Label: CEFUROXIME SODIUM injection, powder, for solution

Microbiology

Prevention

The preoperative prophylactic administration of Cefuroxime for 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 antibiotics in surgery depends on the time of administration. Cefuroxime for Injection, USP 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 for 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 therapy with Cefuroxime for Injection, USP 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 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 for Injection 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 for Injection 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.

Information for Patients

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 for Injection 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.

Drug Interactions

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.

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 for Injection.

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 for Injection 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.

Geriatric Use

Of the 1,914 subjects who received cefuroxime in 24 clinical studies of Cefuroxime for Injection, 901 (47%) were 65 years and older while 421 (22%) were 75 years and older. 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 for Injection 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

In addition to the adverse events reported during clinical trials, the following events have been observed during clinical practice in patients treated with Cefuroxime for Injection 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 for Injection, 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.

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dosage

Preparation of Solution and Suspension

The directions for preparing Cefuroxime for Injection for both IV and IM use are summarized in Table 3.

Administration

After constitution, Cefuroxime for Injection may be given intravenously or by deep IM injection into a large muscle mass (such as the gluteus or lateral part of the thigh). Before injecting intramuscularly, aspiration is necessary to avoid inadvertent injection into a blood vessel.

Intramuscular

When constituted as directed with Sterile Water for Injection, suspensions of cefuroxime for IM injection maintain satisfactory potency for 24 hours at room temperature and for 48 hours under refrigeration (5°C).

After the periods mentioned above any unused suspensions should be discarded.

Intravenous

When the 750 mg and 1.5 g vials are constituted as directed with Sterile Water for Injection, the solutions Cefuroxime for Injection for IV administration maintain satisfactory potency for 24 hours at room temperature and for 48 hours (750 mg and 1.5 g vials) under refrigeration (5°C). More dilute solutions, such as 750 mg or 1.5 g plus 100 mL of Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection, also maintain satisfactory potency for 24 hours at room temperature and for 7 days under refrigeration.

These solutions may be further diluted to concentrations of between 1 and 30 mg/mL in the following solutions and will lose not more than 10% activity for 24 hours at room temperature or for at least 7 days under refrigeration: 0.9% Sodium Chloride Injection; 1/6 M Sodium Lactate Injection; Ringer's Injection, USP; Lactated Ringer's Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 10% Dextrose Injection; and 10% Invert Sugar in Water for Injection.

Unused solutions should be discarded after the time periods mentioned above.

Cefuroxime for Injection has also been found compatible for 24 hours at room temperature when admixed in IV infusion with heparin (10 and 50 U/mL) in 0.9% Sodium Chloride Injection and Potassium Chloride (10 and 40 mEq/L) in 0.9% Sodium Chloride Injection. Sodium Bicarbonate Injection, USP is not recommended for the dilution of Cefuroxime for Injection.

Frozen Stability

Constitute the 750 mg or 1.5 g vial as directed for IV administration in Table 5. Immediately withdraw the total contents of the 750 mg or 1.5 g vial and add to a compatible container containing 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection and freeze. Frozen solutions are stable for 6 months when stored at -20°C. Frozen solutions should be thawed at room temperature and not refrozen. Do not force thaw by immersion in water baths or by microwave irradiation. Thawed solutions may be stored for up to 24 hours at room temperature or for 7 days in a refrigerator.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

As with other cephalosporins, Cefuroxime for Injection powder as well as solutions and suspensions tend to darken, depending on storage conditions, without adversely affecting product potency.

Storage Conditions

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

Sterile, Nonpyrogenic, Preservative-free.
The container closure is not made with natural rubber latex.