Product Name
:
ROSS
Chemical Name
:
Ceftriaxone (Sodium)
Therapeutic Category
:
Antimicrobial
Pharmacologic Category
:
Antibiotic, Cephalosporin (Third Generation)
Pharmaceutical Form
:
Vial
Composition
:
Ceftriaxone (Sodium) 250mg /500mg /1000mg /2000mg
Dosing
 
Dosing: Adult
Dosage range: Usual dose: 1-2 g every 12-24 hours, depending on the type and severity of infection
Arthritis, septic (unlabeled use): I.V.: 1-2 g once daily
Brain abscess (unlabeled use): I.V.: 2 g every 12 hours with metronidazole
Cavernous sinus thrombosis (unlabeled use): I.V.: 2 g once daily with vancomycin or linezolid
Chancroid (unlabeled use): I.M.: 250 mg as single dose (CDC, 2010)
Chemoprophylaxis for high-risk contacts (close exposure to patients with invasive meningococcal disease) (unlabeled use): I.M.: 250 mg in a single dose
Cholecystitis, mild-to-moderate: 1-2 g every 12-24 hours for 4-7 days (provided source controlled)
Gonococcal infections (CDC, 2010):
Conjunctivitis, complicated (unlabeled use): I.M., I.V.: 1 g in a single dose
Disseminated (unlabeled use): I.M., I.V.: 1 g once daily for 24-48 hours may switch to cefixime (after improvement noted) to complete a total of 7 days of therapy
Endocarditis (unlabeled use): I.M., I.V.: 1-2 g every 24 hours for at least 28 days
Epididymitis, acute (unlabeled use): I.M.: 250 mg in a single dose with doxycycline
Meningitis: I.M., I.V.: 1-2 g every 12 hours for 10-14 days
Proctitis (unlabeled use): I.M.: 250 mg in a single dose with doxycycline
Prostatitis (unlabeled use): I.M.: 125-250 mg in a single dose with doxycycline
Uncomplicated cervicitis, pharyngitis, urethritis (unlabeled use): I.M.: 250 mg in a single dose with doxycycline or azithromycin
Infective endocarditis: I.M., I.V.:
Native valve: 2 g once daily for 2-4 weeks; Note: If using 2-week regimen, concurrent gentamicin is recommended
Prosthetic valve: I.M., I.V.: 2 g once daily for 6 weeks (with or without 2 weeks of gentamicin [dependent on penicillin MIC]); Note: For HACEK organisms, duration of therapy is 4 weeks
Enterococcus faecalis (resistant to penicillin, aminoglycoside, and vancomycin), native or prosthetic valve: 2 g twice daily for ≥8 weeks administered concurrently with ampicillin
Prophylaxis: I.M., I.V.: 1 g 30-60 minutes before procedure. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (in combination with metronidazole): 1-2 g every 12-24 hours for 4-7 days (provided source controlled)
Lyme disease (unlabeled use): I.V.: 2 g once daily for 14-28 days
Mastoiditis (hospitalized; unlabeled use): I.V.: 2 g once daily; >60 years old: 1 g once daily
Meningitis: I.V.: 2 g every 12 hours for 7-14 days (longer courses may be necessary for selected organisms)
Orbital cellulitis (unlabeled use) and endophthalmitis: I.V.: 2 g once daily
Pelvic inflammatory disease: I.M.: 250 mg in a single dose plus doxycycline (with or without metronidazole) (CDC, 2010)
Pneumonia, community-acquired: I.V.: 1 g once daily, usually in combination with a macrolide; consider 2 g/day for patients at risk for more severe infection and/or resistant organisms (ICU status, age >65 years, disseminated infection)
Prophylaxis against sexually-transmitted diseases following sexual assault: I.M.: 250 mg as a single dose (in combination with azithromycin and metronidazole) (CDC, 2010)
Pyelonephritis (acute, uncomplicated): Females: I.V.: 1-2 g once daily (Stamm, 1993). Many physicians administer a single parenteral dose before initiating oral therapy (Warren, 1999).
Septic/toxic shock/necrotizing fasciitis (unlabeled use): I.V.: 2 g once daily; with clindamycin for toxic shock
Surgical prophylaxis: I.V.: 1 g 30 minutes to 2 hours before surgery
Cholecystectomy: 1-2 g every 12-24 hours, discontinue within 24 hours unless infection outside gallbladder suspected
Syphilis (unlabeled use): I.M., I.V.: 1 g once daily for 10-14 days; Note: Alternative treatment for early syphilis, optimal dose, and duration have not been defined (CDC, 2010)
Typhoid fever (unlabeled use): I.V.: 2 g once daily for 14 days
Whipple’s disease (unlabeled use): Initial: 2 g once daily for 10-14 days, then oral therapy for ~1 year.

Dosing: Pediatric
Dosage range: Infants and Children: Usual dose: I.M., I.V.:
Mild-to-moderate infections: 50-75 mg/kg/day in 1-2 divided doses every 12-24 hours (maximum: 2 g/day); continue until at least 2 days after signs and symptoms of infection have resolved
Serious infections: 80-100 mg/kg/day in 1-2 divided doses (maximum: 4 g/day)
Chemoprophylaxis for high-risk contacts (close exposure to patients with invasive meningococcal disease) (unlabeled use):
Children <15 years: I.M.: 125 mg in a single dose
Children ≥15 years: Refer to adult dosing.
Epididymitis, acute: Children >8 years (≥45 kg) and Adolescents (unlabeled use): I.M.: 125 mg in a single dose
Epiglottis (unlabeled use): I.M., I.V.: 50-100 mg/kg once daily; reported duration of treatment ranged from 2-14 days
Gonococcal infections:
Conjunctivitis, complicated (unlabeled use): I.M.:
<45 kg: 50 mg/kg in a single dose (maximum: 1 g)
≥45 kg: 1 g in a single dose
Disseminated (unlabeled use): I.M., I.V.:
Infants: 25-50 mg/kg/day as single daily dose for 7 days (10-14 days for meningitis) (CDC, 2010). Note: Use contraindicated in hyperbilirubinemic neonates.
Children <45 kg: 25-50 mg/kg once daily (maximum: 1 g)
Children ≥45 kg: 1 g once daily for 7 days
Endocarditis (unlabeled use):
<45 kg: I.M., I.V.: 50 mg/kg/day every 12 hours (maximum: 2 g/day) for at least 28 days
≥45 kg: I.V.: 1-2 g every 12 hours, for at least 28 days
Prophylaxis (due to maternal gonococcal infection): I.M., I.V.: 25-50 mg/kg as a single dose (maximum: 125 mg) (CDC, 2010)
Uncomplicated cervicitis, pharyngitis, proctitis, urethritis, vulvovaginitis (unlabeled use) (CDC, 2010):
≤45 kg: I.M.: 125 mg as a single dose
>45 kg: Refer to adult dosing.
Infective endocarditis: I.M., I.V.:
Native valve: 100 mg/kg once daily for 2-4 weeks; Note: If using 2-week regimen, concurrent gentamicin is recommended
Prosthetic valve: 100 mg/kg once daily for 6 weeks (with or without 2 weeks of gentamicin [dependent on penicillin MIC]); Note: For HACEK organisms, duration of therapy is 4 weeks
Enterococcus faecalis (resistant to penicillin, aminoglycoside, and vancomycin), native or prosthetic valve: 100 mg/kg once daily for ≥8 weeks administered concurrently with ampicillin
Prophylaxis: 50 mg/kg 30-60 minutes before procedure; maximum dose: 1 g. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.
Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.
Lyme disease, persistent arthritis (unlabeled use): I.M., I.V.: 75-100 mg/kg (maximum: 2 g) for 2-4 weeks
Meningitis: I.M., I.V.:
Uncomplicated: Loading dose of 100 mg/kg (maximum: 4 g), followed by 100 mg/kg/day divided every 12-24 hours (maximum: 4 g/day); usual duration of treatment is 7-14 days
Gonococcal, complicated:
<45 kg: 50 mg/kg/day given every 12 hours (maximum: 2 g/day); usual duration of treatment is 10-14 days
>45 kg: I.V.: 1-2 g every 12 hours; usual duration of treatment is 10-14 days
Ophthalmia neonatorum (unlabeled use): Infants: I.M., I.V.: 25-50 mg/kg as a single dose (maximum: 125 mg) (CDC, 2010)
Otitis media: I.M.:
Acute: 50 mg/kg in a single dose (maximum: 1 g)
Persistent or relapsing (unlabeled use): 50 mg/kg once daily for 3 days
Pneumonia: I.V.: 50-75 mg/kg once daily
Prophylaxis against sexually-transmitted diseases following sexual assault (unlabeled use):
≤45 kg: I.M.: 125 mg in a single dose (in combination with azithromycin and metronidazole) (CDC, 2010)
>45 kg: Refer to adult dosing.
Skin/skin structure infections: I.M., I.V.: 50-75 mg/kg/day in 1-2 divided doses (maximum: 2 g/day)
Typhoid fever (unlabeled use): I.V.: 75-80 mg/kg once daily for 5-14 days

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment is generally necessary in renal impairment; Note: Concurrent renal and hepatic dysfunction: Maximum dose: ≤2 g/day
Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).

Dosing: Hepatic Impairment

No adjustment necessary unless there is concurrent renal dysfunction (see dosage adjustment in renal impairment).
Use
 
Treatment of lower respiratory tract infections, acute bacterial otitis media, skin and skin structure infections, bone and joint infections, intra-abdominal and urinary tract infections, pelvic inflammatory disease (PID), uncomplicated gonorrhea, bacterial septicemia, and meningitis; used in surgical prophylaxis
Use - Unlabeled/Investigational
Treatment of chancroid, epididymitis, complicated gonococcal infections; sexually-transmitted diseases (STD); periorbital or buccal cellulitis; salmonellosis or shigellosis; atypical community-acquired pneumonia; epiglottitis, Lyme disease; used in chemoprophylaxis for high-risk contacts (close exposure to patients with invasive meningococcal disease); sexual assault; typhoid fever, Whipple’s disease
Adverse Reactions
 
>10%: Local: Induration (I.M. 5% to 17%), warmth (I.M.), tightness (I.M.)
1% to 10%:
Dermatologic: Rash (2%)
Gastrointestinal: Diarrhea (3%)
Hematologic: Eosinophilia (6%), thrombocytosis (5%), leukopenia (2%)
Hepatic: Transaminases increased (3%)
Local: Tenderness at injection site (I.V. 1%), pain
Renal: BUN increased (1%)
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alkaline phosphatase increased, allergic dermatitis, allergic pneumonitis, anaphylaxis, anemia, basophilia, biliary lithiasis, bilirubin increased, bronchospasm, chills, colitis, creatinine increased, diaphoresis, dizziness, dysgeusia, dyspepsia, edema, epistaxis, erythema multiforme, exanthema, fever, flatulence, flushing, gallbladder sludge, gallstones, glossitis, glycosuria, headache, hematuria, hemolytic anemia, jaundice, leukocytosis, Lyell’s syndrome, lymphocytosis, lymphopenia, moniliasis, monocytosis, nausea, nephrolithiasis, neutropenia, oliguria, palpitation, pancreatitis, phlebitis, prolonged or decreased PT, pruritus, pseudomembranous colitis, renal and pulmonary ceftriaxone-calcium precipitations (neonates including some fatalities), seizure, serum sickness Stevens-Johnson syndrome, stomatitis, thrombocytopenia , toxic epidermal necrolysis, urinary casts, urticaria, vaginitis, vomiting
Reactions reported with other cephalosporins: Angioedema, allergic reaction, aplastic anemia, asterixis, cholestasis, encephalopathy, hemorrhage, hepatic dysfunction, hyperactivity (reversible), hypertonia, interstitial nephritis, LDH increased, neuromuscular excitability, pancytopenia, paresthesia, renal dysfunction, superinfection, toxic nephropathy
Contraindications
 
Hypersensitivity to ceftriaxone sodium, any component of the formulation, or other cephalosporins; do not use in hyperbilirubinemic neonates, particularly those who are premature since ceftriaxone is reported to displace bilirubin from albumin binding sites; concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days)
Warnings / Precautions Drug
 
Concerns related to adverse effects:
• Elevated INR: May be associated with increased INR (rarely), especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.
• Hemolytic anemia: Severe cases (including some fatalities) of immune-related hemolytic anemia have been reported in patients receiving cephalosporins, including ceftriaxone.
• Pancreatitis: Secondary to biliary obstruction, pancreatitis has been reported rarely.
• 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:
• Gallbladder disease: Abnormal gallbladder sonograms have been reported, possibly due to ceftriaxone-calcium precipitates; discontinue in patients with signs and symptoms of gallbladder disease.
• Gastrointestinal disease: Use with caution in patients with a history of GI disease, especially colitis.
• Renal/hepatic impairment (concurrent) Use with caution in patients with concurrent hepatic dysfunction and significant renal disease; dosage should not exceed 2 g/day.
Special populations:
• Neonates: Use extreme caution in neonates due to risk of hyperbilirubinemia, particularly in premature infants (contraindicated in hyperbilirubinemic neonates). Fatal precipitation reactions in neonates due to coadministration of calcium-containing solutions have been reported; concurrent use in neonates is contraindicated.
Other warnings/precautions:
• Precipitation: Ceftriaxone may complex with calcium causing precipitation. Fatal lung and kidney damage associated with calcium-ceftriaxone precipitates has been observed in premature and term neonates. Due to reports of precipitation reaction in neonates, do not reconstitute, admix, or coadminister with calcium-containing solutions (eg, LR, Hartmann’s solution, parenteral nutrition), even via separate infusion lines/sites or at different times in any neonate. Ceftriaxone should not be diluted or administered simultaneously with any calcium-containing solution via a Y-site in any patient. However, ceftriaxone and calcium-containing solutions may be administered sequentially of one another for use in patients other than neonates if infusion lines are thoroughly flushed (with a compatible fluid) between infusions.
Interactions
 
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Calcium Salts (Intravenous): May enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Ringer's Injection (Lactated): May enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium in the Lactated Ringer's forming an insoluble precipitate. Management: Use of ceftriaxone with calcium-containing solutions (including LR) within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
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
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Pregnancy
 
B
Pregnancy Implications
Teratogenic effects have not been observed in animal studies; therefore, ceftriaxone is classified as pregnancy category B. The pharmacokinetics of ceftriaxone in the third trimester are similar to those of nonpregnant patients, with the possible exception of lower peak concentrations during labor. Ceftriaxone crosses the placenta and distributes to amniotic fluid. Ceftriaxone is recommended for use in pregnant women for the treatment of gonococcal infections.
Lactation
 
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Small amounts of ceftriaxone are excreted in breast milk. The manufacturer recommends that caution be exercised when administering ceftriaxone to nursing women. Nondose-related effects could include modification of bowel flora.
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
 
Absorption: I.M.: Well absorbed
Distribution: Vd: 6-14 L; widely throughout the body including gallbladder, lungs, bone, bile, CSF (higher concentrations achieved when meninges are inflamed)
Protein binding: 85% to 95%
Half-life elimination: Normal renal and hepatic function: 5-9 hours; Renal impairment (mild-to-severe): 12-16 hours
Time to peak, serum: I.M.: 2-3 hours
Excretion: Urine (33% to 67% as unchanged drug); feces (as inactive drug)