Cefotan (Cefotetan Disodium) - Indications and Dosage

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CEFOTAN and other antibacterial drugs, CEFOTAN 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 antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Treatment

CEFOTAN is indicated for the therapeutic treatment of the following infections when caused by susceptible strains of the designated organisms:

Urinary Tract Infections caused by E. coli, Klebsiella spp (including K. pneumoniae), Proteus mirabilis and Proteus spp (which may include the organisms now called Proteus vulgaris, Providencia rettgeri, and Morganella morganii).

Lower Respiratory Tract Infections caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella species (including K. pneumoniae), E. coli, Proteus mirabilis, and Serratia marcescens *.

Skin and Skin Structure Infections due to Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus species (excluding enterococci), Escherichia coli, Klebsiella pneumoniae, Peptococcus niger *, Peptostreptococcus species.

Gynecologic Infections caused by Staphylococcus aureus, (including penicillinase- and nonpenicillinase-producing strains), Staphylococcus epidermidis, Streptococcus species (excluding enterococci), Streptococcus agalactiae, E. coli, Proteus mirabilis, Neisseria gonorrhoeae, Bacteroides species (excluding B. distasonis, B. ovatus, B. thetaiotaomicron), Fusobacterium species*, and gram-positive anaerobic cocci (including Peptococcus niger and Peptostreptococcus species).

Cefotetan, like other cephalosporins, has no activity against

Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of pelvic inflammatory disease, and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

Intra-abdominal Infections caused by E. coli, Klebsiella species (including K. pneumoniae), Streptococcus species (excluding enterococci), Bacteroides species (excluding B. distasonis, B. ovatus, B. thetaiotaomicron) and Clostridium species*.

Bone and Joint Infections caused by Staphylococcus aureus.*

*Efficacy for this organism in this organ system was studied in fewer than ten infections.

Specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to cefotetan. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.

In cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, it is possible to use CEFOTAN concomitantly with an aminoglycoside. Cefotetan combinations with aminoglycosides have been shown to be synergistic in vitro against many Enterobacteriaceae and also some other gram-negative bacteria. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient's condition.

NOTE: Increases in serum creatinine have occurred when CEFOTAN was given alone. If CEFOTAN and an aminoglycoside are used concomitantly, renal function should be carefully monitored, because nephrotoxicity may be potentiated.

Prophylaxis

The preoperative administration of CEFOTAN may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures that are classified as clean contaminated or potentially contaminated (eg, cesarean section, abdominal or vaginal hysterectomy, transurethral surgery, biliary tract surgery, and gastrointestinal surgery).

If there are signs and symptoms of infection, specimens for culture should be obtained for identification of the causative organism so that appropriate therapeutic measures may be initiated.

DOSAGE AND ADMINISTRATION

Treatment

Cefotetan injection in Galaxy ^® plastic container should not be used for intramuscular administration.

CEFOTAN in the ADD-Vantage Vial is intended for intravenous infusion only, after dilution with the appropriate volume of ADD-Vantage diluent solution.

The usual adult dosage is 1 or 2 grams of CEFOTAN (cefotetan disodium for injection) administered intravenously or intramuscularly or CEFOTAN (cefotetan injection) in the Galaxy^® plastic container (PL 2040) administered intravenously every 12 hours for 5 to 10 days. Proper dosage and route of administration should be determined by the condition of the patient, severity of the infection, and susceptibility of the causative organism.

General Guidelines for Dosage of CEFOTAN

Type of Infection	Daily Dose	Frequency and Route
Urinary Tract	1-4 grams	500 mg every 12 hours IV or IM 1 or 2 g every 24 hours IV or IM 1 or 2 g every 12 hours IV or IM
Skin & Skin Structure Mild - Moderate 1	2 grams	2 g every 24 hours IV 1 g every 12 hours IV or IM
Severe	4 grams	2 g every 12 hours IV
Other Sites	2 - 4 grams	1 or 2 g every 12 hours IV or IM
Severe	4 grams	2 g every 12 hours IV
Life-Threatening	6 grams 2	3 g every 12 hours IV

If Chlamydia trachomatis is a suspected pathogen in gynecologic infections, appropriate antichlamydial coverage should be added, since cefotetan has no activity against this organism.

Prophylaxis:

To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 or 2 g of CEFOTAN administered once, intravenously, 30 to 60 minutes prior to surgery. In patients undergoing cesarean section, the dose should be administered as soon as the umbilical cord is clamped.

Impaired Renal Function

When renal function is impaired, a reduced dosage schedule must be employed. The following dosage guidelines may be used.

DOSAGE GUIDELINES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION

Creatinine Clearance mL/min	Dose	Frequency
>30	Usual Recommended Dosage 1	Every 12 hours
10 - 30	Usual Recommended Dosage	Every 24 hours
<10	Usual Recommended Dosage	Every 48 hours

Alternatively, the dosing interval may remain constant at 12 hour intervals, but the dose reduced to one-half the usual recommended dose for patients with a creatinine clearance of 10-30 mL/min, and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min.

When only serum creatinine levels are available, creatinine clearance may be calculated from the following formula. The serum creatinine level should represent a steady state of renal function.

Males: Weight (kg) x (140 - age)

72 x serum creatinine (mg/100 mL)

Females:0.9 x value for males

Cefotetan is dialyzable and it is recommended that for patients undergoing intermittent hemodialysis, one-quarter of the usual recommended dose be given every 24 hours on days between dialysis and one-half the usual recommended dose on the day of dialysis.

CEFOTETAN DISODIUM FOR INJECTION

Preparation of Solution From Cefotetan Disodium For Injection:

For Intravenous Use:

Reconstitute with Sterile Water for Injection. Shake to dissolve and let stand until clear.

Vial Size	Amount of Diluent Added (mL)	Approximate Withdrawable Vol (mL)	Approximate Average Concentration (mg/mL)
1 gram	10	10.5	95
2 grams	10-20	11-21	182-95

Infusion bottles (100 mL) may be reconstituted with 50 to 100 mL of Dextrose Injection 5% or Sodium Chloride Injection 0.9%.

NOTE: ADD-VANTAGE VIALS ARE NOT TO BE USED IN THIS MANNER

For ADD-Vantage Vials: ADD-Vantage Vials of CEFOTAN are to be reconstituted only with Sodium Chloride Injection 0.9% or Dextrose Injection 5% in the 50 mL, 100 mL or 250 mL Flexible Diluent Containers. CEFOTAN supplied in single-use ADD-Vantage Vials should be prepared as directed.

Directions for Use of CEFOTAN (cefotetan disodium for injection) in ADD-Vantage Vials:

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 ADD-Vantage Vial and Flexible Diluent Container: (Use Aseptic Technique)

1.Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:

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 (See Figure 1), then pull straight up to remove the cap. (See Figure 2.)

NOTE: Once the breakaway cap has been removed, do not access vial with syringe.

b.To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (See Figure 3.)

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. (See Figure 4.) 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. (See Figure 4.).

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. (See Figure 5.)

3. Pull the inner cap from the drug vial. (See Figure 6.) Verify that the rubber stopper has been pulled out and invert the system several times, allowing the drug and diluent to mix.

4.Mix 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 two 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 container in series connections.

For Intramuscular Use:

Reconstitute with Sterile Water for Injection; Bacteriostatic Water for Injection; Sodium Chloride Injection 0.9%, USP; 0.5% Lidocaine HCl; or 1% Lidocaine HCl. Shake to dissolve and let stand until clear.

Vial Size	Amount of Diluent Added (mL)	Approximate Withdrawable Vol (mL)	Approximate Average Concentration (mg/mL)
1 gram	2	2.5	400
2 grams	3	4	500

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 of CEFOTAN (cefotetan disodium for injection) in Sterile Water for Injection can be injected over a period of three to five minutes. Using an infusion system, the solution may also be given over a longer period of time through the tubing system by which the patient may be receiving other intravenous solutions. Butterfly® or scalp vein-type needles are preferred for this type of infusion. However, during infusion of the solution containing CEFOTAN (cefotetan disodium for injection), it is advisable to discontinue temporarily the administration of other solutions at the same site.

NOTE: Solutions of CEFOTAN must not be admixed with solutions containing aminoglycosides. If CEFOTAN and aminoglycosides are to be administered to the same patient, they must be administered separately and not as a mixed injection.

Intramuscular Administration

As with all intramuscular preparations, CEFOTAN (cefotetan disodium for injection) should be injected well within the body of a relatively large muscle such as the upper outer quadrant of the buttock (ie, gluteus maximus); aspiration is necessary to avoid inadvertent injection into a blood vessel.

CEFOTETAN INJECTION

The thawed solution in Galaxy^® plastic container (PL 2040) remains chemically stable for 48 hours at room temperature (25°C/77°F) or for 21 days under refrigeration (5°C/41°F).

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

HOW SUPPLIED

CEFOTAN (cefotetan disodium for injection) is a dry, white to pale yellow powder supplied in vials containing cefotetan disodium equivalent to 1 g and 2 g cefotetan activity for intravenous and intramuscular administration. The vials should not be stored at temperatures above 22°C (72°F) and should be protected from light.

1 g ADD-Vantage Vial (NDC 0310-0376-31)

2 g ADD-Vantage Vial (NDC 0310-0377-32)

1 g Vial (NDC 0310-0376-10)

2 g Vial (NDC 0310-0377-20)

1 g Piggyback Vial (NDC 0310-0376-11)

2 g Piggyback Vial (NDC 0310-0377-21)

CEFOTAN is also available as a 10 g pharmacy bulk package.

10 g in 100 mL Vial (NDC 0310-0375-10)

CEFOTAN (cefotetan injection) is supplied as a frozen, iso-osmotic, premixed solution in single dose Galaxy^® plastic containers (PL 2040) as follows:

1 g in 50 mL plastic container (NDC 0310-0378-51)

2 g in 50 mL plastic container (NDC 0310-0379-51)

Store containers at or below -20°C/-4°F. [See DIRECTIONS FOR USE OF CEFOTAN (cefotetan injection) IN GALAXY® PLASTIC CONTAINER (PL 2040)].