No

Antibiotic, Cephalosporin (Third Generation)

Treatment of lower respiratory tract infections, skin and skin structure infections, bone and joint infections, intra-abdominal and urinary tract infections, sepsis and meningitis due to susceptible organisms; documented or suspected infection due to susceptible organisms in home care patients and patients without I.V. line access; treatment of documented or suspected gonococcal infection or chancroid; emergency room management of patients at high risk for bacteremia, periorbital or buccal cellulitis, salmonellosis or shigellosis, and pneumonia of unestablished etiology (<5 years of age); treatment of Lyme disease, depends on the stage of the disease (used in Stage II and Stage III, but not stage I; doxycycline is the drug of choice for Stage I)

B

Hypersensitivity to ceftriaxone sodium, any component, or cephalosporins; do not use in hyperbilirubinemic neonates, particularly those who are premature since ceftriaxone is reported to displace bilirubin from albumin binding sites

Modify dosage in patients with severe renal impairment, prolonged use may result in superinfection; use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, urticaria); may cause antibiotic-associated colitis or colitis secondary to C. difficile

1% to 10%:

Dermatologic: Rash (1.7%)

Gastrointestinal: Diarrhea (2.7%)

Hematologic: Eosinophilia (6%), thrombocytosis (5.1%), leukopenia (2.1%)

Hepatic: Elevated transaminases (3.1% to 3.3%)

Local: Pain, induration at injection site (1%)

Renal: Increased BUN (1.2%)

<1%: Phlebitis, pruritus, fever, chills, anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia, prolonged PT, nausea, vomiting, dysgeusia, increased alkaline phosphatase, increased bilirubin, increased creatinine, urinary casts, headache, dizziness, candidiasis, vaginitis, diaphoresis, flushing

Other reactions with cephalosporins include anaphylaxis, paresthesia, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioedema, pseudomembranous colitis, hemolytic anemia, encephalopathy, asterixis, neuromuscular excitability, seizures, serum-sickness reactions, renal dysfunction, interstitial nephritis, toxic nephropathy, cholestasis, aplastic anemia, hemolytic anemia, pancytopenia, agranulocytosis, colitis, hemorrhage, superinfection

Symptoms of overdose include neuromuscular hypersensitivity, convulsions especially with renal insufficiency; many beta-lactam antibiotics have the potential to cause neuromuscular hyperirritability or seizures

Hemodialysis may be helpful to aid in the removal of the drug from the blood, otherwise most treatment is supportive or symptom directed

Increased effect:

Aminoglycosides may result in synergistic antibacterial activity

High-dose probenecid decreases clearance

Increased toxicity: Aminoglycosides increase nephrotoxic potential

Reconstituted solution (100 mg/mL) is stable for 3 days at room temperature and 3 days when refrigerated; for I.V. infusion in NS or D₅W solution is stable for 3 days at room temperature, 10 days when refrigerated, or 26 weeks when frozen; after freezing, thawed solution is stable for 3 days at room temperature or 10 days when refrigerated

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.

Absorption: I.M.: Well absorbed

Distribution: Widely distributed throughout the body including gallbladder, lungs, bone, bile, CSF (diffuses into the CSF at higher concentrations when the meninges are inflamed); crosses placenta, reaches amniotic fluid and milk

Protein binding: 85% to 95%

Half-life: Normal renal and hepatic function: 5-9 hours

Neonates: Postnatal: 1-4 days: 16 hours; 9-30 days: 9 hours

Time to peak serum concentration: I.M.: Within 1-2 hours

Elimination: Excreted unchanged in urine (33% to 65%) by glomerular filtration and in feces

I.M., I.V.:

Postnatal age less than or equal to 7 days: 50 mg/kg/day given every 24 hours

Postnatal age >7 days:

less than or equal to 2000 g: 50 mg/kg/day given every 24 hours

>2000 g: 50-75 mg/kg/day given every 24 hours

Gonococcal prophylaxis: 25-50 mg/kg as a single dose (dose not to exceed 125 mg)

Gonococcal infection: 25-50 mg/kg/day (maximum dose: 125 mg) given every 24 hours for 10-14 days

Infants and Children: 50-75 mg/kg/day in 1-2 divided doses every 12-24 hours; maximum: 2 g/24 hours

Meningitis: 100 mg/kg/day divided every 12-24 hours, up to a maximum of 4 g/24 hours; loading dose of 75 mg/kg/dose may be given at start of therapy

Otitis media: Single I.M. injection

Uncomplicated gonococcal infections, sexual assault, and STD prophylaxis: I.M.: 125 mg as a single dose plus doxycycline

Complicated gonococcal infections:

Infants: I.M., I.V.: 25-50 mg/kg/day in a single dose (maximum: 125 mg/dose); treat for 7 days for disseminated infection and 7-14 days for documented meningitis

<45 kg: 50 mg/kg/day once daily; maximum: 1 g/day; for ophthalmia, peritonitis, arthritis, or bacteremia: 50-100 mg/kg/day divided every 12-24 hours; maximum: 2 g/day for meningitis or endocarditis

>45 kg: 1 g/day once daily for disseminated gonococcal infections; 1-2 g dose every 12 hours for meningitis or endocarditis

Acute epididymitis: I.M.: 250 mg in a single dose

Adults: 1-2 g every 12-24 hours (depending on the type and severity of infection); maximum dose: 2 g every 12 hours for treatment of meningitis

Uncomplicated gonorrhea: I.M.: 250 mg as a single dose

Surgical prophylaxis: 1 g 30 minutes to 2 hours before surgery

Dosing adjustment in renal or hepatic impairment: No change necessary

Hemodialysis: Not dialyzable (0% to 5%); administer dose postdialysis

Peritoneal dialysis: Administer 750 mg every 12 hours

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Removes 10 mg of ceftriaxone per liter of filtrate per day

Observe for signs and symptoms of anaphylaxis

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

Case reports of euphoria, delusion, illusions, and depersonalization with cephalosporins

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This medication is administered I.M. or I.V. Drink 2-3 L fluid/day. If diarrhea occurs, yogurt or buttermilk may help. May cause false-positive test with Clinitest®; use another form of testing. May interfere with oral contraceptives; additional contraceptive measures are necessary. Report severe, unresolved diarrhea; vaginal itching or drainage; sores in mouth; blood, pus, or mucus in stool or urine; easy bleeding or bruising; unusual fever or chills; rash; or respiratory difficulty. Breast-feeding precautions: Consult prescriber if breast-feeding.

For I.M. injection, the maximum concentration is 250 mg/mL; ceftriaxone can be diluted with 1:1 water and 1% lidocaine for I.M. administration. Do not admix with aminoglycosides in same bottle/bag.

Infusion, as sodium, premixed (frozen): 1 g in D_3.8W (50 mL); 2 g in D_2.4W (50 mL)

Powder for injection, as sodium: 250 mg, 500 mg, 1 g, 2 g, 10 g

"1993 Sexually Transmitted Diseases Treatment Guidelines," MMWR Morb Mortal Wkly Rep, 1993, 42(RR-14):1-102.

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Centers for Disease Control and Prevention, "1998 Guidelines for Treatment of Sexually Transmitted Diseases," MMWR Morb Mortal Wkly Rep, 1998, 47(RR-1):1-111.

Committee on Adolescence, American Academy of Pediatrics, "Sexual Assault and the Adolescent," Pediatrics, 1994, 94(5):761-5.

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.

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Kroh UF, Lennartz H, Edwards DJ, et al, "Pharmacokinetics of Ceftriaxone in Patients Undergoing Continuous Veno-Venous Hemofiltration," J Clin Pharmacol, 1996, 36(12):1114-9.

Luderer JR, Patel IH, Durkin J, et al, "Age and Ceftriaxone Kinetics," Clin Pharmacol Ther, 1984, 35(1):19-25.

Marshall WF and Blair JE, "The Cephalosporins," Mayo Clin Proc, 1999, 74(2):187-95.

Richards DM, Heel RC, Brogden RN, et al, "Ceftriaxone: A Review of Its Antibacterial Activity, Pharmacological Properties and Therapeutic Use," Drugs, 1984, 27(6):469-527.

Schaad UB, Suter S, Gianella-Borradori A, et al, "A Comparison of Ceftriaxone and Cefuroxime for the Treatment of Bacterial Meningitis in Children," N Engl J Med, 1990, 322(3):141-7.