Cefovex

Each vial contains: Cefoxitin (as sodium) 1 g.
White to off-white, somewhat hygroscopic, granules or powder, having a slight characteristic odour. Very soluble in water; slightly soluble in acetone; insoluble in chloroform and in ether; sparingly soluble in dimethylformamide; soluble in methyl alcohol. Cefoxitin is a cephamycin antibacterial that differs structurally from the cephalosporins by the addition of a 7-α-methoxy group to the 7-β-aminocephalosporanic acid nucleus. It is generally classified with the second-generation cephalosporins.

Pharmacology: Pharmacokinetics: Cefoxitin is not absorbed from the gastrointestinal tract; it is given parenterally as the sodium salt. After 1 g by intramuscular injection a peak plasma concentration of up to 30 micrograms/mL at 20 to 30 minutes has been reported whereas concentrations of 125, 72, and 25 micrograms/mL have been achieved after the intravenous administration of 1 g over 3, 30, and 120 minutes respectively. Cefoxitin is about 70% bound to plasma proteins. It has a plasma half-life of 45 to 60 minutes which is prolonged in renal impairment. Cefoxitin is widely distributed in the body but there is normally little penetration into the Cerebrospinal Fluid (CSF), even when the meninges are inflamed. It crosses the placenta and has been detected in breast milk. Relatively high concentrations are achieved in bile.
The majority of a dose is excreted unchanged by the kidneys, up to about 2% being metabolised to descarbamylcefoxitin which is virtually inactive. Cefoxitin is excreted in the urine by glomerular filtration and tubular secretion and about 85% of a dose is recovered within 6 hours; probenecid slows this excretion. After an intramuscular dose of 1 g, peak concentrations in the urine are usually greater than 3 mg/mL. Cefoxitin is removed to some extent by haemodialysis.
Microbiology: Antimicrobial Action: Cefoxitin is a cephamycin antibacterial which, like the other beta lactams, is bactericidal and is considered to act through the inhibition of bacterial cell wall synthesis.
It has a similar spectrum of activity to cefamandole but is more active against anaerobic bacteria, especially Bacteroides fragilis.
Cefoxitin can induce the production of beta-lactamases by some bacteria, and use of cefoxitin with other beta lactams have been shown to be antagonistic in vitro.
Cefoxitin itself is considered to be resistant to a wide range of beta-lactamases, including those produced by Bacteroides spp. However, acquired resistance to cefoxitin has been reported in B. fragilis and has been attributed to beta-lactamase as well as to alterations in penicillin-binding proteins or to outer membrane proteins; there may be cross-resistance to other antibacterials.

Because of the activity of Cefoxitin against Bacteroides fragilis and other anaerobic bacteria, it is used principally in the treatment and prophylaxis of anaerobic and mixed bacterial infections, especially intra-abdominal and pelvic infections. Indications include endometritis (prophylaxis at caesarean section), pelvic inflammatory disease, and surgical infection (prophylaxis). It may also be used in the treatment of gonorrhoea and urinary-tract infections.

Cefoxitin is given as the sodium salt by deep intramuscular injection, by slow intravenous injection over 3 to 5 minutes, or by intermittent or continuous intravenous infusion.
Doses are expressed in terms of the equivalent amount of cefoxitin. 1.05 g of cefoxitin sodium is approximately equivalent to 1 g of cefoxitin.
The usual adult dose: 1 or 2 g every 8 hours although it may be given more frequently (every 4 or 6 hours). In severe infections: up to 12 g daily has been recommended.
Children and neonates: may be given 20 to 40 mg/kg, every 12 hours for neonates up to 1 week old, every 8 hours for those aged 1 to 4 weeks, and every 6 to 8 hours for older infants and children; in severe infections, up to 200 mg/kg daily may be given, to a maximum of 12 g daily.
For the treatment of uncomplicated urinary-tract infections, cefoxitin 1 g twice daily has been given intramuscularly.
For the treatment of uncomplicated gonorrhoea, a single dose of 2 g intramuscularly has been given with probenecid 1 g by mouth.
For surgical infection prophylaxis, the usual adult dose is cefoxitin 2 g intramuscularly or intravenously 30 to 60 minutes prior to the procedure and then every 6 hours, not usually for more than 24 hours. Infants and children undergoing surgical procedures can be given doses of 30 to 40 mg/kg, at the same time intervals as adults; neonates may be given 30 to 40 mg/kg, but at intervals of 8 to 12 hours.
At caesarean section a single 2-g dose may be given intravenously to the mother as soon as the umbilical cord is clamped. If necessary, a 3-dose regimen, with further 2-g doses 4 and 8 hours after the initial dose, may be used.
Dosage in renal impairment: In renal impairment, dosage of cefoxitin should be reduced according to creatinine clearance (CC). In adults, after an initial loading dose of 1 to 2 g, maintenance doses are: CC 30 to 50 mL/minute: 1 to 2 g every 8 to 12 hours.
CC 10 to 29 mL/minute: 1 to 2 g every 12 to 24 hours.
CC 5 to 9 mL/minute: 500 mg to 1 g every 12 to 24 hours.
CC below 5 mL/minute: 500 mg to 1 g every 24 to 48 hours.
In patients undergoing haemodialysis, the loading dose should be repeated after each dialysis session.

Cefoxitin is contraindicated to patients with known hypersensitivity to cephalosporins.

Effect on the Gastrointestinal Tract: Marked changes in anaerobic, facultative, and aerobic faecal flora have been noted with cefoxitin.

Use in Lactation: Cefoxitin is distributed into breast milk but is detectable only in low concentrations. In a study in which cefoxitin was given prophylactically in doses of 2 to 4 g to 18 women undergoing caesarean section, only one sample of breast milk contained measurable concentrations of cefoxitin, 19 hours after the last dose. No adverse effects have been observed in breast-fed infants whose mothers were receiving cefoxitin, and the American Academy of Pediatrics considers that it is therefore usually compatible with breast feeding.

The most common are hypersensitivity reactions, including skin rashes, urticaria, eosinophilia, fever, reactions resembling serum sickness, and anaphylaxis.
There may be a positive response to the Coombs' test although haemolytic anaemia rarely occurs. Neutropenia and thrombocytopenia have occasionally been reported. Agranulocytosis has been associated rarely with some cephalosporins. Bleeding complications related to hypoprothrombinaemia and/or platelet dysfunction have occurred especially with cephalosporins and cephamycins having an N-methylthiotetrazole side-chain, including cefamandole, cefbuperazone, cefmenoxime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotetan, cefpiramide, and latamoxef. The presence of a methylthiadiazolethiol side-chain, as in cefazolin, or an N-methylthiotriazine ring, as in ceftriaxone, might also be associated with such bleeding disorders.
Cefoxitin may interfere with the Jaffe method of measuring creatinine concentrations to reduce falsely high values; this should be borne in mind when measuring renal function.

Probenecid reduces the renal clearance of cefoxitin.

Directions for Reconstitution: For intravenous use: Add 10 mL of Sterile Water for Injections to the 1 g vial. Shake to dissolve and then withdraw entire contents of the vial into a syringe.
For direct intravenous injection: Cefoxitin sodium may be slowly injected into the vein over a period of 3 to 5 minutes.
Alternatively, an intermittent intravenous infusion of cefoxitin sodium may be employed when large amounts of fluid are to be given. However, during infusion of the solution containing cefoxitin sodium, it may be advisable temporarily to discontinue administration of any other infusion solution at the same site (by using an appropriate IV infusion set).
Should be used immediately after reconstitution.
Discard remaining portion after use.

Store at temperatures not exceeding 30°C. Protect from light.

Cephalosporins

J01DC01 - cefoxitin ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.

Rx