Cefoxitin Drug Information

Dosage should be determined by susceptibility of the causative organisms, severity of infection, and the condition of the patient (see Table 1 for dosage guidelines). If C. trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage should be added, because cefoxitin sodium has no activity against this organism. Cefoxitin FOR INJECTION may be used in patients with reduced renal function with the following dosage adjustments: In adults with renal insufficiency, an initial loading dose of 1 gram to 2 grams may be given.

After a loading dose, the recommendations for maintenance dosage (Table 2) may be used as a guide. When only the serum creatinine level is available, the following formula (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: Weight (kg) x (140-age) 72 x serum creatinine (mg/100 mL) Females: 0.85 x above value In patients undergoing hemodialysis, the loading dose of 1 gram to 2 grams should be given after each hemodialysis, and the maintenance dose should be given as indicated in Table 2. Antibiotic therapy for group A beta-hemolytic streptococcal infections should be maintained for at least 10 days to guard against the risk of rheumatic fever or glomerulonephritis. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients: The recommended dosage in pediatric patients 3 months of age and older is 80 to 160 mg/kg of body weight per day divided into four to six equal doses. The higher dosages should be used for more severe or serious infections. The total daily dosage should not exceed 12 grams.

At this time no recommendation is made for pediatric patients from birth to 3 months of age (see PRECAUTIONS ). In pediatric patients with renal insufficiency, the dosage and frequency of dosage should be modified consistent with the recommendations for adults (see Table 2). Prevention: Effective prophylactic use depends on the time of administration.

Cefoxitin FOR INJECTION usually should be given one-half to one hour before the operation, which is sufficient time to achieve effective levels in the wound during the procedure. Prophylactic administration should usually be stopped within 24 hours since continuing administration of any antibiotic increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection. For prophylactic use in uncontaminated gastrointestinal surgery, vaginal hysterectomy, or abdominal hysterectomy, the following doses are recommended: Adults: 2 grams administered intravenously just prior to surgery (approximately one-half to one hour before the initial incision) followed by 2 grams every 6 hours after the first dose for no more than 24 hours.

Pediatric Patients (3 Months and Older): 30 to 40 mg/kg doses may be given at the times designated above. Cesarean Section Patients: For patients undergoing cesarean section, either a single 2 gram dose administered intravenously as soon as the umbilical cord is clamped OR a 3-dose regimen consisting of 2 grams given intravenously as soon as the umbilical cord is clamped followed by 2 grams 4 and 8 hours after the initial dose is recommended (see CLINICAL STUDIES ). Table 1.

Guidelines for Dosage of Cefoxitin FOR INJECTION Including patients in whom bacteremia is absent or unlikely. Table 2. Maintenance Dosage of Cefoxitin FOR INJECTION in Adults with Reduced Table 3.

Preparation of Solution for Intravenous Administration Shake to dissolve and let stand until clear. Preparation of Solution: Table 3 is provided for convenience in constituting Cefoxitin FOR INJECTION for intravenous administration. These primary solutions may be further diluted in 50 mL to 1000 mL of the diluents listed under the Vials portion of the Compatibility and Stability section.

Benzyl alcohol as a preservative has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than 3 months of age, in whom use of Cefoxitin FOR INJECTION may be indicated, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity. Therefore, diluent containing benzyl alcohol should not be used when Cefoxitin FOR INJECTION is constituted for administration to pediatric patients in this age range.

Administration: Cefoxitin FOR INJECTION may be administered intravenously after constitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Intravenous Administration: The intravenous route is preferable for patients with bacteremia, bacterial septicemia, or other severe or life-threatening infections, or for patients who may be poor risks because of lowered resistance resulting from such debilitating conditions as malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.

Using an infusion system, it may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. However, during infusion of the solution containing Cefoxitin FOR INJECTION, it is advisable to temporarily discontinue administration of any other solutions at the same site. For the administration of higher doses by continuous intravenous infusion, a solution of Cefoxitin FOR INJECTION may be added to an intravenous bottle containing 5 percent Dextrose Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose and 0.9 percent Sodium Chloride Injection.

BUTTERFLY ® or scalp vein-type needles are preferred for this type of infusion. Solutions of Cefoxitin FOR INJECTION, like those of most beta-lactam antibiotics, should not be added to aminoglycoside solutions (e.g., gentamicin sulfate, tobramycin sulfate, amikacin sulfate) because of potential interaction. However, Cefoxitin FOR INJECTION and aminoglycosides may be administered separately to the same patient.

• REACTIONS: CEFOXITIN FOR INJECTION is generally well tolerated. The most common adverse reactions have been local reactions following intravenous injection. Other adverse reactions have been encountered infrequently.
• Local Reactions: Thrombophlebitis has occurred with intravenous administration.
• Allergic Reactions: Rash (including exfoliative dermatitis and toxic epidermal necrolysis), urticaria, flushing, pruritus, eosinophilia, fever, dyspnea, and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been noted.
• Cardiovascular: Hypotension.
• Gastrointestinal: Diarrhea, including documented pseudomembranous colitis which can appear during or after antibiotic treatment. Nausea and vomiting have been reported rarely.
• Neuromuscular: Possible exacerbation of myasthenia gravis. Blood: Eosinophilia, leukopenia including granulocytopenia, neutropenia, anemia, including hemolytic anemia, thrombocytopenia, and bone marrow depression. A positive direct Coombs test may develop in some individuals, especially those with azotemia.
• Liver Function: Transient elevations in SGOT, SGPT, serum LDH, and serum alkaline phosphatase; and jaundice have been reported.
• Renal Function: Elevations in serum creatinine and/or blood urea nitrogen levels have been observed. As with the cephalosporins, acute renal failure has been reported rarely. The role of CEFOXITIN FOR INJECTION in changes in renal function tests is difficult to assess, since factors predisposing to prerenal azotemia or to impaired renal function usually have been present. In addition to the adverse reactions listed above which have been observed in patients treated with CEFOXITIN FOR INJECTION, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics: Urticaria, erythema multiforme, Stevens-Johnson syndrome, serum sickness-like reactions, abdominal pain, colitis, renal dysfunction, toxic nephropathy, false-positive test for urinary glucose, hepatic dysfunction including cholestasis, elevated bilirubin, aplastic anemia, hemorrhage, prolonged prothrombin time, pancytopenia, agranulocytosis, superinfection, vaginitis including vaginal candidiasis. Several cephalosporins 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 occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated. To report SUSPECTED ADVERSE EVENTS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov.

Drug Interactions: Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics.

Pregnancy: Reproduction studies performed in rats and mice at parenteral doses of approximately one to seven and one-half times the maximum recommended human dose did not reveal teratogenic or fetal toxic effects, although a slight decrease in fetal weight was observed. 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.

In the rabbit, cefoxitin was associated with a high incidence of abortion and maternal death. This was not considered to be a teratogenic effect but an expected consequence of the rabbit's unusual sensitivity to antibiotic-induced changes in the population of the microflora of the intestine.

Pediatric Use: Safety and efficacy in pediatric patients from birth to 3 months of age have not yet been established. In pediatric patients 3 months of age and older, higher doses of CEFOXITIN FOR INJECTION have been associated with an increased incidence of eosinophilia and elevated SGOT.

CONTRAINDICATIONS: Cefoxitin FOR INJECTION is contraindicated in patients who have shown hypersensitivity to cefoxitin and the cephalosporin group of antibiotics.

OVERDOSAGE: The acute intravenous LD 50 in the adult female mouse and rabbit was about 8 g/kg and greater than 1 g/kg, respectively. The acute intraperitoneal LD 50 in the adult rat was greater than 10 g/kg.