cefoTEtan (Monograph)

Drug class: Cephamycins
Chemical name: [6R-(6α,7α)]-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-carboxylic acid disodium salt
CAS number: 74356-00-6

Medically reviewed by Drugs.com on Sep 23, 2024. Written by ASHP.

Introduction

Antibacterial; β-lactam antibiotic; cephamycin.

Uses for cefoTEtan

Bone and Joint Infections

Treatment of bone and joint infections caused by Staphylococcus aureus.

Gynecologic Infections

Treatment of gynecologic infections caused by susceptible S. aureus (including penicillinase-producing strains), S. epidermidis, Streptococcus agalactiae (group B streptococci), other streptococci (except enterococci), Escherichia coli, Neisseria gonorrhoeae, Proteus mirabilis, Bacteroides (except B. distasonis, B. ovatus, B. thetaiotaomicron), Fusobacterium, and gram-positive anaerobic cocci (including Peptococcus and Peptostreptococcus).

Treatment of pelvic inflammatory disease (PID). Cefotetan (or cefoxitin) in conjunction with doxycycline considered a regimen of choice by CDC and others when a parenteral regimen indicated for treatment of PID. Because cefotetan (like cephalosporins) is not active against Chlamydia, concomitant use of a drug active against Chlamydia (e.g., doxycycline) is necessary when these organisms are suspected pathogens.

Intra-abdominal Infections

Treatment of intra-abdominal infections caused by susceptible Streptococcus (except enterococci), E. coli, Klebsiella (including K. pneumoniae), Bacteroides (except B. distasonis, B. ovatus, B. thetaiotaomicron), or Clostridium.

May be effective for treatment of mild to moderate infections caused by B. fragilis, but other anti-infectives (e.g., metronidazole, clindamycin) preferred, especially for severe or life-threatening infections.

IDSA states cefotetan not recommended for empiric treatment of intra-abdominal infections because of increasing prevalence of B. fragilis resistant to the drug.

Respiratory Tract Infections

Treatment of lower respiratory tract infections caused by susceptible S. pneumoniae, S. aureus (including penicillinase-producing strains), Haemophilus influenzae (including ampicillin-resistant strains), E. coli, Klebsiella (including K. pneumoniae), P. mirabilis, or Serratia marcescens.

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible S. aureus (including penicillinase-producing strains), S. epidermidis, S. pyogenes (group A β-hemolytic streptococci), other streptococci (except enterococci), E. coli, K. pneumoniae, Peptococcus niger, or Peptostreptococcus.

Urinary Tract Infections (UTIs)

Treatment of UTIs caused by susceptible E. coli, Klebsiella (including K. pneumoniae), P. mirabilis, P. vulgaris, Providencia rettgeri, or Morganella morganii.

Should not be used alone for UTIs if Pseudomonas aeruginosa is a possible pathogen since most strains are resistant.

Perioperative Prophylaxis

Perioperative prophylaxis in women undergoing hysterectomy or cesarean section. Cefazolin, cefotetan, cefoxitin, or ampicillin and sulbactam usually recommended for women undergoing vaginal, abdominal, or laparoscopic hysterectomy; cefazolin usually recommended for women undergoing cesarean section.

Perioperative prophylaxis in patients undergoing colorectal or other GI surgery. Cefoxitin, cefotetan, cefazolin (in conjunction with metronidazole), ampicillin and sulbactam, or ertapenem usually recommended. Many clinicians recommend using both a parenteral and oral regimen (i.e., neomycin in conjunction with erythromycin or metronidazole and mechanical bowel preparation) for perioperative prophylaxis in patients undergoing colorectal surgery,

Perioperative prophylaxis in patients undergoing uncomplicated (nonperforated) appendectomy. Cefoxitin, cefotetan, or cefazolin (in conjunction with metronidazole) usually recommended for patients undergoing appendectomy.

Perioperative prophylaxis in patients undergoing biliary tract surgery. Cefazolin usually recommended for high-risk patients undergoing open biliary tract surgery; alternatives include cefotetan, cefoxitin, or ampicillin and sulbactam. Prophylaxis not considered necessary for low-risk patients undergoing elective laparoscopic cholecystectomy.

Has been used for perioperative prophylaxis in patients undergoing transurethral surgery; not usually recommended for urinary tract surgery.

cefoTEtan Dosage and Administration

Administration

Administer by IV injection or infusion or by deep IM injection.

IV route preferred for treatment of bacteremia, septicemia, or other severe or life-threatening infections and in patients with lowered resistance resulting from debilitating conditions (e.g., malnutrition, trauma, surgery, diabetes, heart failure, malignancy), particularly if shock is present or impending.

For solution and drug compatibility information, see Compatibility under Stability.

IV Injection

Reconstitution

Vials containing 1 or 2 g of cefotetan: Reconstitute with 10 or 10–20 mL, respectively, of sterile water for injection to provide solution containing approximately 95 or 95–182 mg/mL, respectively. Shake to dissolve; let stand until clear.

Rate of Administration

Inject appropriate dose of reconstituted solution directly into a vein over a 3- to 5-minute period or slowly into the tubing of a compatible IV solution.

IV Infusion

IV infusions should preferably be given using butterfly or scalp vein-type needles. Other IV solutions flowing through a common administration tubing or set should be discontinued while cefotetan is infused.

Reconstitution

Vials containing 1 or 2 g of cefotetan: Reconstitute with 10 or 10–20 mL, respectively, of sterile water for injection to provide solutions containing approximately 95 or 95–182 mg/mL, respectively. Shake to dissolve; let stand until clear.

Pharmacy bulk package vial containing 10 g of cefotetan: Reconstitute with 50 or 100 mL of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection to provide solution containing approximately 180 or 95 mg/mL, respectively. Shake to dissolve; let stand until clear. Not intended for direct IV infusion; prior to administration, doses from reconstituted pharmacy bulk package vial must be further diluted in a compatible IV infusion solution within 4 hours. Transfer individual doses to a compatible IV solution using suitable sterile transfer device or dispensing set; do not use syringe with needle since leakage could occur. Consult manufacturer’s directions for additional information.

Duplex drug delivery system containing 1 or 2 g of cefotetan powder and 50 mL of 3.58 or 2.08% dextrose injection, respectively, in separate chambers: Reconstitute (activate) according to the manufacturer’s directions. If refrigerated after reconstitution (see Storage under Stability), allow solution to reach room temperature prior to administration.

Rate of Administration

Administer by IV infusion over 20–60 minutes.

IM Administration

Administer IM injections deeply into a large muscle, such as upper outer quadrant of gluteus maximus. Use aspiration to ensure needle is not in a blood vessel.

Reconstitution

Vials containing 1 or 2 g of cefotetan: Prepare IM injections by adding 2 or 3 mL of sterile or bacteriostatic water for injection, 0.9% sodium chloride injection, or 0.5 or 1% lidocaine hydrochloride injection to provide solutions containing approximately 400 or 500 mg/mL, respectively. Shake to dissolve; let stand until clear.

Dosage

Available as cefotetan disodium; dosage expressed in terms of cefotetan.

Pediatric Patients

General Pediatric Dosage† [off-label]

Mild to Moderate Infections in Children Beyond Neonatal Period† [off-label]

IV or IM

AAP recommends 60 mg/kg daily given in 2 divided doses.

Severe Infections in Children Beyond Neonatal Period† [off-label]

IV or IM

AAP recommends 100 mg/kg daily given in 2 divided doses.

Perioperative Prophylaxis

Colorectal Surgery, Appendectomy (Nonperforated), Biliary Tract, or Other GI Surgery

IV

Children ≥1 year of age^{† [off-label]}: Some clinicians recommend 40 mg/kg given within 1 hour prior to incision.

If procedure is prolonged >3–4 hours, major blood loss occurs, or other factors are present that shorten drug half-life, additional intraoperative doses may be given.

Duration of prophylaxis should be <24 hours for most procedures; no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.

Adults

General Adult Dosage

Less Severe Infections

IV or IM

1 or 2 g every 12 hours.

Severe Infections

IV

2 g every 12 hours.

Life-threatening Infections

IV

3 g every 12 hours.

Gynecologic Infections

Pelvic Inflammatory Disease (PID)

IV

2 g every 12 hours; used in conjunction with IV or oral doxycycline (100 mg every 12 hours).

Cefotetan may be discontinued 24–48 hours after clinical improvement occurs and oral doxycycline (100 mg every 12 hours) continued to complete 14 days of treatment.

Skin and Skin Structure Infections

Mild to Moderate Infections

IV

1 g every 12 hours or 2 g every 24 hours. For infections caused by K. pneumoniae, 1 or 2 g every 12 hours.

IM

1 g every 12 hours. For infections caused by K. pneumoniae, 1 or 2 g every 12 hours.

Severe Infections

IV

2 g every 12 hours.

Urinary Tract Infections (UTIs)

IV or IM

500 mg every 12 hours; 1 or 2 g every 12 hours; or 1 or 2 g every 24 hours.

Perioperative Prophylaxis

Gynecologic and Obstetric Surgery

IV

Hysterectomy (vaginal, abdominal, laparoscopic): 1 or 2 g given within 0.5–1 hour prior to incision.

Cesarean section: 1 or 2 g given within 0.5–1 hour prior to incision. Manufacturers recommend giving dose as soon as umbilical cord is clamped, but there is some evidence that giving dose prior to incision is more effective than after clamping.

If procedure is prolonged >3–4 hours, major blood loss occurs, or other factors are present that shorten drug half-life, additional intraoperative doses may be given (e.g., every 6 hours, measured from time preoperative dose is initiated).

Duration of prophylaxis should be <24 hours for most procedures; no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.

Colorectal Surgery, Appendectomy (Nonperforated), Biliary Tract, or Other GI Surgery

IV

1 or 2 g given within 0.5–1 hour prior to incision.

If procedure is prolonged >3–4 hours, major blood loss occurs, or other factors are present that shorten drug half-life, additional intraoperative doses may be given (e.g., every 6 hours, measured from time preoperative dose is initiated).

Duration of prophylaxis should be <24 hours for most procedures; no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.

Transurethral Surgery

IV

1 or 2 g given within 0.5–1 hour prior to incision.

Prescribing Limits

Adults

Maximum 6 g daily.

Special Populations

Renal Impairment

Adults with renal impairment: Dosage adjustments required based on Cl_cr. (See Table 1.)

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal function. (See Renal Impairment under Dosage and Administration.)

Cautions for cefoTEtan

Contraindications

• Known hypersensitivity to cefotetan or cephalosporins.

• History of cephalosporin-associated hemolytic anemia.

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Careful observation of patient is essential. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including cefotetan, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD suspected or confirmed, discontinue anti-infective therapy not directed against C. difficile whenever possible. Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Hemolytic Anemia

Severe hemolytic anemia (including fatalities) reported rarely with cefotetan; hemolytic anemia reported in a few women undergoing obstetric and gynecologic procedures who received a single dose for perioperative prophylaxis. Similar immune-mediated hemolytic anemia reported with some cephalosporins (e.g., cefotaxime, ceftizoxime [no longer commercially available in the US], ceftriaxone).

Periodically monitor for signs and symptoms of hemolytic anemia; assess hematologic parameters when appropriate.

If hemolytic anemia develops within 2–3 weeks after initiation of cefotetan, the diagnosis of immune-mediated hemolytic anemia should be considered and the drug discontinued until the etiology of anemia is determined. Consider blood transfusions as needed.

Prolonged PT

Prolonged PT (with or without bleeding) reported rarely.

Monitor PT in patients at risk, including geriatric patients and those with renal or hepatic impairment, malnutrition, or cancer. Administer vitamin K when indicated.

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

If allergic reaction occurs, discontinue cefotetan and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).

Cross-hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and cephamycins.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cefotetan, cephalosporins, penicillins, or other drugs. Cautious use recommended in individuals hypersensitive to penicillins; avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.

General Precautions

History of GI Disease

Use with caution in patients with history of GI disease, particularly colitis. (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis [CDAD] under Cautions.)

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefotetan and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

In certain serious infections when causative organism is unknown and in cases of confirmed or suspected gram-positive or -negative sepsis, concomitant use of an aminoglycoside may be indicated pending results of in vitro susceptibility tests. (See Aminoglycosides under Interactions.)

Patients with Diabetes

Like other dextrose-containing solutions, use Duplex drug delivery system containing 1 or 2 g of cefotetan powder and 50 mL of 3.58 or 2.08% dextrose injection, respectively, with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.

Sodium Content

Contains approximately 80 mg (3.5 mEq) of sodium per g of cefotetan.

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk in low concentrations; use with caution.

Pediatric Use

Safety and efficacy not established in children. (See Pediatric Patients under Dosage and Administration.)

Geriatric Use

Safety and efficacy in those ≥60 years of age similar to that in younger adults, but possibility exists of greater sensitivity to the drug in some geriatric patients.

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function. Select dosage with caution and consider monitoring renal function because of age-related decreases in renal function. (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance and increased half-life.

Reduce dosage in those with renal impairment. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects, hematologic effects (eosinophilia, positive direct Coombs test, thrombocytosis), elevated hepatic enzymes, hypersensitivity reactions, local reactions at administration site.

Drug Interactions

Specific Drugs and Laboratory Tests

cefoTEtan Pharmacokinetics

Absorption

Bioavailability

Not absorbed from the GI tract; must be given parenterally.

Appears to be completely absorbed following IM administration; peak plasma concentrations attained 1.5–4 hours after a dose.

Distribution

Extent

Widely distributed into body tissues and fluids including gallbladder, skin, muscle, fat, myometrium, endometrium, fallopian tube, cervix, ovary, uterus and adnexa, prostatic tissue, kidney, ureter, bladder, maxillary sinus mucosa, tonsils, sputum, bile, and wound, prostatic, and peritoneal fluids.

Only low concentrations attained in CSF.

Crosses the placenta and is distributed into milk in low concentrations.

Plasma Protein Binding

76–91%.

Elimination

Metabolism

Does not appear to be metabolized, but 1–10% of a dose is present in plasma and urine as a tautomer of the drug. This tautomer has microbiologic activity and pharmacokinetics similar to cefotetan.

Elimination Route

Eliminated principally in urine by glomerular filtration; also eliminated by biliary excretion.

49–81% of a dose eliminated unchanged in urine; approximately 20% excreted in bile.

Half-life

Adults with normal renal function: Distribution half-life 0.2–1.1 hours and elimination half-life 2.8–4.6 hours.

Special Populations

Patients with impaired renal function: Renal elimination decreased, serum concentrations increased, and half-life prolonged. Half-life may be 10 hours in those with moderate renal impairment.

Stability

Storage

Parenteral

Powder for Injection or IV Infusion

Vials containing 1 or 2 g of cefotetan: ≤22° C; protect from light.

IV solutions containing 95–182 mg of cefotetan/mL prepared using sterile water are stable for 24 hours at 25°C, 96 hours when refrigerated at 5°C, or at least 1 week when frozen at -20°C.

IM solutions containing 400 or 500 mg/mL prepared using sterile or bacteriostatic water, 0.9% sodium chloride, or 0.5 or 1% lidocaine hydrochloride are stable for 24 hours at 25°C, 96 hours when refrigerated at 5°C, or at least 1 week when frozen at -20°C. Reconstituted solutions transferred to disposable glass or plastic syringes are stable for 24 hours at room temperature or 96 hours when refrigerated.

Powder and reconstituted solutions may darken to a deeper yellow; does not indicate loss of potency.

Powder for IV Infusion

Pharmacy bulk package vial containing 10 g of cefotetan: 20–25°C; protect from light. Transfer reconstituted solution and dilute in compatible IV infusion solution within 4 hours after vial originally entered; discard any portion of reconstituted pharmacy bulk package not used within 4 hours. Following dilution in compatible IV infusion solution, use within 24 hours if stored at room temperature, within 96 hours if refrigerated at 5°C, or within 1 week if frozen.

Duplex drug delivery system containing 1 or 2 g of cefotetan powder and 50 mL of dextrose injection in separate chambers: 20–25°C (may be exposed to 15–30°C). Following reconstitution (activation), use within 12 hours if stored at room temperature or within 5 days if stored in a refrigerator; do not freeze.

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions and Spectrum

• Cephamycin; sometimes classified as a second generation cephalosporin based on spectrum of activity.

• Usually bactericidal.

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.

• Spectrum of activity includes some gram-positive and -negative aerobic bacteria and some anaerobic bacteria; inactive against Chlamydia, fungi, and viruses.

• Gram-positive aerobes: Active in vitro and in clinical infections against S. aureus (including penicillinase-producing strains), S. epidermidis, S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and S. agalactiae (group B streptococci). Oxacillin-resistant staphylococci (methicillin-resistant staphylococci) and most enterococci (e.g., Enterococcus faecalis) are resistant.

• Gram-negative aerobes: Active in vitro and in clinical infections against E. coli, H. influenzae (including ampicillin-resistant strains), Klebsiella (including K. pneumoniae), M. morganii, N. gonorrhoeae, P. mirabilis, P. vulgaris, P. rettgeri, and S. marcescens. Also active in vitro against Citrobacter, K. oxytoca, Moraxella catarrhalis, Salmonella, Shigella, and Yersinia enterocolitica. Many strains of Enterobacter (e.g., E. aerogenes, E. cloacae) and most Ps. aeruginosa and Acinetobacter are resistant.

• Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, B. vulgatus, Prevotella bivia, P. disiens, P. melaninogenica, Fusobacterium, Clostridium (except C. difficile), Peptococcus, and Peptostreptococcus. Also active in vitro against B. splanchnicus, Prevotella oralis, Propionibacterium, and Veillonella.

Advice to Patients

• Advise patients that antibacterials (including cefotetan) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

• Importance of completing full course of therapy, even if feeling better after a few days.

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefotetan or other antibacterials in the future.

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.

• Advise patients to avoid ingesting alcohol for 72 hours after cefotetan.

• Importance of informing clinicians if an allergic reaction occurs.

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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