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Pronunciation
(sef oh TAKS eem)
Generic Available (U.S.)
Yes: Powder
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of susceptible organisms in lower respiratory tract, skin and skin structure, bone and joint, urinary tract, intra-abdominal, gynecologic as well as bacteremia/septicemia, and documented or suspected central nervous system infections (eg, meningitis). Active against most gram-negative bacilli (not Pseudomonas spp) and gram-positive cocci (not enterococcus). Active against many penicillin-resistant pneumococci.
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. Cefotaxime crosses the human placenta and can be found in fetal tissue. An increased risk of teratogenic effects has not been observed following maternal use. During pregnancy, peak cefotaxime serum concentrations are decreased and the serum half-life is shorter.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Very small amounts of cefotaxime are excreted in breast milk. The manufacturer recommends that caution be exercised when administering cefotaxime to nursing women. Nondose-related effects could include modification of bowel flora. The pregnancy-related changes in cefotaxime pharmacokinetics continue into the early postpartum period.
Contraindications
Hypersensitivity to cefotaxime, any component of the formulation, or other cephalosporins
Warnings/Precautions
Concerns related to adverse effects:
• Arrhythmia: A potentially life-threatening arrhythmia has been reported in patients who received a rapid (<1 minute) bolus injection via central venous catheter.
• Granulocytopenia: Granulocytopenia and more rarely agranulocytosis may develop during prolonged treatment (>10 days).
• Penicillin allergy: Use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tissue inflammation: Minimize tissue inflammation by changing infusion sites when needed.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; modify dosage in severe impairment.
Adverse Reactions
1% to 10%:
Dermatologic: Pruritus, rash
Gastrointestinal: Colitis, diarrhea, nausea, vomiting
Local: Pain at injection site
<1%, postmarketing and/or case reports: Agranulocytosis, alkaline phosphatase increased, ALT increased, anaphylaxis, arrhythmia (after rapid I.V. injection via central catheter), AST increased, bilirubin increased, BUN increased, candidiasis, cholestasis, Coombs test (direct) positive, creatinine increased, encephalopathy, eosinophilia, erythema multiforme, fever, GGT increased, headache, hemolytic anemia, hepatitis, interstitial nephritis, jaundice, LDH increased, leukopenia, moniliasis, neutropenia, phlebitis, pseudomembranous colitis, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, transaminases increased, urticaria, vaginitis
Reactions reported with other cephalosporins: Aplastic anemia, hemorrhage, pancytopenia, renal dysfunction, seizure, superinfection, toxic nephropathy
Metabolism/Transport Effects
None known.
Drug Interactions
Aminoglycosides: Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Probenecid: May increase the serum concentration of Cefotaxime. Management: Avoid cefotaxime doses greater than 6 g/day with concurrent probenecid. Any patients receiving this combination should be monitored closely for evidence of cefotaxime toxicity. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Reconstitution
Reconstituted solution is stable for 12-24 hours at room temperature and 7-10 days when refrigerated and for 13 weeks when frozen. For I.V. infusion in NS or D5W, solution is stable for 24 hours at room temperature, 5 days when refrigerated, or 13 weeks when frozen in Viaflex® plastic containers. Thawed solutions previously of frozen premixed bags are stable for 24 hours at room temperature or 10 days when refrigerated.
Compatibility
Stable in D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, NS; variable stability (consult detailed reference) in peritoneal dialysis solutions
Y-site administration: Compatible: Acyclovir, alprostadil, amifostine, aztreonam, bivalirudin, caffeine citrate, cyclophosphamide, cyclosporine, dexmedetomidine, diltiazem, docetaxel, etoposide phosphate, famotidine, fenoldopam, fentanyl, fludarabine, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend®), hydromorphone, levofloxacin, lorazepam, magnesium sulfate, melphalan, meperidine, milrinone, morphine, ondansetron, oxytocin, propofol, remifentanil, sargramostim, teniposide, thiotepa, tigecycline, vinorelbine. Incompatible: Allopurinol, azithromycin, filgrastim, fluconazole, gemcitabine, hetastarch in NS, pantoprazole, pemetrexed, pentamidine. Variable (consult detailed reference): Anakinra, cisatracurium, midazolam, vancomycin.
Compatibility in syringe: Compatible: Caffeine citrate, dimenhydrinate, heparin. Incompatible: Doxapram, pantoprazole.
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Pharmacodynamics/Kinetics
Distribution: Widely to body tissues and fluids including aqueous humor, ascitic and prostatic fluids, bone; penetrates CSF best when meninges are inflamed
Metabolism: Partially hepatic to active metabolite, desacetylcefotaxime
Half-life elimination:
Cefotaxime: Infants ≤1500 g: 4.6 hours; Infants >1500 g: 3.4 hours; Adults: 1-1.5 hours; prolonged with renal and/or hepatic impairment
Desacetylcefotaxime: 1.5-1.9 hours; prolonged with renal impairment
Time to peak, serum: I.M.: Within 30 minutes
Excretion: Urine (~60% as unchanged drug and metabolites)
Dosage
Usual dosage range:
Infants and Children 1 month to 12 years <50 kg: I.M., I.V.: 50-200 mg/kg/day in divided doses every 6-8 hours
Children ≥50 kg, Children >12 years, and Adults: I.M., I.V.: 1-2 g every 4-12 hours
Uncomplicated infections: I.M., I.V.: 1 g every 12 hours
Moderate-to-severe infections: I.M., I.V.: 1-2 g every 8 hours
Life-threatening infections: I.V.: 2 g every 4 hours
Indication-specific dosing:
Infants and Children:
Community-acquired pneumonia (CAP) (IDSA/PIDS, 2011): Infants >3 months and Children: I.V.: Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out.
Empiric treatment, Haemophilus influenzae, group A Streptococcus, or S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), patient fully immunized for H. influenzae type b and S. pneumoniae, or minimal local resistance to penicillin in invasive pneumococcal strains (alternative to ampicillin or penicillin): 50 mg/kg/dose every 8 hours
Moderate-to-severe infection, patient not fully immunized for H. influenzae type b and S. pneumoniae, or significant local resistance to penicillin in invasive pneumococcal strains (preferred): 50 mg/kg/dose every 8 hours
Moderate-to-severe infection, H. influenzae (beta-lactamase producing) (preferred): 50 mg/kg/dose every 8 hours
Complicated community-acquired intra-abdominal infection (in combination with metronidazole): I.V.: 150-200 mg/kg/day divided every 6-8 hours (Solomkin, 2010)
Lyme disease (as an alternative to ceftriaxone): Cardiac or CNS manifestations: I.V.: 150-200 mg/kg/day in divided doses every 6-8 hours for 14-28 days; maximum daily dose: 6 g/day (Halperin, 2007; Wormser, 2006)
Meningitis (in combination with vancomycin): I.V.: 225-300 mg/kg/day in divided doses every 6-8 hours (Tunkel, 2004)
Sepsis: I.V.: 150 mg/kg/day divided every 8 hours
Infants and Children ≤12 years:
Typhoid fever: I.M., I.V.: 150-200 mg/kg/day in 3-4 divided doses (maximum: 12 g/day); fluoroquinolone resistant: 80 mg/kg/day in 3-4 divided doses (maximum: 12 g/day)
Children ≥50 kg, Children >12 years, and Adults:
Arthritis (septic): I.V.: 1 g every 8 hours
Brain abscess, meningitis: I.V.: 2 g every 4-6 hours in combination with other antimicrobial therapy as warranted (Kowlessar, 2006; Tunkel, 2004)
Caesarean section: I.M., I.V.: 1 g as soon as the umbilical cord is clamped, then 1 g at 6- and 12-hour intervals
Gonorrhea (CDC, 2010) (as an alternative to ceftriaxone):
Uncomplicated: I.M.: 0.5 g as a single dose; may also administer 1 g as a single dose for rectal gonorrhea in males (per the manufacturer).
Disseminated: I.V.: 1 g every 8 hours
Lyme disease (as an alternative to ceftriaxone):
Cardiac manifestations: I.V.: 2 g every 8 hours for 14-21 days (Wormser, 2006)
CNS manifestations: I.V.: 2 g every 8 hours for 10-28 days (Halperin, 2007; Wormser, 2006)
Peritonitis (spontaneous): I.V.: 2 g every 8 hours, unless life-threatening then 2 g every 4 hours (Gilbert, 2011; Runyon, 2009)
Sepsis: I.V.: 2 g every 6-8 hours
Skin and soft tissue:
Bite wounds (animal): I.V.: 2 g every 6 hours
Mixed, necrotizing: I.V.: 2 g every 6 hours, with metronidazole or clindamycin (Stevens, 2005)
Adults:
Complicated community-acquired intra-abdominal infection of mild-to-moderate severity, including hepatic abscess (in combination with metronidazole): I.V.: 1-2 g every 6 -8 hours for 4-7 days (provided source controlled). Note: For severe infections, consider other antimicrobial agents (Bradley, 1987; Kim, 2010; Solomkin, 2010).
Dosing interval in renal impairment:
Manufacturer's labeling: Note: Renal function may be estimated using Cockcroft-Gault formula for dosage adjustment purposes.
Clcr <20 mL/minute/1.73 m2: Dose should be decreased by 50%.
Alternate recommendations:
Children: Note: Glomerular filtration rate (GFR) should be estimated using an acceptable pediatric method (eg, Schwartz equation, Traub-Johnson equation, or a height/weight nomogram):
The following dosage adjustments have been used by some clinicians (Aronoff, 2007):
GFR 30-50 mL/minute/1.73 m2: 35-70 mg/kg/dose every 8-12 hours
GFR 10-29 mL/minute/1.73 m2: 35-70 mg/kg/dose every 12 hours
GFR <10 mL/minute/1.73 m2: 35-70 mg/kg/dose every 24 hours
Intermittent hemodialysis (IHD): 35-70 mg/kg/dose every 24 hours
Peritoneal dialysis: 35-70 mg/kg/dose every 24 hours
Continuous renal replacement therapy (CRRT): 35-70 mg/kg/dose every 12 hours
Adults: The following dosage adjustments have been used by some clinicians (Aronoff, 2007; Heintz, 2009; Trotman, 2005):
GFR >50 mL/minute: Administer every 6 hours (Aronoff, 2007)
GFR 10-50 mL/minute: Administer every 6-12 hours (Aronoff, 2007)
GFR <10 mL/minute: Administer every 24 hours or decrease the dose by 50% (and administer at usual intervals) (Aronoff, 2007)
Intermittent hemodialysis (IHD): Administer 1-2 g every 24 hours (on dialysis days, administer after hemodialysis). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions (Heintz, 2009).
Peritoneal dialysis (PD): 1 g every 24 hours (Aronoff, 2007)
Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH: 1-2 g every 8-12 hours
CVVHD: 1-2 g every 8 hours
CVVHDF: 1-2 g every 6-8 hours
Dosing adjustment in hepatic impairment: Dosage reduction generally not necessary unless concurrent severe renal impairment. Consider dose reduction to 0.5 g every 12 hours in patients with Clcr <5 mL/minute (Wise, 1985).
Administration: I.M.
Inject deep I.M. into large muscle mass.
Administration: I.V.
Inject direct I.V. over at least 3-5 minutes. Infuse intermittent infusion over 30 minutes.
Administration: I.V. Detail
pH: 5.0-7.5 (injectable solution)
Monitoring Parameters
Observe for signs and symptoms of anaphylaxis during first dose; CBC with differential (especially with long courses); renal function
Test Interactions
Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction
Dietary Considerations
Some products may contain sodium.
Patient Education
This medication is administered by injection or infusion. Report immediately any redness, swelling, burning, or pain at injection/infusion site; chest pain, palpitations, respiratory difficulty or swallowing; or itching or hives. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause diarrhea, GI distress, or nausea. Report unresolved or persistent diarrhea, opportunistic infection (vaginal itching or drainage, sores in mouth, blood in stool or urine, easy bleeding or bruising, unusual fever or chills), or respiratory difficulty.
Geriatric Considerations
Adjust dose for renal impairment.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause nervousness; case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins
Mental Health: Effects on Psychiatric Treatment
May rarely cause neutropenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess results of culture/sensitivity tests and patient's allergy history prior to therapy. Evaluate CBC with differential. Monitor for diarrhea, nausea/vomiting, and nephrotoxicity regularly during therapy. Teach patient to report hypersensitivity and opportunistic infection.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Infusion, premixed iso-osmotic solution:
Claforan®: 1 g (50 mL); 2 g (50 mL) [contains sodium ~50.5 mg (2.2 mEq) per cefotaxime 1 g]
Injection, powder for reconstitution: 500 mg, 1 g, 2 g, 10 g, 20 g [DSC]
Claforan®: 500 mg, 1 g, 2 g, 10 g [contains sodium ~50.5 mg (2.2 mEq) per cefotaxime 1 g]
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 55, 149.
Bradley JS, Byington CL, Shah SS, et al. “The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America”, Clin Infect Dis, 2011, 53(7):e25-76.
Brogden RN and Spencer CM, “Cefotaxime. A Reappraisal of Its Antibacterial Activity and Pharmacokinetic Properties, and a Review of Its Therapeutic Efficacy When Administered Twice Daily for the Treatment of Mild-to-Moderate Infections,” Drugs, 1997, 53(3):483-510.
Chow AW, Benninger MS, Brook I, et al, “IDSA Clinical Practice Guideline for Acute Bacterial Rhinosinusitis in Children and Adults,” Clin Infect Dis, 2012, 54(8):e72-112.
Deeter RG, Weinstein MP, Swanson KA, et al, “Crossover Assessment of Serum Bactericidal Activity and Pharmacokinetics of Five Broad-Spectrum Cephalosporins in the Elderly,” Antimicrob Agents Chemother, 1990, 34(6):1007-13.
Gilbert DN, Moellering RC, Eliopoulos GM, et al, eds, The Sanford Guide To Antimicrobial Therapy, 41st ed, Sperryville, VA: Antimicrobial Therapy, Inc, 2011, 55.
Halperin JJ, Shapiro ED, Logigian E, et al, “Practice Parameter: Treatment of Nervous System Lyme Disease (an Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology," Neurology, 2007, 69(1):91-102.
Heintz BH, Matzke GR, Dager WE, “Antimicrobial Dosing Concepts and Recommendations for Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis,” Pharmacotherapy, 2009, 29(5):562-77.
Klein NC and Cunha BA, “Third-Generation Cephalosporins,” Med Clin North Am, 1995, 79(4):705-19.
Ludwig E, Székely É, Csiba A, et al, “Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Elderly Patients,” Drugs, 1988, 35(Suppl 2):51-6.
Marshall WF and Blair JE, “The Cephalosporins,” Mayo Clin Proc, 1999, 74(2):187-95.
Runyon BA, “Management of Adult Patients With Ascites Due to Cirrhosis: An Update,” Hepatology, 2009, 49(6):2087-107.
Solomkin JS, Mazuski JE, Bradley JS, et al, “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America,” Clin Infect Dis, 2010, 50(2):133-64.
Spritzer R, Kamp HJ, Dzoljic G, et al, “Five Years of Cefotaxime Use in a Neonatal Intensive Care Unit,” Pediatr Infect Dis J, 1990, 9(2):92-6.
Stevens DL, Bisno AL, Chambers HF, et al, “Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections,” Clin Infect Dis, 2005; 41(10):1373–406.
Trotman RL, Williamson JC, Shoemaker DM, et al, "Antibiotic Dosing in Critically Ill Adult Patients Receiving Continuous Renal Replacement Therapy," Clin Infect Dis, 2005, 41(8):1159-66.
Tunkel AR, Hartman BJ, Kaplan SL, et al, “Practice Guidelines for the Management of Bacterial Meningitis,” Clin Infect Dis, 2004, 39(9):1267-84.
Wormser GP, Dattwyler RJ, Shapiro ED, et al, “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America,” Clin Infect Dis, 2006, 43(9):1089-134.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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