Foxitin

Foxitin

cefoxitin

Manufacturer:

Guangzhou

Distributor:

PHARMASIA
Full Prescribing Info
Contents
Cefoxitin sodium.
Description
Each vial contains Cefoxitin (as sodium), USP 1 g.
Cefoxitin for injection is a semi-synthetic, broad-spectrum cepha antibiotic sealed under nitrogen for intravenous administration. It is derived from cephamycin C, which is produced by Streptomyces lactamdurans. Its chemical name is sodium (6R, 7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylate carbamate (ester). The molecular formula is C16H16N3NaO7S2.
Action
Pharmacology: Pharmacodynamics: Following an intravenous dose of 1 gram, serum concentrations were 110 mcg/mL at 5 minutes, declining to less than 1 mcg/mL at 4 hours. The half-life after an intravenous dose is 41 to 59 minutes. Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6 hour period, resulting in high urinary concentrations. Probenecid slows tubular excretion and produces higher serum levels and increases the duration of measurable serum concentrations.
Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile.
In a published study of geriatric patients ranging in age from 64 to 88 years with normal renal function for their age (creatinine clearance ranging from 31.5 to 174 mL/min), the half-life for cefoxitin ranged from 51 to 90 minutes, resulting in higher plasma concentrations than in younger adults. These changes were attributed to decreased renal function associated with the aging process.
Microbiology: The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. Cefoxitin has in vitro activity against a wide range of gram-positive and gram-negative organisms. The methoxy group in the 7α position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.
Cefoxitin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the Indications and Caution for Usage.
Aerobic gram-positive microorganisms: Staphylococcus aureusa (including penicillinase-producing strains); Staphylococcus epidermidisa; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes.
aStaphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin.
Most strains of enterococci, e.g., Enterococcus faecalis, are resistant.
Aerobic gram-negative microorganisms: Escherichia coli; Haemophilus influenzae; Klebsiella spp. (including K. pneumoniae); Morganella morganii; Neisseria gonorrhoeae (including penicillinase-producing strains); Proteus mirabilis; Proteus vulgaris; Providencia spp. (including Providencia rettgeri).
Anaerobic gram-positive microorganisms: Clostridium spp.; Peptococcus niger; Peptostreptococcus spp.
Anaerobic gram-negative microorganisms: Bacteroides distasonis; Bacteroides fragilis; Bacteroides ovatus; Bacteroides thetaiotaomicron; Bacteroides spp.
The following in vitro data are available, but their clinical significance is unknown.
Cefoxitin exhibits in vitro minimum inhibitory concentrations (MICs) of 8 mcg/mL or less for aerobic microorganisms and 16 mcg/mL or less for anaerobic microorganisms against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefoxitin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-negative microorganisms: Eikenella corrodens [non-β-lactamase producers]; Klebsiella oxytoca.
Anaerobic gram-positive microorganisms: Clostridium perfringens;
Anaerobic gram-negative microorganisms: Prevotella bivia (formerly Bacteroides bivius).
Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae.
Indications/Uses
Many infections caused by aerobic and anaerobic gram-negative bacteria resistant to some cephalosporins respond to cefoxitin. Similarly, many infections caused by aerobic and anaerobic bacteria resistant to some penicillin antibiotics (ampicillin, carbenicillin, penicillin G) respond to treatment with cefoxitin. Many infections caused by mixtures of susceptible aerobic and anaerobic bacteria respond to treatment with cefoxitin.
Cefoxitin for injection is indicated for the treatment of serious infections caused by susceptible strains of the designated microorganisms in the diseases listed as follows.
Lower respiratory tract infections, including pneumonia and lung abscess, caused by Streptococcus pneumoniae, other streptococci (excluding enterococci, e.g., Enterococcus faecalis [formerly Streptococcus faecalis]), Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella species, Haemophilus influenzae, and Bacteroides species; Urinary tract infections caused by Escherichia coli, Klebsiella species, Proteus mirabilis, Morganella morganii, Proteus vulgaris and Providencia species (including P. rettgeri); Intra-abdominal infections, including peritonitis and intra-abdominal abscess, caused by Escherichia coli, Klebsiella species, Bacteroides species including Bacteroides fragilis, and Clostridium species; Gynecological infections, including endometritis, pelvic cellulitis, and pelvic inflammatory disease caused by Escherichia coli, Neisseria gonorrhoeae (including penicillinase-producing strains), Bacteroides species including B. fragilis, Clostridium species, Peptococcus niger, Peptostreptococcus species, and Streptococcus agalactiae. Cefoxitin, like cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cefoxitin is used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added; Septicemia caused by Streptococcus pneumoniae, Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella species, and Bacteroides species including B. fragilis; Bone and joint infections caused by Staphylococcus aureus (including penicillinase-producing strains); Skin and skin structure infections caused by Staphylococcus aureus (including penicillinase producing strains), Staphylococcus epidermidis, Streptococcus pyogenes and other streptococci (excluding enterococci e.g., Enterococcus faecalis [formerly Streptococcus faecalis]), Escherichia coli, Proteus mirabilis, Klebsiella species, Bacteroides species including B. fragilis, Clostridium species, Peptococcus niger, and Peptostreptococcus species.
Appropriate culture and susceptibility studies should be performed to determine the susceptibility of the causative organisms to cefoxitin. Therapy may be started while awaiting the results of these studies.
In randomized comparative studies, cefoxitin and cephalothin were comparably safe and effective in the management of infections caused by gram-positive cocci and gram-negative rods susceptible to the cephalosporins. Cefoxitin has a high degree of stability in the presence of bacterial beta-lactamases, both penicillinases and cephalosporinases.
Dosage/Direction for Use
Treatment: Adults: The usual adult dosage range is 1 gram to 2 grams every six to eight hours. 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: (See equation.)

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Females: 0.85 x above value.
In patients undergoing hemodialysis, the loading dose of 1 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 three 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 three 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 previously.
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 Table 1, Table 2, and Table 3.)

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Direction for Reconstitution: Table 3 is provided for convenience in constituting cefoxitin for injection for intravenous administration.
For Vials: One gram should be constituted with at least 10 mL of Sterile Water for Injection, Bacteriostatic Water for Injection, 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection. These primary solutions may be further diluted in 50 to 1000 mL of the diluents listed under the Vials and Bulk Packages 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 three 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.
For intermittent intravenous administration, a solution containing 1 gram or 2 grams in 10 mL of Sterile Water for Injection can be injected over a period of three to five minutes. 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, 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 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 (registered trademark of Abbott Laboratories, Inc.) or scalp vein-type needles are preferred for this type of infusion.
Solutions of cefoxitin, 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 and aminoglycosides may be administered separately to the same patient.
Overdosage
The acute intravenous LD50 in the adult female mouse and rabbit was about 8 g/kg and greater than 1 g/kg, respectively. The acute intraperitoneal LD50 in the adult rat was greater than 10 g/kg.
Prevention: Cefoxitin for injection is indicated for the prophylaxis of infection in patients undergoing uncontaminated gastrointestinal surgery, vaginal hysterectomy, abdominal hysterectomy, or cesarean section.
If there are signs of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate treatment may be instituted.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefoxitin for injection and other antibacterial drugs, cefoxitin 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.
Contraindications
Cefoxitin for injection is contraindicated in patients who have shown hypersensitivity to cefoxitin and the cephalosporin group of antibiotics.
Warnings
Before therapy with Cefoxitin for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to Cefoxitin, Cephalosporins, Penicillins, or other drugs. This product should be given with caution 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 Cefoxitin Injection occurs, discontinue the drug. Serious hypersensitivity reactions may require epinephrine and other emergency measures.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefoxitin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis".
After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
Special Precautions
General: Prescribing cefoxitin 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.
The total daily dose should be reduced when cefoxitin for injection is administered to patients with transient or persistent reduction of urinary output due to renal insufficiency (see DOSAGE & ADMINISTRATION), because high and prolonged serum antibiotic concentrations can occur in such individuals from usual doses.
Antibiotics (including cephalosporins) should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.
As with other antibiotics, prolonged use of cefoxitin may result in overgrowth of nonsusceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Laboratory Tests: As with any potent antibacterial agent, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy.
Drug Interactions: Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics.
Drug/Laboratory Test Interactions: As with cephalothin, high concentrations of cefoxitin (>100 micrograms/mL) may interfere with measurement of serum and urine creatinine levels by the Jaffé reaction, and produce false increases of modest degree in the levels of creatinine reported. Serum samples from patients treated with cefoxitin should not be analyzed for creatinine if withdrawn within 2 hours of drug administration.
High concentrations of cefoxitin in the urine may interfere with measurement of urinary 17-hydroxy-corticosteroids by the Porter-Silber reaction, and produce false increases of modest degree in the levels reported.
A false-positive reaction for glucose in the urine may occur. This has been observed with CLINITEST (registered trademark of Ames Company, Division of Miles Laboratories, Inc.) reagent tablets.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed with cefoxitin to evaluate carcinogenic or mutagenic potential. Studies in rats treated intravenously with 400 mg/kg of cefoxitin (approximately three times the maximum recommended human dose) revealed no effects on fertility or mating ability.
Use in pregnancy: Pregnancy Category B. 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.
Use in lactation: Cefoxitin is excreted in human milk in low concentrations. Caution should be exercised when cefoxitin is administered to a nursing woman.
Use in children: Safety and efficacy in pediatric patients from birth to three months of age have not yet been established. In pediatric patients three months of age and older, higher doses of cefoxitin have been associated with an increased incidence of eosinophilia and elevated SGOT.
Use in elderly: No overall differences in safety or effectiveness were observed between subjects >65 years old and younger subjects in clinical studies. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out (see Pharmacology under Actions).
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 & Administration and Precautions).
Use In Pregnancy & Lactation
Use in pregnancy: Pregnancy Category B. 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.
Use in lactation: Cefoxitin is excreted in human milk in low concentrations. Caution should be exercised when cefoxitin is administered to a nursing woman.
Adverse Reactions
Cefoxitin 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 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, 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 & Administration.) If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
Caution For Usage
Compatibility and Stability: Vials: Cefoxitin for injection, as supplied in vials and constituted to 1 gram/10 mL with Sterile Water for Injection, Bacteriostatic Water for Injection, (see Preparation of Solution), 0.9 percent Sodium Chloride Injection, or 5 percent Dextrose Injection, maintains satisfactory potency for 6 hours at a temperature not exceeding 25°C or for one week under refrigeration (below 5°C).
These primary solutions may be further diluted in 50 to 1000 mL of the following diluents and maintain potency for an additional 18 hours at room temperature or an additional 48 hours under refrigeration:
0.9 percent Sodium Chloride Injection;
5 percent or 10 percent Dextrose Injection;
5 percent Dextrose and 0.9 percent Sodium Chloride Injection;
5 percent Dextrose Injection with 0.2 percent or 0.45 percent Sodium Chloride Injection.
Lactated Ringer's Injection;
5 percent Dextrose in Lactated Ringer's Injection;
5 percent Sodium Bicarbonate Injection;
M/6 sodium lactate solution;
Mannitol 5% and 10%;
After the periods previously mentioned, any unused solutions should be discarded.
Storage
Store at temperatures not exceeding 30°C.
MIMS Class
Cephalosporins
ATC Classification
J01DC01 - cefoxitin ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
Powd for inj (vial) 1 g x 1's.
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