Mefoxin (Cefoxitin)

MEFOXIN®

MSD

Cefoxitin Sodium

Antibiotic

Action And Clinical Pharmacology: In vitro studies demonstrate that the bactericidal action of cefoxitin, a cephamycin derived from cephamycin C, results from the inhibition of bacterial cell wall synthesis. Evidence suggests that the methoxy group in the 7a position is responsible for the resistance of cefoxitin to degradation by bacterial beta-lactamases.

Cefoxitin is poorly absorbed orally in humans.

Cefoxitin, administered parenterally, produces high serum and urine concentrations. It is excreted virtually unchanged (up to 6% is excreted as the deacylated metabolite) as active cefoxitin by the kidneys, and has a mean terminal serum half-life of approximately 1 hour in adults. The mean terminal serum half-life in neonates 0 to 7 days of age is 5.6±0.5 hours, in neonates 7 days to 1 month of age 2.5±0.5 hours and in infants 1 to 3 months of age 1.7±0.4 hours. Cefoxitin passes rapidly into the bile. Probenecid slows tubular excretion and increases and prolongs blood levels. Lidocaine had no effect on cefoxitin’s absorption or elimination.

Indications And Clinical Uses: Treatment: The treatment of the following infections when due to susceptible organisms: intra-abdominal infections such as peritonitis and intra-abdominal abscess, gynecological infections such as endometritis and pelvic cellulitis, septicemia, urinary tract infections (including those caused by S. marcescens and Serratia spp.), lower respiratory tract infections, bone and joint infections caused by S. aureus, soft tissue infections such as cellulitis, abscesses and wound infections.

Appropriate culture and susceptibility studies should be performed to determine the susceptibility of the causative organism(s) to cefoxitin. Therapy may be started while awaiting the results of these tests; however, treatment modification may be required once these results become available.

Organisms particularly appropriate for therapy with cefoxitin are: Gram-Positive: staphylococci, penicillinase producing and nonproducing; streptococci excluding enterococci.

Gram-negative (beta-lactamase producing and nonproducing strains): E. coli; Klebsiella species (including K. pneumoniae); Proteus, indole positive and negative; H. influenzae; Providencia species.

Anaerobes: B. fragilis.

Cefoxitin may also be appropriate for the treatment of infections involving susceptible strains of both aerobic and anaerobic bacteria.

Clinical experience has demonstrated that cefoxitin can be administered to patients who are also receiving carbenicillin, gentamicin, tobramycin, or amikacin (see Precautions).

Prophylactic Use: Cefoxitin may be administered perioperatively (preoperatively, intraoperatively and postoperatively) to patients undergoing vaginal or abdominal hysterectomy and abdominal surgery when there is a significant risk of postoperative infection or where the occurrence of postoperative infection is considered to be especially serious.

In patients undergoing cesarean section, intraoperative (after clamping the umbilical cord) and postoperative use of cefoxitin may reduce the incidence of surgery related postoperative infections.

Effective prophylactic use depends on the time of administration. Cefoxitin usually should be given 1/2 to 1 hour before the operation. Prophylactic administration should usually be stopped within 12 hours. It has been generally reported that continuing administration of any antibiotic beyond 24 hours following surgery increases the possibility of adverse reactions but, in the majority of surgical procedures, does not reduce the incidence of subsequent infection.

If signs of postsurgical infection should appear, specimens for culture should be obtained for identification of the causative organism(s) so that appropriate treatment may be instituted.

Contra-Indications: Hypersensitivity to cefoxitin or to the cephalosporin group of antibiotics. tag_WarningWarnings

Manufacturers’ Warnings In Clinical States: Before cefoxitin therapy is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefoxitin, cephalosporins, penicillins or other drugs. Cefoxitin should be given with caution to penicillin-sensitive patients.

There is some clinical and laboratory evidence of partial cross-allergenicity between cephamycins and the other beta-lactam antibiotics, penicillins and cephalosporins. Severe reactions (including anaphylaxis) have been reported with most beta-lactam antibiotics.

Pseudomembranous colitis has been reported with virtually all antibiotics including cefoxitin. This colitis can range from mild to life-threatening in severity. Antibiotics should therefore be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis. It is important to consider a diagnosis of pseudomembranous colitis in patients who develop diarrhea in association with antibiotic use. While studies indicate that a toxin produced by C. difficile is one primary cause of antibiotic-associated colitis, other causes should also be considered.

Any patient who has demonstrated some form of allergy, particularly to drugs, should receive antibiotics including cefoxitin with caution.

If an allergic reaction to cefoxitin occurs, administration of the drug should be discontinued. Serious hypersensitivity reactions may require treatment with epinephrine and other emergency measures.

Precautions: General: Prolonged use of cefoxitin may result in the overgrowth of nonsusceptible organisms. Repeated evaluation of the patient’s condition is essential and if superinfection occurs during therapy, appropriate measures should be taken. Should an organism become resistant during antibiotic therapy, another antibiotic should be substituted.

Children: In children 3 months of age or older, higher doses of cefoxitin (100 mg/kg/day and above) have been associated with an increased incidence of eosinophilia and elevated AST.

Pregnancy: The safety of cefoxitin in the treatment of infections during pregnancy has not been established. If the administration of cefoxitin during pregnancy is considered necessary, its use requires that the anticipated benefits be weighed against possible hazards to the fetus. Reproductive and teratogenic studies performed in mice and rats have revealed no evidence of impaired fertility or harm to the fetus due to cefoxitin.

There are no controlled studies in pregnant women.

Lactation: Cefoxitin is excreted in human milk. Caution should be exercised if use is indicated.

Patients with Special Diseases and Conditions: Renal Insufficiency: The total daily dosage should be reduced when cefoxitin is administered to patients with transient or persistent reduction of urinary output due to renal insufficiency (see Dosage) because high and prolonged serum antibiotic concentrations can occur from usual doses.

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

Laboratory Tests: In patients treated with cefoxitin a false-positive reaction to glucose in the urine may occur with Benedict’s or Fehling’s solutions but not with the use of specific glucose oxidase methods.

Using the Jaffe Method falsely high creatinine values in serum may occur if serum concentrations of cefoxitin exceed 100 g/mL. 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.

Adverse Reactions: Cefoxitin is generally well tolerated. Adverse reactions rarely required cessation of treatment and usually have been mild and transient.

Local: Thrombophlebitis has occurred with i.v. administration. Some degree of pain and tenderness is usually experienced after i.m. injections using water. Induration has occasionally been reported.

Allergic: Rash (including exfoliative dermatitis, and toxic epidermal necrolysis), urticaria, pruritus, eosinophilia, fever and other allergic reactions including anaphylaxis, interstitial nephritis and angioedema have been reported.

Gastrointestinal: Diarrhea, including pseudomembranous colitis can appear during or after antibiotic treatment. Nausea and vomiting have been reported rarely.

Hematologic: Eosinophilia, leukopenia, neutropenia, hemolytic anemia, thrombocytopenia and bone marrow depression have been reported. Some individuals, particularly those with azotemia may develop positive direct Coombs’ tests during therapy with cefoxitin.

Liver Function: Transient elevations in AST, ALT, serum LDH, serum alkaline phosphatase and jaundice have been reported.

Cardiovascular Function: hypotension.

Renal Function: Elevations in serum creatinine and/or BUN have been observed. As with the cephalosporins, acute renal failure has been reported rarely. Cefoxitin’s role in changes in renal function tests is difficult to assess, since factors predisposing to prerenal azotemia or to impaired renal function have often been present.

Musculoskeletal: worsening myasthenia gravis (single case).

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Other than general supportive treatment, no specific antidote is known. Cefoxitin can be eliminated by dialysis in patients with renal insufficiency.

Dosage And Administration: Cefoxitin may be administered i.v. or i.m. as required (see below Reconstitution for each route).

The i.v. 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.

Therapeutic Use: Adults: The usual adult dosage is 1 or 2 g every 6 to 8 hours. Dosage and route of administration should be determined by severity of infection, susceptibility of the causative organisms, and condition of the patient.

Mefoxin Usual Adult Dosage Type of Infection, Daily Dosage, Frequency and Route Uncomplicated forms* of infections such as pneumonia, urinary tract infection, soft tissue infection, 3-4 g, 1 g every 6 to 8 hours i.v. or i.m. Moderately severe or severe infections, 6-8 g, 1 g every 4 hours or 2 g every 6 to 8 hours i.v. Infections commonly needing antibiotics in higher dosage (i.e., gas gangrene), 12 g, 2 g every 4 hours or 3 g every 6 hours i.v. *Including patients in whom bacteremia is absent or unlikely.

Therapy may be started while awaiting the results of susceptibility testing.

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.

Adults with Impaired Renal Function: Cefoxitin may be used in patients with reduced renal function but a reduced dosage should be employed and it is advisable to monitor serum levels in patients with severe impairment.

In adults with renal insufficiency, an initial loading dose of 1 to 2 g should be given.

In severe infections, the total daily dosage in infants and children may be increased to 200 mg/kg, but not to exceed 12 g/day.

Cefoxitin is not recommended for the therapy of meningitis. If meningitis is suspected, an appropriate antibiotic should be used.

At present there are insufficient data to recommend a specific dosage for children with impaired renal function. However, if the administration of cefoxitin is deemed to be essential the dosage should be modified consistent with the recommendations for adults.

Prophylactic Use: Vaginal or Abdominal Hysterectomy, Abdominal Surgery and Cesarean Section: For prophylactic use, a 3-dose regimen of cefoxitin is recommended as follows: Vaginal or Abdominal Hysterectomy and Abdominal Surgery: 2 g i.m. or i.v. just prior to surgery (approximately 1/2 to 1 hour before initial incision). The second and third 2 g doses should be administered at 2- to 6-hour intervals after the initial dose.

Cesarean Section: The first dose of 2 g should be administered i.v. as soon as the umbilical cord has been clamped. The second and third 2 g doses should be given i.v. or i.m. 4 and 8 hours after the first dose.

Administration: Warning for Neonates: Solutions containing preservatives should not be used for injection or for flushing catheters in treating neonates.

Benzyl alcohol as a preservative in bacteriostatic water for injection and bacteriostatic sodium chloride injection has been associated with toxicity in neonates. Data are unavailable on the toxicity of other preservatives in this age group. Therefore, any diluent used with cefoxitin in the treatment of neonates should be free of any preservative.

I.M.: Cefoxitin should be injected into a large muscle mass such as the upper outer quadrant of the buttock (i.e., gluteus maximus); aspiration is necessary to avoid inadvertent injection into a blood vessel.

I.V.: The i.v. route is preferable for patients with severe or life-threatening infections.

Cefoxitin may be administered by i.v. injection either by continuous or intermittent infusion. The reconstituted cefoxitin must be further diluted to desired volume with any of the diluents recommended.

Intermittent I.V. Administration: A solution of cefoxitin in sterile water for injection may be administered slowly over a period of 3 to 5 minutes. Using an infusion system cefoxitin may be given through the tubing by which the patient is receiving other parenteral solutions. However, during infusion of the solution containing cefoxitin, it is advisable to temporarily discontinue administration of any other infusion solution at the same site (by using an appropriate i.v. infusion set). Any unused portion must be discarded.

Continuous I.V. Infusions: A solution of cefoxitin may be added to an i.v. bottle containing an appropriate i.v. infusion fluid in the amount calculated to give the desired antibiotic dose. Butterfly or scalp vein-type needles are preferred for this type of infusion.

Reconstitution: I.M.: Solutions for reconstitution: sterile water for injection or bacteriostatic water for injection (see Warnings for Neonates under Administration) or 0.5% lidocaine HCl injection (without epinephrine).

I.V. Solutions for reconstitution: sterile water for injection or 0.9% Sodium Chloride Injection or 5% and 10% Dextrose Injection. Vials (1 and 2 g): Reconstitute as directed in Table V.

Pharmacy Bulk Vial: The 10 g Pharmacy Bulk Vial contains many single doses for multiple dispensing. The closure shall be penetrated only one time after reconstitution (single puncture). Any unused stock solution remaining after a period of 8 hours should be promptly discarded.

The Pharmacy Bulk Vial is intended for use in hospitals with a recognized I.V. admixture program, and is restricted to the preparation of admixtures for infusion. It is not for direct infusion.

Solutions for I.V. Infusion: 0.9% Sodium Chloride Injection, 5% or 10% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose Injection with 0.2% or 0.45% saline solution, Ringer’s Injection, 5% Dextrose Injection with 0.02% Sodium Bicarbonate Solution, Lactated Ringer’s Injection, 5% Dextrose in Lactated Ringer’s Injection, 5% or 10% Invert Sugar in water, 10% Invert Sugar in saline solution, 5% Sodium Bicarbonate Injection, M/6 Sodium Lactate solution, Normosol-M in D5-W, Ionosol B w/Dextrose 5%, Mannitol 5% and 2.5%, Mannitol 10%.

Mefoxin has also been found compatible when admixed in i.v. infusions with the following: Heparin 0.1 unit/mL (at room temperature 8 hours), Heparin 100 units/mL, Insulin in normal saline, Insulin in 10% invert sugar.

ADD-Vantage Vials: When administering cefoxitin using the ADD-Vantage drug delivery system, cefoxitin sterile powder is added directly to a single-dose flexible plastic ADD-Vantage diluent container.

Solutions for Reconstitution: Use Abbott Laboratories’ ADD-Vantage diluent containers containing 50 or 100 mL of either: 5% Dextrose Injection or 0.9% Sodium Chloride Injection.

Instructions for Use (ADD-Vantage): To Open Diluent Container: Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container (use aseptic technique): see package insert for figures:

1) Remove the protective covers from the top of the vial and the vial port on the diluent container as follows: a) To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening. Pull the ring approximately half way around the cap and then pull straight up to remove the cap. b) To remove the vial port cover, grasp the tab on the pull ring, pull up to break the 3 tie strings, then pull back to remove the cover.

2) Screw the vial into the vial port until it will go no further. The vial must be screwed in tightly to assure a seal. This occurs approximately 1/2 turn (180°) after the first audible click. The clicking sound does not assure a seal; the vial must be turned as far as it will go. Note: Once vial is seated, do not attempt to remove.

3) Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.

4) Label appropriately.

To Prepare Admixture:

1) Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.

2) With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container.

3) Pull the inner cap from the drug vial. Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.

4) Mix container contents thoroughly and use within the specified time.

Preparation for Administration (use aseptic technique):

1) Confirm the activation and admixture of vial contents.

2) Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.

3) Close flow control clamp of administration set.

4) Remove cover from outlet port at bottom of container.

5) Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. Note: See full directions on administration set carton.

6) Lift the free end of the hanger loop on the bottom of the vial, breaking the 2 tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.

7) Squeeze and release drip chamber to establish proper fluid level in chamber.

8) Open flow control clamp and clear air from set. Close clamp.

9) Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.

10) Regulate rate of administration with flow control clamp.

Warning: Do not use flexible containers in series connections.

Stability of Solutions: Store powder below 30°C. The powder and solutions tend to darken, depending on storage conditions; however, product potency is not adversely affected.

Storage: Vials: Reconstituted solution for i.m. injection and i.v. injection should be used within 24 hours if kept at room temperature (15 to 30°C) or 72 hours if stored under refrigeration (2 to 8°C).

The further diluted solutions for i.v. infusion should be used within 12 hours if kept at room temperature (15 to 30°C) or 24 hours if stored under refrigeration (2 to 8°C).

ADD-Vantage Vials: Prepared as directed, ADD-Vantage vials should be used within 12 hours if kept at room temperature or 36 hours if stored under refrigeration (2 to 8°C).

Dark brown solution should not be used.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Incompatibility: Solutions of Mefoxin, 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.

Availability And Storage: ADD-Vantage Vials: Each ADD-Vantage vial of sterile powder contains: cefoxitin 1 or 2 g as sodium salt for i.v. use. Boxes of 10.

Pharmacy Bulk Vials: Each bottle of Pharmacy Bulk solution contains: cefoxitin 10 g as sodium salt for i.v. use. Boxes of 6.

Vials: Each vial of dry white to off-white sterile powder contains: cefoxitin 1 or 2 g as sodium salt for i.m. and i.v. use. Boxes of 10.

Solutions of cefoxitin sodium range from clear to light amber in color. The pH of freshly constituted solutions ranges from 4.2 to 7.0. Each g of cefoxitin sodium contains approximately 2.3 mmol sodium.

MEFOXIN® MSD Cefoxitin Sodium Antibiotic

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