after the surgical procedure ends. If an infection is present, specimens for culture should be obtained for the identification of the causative organism, and appropriate antimicrobial therapy should be instituted.

   Cefuroxime for Injection is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

BEFORE THERAPY WITH CEFUROXIME FOR INJECTION IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY  TO DRUGS. IF AN ALLERGIC REACTION TO CEFUROXIME OCCURS, DISCONTINUE THE DRUG.  SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefuroxime, 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. 

   When the colitis is not relieved by drug discontinuation or when it is severe, oral vancomycin is the treatment of choice for antibiotic-associated pseudomembranous colitis produced by Clostridium difficile. Other causes of colitis should also be considered.

 Although cefuroxime rarely produces alterations in kidney function, evaluation of renal status during therapy is recommended, especially in seriously ill patients receiving the maximum doses. Cephalosporins should be given with caution to patients receiving concurrent treatment with potent diuretics as these regimens are suspected of adversely affecting renal function.

   The total daily dose of cefuroxime should be reduced in patients with transient or persistent renal insufficiency (see DOSAGE AND ADMINISTRATION), because high and prolonged serum antibiotic concentrations can occur in such individuals from usual doses.

   As with other antibiotics, prolonged use of cefuroxime may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

   Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

   Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporins.

   As with other therapeutic regimens used in the treatment of meningitis, mild-to-moderate hearing loss has been reported in a few pediatric patients treated with cefuroxime. Persistence of positive CSF (cerebrospinal fluid) cultures at 18 to 36 hours has also been noted with cefuroxime injection, as well as with other antibiotic therapies; however, the clinical relevance of this is unknown.

    Cephalosporins may be 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, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated.

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

Patients should be counseled that antibacterial drugs, including Cefuroxime for Injection, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefuroxime for Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2)  increase the likelihood that bacteria will develop resistance and will not be treatable by cefuroxime or other antibacterial drugs in the future.

   Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic 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 the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

In common with other antibiotics, cefuroxime may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined estrogen/progesterone oral contraceptives.

A false-positive reaction for glucose in the urine may occur with copper reduction tests (Benedict’s or Fehling’s solution or with CLINITEST® tablets) but not with enzyme-based tests for glycosuria. As a false-negative result may occur in the ferricyanide test; it is recommended that either the glucose oxidase or hexokinase method be used to determine blood plasma glucose levels in patients receiving cefuroxime.

   Cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.

Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic activity was found for cefuroxime in the mouse lymphoma assay and a battery of bacterial mutation tests. Positive results were obtained in an in vitro chromosome aberration assay; however, negative results were found in an in vivo micronucleus test at doses up to 10 g/kg. Reproduction studies in mice at doses up to 3,200 mg/kg/day (3.1 times the recommended maximum human dose based on mg/m²) have revealed no impairment of fertility.

  Reproductive studies revealed no impairment of fertility in animals.

Pregnancy Category B. Reproduction studies have been performed in mice at doses up to 6,400 mg/kg/day (6.3 times the recommended maximum human dose based on mg/m²) and rabbits at doses up to 400 mg/kg/day (2.1 times the recommended maximum human dose based on mg/m²) and have revealed no evidence of impaired fertility or harm to the fetus due to cefuroxime. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Since cefuroximeis excreted in human milk, caution should be exercised when cefuroxime is administered to a nursing woman.

Safety and effectiveness in pediatric patients below 3 months of age have not been established. Accumulation of other members of the cephalosporin class in newborn infants (with resulting prolongation of drug half-life) has been reported.

Of the 1,914 subjects who received cefuroxime in 24 clinical studies of cefuroxime, 901 (47%) were 65 and over while 421 (22%) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater susceptibility of some older individuals to drug effects cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION).

Cefuroxime is generally well tolerated. The most common adverse effects have been local reactions following intravenous administration. Other adverse reactions have been encountered only rarely.

Local Reactions: Thrombophlebitis has occurred with intravenous administration in 1 in 60 patients.

Gastrointestinal: Gastrointestinal symptoms occurred in 1 in 150 patients and included diarrhea (1 in 220 patients) and nausea (1 in 440 patients). The onset of pseudomembranous colitis may occur during or after antibacterial treatment (see WARNINGS).

Hypersensitivity Reactions: Hypersensitivity reactions have been reported in fewer than 1% of the patients treated with cefuroxime and include rash (1 in 125). Pruritus, urticaria, and positive Coombs’ test each occurred in fewer than 1 in 250 patients, and, as with other cephalosporins, rare cases of anaphylaxis, drug fever, erythema multiforme, interstitial nephritis, toxic epidermal necrolysis, and Stevens-Johnson syndrome have occurred.

Blood: A decrease in hemoglobin and hematocrit has been observed in 1 in 10 patients and transient eosinophilia in 1 in 14 patients. Less common reactions seen were transient neutropenia (fewer than 1 in 100 patients) and leukopenia (1 in 750 patients). A similar pattern and incidence were seen with other cephalosporins used in controlled studies. As with other cephalosporins, there have been rare reports of thrombocytopenia.

Hepatic: Transient rise in SGOT and SGPT (1 in 25 patients), alkaline phosphatase (1 in 50 patients), LDH (1 in 75 patients), and bilirubin (1 in 500 patients) levels has been noted.

Kidney: Elevations in serum creatinine and/or blood urea nitrogen and a decreased creatinine clearance have been observed, but their relationship to cefuroxime is unknown.

Postmarketing Experience with Cefuroxime for Injection Products: In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with cefuroxime and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation.

   Immune System Disorders : Cutaneous vasculitis  

   Neurologic: Seizure.

   Non-site specific: Angioedema.

Cephalosporin-class Adverse Reactions: In addition to the adverse reactions listed above that have been observed in patients treated with cefuroxime, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibiotics:

   Adverse Reactions: Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage.

   Several cephalosporins, including cefuroxime, have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION). If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

   Altered Laboratory Tests: Prolonged prothrombin time, pancytopenia, agranulocytosis.

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

THIS IS A PHARMACY BULK PACKAGE – NOT FOR DIRECT INJECTION.

BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 95 mg/mL OR 100 mg/mL AND TRANSFER INTO STERILE SYRINGES.

Dosage: Adults: The usual adult dosage range for Cefuroxime for Injection is 750 mg to 1.5 grams every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract infections, skin and skin-structure infections, disseminated gonococcal infections, and uncomplicated pneumonia, a 750-mg dose every 8 hours is recommended. In severe or complicated infections, a 1.5-gram dose every 8 hours is recommended.

   In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In clinical trials, surgical intervention was performed when indicated as an adjunct to therapy with cefuroxime.  A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of cefuroxime.

   In life-threatening infections or infections due to less susceptible organisms, 1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage should not exceed 3 grams every 8 hours.  For preventive use for clean-contaminated or potentially contaminated surgical procedures, a 1.5-gram dose administered intravenously just before surgery (approximately one-half to 1 hour before the initial incision) is recommended. Thereafter, give 750 mg intravenously every 8 hours when the procedure is prolonged.

   For preventive use during open-heart surgery, a 1.5-gram dose administered intravenously at the induction of anesthesia and every 12 hours thereafter for a total of 6 grams is recommended.

Impaired Renal Function : A reduced dosage must be employed when renal function is impaired. Dosage should be determined by the degree of renal impairment and the susceptibility of the causative organism (see Table 2).

Table 2. Dosage of Cefuroxime For Injection in Adults With Reduced Renal Function

­­­­­­­­­­­­­­­­­­­­­­­­­­­­*Since cefuroxime is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.

   When only serum creatinine is available, the following formula² (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

Males: Creatinine clearance (mL/min) = Weight (kg) x (140 - age)
                                                                    72 x serum creatinine (mg/dL)

Females: 0.85 x male value

Note: As with antibiotic therapy in general, administration of cefuroxime should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infection caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Administration of 50 to 100 mg/kg/day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to cefuroxime. The higher dosage of 100 mg/kg/day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

   In bone and joint infections, 150 mg/kg/day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of cefuroxime.

   In cases of bacterial meningitis, a larger dosage of Cefuroxime for Injection is recommended, 200 to 240 mg/kg/day intravenously in divided doses every 6 to 8 hours.

   In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

The directions for preparing cefuroxime for intravenous use are summarized in Table 3. 

AFTER INITIAL ENTRY USE ENTIRE CONTENTS OF THE PHARMACY BULK PACKAGE PROMPTLY; ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS.

As with other cephalosporins, cefuroxime powder as well as solutions tend to darken, depending on storage conditions, without adversely affecting potency.

Note: Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration whenever solution and container permit.  If particulate matter is evident in reconstituted fluids the drug solutions should be discarded.

Table 3. Preparation of Solution For Intravenous Use Only

*Cefuroxime as Cefuroxime Sodium.

Directions for Proper Use of a Pharmacy Bulk Package

Not for direct infusion. The Pharmacy Bulk Package is for use in the hospital pharmacy admixture service only in a suitable work area, such as a laminar flow hood. Using aseptic technique, the container closure may be penetrated only one time using a new suitable sterile dispensing set or transfer device that allows measured dispensing of the contents. Use of a syringe and needle is not recommended as it may cause leakage. The withdrawal of container contents should be accomplished without delay. However, should this not be possible, a maximum time of 4 HOURS from initial port closure entries is permitted to complete fluid transfer operations. This time limit should begin with the introduction of the solvent or diluent into the Pharmacy Bulk Pack.

Instructions for Reconstitution:  Visually examine outer (natural foil) bag for damage.  IF THE SEAL IS BROKEN OR DAMAGE IS OBSERVED, DO NOT OPEN THE OUTER BAG.  STERILITY OF THE INNER BAG SURFACE MAY BE COMPROMISED.  DISCARD BOTH BAGS IMMEDIATELY.  Using aseptic technique, open outer bag at tear notch.  Remove, unfold and lay inner bag flat in a laminar flow hood.  DO NOT USE THE INNER BAG IF PARTICULATE OR FOREIGN MATTER IS PRESENT, IF THE DRY POWDER IS DARK YELLOW OR BROWN, IF THE SEALS ARE NOT INTACT, OR IF THERE IS ANY OTHER DAMAGE TO THE BAG.  IN SUCH CASES, DISCARD THE BAG IMMEDIATELY.  Remove the translucent unthreaded cap from the reconstitution (smaller) port and discard it.  Follow the above “Directions for Proper Use of a Pharmacy Bulk Package” and proceed to reconstitute the powder through the reconstitution (smaller) port, using Sterile Water for Injection.  Mix gently by picking up the bag and gently moving from side to side or by recirculating via a tubing loop until dissolution is complete. Once the powder is completely dissolved, approximately 15 minutes for 75 grams or 25 minutes for 225 grams, hang the bag from the eyelets support. 

If a pump is used, the following general procedure is recommended:

1.         For the reconstitution procedure, assemble a sterile transfer tubing set, an individually packaged sterile spike, a bag of Sterile Water for Injection and the SmartPak^® Pharmacy Bulk Package.  Using aseptic technique

a.     Open the package containing the transfer tubing set.

b.     Attach the individually packaged spike to the unspiked end of the transfer tubing set.

c.     Insert this [removable] spike into the spike port of the bag of Sterile Water for Injection [diluent].

d.     Attach the non removable spike of the same tubing set into the Transfer Port of the SmartPak^® Pharmacy Bulk Package.

2.         Transfer the appropriate amount of Sterile Water for Injection into the SmartPak^® Pharmacy Bulk Package by pressing the reverse button of the pump.

3.         After completing the transfer of the appropriate amount of Sterile Water for Injection, aseptically remove the spike from the bag of Sterile Water for Injection, and disconnect the spike from this end of the tubing set. 

4.         Aseptically replace this spike with a transfer needle, and insert this needle into the Reconstitution Port of the SmartPak^® Pharmacy Bulk Package.

5.         Using the pump, circulate the reconstituted drug through the tubing set and SmartPak^® Pharmacy Bulk Package to thoroughly mix (about 15 minutes for the 75 gram container and 25 minutes for the 225 gram container).

6.         After solution is complete, aseptically remove the transfer needle from the Reconstitution Port of the SmartPak^® Pharmacy Bulk Package, and replace it with a syringe filling adaptor.

7.         Hang the bag from the eyelets support.  Using a pump, aseptically transfer the reconstituted solution from the SmartPak^® Pharmacy Bulk Package, through the tubing set in the Transfer Port, into syringes via the syringe filling adaptor.

It should be noted that the spike placed into the SmartPak^® Pharmacy Bulk Package in Step1.d. is NEVER removed during this procedure and that the Reconstitution Port is self-sealing.   

Solutions should be allowed to stand after dissolution to allow any foaming to dissipate in order to permit visual inspection for completed solubilization.  CAUTION:  TO AVOID POSSIBLE LEAKAGE CAUSED BY THE HEAVY WEIGHT OF THE ADDED WATER, DO NOT SHAKE VIGOROUSLY OR PULL STRONGLY ON THE BAG.

Dispensing Reconstituted Cefuroxime/Instructions for Filling Empty Syringes:  Unscrew the clear threaded cap from the transfer (larger) port and discard it.  Using this transfer port, fill sterile empty syringes, using a new transfer device.  Syringes may be filled using aseptic technique following the usual practice of the individual institution.  Such practices may range from the use of a three-way stop cock to use of a calibrated peristaltic pump.  If reconstituted to 95 mg/mL:  dispense 8 mL for 750 mg or 16 mL for 1.5 grams.  If reconstituted to 100 mg/mL: dispense 7.5 mL for 750 mg or 15 mL for 1.5 grams.  For pediatric dosages, see Pediatric Patients Above 3 Months of Age.

RECONSTITUTION PHASE

1.   Remove translucent reconstitution port cap by pulling

2.   Insert new transfer device for reconstitution

3.   Add appropriate volume of Sterile Water for Injection

4.   Disconnect injection transfer device

5.   See text of Package Insert for further details

MIXING PHASE

1.   Mix gently: either recirculate via a tubing loop or by picking up the bag and gently moving it from side to side until dissolution is completed (15 to 25 minutes) and foam, if any, dissipates

2.   Check for particulate matter, leaks and discoloration (dark yellow or brown)

3.   If any of the above are found, discard bag immediately

4.   If satisfactory, hang bag, using the eyelets

5.   See text of Package Insert for further details

DISPENSING PHASE

1.   Unscrew clear transfer  port cap

2.   Insert new transfer device

3.   Transfer dose into sterile empty syringe

4.   Properly label syringes

5.   See text of Package Insert for further details

BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION TO A CONCENTRATION OF 95 mg/mL OR 100 mg/mL AND TRANSFER INTO STERILE SYRINGES.

Cefuroxime for Injection, USP, SmartPak^® Pharmacy Bulk Packages are for intravenous use only following reconstitution and transfer into syringes.

Intravenous Administration :  The intravenous route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For direct intermittent intravenous administration , slowly inject the solution into a vein over a period of 3 to 5 minutes or give it through the tubing system by which the patient is also receiving other intravenous solutions.

For intermittent intravenous infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other intravenous solutions.  However, during infusion of the solutions containing cefuroxime, it is advisable to temporarily discontinue administration of any other solutions at the same site. 

Solutions of cefuroxime, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.  However, if concurrent therapy with cefuroxime and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Stability of Filled Syringes  

In those situations in which the drug has been reconstituted with water and transferred to empty syringes, but not immediately administered to the patient, the syringes may be stored under the following conditions:

• 24 hours at room temperature
• 7 days under refrigeration, 2º to 8ºC (36º to 46ºF), if immediately refrigerated after transfer.
• 12 weeks at –20° C, if immediately frozen after transfer.  

THAW FROZEN SYRINGES CONTAINING CEFUROXIME AT ROOM TEMPERATURE OR UNDER REFRIGERATION.  DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE IRRADIATION.  IF, AFTER VISUAL INSPECTION, THE SOLUTION IS CLOUDY, CONTAINS PARTICULATE MATTER OR LEAKS ARE DETECTED, DISCARD THE SYRINGE AS STERILITY MAY BE IMPAIRED. DO NOT REFREEZE THAWED SYRINGES. 

Cefuroxime for Injection in the dry state should be stored between 15° to 30°C (59° to 86°F) and protected from light.  [See USP Controlled Room Temperature].   Cefuroxime is a dry, white to yellow powder.

Cefuroxime for Injection, USP, is available in the following SmartPak^® Pharmacy Bulk Packages:

75 gram* (1 Pharmacy Bulk Package), Product No. 2075 NDC 66288-2075-1

225 gram ** (1 Pharmacy Bulk Package), Product No. 2225 NDC 66288-2225-1

* Each 75 gram Pharmacy Bulk Package contains sterile cefuroxime sodium equivalent to 75 grams of cefuroxime

** Each 225 gram Pharmacy Bulk Package contains sterile cefuroxime sodium equivalent to 225 grams of cefuroxime

REFERENCES

1. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing. Third Informational Supplement. NCCLS Document M100-S3, Vol. 11, No. 17. Villanova, Pa: NCCLS; 1991.

2. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron.  1976;16:31-41.

Literature issued January 2010                                                                                                                        C2075c 

Manufactured for

SAMSON
MEDICAL TECHNOLOGIES L.L.C.
Cherry Hill, NJ 08003

by

ACS Dobfar S.p.A.
20067 Tribiano (Milano) Italy