|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(SEF tay zi deem)
Generic Available (U.S.)
Yes: Injection
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of documented susceptible Pseudomonas aeruginosa infection and infections due to other susceptible aerobic gram-negative organisms; empiric therapy of a febrile, granulocytopenic patient
Use: Unlabeled
Bacterial endophthalmitis
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; therefore, ceftazidime is classified as pregnancy category B. Ceftazidime crosses the placenta and reaches the cord serum and amniotic fluid. Maternal peak serum concentration is unchanged in the first trimester. After the first trimester, serum concentrations decrease by approximately 50% of those in nonpregnant patients. Renal clearance is increased during pregnancy.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Very small amounts of ceftazidime are excreted in breast milk. The manufacturer recommends that caution be exercised when administering ceftazidime to nursing women. Ceftazidime in not absorbed when given orally; therefore, any medication that is distributed to human milk should not result in systemic concentrations in the nursing infant. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to ceftazidime, any component of the formulation, or other cephalosporins
Warnings/Precautions
Concerns related to adverse effects:
• Elevated INR: May be associated with increased INR, especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.
• 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.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; modify dosage in severe impairment.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
Adverse Reactions
1% to 10%:
Gastrointestinal: Diarrhea (1%)
Local: Pain at injection site (1%)
Miscellaneous: Hypersensitivity reactions (2%)
<1%: Anaphylaxis, angioedema, asterixis, BUN increased, candidiasis, creatinine increased, dizziness, encephalopathy, eosinophilia, erythema multiforme, fever, headache, hemolytic anemia, hyperbilirubinemia, jaundice, leukopenia, myoclonus, nausea, neuromuscular excitability, paresthesia, phlebitis, pruritus, pseudomembranous colitis, rash, Stevens-Johnson syndrome, thrombocytosis, toxic epidermal necrolysis, transaminases increased, vaginitis, vomiting
Reactions reported with other cephalosporins: Seizure, urticaria, serum-sickness reactions, renal dysfunction, interstitial nephritis, toxic nephropathy, elevated BUN, elevated creatinine, cholestasis, aplastic anemia, hemolytic anemia, pancytopenia, agranulocytosis, colitis, prolonged PT, hemorrhage, superinfection
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 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
Storage
Fortaz®: Store dry vials at 15°C to 30°C (59°F to 86°F). Protect from light. Reconstituted solution and solution further diluted for I.V. infusion are stable for 12 hours at room temperature, for 3 days when refrigerated, or for 12 weeks when frozen at -20°C (-4°F). After freezing, thawed solution in SWFI for I.M. administration is stable for 3 hours at room temperature or for 3 days when refrigerated; thawed solution in NS in a Viaflex® small volume container for I.V. administration is stable for 12 hours at room temperature or for 3 days when refrigerated; and thawed solution in SWFI in the original container is stable for 8 hours at room temperature or for 3 days when refrigerated.
Premixed frozen solution: Store frozen at -20°C (-4°F). Thawed solution is stable for 8 hours at room temperature or for 3 days under refrigeration; do not refreeze.
Fortaz®, Tazicef®: ADD-Vantage® vials: Following dilution, may be stored for up to 12 hours at room temperature or for 3 days under refrigeration. Freezing solutions in the ADD-Vantage® system is not recommended. Joined vials that have not been activated may be used within 14 days.
Tazicef® vials: Store dry vials at 20°C to 25°C (68°F to 77°F). Protect from light. Reconstituted vials and solution further diluted for I.V. infusion are stable for 24 hours at room temperature, for 7 days when refrigerated, or for 12 weeks when frozen at -20°C (-4°F). When thawed, solution is stable for 8 hours at room temperature and 4 days when refrigerated.
Reconstitution
I.M.: Using SWFI, bacteriostatic water, lidocaine 0.5%, or lidocaine 1%, reconstitute the 500 mg vials with 1.5 mL or the 1 g vials with 3 mL; final concentration of ~280 mg/mL
I.V.: Using SWFI, reconstitute as follows (Note: After reconstitution, may dilute further with a compatible solution to administer via I.V. infusion):
Fortaz®:
~100 mg/mL solution:
500 mg vial: 5.3 mL SWFI (withdraw 5 mL from the reconstituted vial to obtain a 500 mg dose)
1 g vial: 10 mL SWFI (withdraw 10 mL from the reconstituted vial to obtain a 1 g dose)
6 g vial: 56 mL SWFI (withdraw 10 mL from the reconstituted vial to obtain a 1 g dose)
~170 mg/mL solution: 2 g vial: 10 mL SWFI (withdraw 11.5 mL from the reconstituted vial to obtain a 2 g dose)
~200 mg/mL solution: 6 g vial: 26 mL SWFI (withdraw 5 mL from the reconstituted vial to obtain a 1 g dose)
Tazicef®:
~95 mg/mL solution: 1 g vial: 10 mL SWFI (withdraw 10.6 mL from the reconstituted vial to obtain a 1 g dose)
~180 mg/mL solution: 2 g vial: 10 mL SWFI (withdraw 11.2 mL from the reconstituted vial to obtain a 2 g dose)
Fortaz®, Tazicef®: ADD-Vantage® vials: Dilute in 50 or 100 mL of D5W, NS, or 0.45% sodium chloride in an ADD-Vantage® flexible diluent container only.
Compatibility
Stable in D5NS, D5W, D10W, LR, NS, Ringer's injection, sterile water for injection, in peritoneal dialysis solutions
Y-site administration: Compatible: Acyclovir, allopurinol, amifostine, amikacin, anidulafungin, aztreonam, bivalirudin, ciprofloxacin, daptomycin, dexmedetomidine, diltiazem, docetaxel, dopamine, enalaprilat, epinephrine, esmolol, etoposide phosphate, famotidine, fenoldopam, filgrastim, fludarabine, foscarnet, furosemide, gallium nitrate, gemcitabine, gentamicin, granisetron, heparin, hetastarch in lactate electrolyte injection (Hextend®), hydromorphone, insulin (regular), ketamine, labetalol, linezolid, melphalan, meperidine, methylprednisolone sodium succinate, milrinone, morphine, ondansetron, paclitaxel, ranitidine, remifentanil, sufentanil, tacrolimus, telavancin, teniposide, thiotepa, tigecycline, tobramycin, valproate sodium, vinorelbine, zidovudine. Incompatible: Acetylcysteine, amiodarone, amphotericin B cholesteryl sulfate complex, amsacrine, azithromycin, caspofungin, dobutamine, doxorubicin liposome, erythromycin lactobionate, idarubicin, midazolam, pantoprazole, pemetrexed, pentamidine, phenytoin, warfarin. Variable (consult detailed reference): Aminopylline, cisatracurium, doxapram, drotrecogin alfa, fluconazole, nicardipine, propofol, sargramostim, theophylline, vancomycin.
Compatibility in syringe: Compatible: Dimenhydrinate, hydromorphone. Incompatible: 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 throughout the body including bone, bile, skin, CSF (higher concentrations achieved when meninges are inflamed), endometrium, heart, pleural and lymphatic fluids
Protein binding: 17%
Half-life elimination: 1-2 hours, prolonged with renal impairment; Neonates <23 days: 2.2-4.7 hours
Time to peak, serum: I.M.: ~1 hour
Excretion: Urine (80% to 90% as unchanged drug)
Dosage
Usual dosage range:
Infants and Children 1 month to 12 years: I.V.: 30-50 mg/kg/dose every 8 hours (maximum dose: 6 g/day)
Adults: I.M., I.V.: 500 mg to 2 g every 8-12 hours
Indication-specific dosing:
Bacterial arthritis (gram-negative bacilli): I.V.: 1-2 g every 8 hours
Cystic fibrosis: I.V.: 30-50 mg/kg/dose every 8 hours (maximum: 6 g/day)
Endophthalmitis, bacterial (unlabeled use): Intravitreal: 2.25 mg/0.1 mL NS in combination with vancomycin
Intra-abdominal infection, severe (in combination with metronidazole): I.V.: 2 g every 8 hours for 4-7 days (provided source controlled). Not recommended for hospital-acquired intra-abdominal infections (IAI) associated with multidrug-resistant gram negative organisms or in mild-to-moderate community-acquired IAIs due to risk of toxicity and the development of resistant organisms (Solomkin, 2010).
Melioidosis: I.V.: 40 mg/kg/dose every 8 hours for 10 days, followed by oral therapy with doxycycline or TMP/SMX
Otitis externa: I.V.: 2 g every 8 hours
Peritonitis (CAPD):
Anuric, intermittent: 1000-1500 mg/day
Anuric, continuous (per liter exchange): Loading dose: 250 mg; maintenance dose: 125 mg
Severe infections, including meningitis, complicated pneumonia, endophthalmitis, CNS infection, osteomyelitis, gynecological, skin and soft tissue: I.V.: 2 g every 8 hours
Dosing interval in renal impairment:
Clcr 30-50 mL/minute: Administer every 12 hours
Clcr 10-30 mL/minute: Administer every 24 hours
Clcr <10 mL/minute: Administer every 48-72 hours
Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (50% to 100%): 0.5-1 g every 24 hours or 1-2 g every 48-72 hours (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD): Loading dose of 1 g, followed by 500 mg every 24 hours
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: Loading dose of 2 g followed by 1-2 g every 12 hours
CVVHD/CVVHDF: Loading dose of 2 g followed by either 1 g every 8 hours or 2 g every 12 hours. Note: Dosage of 1 g every 8 hours results in similar steady-state concentrations as 2 g every 12 hours and is more cost effective. Dosage of 2 g every 8 hours may be needed for gram-negative rods with MIC ≥4 mg/L (Heintz, 2009).
Note: For patients receiving CVVHDF, some recommend giving a loading dose of 2 g followed by 3 g over 24 hours as a continuous I.V. infusion to maintain concentrations ≥4 times the MIC for susceptible pathogens (Heintz, 2009).
Administration: I.M.
Inject deep I.M. into large mass muscle.
Administration: I.V.
Ceftazidime can be administered IVP over 3-5 minutes or I.V. intermittent infusion over 15-30 minutes.
Administration: I.V. Detail
Any carbon dioxide bubbles that may be present in the withdrawn solution should be expelled prior to injection. Administer around-the-clock to promote less variation in peak and trough serum levels.
pH: 5-8 (Fortaz®); 5.0-7.5 (Tazicef®)
Monitoring Parameters
Observe for signs and symptoms of anaphylaxis during first dose
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 infusion or injection. Report immediately any redness, swelling, burning, or pain at injection/infusion site. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause diarrhea. Report rash; breathing or swallowing difficulty; persistent diarrhea, nausea, vomiting, or abdominal pain; changes in urinary pattern or pain on urination; opportunistic infection (eg, vaginal itching or drainage, sores in mouth, blood in stool or urine, unusual fever or chills); or CNS changes (eg, irritability, agitation, nervousness, insomnia, hallucinations).
Geriatric Considerations
Changes in renal function associated with aging and corresponding alterations in pharmacokinetics result in every 12-hour dosing being an adequate dosing interval. Adjust dose based on renal function.
Additional Information
With some organisms, resistance may develop during treatment (including Enterobacter spp and Serratia spp). Consider combination therapy or periodic susceptibility testing for organisms with inducible resistance.
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
Monitor for nephrotoxicity. Assess prothrombin time. Monitor for hemolytic anemia, hypoprothrombinemia, and bleeding. Teach patient to report opportunistic infection and hypersensitivity reaction.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Infusion, premixed iso-osmotic solution, as sodium [strength expressed as base]:
Fortaz®: 1 g (50 mL); 2 g (50 mL) [contains sodium ~54 mg (2.3 mEq)/g]
Injection, powder for reconstitution: 500 mg [DSC], 1 g, 2 g, 6 g
Fortaz®: 500 mg, 1 g, 2 g, 6 g [contains sodium ~54 mg (2.3 mEq)/g]
Tazicef®: 1 g, 2 g, 6 g [contains sodium ~54 mg (2.3 mEq)/g]
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
American Thoracic Society and Infectious Diseases Society of America, “Guidelines for the Management of Adults With Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia,” Am J Respir Crit Care Med, 2005, 171(4):388-416.
Davies SP, Lacey LF, Kox WJ, et al, “Pharmacokinetics of Cefuroxime and Ceftazidime in Patients With Acute Renal Failure Treated by Continuous Arteriovenous Haemodialysis,” Nephrology, Dialysis, Transplantation, 1991, 6(120):971-6.
Donowitz GR and Mandell GL, “Beta-Lactam Antibiotics,” N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.
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.
Marshall WF and Blair JE, “The Cephalosporins,” Mayo Clin Proc, 1999, 74(2):187-95.
McCracken GH Jr, Threlkeld N, and Thomas ML, “Pharmacokinetics of Ceftazidime in Newborn Infants,” Antimicrob Agents Chemother, 1984, 26(4):583-4.
Rains CP, Bryson HM, and Peters DH, “Ceftazidime. An Update of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Efficacy,” Drugs, 1995, 49(4):577-617.
“Results of the Endophthalmitis Vitrectomy Study. A Randomized Trial of Immediate Vitrectomy and of Intravenous Antibiotics for the Treatment of Postoperative Bacterial Endophthalmitis. Endophthalmitis Vitrectomy Study Group,” Arch Ophthalmol, 1995, 113(12):1479-96.
Robinson DG, Cookson TL, and Frisafe JA, “Concentration Guidelines for Parenteral Antibiotics in Fluid-Restricted Patients,” Drug Intell Clin Pharm, 1987, 21(12):985-9.
Roth DB and Flynn HW Jr, “Antibiotic Selection in the Treatment of Endophthalmitis: The Significance of Drug Combinations and Synergy,” Surv Ophthalmol, 1997, 41(5):395-401.
Sirgo MA and Norris S, “Ceftazidime in the Elderly: Appropriateness of Twice-Daily Dosing,” DICP Ann Pharmacother, 1991, 25(3):284-8.
Slaker RA and Danielson B, “Neurotoxicity Associated With Ceftazidime Therapy in Geriatric Patients With Renal Dysfunction,” Pharmacotherapy, 1991, 11(4):351-2.
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.
Stea S, Bachelor T, Cooper M, et al, “Disposition and Bioavailability of Ceftazidime After Intraperitoneal Administration in Patients Receiving Continuous Ambulatory Peritoneal Dialysis,” J Am Soc Nephrol, 1996, 7(11):2399-402.
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.
Vlasses PH, Bastion WA, Behal R, et al, “Ceftazidime Dosing in the Elderly: Economic Implications,” Ann Pharmacother, 1993, 27(7-8):967-71.
Wilson W, Taubert KA, Gewitz M, et al, “Prevention of Infective Endocarditis. Guidelines From the American Heart Association. A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group,” Circulation, 2007, 116(15):1736-54.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
| 
