Microbiology

Prevention:

The preoperative prophylactic administration of Cefuroxime for Injection USP and Dextrose Injection USP 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 antibacterials in surgery depends on the time of administration. Cefuroxime for Injection USP and Dextrose Injection USP should usually be given one-half to 1 hour before the operation to allow sufficient time to achieve effective antibacterial 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 antibacterial 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 for Injection USP and Dextrose Injection USP 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 cefuroxime therapy 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.

General

Although Cefuroxime for Injection USP and Dextrose Injection USP 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 antibacterial concentrations can occur in such individuals from usual doses.

As with other antibacterials, 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 antibacterials should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibacterials 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 antibacterial 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.

As with other dextrose-containing solutions, Cefuroxime for Injection USP and Dextrose Injection USP should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

Prescribing Cefuroxime for Injection USP and Dextrose Injection USP 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.

Information for Patients

Diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs including Cefuroxime for Injection USP and Dextrose Injection USP should only be used to treat bacterial infections. They do not treat viral infections ( e.g., the common cold). When Cefuroxime for Injection USP and Dextrose Injection USP 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 for Injection USP and Dextrose Injection USP or other antibacterial drugs in the future.

Drug/Laboratory Test Interactions

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Nursing Mothers

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

Pediatric Use

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.

Cefuroxime for Injection USP and Dextrose Injection USP in the DUPLEX® Container is designed to deliver a 750 mg or 1.5 g dose of cefuroxime. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the full adult dose of cefuroxime.

Geriatric Use

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).

Local Reactions:

Thrombophlebitis has occurred with IV 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:

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:

Angioedema, acute myocardial ischemia with or without myocardial infarction may occur as part of an allergic reaction.

Neurologic System Disorders:

Seizure.

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 antibacterials:

Adverse Reactions:

Vomiting, abdominal pain, colitis, vaginitis including vaginal candidiasis, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, and 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.

Dosage:

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).

When only serum creatinine is available, the following formula1 (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.

Note: As with antibacterial therapy in general, administration of Cefuroxime for Injection USP and Dextrose Injection USP 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 infections 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.

Pediatric Patients Above 3 Months of Age:

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 antibacterials was administered to pediatric patients following the completion of parenteral administration of cefuroxime.

In cases of bacterial meningitis, a larger dosage of cefuroxime 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.

Cefuroxime for Injection USP and Dextrose for Injection USP in the DUPLEX® Container is designed to deliver a 750 mg or 1.5 g dose of cefuroxime. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the full adult dose.

For intermittent IV infusion with a Y-type administration set, dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution 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 antibacterials, should not be added to solutions of aminoglycoside antibacterials because of potential interaction.

However, if concurrent therapy with cefuroxime and an aminoglycoside is indicated, each of these antibacterials can be administered separately to the same patient.

Use sterile equipment.

Caution: Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

DUPLEX® Container Directions for Use

• To avoid inadvertent activation, DUPLEX® Container should remain in the folded position until activation is intended.

Patient Labeling and Drug Powder/Diluent Inspection

• Apply patient-specific label on foil side of container. USE CARE to avoid activation. Do not cover any portion of foil strip with patient label.
• Unlatch side tab and unfold DUPLEX® Container. (See Diagram 1.)

• Visually inspect diluent chamber for particulate matter.
• Use only if container and seals are intact.
• To inspect the drug powder for foreign matter or discoloration, peel foil strip from drug chamber. (See Diagram 2.)

• Protect from light after removal of foil strip.
  
  

  Note: If foil strip is removed, product must be used within 7 days, but not beyond the labeled expiration date.

  
  
• The product should be re-folded and the side tab latched until ready to activate.

Reconstitution (Activation)

• Do not use directly after storage by refrigeration, allow the product to equilibrate to room temperature before patient use.
• Unfold the DUPLEX® Container and point the set port in a downward direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the diluent meniscus trapping all air above the fold. To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber. (See Diagram 3.)

• Agitate the liquid-powder mixture until the drug powder is completely dissolved.

  Note: Following reconstitution (activation), product must be used within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.

Administration

• Visually inspect the reconstituted solution for particulate matter.
• Point the set port in a downwards direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the solution meniscus trapping all air above the fold. Squeeze the folded DUPLEX® Container until the seal between reconstituted drug solution and set port opens, releasing liquid to set port. (See Diagram 4.)

• Prior to attaching the IV set, check for minute leaks by squeezing container firmly. If leaks are found, discard container and solution as sterility may be impaired.
• Using aseptic technique, peel foil cover from the set port and attach sterile administration set. (See Diagram 5.)

• Refer to Directions for Use accompanying the administration set.

Precautions

• As with other cephalosporins, reconstituted Cefuroxime for Injection USP and Dextrose Injection USP tends to darken depending on storage conditions, within the stated recommendations. However, product potency is not adversely affected.
• Use only if prepared solution is clear and free from particulate matter.
• Do not use in series connection.
• Do not introduce additives into the DUPLEX® Container.
• Do not freeze.

Store the unactivated unit at 20–25°C (68–77°F). Excursions permitted to 15–30°C (59–86°F).