Cefotan (Cefotetan)

CEFOTAN®

Wyeth-Ayerst

Cefotetan Disodium

Antibiotic

Action And Clinical Pharmacology: Cefotetan disodium is a semisynthetic, beta-lactamase resistant, cephalosporin (cephamycin) antibiotic. In vitro studies indicate that the bactericidal action of cefotetan results from an interference of bacterial cell wall synthesis by inhibiting the cross-linking of peptidoglycan. Studies with 4-labeled cefotetan have shown that on reaching the target penicillin-binding proteins (PBPs) in the inner membrane, the radiolabeled antibiotic binds principally to PBP 3 followed by PBP 1A and 1B. Cefotetan, like other cephamycins, does not bind to PBP 2.

The plasma elimination half-life of cefotetan is 3 to 4.6 hours after either i.v. or i.m. administration. In normal patients, from 51 to 81% of the administered dose is excreted unchanged by the kidney in 24 hours. The biliary tract is the other major route of elimination.

Indications And Clinical Uses: Treatment: For the treatment of the following infections when caused by susceptible strains of the designated organisms: Urinary tract infections caused by E. coli and Klebsiella species (including K. pneumoniae), P. mirabilis and indole-positive Proteus.

Lower respiratory tract infections caused by S. pneumoniae (formerly D. pneumoniae), S. aureus (penicillinase and nonpenicillinase-producing), H. influenzae (including ampicillin-resistant strains), Klebsiella species (including K. pneumoniae) and E. coli.

Skin and skin structure infections caused by S. aureus (penicillinase and non-penicillinase-producing), S. epidermidis, S. pyogenes, Streptococcus species (excluding Enterococci) and E. coli.

Gynecologic infections caused by S. aureus (penicillinase and non-penicillinase-producing), S. epidermidis, Streptococcus species (excluding Enterococci), E. coli, P. mirabilis, N. gonorrhoeae, anaerobic gram-positive cocci and gram-negative bacilli, Bacteroides species (excluding B. distasonis, B. ovatus and B. thetaiotaomicron).

Intra-abdominal infections caused by E. coli, anaerobic gram-negative bacilli, Bacteroides species (excluding B. distasonis, B. ovatus and B. thetaiotaomicron).

Bone and joint infections caused by S. aureus.

Specimens for bacteriological examination should be obtained prior to therapy 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.

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

The prophylactic dose of cefotetan should be administered 30 to 60 minutes prior to surgery. In patients undergoing cesarean section, cefotetan should be administered i.v. after the clamping of the umbilical cord.

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.

Contra-Indications: In patients with a known allergy to the cephalosporin group of antibiotics and in those individuals who have experienced a cephalosporin associated hemolytic anemia. tag_WarningWarnings

Manufacturers’ Warnings In Clinical States: Before therapy with cefotetan is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cefotetan, cephalosporins, penicillins or other drugs. Cefotetan should be given cautiously to penicillin-sensitive patients. Antibiotics, including cefotetan, should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs. If an allergic reaction to cefotetan occurs, administration should be discontinued. Serious acute hypersensitivity reactions may require epinephrine and other emergency measures.

Pseudomembranous colitis has been reported with the use of cephalosporins, including cefotetan, (and other broad-spectrum antibiotics); therefore, it is important to consider this diagnosis in patients who develop diarrhea in association with antibiotic use.

An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibiotics. Rare cases of severe hemolytic anemia, including fatalities, have been reported in association with cefotetan and other cephalosporins. If a patient develops anemia anytime within 2 to 3 weeks subsequent to the administration of cefotetan, the diagnosis of a cephalosporin associated anemia should be considered and the drug stopped until the etiology is determined with certainty. Blood transfusions may be administered if considered to be necessary (see Contraindications).

Patients who receive prolonged courses of cefotetan for treatment of infections should have periodic monitoring for signs and symptoms of hemolytic anemia including a measurement of hematological parameters where appropriate.

Treatment with broad-spectrum antibiotics may alter normal flora of the colon and may permit overgrowth of clostridia. Studies indicate a toxin produced by C. difficile is one primary cause of antibiotic-associated colitis.

Mild cases of colitis may respond to drug discontinuance alone.

Moderate to severe cases should be managed with fluid, electrolyte and protein supplementation as indicated. When the colitis is not relieved by drug discontinuance or when it is severe, consideration should be given to the administration of oral vancomycin for antibiotic-associated pseudomembranous colitis produced by C. difficile. Other causes should also be considered.

Precautions: Prolonged use of cefotetan may result in overgrowth of nonsusceptible organisms and organisms initially sensitive to the drug. Careful observation of the patients is essential. If superinfection does occur during therapy, appropriate measures should be taken.

Cefotetan may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, poor nutritional state, the elderly and patients with cancer. Prothrombin times should be monitored in patients at risk and exogenous vitamin K administered as indicated.

Cefotetan should be used with caution in individuals with a history of gastrointestinal disease, particularly colitis.

A disulfiram-like reaction characterized by flushing, sweating, headache and tachycardia may occur when alcohol (beer, wine, etc.) is ingested within 72 hours after cefotetan administration. Patients should be cautioned about the ingestion of alcoholic beverages following the administration of cefotetan.

Patients with impaired renal function; i.e., creatinine clearance of 30 mL/min or less, should be placed on a special dosage schedule for cefotetan recommended under Dosage.

Drug Interactions: Renal function should be carefully monitored, especially if high dosages of the aminoglycosides are to be administered or if therapy is prolonged, because of the potential nephrotoxicity and ototoxicity of aminoglycosidic antibiotics. Although, to date, this has not been noted when cefotetan was given alone, increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics. However, at the recommended dose, enhancement of nephrotoxicity is unlikely to be a problem with cefotetan.

Drug/Laboratory Test Interactions : A false positive reaction for glucose in urine may occur with Benedict’s or Fehling’s solution.

High concentrations of cefotetan may interfere with measurement of serum and urine creatinine levels by Jaffe reaction and produce false increases in the levels of creatinine reported.

Pregnancy: The safety of cefotetan in the treatment of infection during pregnancy has not been established. The use of cefotetan in pregnant women requires that the likely benefit from the drug be weighed against the possible risks to the mother and fetus. Reproduction studies have been performed in rats and monkeys at doses up to 20 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cefotetan. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, cefotetan should be used during pregnancy only if clearly needed.

Lactation: Cefotetan is excreted in human milk in very low concentrations. Caution should be exercised when cefotetan is administered to a nursing woman.

Children: Safety and effectiveness in children have not been established.

Adverse Reactions: In clinical studies, the following adverse effects were considered related to cefotetan therapy.

Gastrointestinal: Gastrointestinal symptoms occurred in 1.5% of patients, the most frequent were diarrhea (1 in 80) and nausea (1 in 700).

Hematologic: Hematologic laboratory abnormalities occurred in 1.4% of patients and included eosinophilia (1 in 200), positive direct Coombs’ test (1 in 250) and thrombocytosis (1 in 300). Transient thrombocytopenia and leukopenia have been reported.

Hepatic: Hepatic enzyme elevations occurred in 1.2% of patients and included a rise in SGPT (1 in 150), SGOT (1 in 300), alkaline phosphatase (1 in 700) and LDH (1 in 700).

Hypersensitivity: Hypersensitivity reactions were reported in 1.2% of patients and included rash (1 in 150) and itching (1 in 700). During postmarketing experience with cefotetan, anaphylactic reactions have been reported.

Local Effects: Local effects were reported in less than 1% of patients and included phlebitis at the site of injection (1 in 300) and discomfort (1 in 500).

Symptoms And Treatment Of Overdose: Symptoms and Treatment: To date, there have been no documented cases of overdosage with cefotetan. If overdosage should occur, it should be treated symptomatically. Cefotetan may be removed by dialysis.

Dosage And Administration: Treatment: Adults: The usual adult dosage is 1 or 2 g administered i.v. or i.m. 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 (see Table I). Therapy may be started while awaiting the results of susceptibility testing.

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 at risk particularly if shock is present or impending.

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 to 30 mL/min (0.17 to 0.50 mL/sec) and one-quarter the usual recommended dose for patients with a creatinine clearance of less than 10 mL/min (0.17 mL/sec).

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: Creatinine Weight (kg)x(140 – age) clearance = 72xserum creatinine (mg/100 mL) (mL/min)

Creatinine clearance = Weight (kg)x(140 – age) (mL/s) 49xserum creatinine (mmol/L)

Females: 0.85xmale value

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 dosage on the day of dialysis.

Children: The safety and effectiveness in children has not been established.

Prophylaxis: To prevent postoperative infection in clean contaminated or potentially contaminated surgery in adults, the recommended dosage is 1 to 2 g of cefotetan administered once, i.v., 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.

Administration: I.V.: For intermittent i.v. administration, a solution containing 1 g or 2 g of cefotetan in Sterile Water for Injection can be injected over a period of 3 to 5 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 i.v. solutions.

Butterfly or scalp vein-type needles are preferred for this type of infusion. However, during infusion of the solution containing cefotetan, it is advisable to discontinue temporarily the administration of other solutions at the same site.

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

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

Reconstitution: I.M.: Reconstitute with Sterile Water for Injection; Normal Saline, USP; 0.5% Lidocaine HCl or 1.0% Lidocaine HCl. Shake to dissolve and let stand until clear.

A solution prepared with sterile water for injection may be further diluted to the desired volume with any of the Solutions for I.V. Infusion listed below: Solutions for I.V. Infusion: 0.9% Sodium Chloride for Injection; 5% Dextrose Injection; 10% Dextrose Injection; Ringers Injection; Lactated Ringers Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 5% Dextrose and Ringers Injection; 5% Dextrose and Lactated Ringers Injection; 10% Invert Sugar Injection; 5% Sodium Bicarbonate Injection; Sodium Lactate Injection, 1/6 Molar; Isolyte-S Injection.

Compatibility and Stability: Cefotetan reconstituted as described above (Reconstitution) maintains satisfactory potency for 24 hours at room temperature (25°C), or 72 hours under refrigeration (5°C).

Any unused portions of the reconstituted solutions should be discarded.

Cefotetan should not be physically mixed with other antimicrobial agents.

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

Availability And Storage: 1 g: Each vial of dry, white to pale yellow powder contains: cefotetan disodium equivalent to 1 g cefotetan activity for i.v. and i.m. administration. Nonmedicinal ingredients: sodium bicarbonate. Sodium: 3.4 mmol (78.7 mg). Vials of 10 mL.

2 g: Each vial of dry, white to pale yellow powder contains: cefotetan disodium equivalent to 2 g cefotetan activity for i.v. and i.m. administration. Nonmedicinal ingredients: sodium bicarbonate. Sodium: 6.8 mmol (157.4 mg). Vials of 20 mL.

Store below 25°C and protect from light.

CEFOTAN® Wyeth-Ayerst Cefotetan Disodium Antibiotic

Connected Diseases :

Bacterial Infections

Description: Bacterial infections include a huge group of diseases caused by microorganisms – bacteria. These are small unicellular microorganisms that have a strong cell wall…