Claforan

Generic Name: Cefotaxime Sodium
Class: Third Generation Cephalosporins
VA Class: AM117
CAS Number: 64485-93-4

Introduction

Antibacterial; β-lactam antibiotic; third generation cephalosporin.^{a b}

Uses for Claforan

Bone and Joint Infections

Treatment of serious bone and joint infections caused by susceptible S. aureus, streptococci (including S. pyogenes), Pseudomonas (including Ps. aeruginosa), or P. mirabilis.²³⁰

Genitourinary Tract Infections

Treatment of serious genitourinary tract infections caused by susceptible S. aureus (including penicillinase-producing strains), S. epidermidis, enterococci, Citrobacter, Enterobacter, E. coli, Klebsiella, Morganella morganii, P. mirabilis, P. vulgaris, Providencia stuartii, P. rettgeri, Pseudomonas (including Ps. aeruginosa), or S. marcescens.²³⁰

Gynecologic Infections

Treatment of gynecologic infections (including pelvic inflammatory disease [PID], endometritis, pelvic cellulitis) caused by susceptible S. epidermidis, streptococci (including enterococci), E. coli, Enterobacter, Klebsiella, P. mirabilis, Bacteroides (including B. fragilis), Clostridium, Fusobacterium (including F. nucleatum), Peptococcus, and Peptostreptococcus.²³⁰

CDC states cefotaxime may be effective for PID, but is less active than cefoxitin against anaerobic bacteria.²⁰⁰ When an oral regimen is used for treatment of mild to moderately severe acute PID, CDC recommends a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or other parenteral third-generation cephalosporin (e.g., cefotaxime) given in conjunction with oral doxycycline (with or without oral metronidazole).^{200 369} Because cefotaxime (like other 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.^{230 290}

Intra-abdominal Infections

Treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible streptococci, E. coli, Klebsiella, P. mirabilis, Clostridium, Bacteroides, or anaerobic cocci (including Peptococcus and Peptostreptococcus).²³⁰

Meningitis and Other CNS Infections

Treatment of meningitis and ventriculitis caused by susceptible H. influenzae, N. meningitidis, S. pneumoniae,^{230 275 291 294 296 335} E. coli, or K. pneumoniae.^{230 275 291 294 296 336}

A drug of choice when a third generation cephalosporin is indicated for empiric treatment of bacterial meningitis;^{275 290 296 319} should not be used alone for empiric treatment when Listeria monocytogenes, enterococci, staphylococci, or Ps. aeruginosa may be involved.^{275 290 296 319}

Treatment of brain abscesses and other CNS infections† (e.g., subdural empyema, intracranial epidural abscesses).^{319 336 347} Concomitant metronidazole usually recommended for empiric therapy;^{319 347} used in conjunction with a penicillinase-resistant penicillin or vancomycin if staphylococci suspected.^{319 347}

Respiratory Tract Infections

Treatment of serious lower respiratory tract infections, including community-acquired pneumonia (CAP)^{211 269 342} caused by susceptible Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci), other streptococci (except enterococci), Staphylococcus aureus (including penicillinase-producing strains), Escherichia coli, Klebsiella, Haemophilus influenzae (including ampicillin-resistant strains), H. parainfluenzae, Proteus mirabilis, indole-positive Proteus, Serratia marcescens, Enterobacter, or Pseudomonas (including Ps. aeruginosa).²³⁰

Recommended by ATS and IDSA as an alternative for treatment of CAP caused by penicillin-susceptible S. pneumoniae and as a preferred drug for treatment of CAP caused by penicillin-resistant S. pneumoniae, provided in vitro susceptibility has been demonstrated.²⁶⁹ Also recommended in certain combination regimens used for empiric treatment of CAP.²⁶⁹ Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).²⁶⁹

For empiric inpatient treatment of CAP in patients not requiring treatment in an intensive care unit (non-ICU patients), IDSA and ATS recommend monotherapy with a fluoroquinolone (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin).²⁶⁹

For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) S. aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (moxifloxacin, gemifloxacin, levofloxacin).²⁶⁹

Septicemia

Treatment of bacteremia/septicemia caused by E. coli, Klebsiella, S. marcescens, S. aureus, or streptococci (including S. pneumoniae).²³⁰ An aminoglycoside often is used concomitantly.²³⁰

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible S. aureus, S. epidermidis, S. pyogenes, other streptococci (including enterococci), Acinetobacter, E. coli, Citrobacter (including C. freundii), Enterobacter, Klebsiella, P. mirabilis, P. vulgaris, M. morganii, P. rettgeri, Pseudomonas, Serratia, Bacteroides (including B. fragilis), Fusobacterium (including F. nucleatum), or anaerobic cocci (including Peptococcus and Peptostreptococcus).²³⁰

Capnocytophaga Infections

Alternative to penicillin G for treatment of infections caused by Capnocytophaga† (e.g., septicemia, meningitis, endocarditis).²¹¹

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated cervical, urethral, or rectal gonorrhea caused by susceptible Neisseria gonorrhoeae in adults or adolescents.^{200 230 366 367 369} Drug of choice is IM ceftriaxone or oral cefixime.^{200 251 275 369} Although effective, CDC states that IM cefotaxime appears to offer no advantage over IM ceftriaxone.²⁰⁰

Alternative for initial treatment of disseminated gonococcal infections† caused by susceptible N. gonorrhoeae.^{200 275 369} Ceftriaxone is usual drug of choice for initial parenteral treatment of disseminated gonorrhea in adults, adolescents, or children; CDC and AAP consider cefotaxime an alternative.^{200 275 369}

Treatment of disseminated gonococcal infections†,^{200 275} gonococcal scalp abscesses†,^{200 275} and gonococcal ophthalmia neonatorum† in neonates.^{200 275}

Lyme Disease

Treatment of early neurologic Lyme disease† with acute neurologic manifestations such as meningitis or radiculopathy.^{273 275 351 354} IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G.^{273 275 351 354} Although an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) may be effective for early localized or early disseminated Lyme disease associated with erythema migrans in the absence of specific neurologic manifestations or advanced atrioventricular (AV) heart block,^{270 273 275 284 285 286 287 338 351 353 355 356 357} a parenteral regimen usually is recommended when there are acute neurologic manifestations.^{270 273 275 284 285 286 287 338 351 353 355 356}

Treatment of Lyme carditis† when a parenteral regimen is indicated.^{273 275 351 354} IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G.^{273 275 351 354} Although a parenteral regimen usually is recommended for initial treatment of hospitalized patients, an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) can be used to complete therapy and for the treatment of outpatients.^{273 275 351 354}

Treatment of Lyme arthritis† when a parenteral regimen is indicated.^{273 275 351 354 361} IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G.^{273 275 351 354 361} Although the comparative safety and efficacy of oral versus IV anti-infectives for treatment of Lyme arthritis have not been fully evaluated,³⁵¹ those with concomitant neurologic disease generally should receive a parenteral regimen.^{273 275 351 354 361}

Treatment of late neurologic Lyme disease† affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy).³⁵¹ IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G.³⁵¹

Typhoid Fever and Other Salmonella Infections

Treatment of typhoid fever (enteric fever) or septicemia caused by Salmonella typhi or S. paratyphi†, including multidrug-resistant strains.^{275 306}

Treatment of >;Salmonella gastroenteritis† caused by non-typhi Salmonella (e.g., S. enteritidis, S. typhimurium).^{211 245 275 309} Anti-infective treatment is indicated only in those with severe disease and in those at increased risk of invasive disease, including those <3–6 months of age or >50 years of age, those with hemoglobinopathies, severe atherosclerosis or valvular heart disease, prostheses, uremia, chronic GI disease, or severe colitis, and those immunocompromised because of malignancy, immunosuppressive therapy, HIV infection, or other immunosuppressive illness.^{211 245 275 309} Choice of anti-infective is based on in vitro susceptibility.^{211 245 275 309}

Vibrio Infections

Treatment of severe Vibrio parahaemolyticus† infection when anti-infective therapy is indicated in addition to supportive care.²¹⁸

Treatment of infections caused by V. vulnificus†.^{211 250} Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.^{211 218 250} Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.^{250 294}

Yersinia Infections

Treatment of GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis†.^{218 245 275} Usually self-limited infections, but anti-infectives may be indicated in immunocompromised individuals, for severe infections, or when septicemia or other invasive disease occurs.^{218 245 275}

Perioperative Prophylaxis

Perioperative prophylaxis to reduce the incidence of infection in patients undergoing contaminated or potentially contaminated surgery (e.g., GI and genitourinary surgery, abdominal or vaginal hysterectomy) and in patients undergoing cesarean section.²³⁰

Other cephalosporins or cephamycins (cefazolin, cefotetan, cefoxitin) are the preferred drugs for perioperative prophylaxis.²⁰¹ Cefotaxime and other third generation cephalosporins usually not used for perioperative prophylaxis since they are expensive, some are less active against staphylococci than cefazolin, they have a spectrum of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis promotes emergence of resistant organisms.²⁰¹

Claforan Dosage and Administration

Administration

Administer by IV injection or infusion or by deep IM injection.²³⁰

IV route preferred in patients with septicemia, bacteremia, peritonitis, meningitis, or other severe or life-threatening infections or in patients with lowered resistance resulting from debilitating conditions (e.g., malnutrition, trauma, surgery, diabetes, heart failure, malignancy), particularly if shock is present.²³⁰

Large IM doses may be painful; IV administration may be preferred when large doses are indicated.^b

Cefotaxime ADD-Vantage vials and the commercially available frozen cefotaxime injection in dextrose should be used only for IV infusion.

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

IV Injection

Reconstitution

Reconstitute vials containing 500 mg, 1 g, or 2 g of cefotaxime with 10 mL of sterile water for injection to provide solutions containing approximately 50, 95, or 180 mg/mL, respectively.²³⁰

Rate of Administration

Inject directly into a vein over a period of 3-5 minutes or slowly into the tubing of a freely flowing compatible IV solution.²³⁰

Do not inject IV over <3 minutes; rapid (over <1 minute) injection is associated with potentially life-threatening arrhythmias.²³⁰

IV Infusion

Reconstitution and Dilution

Reconstitute infusion bottles containing 1 or 2 g of cefotaxime with 50–100 mL of 0.9% sodium chloride injection or 5% dextrose injection to provide solutions containing 10–20 or 20–40 mg/mL, respectively.²³⁰ May be diluted further in 50 mL to 1 L of compatible IV solution.²³⁰

Reconstitute 10-g pharmacy bulk package according to the manufacturer’s directions and then dilute further in a compatible IV solution.²³⁰

Reconstitute ADD-Vantage vials or infusion bottles containing 1 or 2 g of cefotaxime according to the manufacturer’s directions.²³⁰

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation.²³⁰ A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.²³⁰ Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.²³⁰ The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.²³⁰

Rate of Administration

For intermittent IV infusion, infuse over 20–30 minutes via butterfly or scalp vein-type needles.^b

During infusion, discontinue other IV solutions flowing through a common administration tubing or site²³⁰ unless the solutions are known to be compatible and the flow-rate is adequately controlled.^b

IM Injection

Inject IM deeply into a large muscle mass such as the upper outer quadrant of the gluteus maximus.²³⁰ Use aspiration to avoid inadvertent injection into a blood vessel.²³⁰

2-g IM doses should be divided and administered at 2 different injection sites.²³⁰

Reconstitution

Reconstitute vials containing 500 mg, 1 g, or 2 g of cefotaxime with 2, 3, or 5 mL, respectively, of sterile or bacteriostatic water for injection to provide solutions containing approximately 230, 300, or 330 mg/mL, respectively.²³⁰

Dosage

Available as cefotaxime sodium; dosage expressed in terms of cefotaxime.²³⁰

Pediatric Patients

General Dosage in Neonates <1 Week of Age

IV

50 mg/kg every 12 hours for premature or full-term neonates <1 week of age recommended by manufacturers.^{230 366 367}

IV or IM

AAP recommends 50 mg/kg every 12 hours for neonates <1 week of age weighing ≤2 kg and 50 mg/kg every 8 or 12 hours for those weighing >2 kg.²⁷⁵

General Dosage in Neonates 1–4 Weeks of Age

IV

50 mg/kg every 8 hours recommended by manufacturers.^{230 366 367}

IV or IM

AAP recommends 50 mg/kg every 12 hours for neonates 1–4 weeks of age weighing <1.2 kg; 50 mg/kg every 8 hours for those weighing 1.2–2 kg; and 50 mg/kg every 6 or 8 hours for those weighing >2 kg.²⁷⁵

General Dosage in Children 1 Month to 12 Years of Age

IV or IM

50–180 mg/kg daily given in 4–6 equally divided doses in those weighing <50 kg.^{230 366 367} The higher dosage should be used for more severe or serious infections.^{230 366 367}

AAP recommends 75–100 mg/kg daily given in 3 or 4 equally divided doses for mild to moderate infections and 150–200 mg/kg daily given in 3 or 4 equally divided doses for severe infections.²⁷⁵

Children weighing >50 kg should receive the usual adult dosage.^{230 366 367} (See Adult Dosage under Dosage and Administration.)

Meningitis and Other CNS Infections

IV

Manufacturers recommend that children 1 month to 12 years of age weighing <50 kg receive dosage at the high end of the range of 50–180 mg/kg daily.^{230 366 367} Some clinicians recommend that infants and children <18 years of age with meningitis receive 50 mg/kg IV every 6 hours.²⁹⁶ Others recommend 100–150 mg/kg daily given in divided doses every 8–12 hours in neonates ≤7 days of age, 150–200 mg/kg daily given in divided doses every 6–8 hours in neonates 8–28 days of age, and 225–300 mg/kg daily given in divided doses every 6–8 hours in older infants and children.³⁶⁵

AAP recommends 300 mg/kg daily given in 3 or 4 divided doses for treatment of meningitis in pediatric patients beyond the neonatal period.²⁷⁵ If meningitis is known or suspected to be caused by S. pneumoniae, AAP recommends that infants and children ≥1 month of age or older receive 225–300 mg/kg daily given in divided doses every 6–8 hours.^{275 297}

Duration of treatment is 7 days for uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis; ≥10–14 days for complicated cases or meningitis caused by S. pneumoniae; and ≥21 days for meningitis caused by susceptible Enterobacteriaceae.^{275 296 318}

Gonorrhea and Associated Infections

Disseminated Gonococcal Infection or Gonococcal Scalp Abscess in Neonates†

IV or IM

25 mg/kg every 12 hours for 7 days recommended by CDC and AAP; if meningitis is documented, continue for 10–14 days.^{200 275}

Disseminated Gonorrhea in Children ≥8 Years of Age or Weighing ≥45 kg†

IV

1 g every 8 hours recommended by CDC and AAP.^{200 275 369} Continue for 7 days²⁷⁵ or discontinue 24–48 hours after improvement occurs and switch to an oral regimen (e.g., cefixime or cefpodoxime) to complete ≥7 days of treatment.^{200 275 369}

Lyme Disease†

Early Neurologic Lyme Disease†

IV

150–200 mg/kg daily (up to 6 g daily) given in divided doses every 6–8 hours for 14 days (range: 10–28 days) recommended by IDSA and others for early Lyme disease in children with acute neurologic manifestations (e.g., meningitis, radiculopathy).^{273 351 354}

Lyme Carditis†

IV

150–200 mg/kg daily (up to 6 g daily) given in divided doses every 6–8 hours for 14 days (range: 14–21 days) recommended by IDSA and others for those with AV heart block and/or myopericarditis associated with early Lyme disease when a parenteral regimen is indicated (e.g., hospitalized patients).^{273 351 354}

Parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy when clinically indicated.³⁵¹

Lyme Arthritis†

IV

150–200 mg/kg daily (up to 6 g daily) given in divided doses every 6–8 hours for 14 days (range: 14–28 days) for children with evidence of neurologic disease or when arthritis has not responded to an oral regimen.³⁵¹

Late Neurologic Lyme Disease†

IV

150–200 mg/kg daily (up to 6 g daily) given in divided doses every 6–8 hours for 14 days (range: 14–28 days) recommended by IDSA for children with late neurologic disease affecting the CNS or peripheral nervous system.^{273 351}

Response to anti-infective treatment usually is slow and may be incomplete in such patients.³⁵¹ IDSA states that retreatment is not recommended unless relapse is shown by reliable objective measures.³⁵¹

Adults

General Adult Dosage

Uncomplicated Infections

IV or IM

1 g every 12 hours.^{230 366 367}

Moderate to Severe Infections

IV or IM

1–2 g every 8 hours.^{230 366 367}

Severe or Life-threatening Infections

IV

2 g every 6–8 hours.^{230 366 367} For life-threatening infections, 2 g every 4 hours.^{230 366 367}

Meningitis and Other CNS Infections

IV

2 g every 6–8 hours for 7–21 days.^{230 296} Some clinicians recommend 8–12 g daily in divided doses every 4–6 hours.³⁶⁵

Duration of treatment is 7 days for uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis; ≥10–14 days for complicated cases or meningitis caused by S. pneumoniae; and ≥21 days for meningitis caused by susceptible Enterobacteriaceae.^{275 296 318}

Meningitis Caused by S. pneumoniae

IV

Initially, 350 mg/kg daily given in 4 divided doses; reduce dosage to 225 mg/kg daily given in 3 divided doses if organism is susceptible to penicillin.^{327 335}

Respiratory Tract Infections

Community-acquired Pneumonia

IV or IM

1 g every 6–8 hours.²⁶⁹

Duration of treatment depends on the causative pathogen, illness severity at the onset of anti-infective therapy, response to treatment, comorbid illness, and complications.²⁶⁹

Gonorrhea and Associated Infections

Uncomplicated Urethral, Cervical, or Rectal Gonorrhea

IM

500 mg as a single dose.^{200 230 366 367 369}

Manufacturers recommend 1 g as a single dose for treatment of rectal gonorrhea in males.^{230 366 367}

Disseminated Gonorrhea†

IV

CDC recommends 1 g every 8 hours; continue for 24–48 hours after improvement begins and switch to an oral regimen (cefixime or cefpodoxime) to complete ≥1 week of treatment.^{200 369}

Lyme Disease†

Early Neurologic Lyme Disease†

IV

2 g every 8 hours for 14 days (range: 10–28 days) recommended by IDSA and others for adults with acute neurologic manifestations (e.g., meningitis, radiculopathy).^{273 351 354}

Lyme Carditis†

IV

2 g every 8 hours for 14 days (range: 14–21 days) recommended by IDSA and others for adults with AV heart block and/or myopericarditis associated with early Lyme disease when a parenteral regimen is indicated (e.g., hospitalized patients).^{351 354}

Parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy when clinically indicated.³⁵¹

Lyme Arthritis†

IV

2 g every 8 hours for 14 days (range: 14–28 days) recommended by IDSA for adults with evidence of neurologic disease or when arthritis has not responded to an oral regimen.³⁵¹

Late Neurologic Lyme Disease†

IV

2 g every 8 hours for 14 days (range: 14–28 days) recommended by IDSA for adults with late neurologic disease affecting the CNS or peripheral nervous system.^{273 351}

Response to anti-infective treatment usually is slow and may be incomplete in such patients.³⁵¹ IDSA states that retreatment is not recommended unless relapse is shown by reliable objective measures.³⁵¹

Perioperative Prophylaxis

Contaminated or Potentially Contaminated Surgery

IV or IM

1 g 30–90 minutes prior to surgery.²³⁰

Cesarean Section

IV or IM

1 g IV as soon as the umbilical cord is clamped, followed by additional 1-g IM or IV doses given 6 and 12 hours after the first dose.²³⁰

Prescribing Limits

Pediatric Patients

Maximum 12 g daily for children weighing >50 kg.^{230 366 367}

Adults

Maximum 12 g daily.^{230 366 367}

Special Populations

Hepatic Impairment

No dosage adjustments required.^{289 290}

Renal Impairment

Patients with Cl_cr <20 mL/minute per 1.73 m² should receive 50% of the usual dose given at the usual time intervals.²³⁰

Patients undergoing hemodialysis should receive 0.5–2 g as a single daily dose with a supplemental dose after each dialysis period.²⁶⁵

Cautions for Claforan

Contraindications

• 
  

  Known hypersensitivity to cefotaxime or other cephalosporins.²³⁰

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible organisms, especially Enterobacter, Pseudomonas, enterococci, or Candida.²³⁰ Careful observation of the patient is essential.²³⁰ Institute appropriate therapy if superinfection occurs.²³⁰

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.²³⁰ C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including cefotaxime, and may range in severity from mild diarrhea to fatal colitis.²³⁰ 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.²³⁰

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.²³⁰ Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.²³⁰

If CDAD is suspected or confirmed, the anti-infective may need to be discontinued.²³⁰ Some mild cases of CDAD may respond to discontinuance alone.^{230 342 343 344 345 346} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{230 342 343 344 345 346}

Cardiac Effects

Potentially life-threatening arrhythmia reported with rapid injection (<1 minute) through a central venous catheter.²³⁰ Do not inject IV over <3 minutes.²³⁰ (See IV Injection under Dosage and Administration.)

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.²³⁰

If a hypersensitivity reaction occurs, discontinue cefotaxime and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).²³⁰

Cross-hypersensitivity

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

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.²³⁰ Cautious use recommended in individuals hypersensitive to penicillins:^a 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.^a

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefotaxime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.²³⁰

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.²³⁰ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.²³⁰

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis.²³⁰ (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Local Effects

May be locally irritating to tissues.²³⁰ Inflammation, phlebitis, and thrombophlebitis reported with IV administration;^b pain, induration, and tenderness may occur at IM injection sites.²³⁰

Perivascular extravasation responds to changing the infusion site;²³⁰ extensive perivascular extravasation may result in tissue damage requiring surgery.²³⁰

Regularly monitor infusion sites and change site when appropriate.²³⁰

Hematologic Effects

Possible transient neutropenia, granulocytopenia, leukopenia, eosinophilia, or thrombocytopenia.²³⁰

Agranulocytosis may occur rarely during prolonged therapy.²³⁰ Monitor blood cell counts if treatment lasts >10 days.²³⁰

CNS Effects

Seizures reported with some cephalosporins, especially in patients with renal impairment who received dosages inappropriate for the degree of renal impairment.²³⁰

If seizures occur, discontinue cefotaxime and administer anticonvulsant therapy as indicated.²³⁰

Sodium Content

Contains approximately 50.5 mg (2.2 mEq) of sodium per g of cefotaxime.^{230 366 367}

Specific Populations

Pregnancy

Category B.²³⁰

Lactation

Distributed into milk; use with caution.²³⁰

Pediatric Use

Adverse effects similar to those reported in adults.²⁹¹

Safety of the chemical components that may leach out of the plastic containing commercially available frozen cefotaxime sodium injections not established.²³⁰

Geriatric Use

No overall differences in safety or efficacy in those ≥65 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.^{230 366 367}

Substantially eliminated by kidneys; risk of toxicity may be greater in those with impaired renal function.^{230 366 367} Select dosage with caution and consider monitoring renal function because of age-related decreases in renal function.^{230 366 367} (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Possible increased plasma half-life and clearance of cefotaxime and its major metabolite.^{117 289}

Renal Impairment

Plasma half-life of cefotaxime and its major metabolite increased in severe renal impairment.^{13 16 19} Possibility of seizures if dosage is inappropriately high for the degree of renal impairment.²³⁰

Dosage adjustment recommended in those with Cl_cr <20 mL/minute per 1.73 m³.²³⁰

Common Adverse Effects

Local reactions at injection sites, hypersensitivity reactions, GI effects.²³⁰

Interactions for Claforan

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	Possible increased risk of nephrotoxicity.230 In vitro evidence of additive or synergistic antibacterial activity; antagonism also reported.a	Closely monitor renal function, especially if high aminoglycoside dosage is used or therapy is prolonged.230 Administer separately; do not admix.230
Probenecid	Decreased renal clearance and increased concentrations of cefotaxime and its metabolites.b
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution.a	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape.)a

Claforan Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed from GI tract; must be administered parenterally.^b

Following IM administration, peak serum concentrations attained within 30 minutes.^{6 8 11 230}

Distribution

Extent

Widely distributed into body tissues and fluids, including aqueous humor, bronchial secretions,²²⁴ sputum, middle ear effusions, bone,¹¹⁵ bile,^{115 116} and ascitic,¹¹⁷ pleural, and prostatic fluids.⁹

Distributed into CSF; highest concentrations attained in those with inflamed meninges.^{263 264 288 290 b}

Crosses the placenta²¹ and is distributed into milk.²¹

Plasma Protein Binding

13–38%.^{2 6 11}

Elimination

Metabolism

Partially metabolized in the liver to desacetylcefotaxime, which has antibacterial activity.^{2 7 14} Desacetylcefotaxime is further metabolized into inactive metabolites in the liver.^{2 7 14 18}

Elimination Route

Cefotaxime and its metabolites excreted principally in urine.^{2 14} In adults with normal renal function, 40–60% of a dose excreted as unchanged drug; 24% excreted as the active metabolite.^b

Half-life

Terminal serum half-life of cefotaxime and desacetylcefotaxime is 0.9–1.7 and 1.4–1.9 hours, respectively.^{2 7 10 11 13 14 19}

Special Populations

Terminal half-lives of cefotaxime and desacetylcefotaxime may be prolonged in patients with hepatic impairment.^{117 289}

Terminal half-life of cefotaxime only slightly prolonged in adults with Cl_cr ≥20 mL/minute per 1.73 m².^{13 16} In those with Cl_cr of ≤10 mL/minute per 1.73 m², terminal half-lives of 1.4–11.5 and 8.2–56.8 hours reported for cefotaxime and desacetylcefotaxime, respectively.^{13 16 19}

Stability

Storage

Parenteral

Powder for Injection

15–30°C;^{230 366 367} protect from light.^{230 366 367}

Powder for injection and solution