cefotan

DESCRIPTION
CEFOTAN (cefotetan disodium for injection) and CEFOTAN (cefotetan injection)in Galaxy® plastic container (PL 2040) as cefotetan disodium are sterile,semisynthetic, broad-spectrum, beta-lactamase resistant cephalosporin (cephamycin)antibiotics for parenteral administration cefotan. It is the disodium salt of [6R-(6(alpha),7(alpha))]-7-[[[4-(2-amino-1-carboxy-2-oxoethylidene)-1,3-dithietan-2-yl]carbonyl]amino]-7-methoxy-3-[[(1-methyl-1H -tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo(4,2,0)oct-2-ene-2-carboxylicacid cefotan. Its molecular formula is C 17 H 15 N 7 Na 2 O 8 S 4 with a molecular weightof 619.57 cefotan.

Structural Formula

CEFOTAN (cefotetan disodium for injection) is supplied in vials containing80 mg (3.5 mEq) of sodium per gram of cefotetan activity cefotan. It is a white to paleyellow powder which is very soluble in water cefotan. Reconstituted solutions of CEFOTAN(cefotetan disodium for injection) are intended for intravenous and intramuscularadministration cefotan. The solution varies from colorless to yellow depending on theconcentration cefotan. The pH of freshly reconstituted solutions is usually between4.5 to 6.5 cefotan.

CEFOTAN in the ADD-Vantage Vial † is intended for intravenous use onlyafter dilution with the appropriate volume of ADD-Vantage diluent solution cefotan.

CEFOTAN is available in two vial strengths cefotan. Each CEFOTAN 1 g vial containscefotetan disodium equivalent to 1 g cefotetan activity cefotan. Each CEFOTAN 2 g vialcontains cefotetan disodium equivalent to 2 g cefotetan activity cefotan.

CEFOTAN (cefotetan injection) in the Galaxy® plastic container (PL 2040)is a frozen, iso-osmotic, sterile, nonpyrogenic premixed 50 mL solution containing1 g or 2 g cefotetan as cefotetan disodium cefotan. Dextrose, USP has been added toadjust the osmolality to 300 mOsmol/kg (approximately 1.9 g and 1.1 g to the1 g and 2 g dosages, respectively); sodium bicarbonate has been added to convertcefotetan free acid to the sodium salt cefotan. The pH has been adjusted between 4 and6.5 with sodium bicarbonate and may have been adjusted with hydrochloric acid cefotan. CEFOTAN (cefotetan injection) in the Galaxy® plastic container (PL 2040)contains 80 mg (3.5 mEq) of sodium per gram of cefotetan activity cefotan. After thawingto room temperature, the solution is intended for intravenous use only cefotan.

This Galaxy® container is fabricated from a specially designed multilayerplastic (PL 2040) cefotan. Solutions are in contact with the polyethylene layer of thiscontainer and can leach out certain chemical components of the plastic in verysmall amounts within the expiration dating period cefotan. The suitability of the plastichas been confirmed in tests in animals according to the USP biological testsfor plastic containers as well as by tissue culture toxicity cefotan.

CLINICAL PHARMACOLOGY
High plasma levels of cefotetan are attained after intravenous and intramuscularadministration of single doses to normal volunteers cefotan.

PLASMA CONCENTRATIONS AFTER
1 GRAM IV a OR IM DOSE
Mean Plasma Concentration (µg/mL) Time After Injection
Route 15 min 30 min 1h 2h 4h 8h 12h
IV 92 158 103 72 42 18 9
IM 34 56 71 68 47 20 9
a 30-minute infusion
PLASMA CONCENTRATIONS AFTER
2 GRAM IV a OR IM DOSE
Mean Plasma Concentration (µg/mL)
Time After Injection
Route 5 min 10 min 1h 3h 5h 9h 12h
IV 237 223 135 74 48 22 12 b
IM -- 20 75 91 69 33 19
a Injected over 3 minutes
b Concentrations estimated from regression line

The plasma elimination half-life of cefotetan is 3 to 4.6 hours after eitherintravenous or intramuscular administration cefotan.

Repeated administration of CEFOTAN does not result in accumulation of the drugin normal subjects cefotan.

Cefotetan is 88% plasma protein bound cefotan.

No active metabolites of cefotetan have been detected; however, small amounts(less than 7%) of cefotetan in plasma and urine may be converted to its tautomer,which has antimicrobial activity similar to the parent drug cefotan.

In normal patients, from 51% to 81% of an administered dose of CEFOTAN is excretedunchanged by the kidneys over a 24 hour period, which results in high and prolongedurinary concentrations cefotan. Following intravenous doses of 1 gram and 2 grams, urinaryconcentrations are highest during the first hour and reach concentrations ofapproximately 1700 and 3500 µg/mL respectively cefotan.

In volunteers with reduced renal function, the plasma half-life of cefotetanis prolonged cefotan. The mean terminal half-life increases with declining renal function,from approximately 4 hours in volunteers with normal renal function to about10 hours in those with moderate renal impairment cefotan. There is a linear correlationbetween the systemic clearance of cefotetan and creatinine clearance cefotan. When renalfunction is impaired, a reduced dosing schedule based on creatinine clearancemust be used (see DOSAGE AND ADMINISTRATION ) cefotan.

In pharmacokinetics studies of eight elderly patients (greater than 65 years)with normal renal function and six healthy volunteers (aged 25 to 28 years),mean (± lsd) Total Body Clearance (1.8(0.1) L/h vs cefotan. 1.8 (0.3) L/h) andmean Volume of Distribution (10.4(1.2) L vs 10.3 (1.6)L) were similar followingadministration of a one gram intravenous bolus dose cefotan.

Therapeutic levels of cefotetan are achieved in many body tissues and fluidsincluding:

skin ureter
muscle bladder
fat maxillary sinus mucosa
myometrium tonsil
endometrium bile
cervix peritoneal fluid
ovary umbilical cord serum
kidney amniotic fluid

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