Generic Name: CEFUROXIME SODIUM
Brand Name: Cefuroxime sodium
- Substance Name(s):
- CEFUROXIME SODIUM
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 FOR INJECTION OCCURS, DISCONTINUE THE DRUG.
SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.
Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefuroxime for Injection, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C.
difficile 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 Clostridioides difficile .
Other causes of colitis should also be considered.
Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.
Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.
Cefuroxime is a sterile semisynthetic, broad-spectrum, cephalosporin antibiotic for parenteral administration.
It is the sodium salt of (6R,7R)-3-[(carbamoyloxy)methyl]-7-[[(Z)-(furan-2-yl) (methoxyimino)acetyl] amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, and it has the following chemical structure: The empirical formula is C 16 H 15 N 4 NaO 8 S, representing a molecular weight of 446.37.
Cefuroxime for Injection, USP contains approximately 54.2 mg (2.4 mEq) of sodium per gram of cefuroxime activity.
Cefuroxime for Injection, USP in sterile crystalline form is supplied in vials equivalent to 750 mg or 1.5 g of cefuroxime as cefuroxime sodium.
Solutions of Cefuroxime for Injection, USP 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.
Cefuroxime for Injection, USP is supplied as follows: NDC Cefuroxime for Injection, USP Package Factor 25021-118-10 750 mg equivalent of cefuroxime 25 vials per carton in a Single-Dose Vial 25021-119-20 1.5 grams equivalent of cefuroxime 25 vials per carton in a Single-Dose Vial Cefuroxime for Injection, USP is a dry, white to off-white powder.
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.
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 ).
MECHANISM OF ACTION
Mechanism of Action Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis.
Cefuroxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
INDICATIONS AND USAGE
Cefuroxime for Injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases: 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 .
Urinary Tract Infections caused by Escherichia coli and Klebsiella spp.
Skin and Skin-Structure Infections caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes , Escherichia coli, Klebsiella spp., and Enterobacter spp.
Septicemia caused by Staphylococcus aureus (penicillinase- and non-penicillinase- producing strains), Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp.
Meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Neisseria meningitidis , and Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains).
Gonorrhea: Uncomplicated and disseminated gonococcal infections due to Neisseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains) in both males and females.
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, USP 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, USP 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, USP and other antibacterial drugs, Cefuroxime for Injection, USP 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 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.
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.
Pregnancy Teratogenic Effects 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/m 2 ) and rabbits at doses up to 400 mg/kg/day (2.1 times the recommended maximum human dose based on mg/m 2 ) 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.
Nursing Mothers Since cefuroxime is excreted in human milk, caution should be exercised when Cefuroxime for Injection is administered to a nursing woman.
INFORMATION FOR PATIENTS
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.
DOSAGE AND ADMINISTRATION
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 for Injection.
A course of oral antibiotics was administered when appropriate following the completion of parenteral administration of Cefuroxime for Injection.
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.
The recommended dosage for uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a single dose at 2 different sites together with 1 gram of oral probenecid.
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 or intramuscularly 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 ).
Dosage of Cefuroxime for Injection in Adults with Reduced Renal Function a Since Cefuroxime for Injection is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.
Creatinine Clearance (mL/min) Dose Frequency > 20 750 mg to 1.5 grams q8h 10 to 20 750 mg q12h < 10 750 mg q24h a When only serum creatinine is available, the following formula 1 (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 antibiotic therapy in general, administration of Cefuroxime for Injection 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.
Equation 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 antibiotics was administered to pediatric patients following the completion of parenteral administration of Cefuroxime for Injection.
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.
Preparation of Solution and Suspension The directions for preparing Cefuroxime for Injection for both IV and IM use are summarized in Table 3 .
For Intramuscular Use Each 750-mg vial of Cefuroxime for Injection should be constituted with 3 mL of Sterile Water for Injection.
Shake gently to disperse and withdraw completely the resulting suspension for injection.
For Intravenous Use Each 750-mg vial should be constituted with 8.3 mL of Sterile Water for Injection.
Withdraw completely the resulting solution for injection.
Each 1.5-gram vial should be constituted with 16 mL of Sterile Water for Injection, and the solution should be completely withdrawn for injection.
Preparation of Solution and Suspension a Note: Cefuroxime for Injection is a suspension at IM concentrations.
Strength Amount of Diluent to be Added (mL) Volume to be Withdrawn Approximate Cefuroxime Concentration (mg/mL) 750-mg Vial 3 (IM) Total a 225 750-mg Vial 8.3 (IV) Total 90 1.5-gram Vial 16 (IV) Total 90 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.
Intravenous Administration The IV 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 IV 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 IV solutions.
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 for Injection, it is advisable to temporarily discontinue administration of any other solutions at the same site.
For continuous IV infusion , a solution of Cefuroxime for Injection may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.
Solutions of Cefuroxime for Injection, 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 for Injection and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.