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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Ceftriaxone: Drug information

Ceftriaxone: Drug information
(For additional information see "Ceftriaxone: Patient drug information" and see "Ceftriaxone: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Special Alerts
Ceftriaxone Safety Review February 2021

Health Canada has reviewed the potential risk of encephalopathy with the use of ceftriaxone and concluded there is a possible link between the use of ceftriaxone and the risk of encephalopathy. Health Canada will work with the manufacturers to update the Canadian product safety information to include the risk of encephalopathy.

Further information may be found at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00257.

Brand Names: Canada
  • SANDOZ CefTRIAXone [DSC]
Pharmacologic Category
  • Antibiotic, Cephalosporin (Third Generation)
Dosing: Adult
Actinomycosis, severe or extensive

Actinomycosis, severe or extensive (alternative agent) (off-label use):

IV: 1 to 2 g once daily for 4 to 6 weeks, followed by appropriate long-term oral therapy (Brook 2020; Onal 2009).

Bite wound infection, treatment

Bite wound infection, treatment (animal or human bite) (off-label use):

IV: 2 g once daily or 1 g every 12 hours in combination with an agent appropriate for anaerobes. Duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).

Bloodstream infection

Bloodstream infection: For pathogen-directed therapy of susceptible organisms in the absence of CNS infection:

IV: 2 g once daily (Moehring 2019). For patients with pneumococcal bacteremia, administer 2 g every 12 hours in combination with vancomycin until meningitis is ruled out (Sexton 2019a). May also be given as empiric therapy for gram-negative bloodstream infection in hemodynamically stable, immunocompetent patients without health care exposures (Moehring 2019).

Duration of therapy: Usual duration is 7 to 14 days; individualize depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019; Yahav 2018).

Chronic obstructive pulmonary disease, acute exacerbation

Chronic obstructive pulmonary disease, acute exacerbation (hospitalized patients without risk factors for Pseudomonas aeruginosa) (off-label use):

IV: 1 g once daily for 5 to 7 days; may switch to oral therapy following clinical improvement (Friedland 2004; GOLD 2021; Sethi 2020; Wilson 2003).

Diabetic foot infection, moderate to severe

Diabetic foot infection, moderate to severe (off-label use):

IV: 1 to 2 g once daily in combination with other appropriate agents. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (Clay 2004; IDSA [Lipsky 2012]; Weintrob 2020). Note: Do not use for empiric therapy of patients at risk for Pseudomonas (eg, significant water exposure, macerated wound) (Weintrob 2020).

Endocarditis, prophylaxis

Endocarditis, prophylaxis (dental or invasive respiratory tract procedures) (alternative agent for patients with nonsevere, non-IgE-mediated allergy to penicillin who cannot take oral therapy) (off-label use):

IM, IV: 1 g 30 to 60 minutes before procedure. Note: Only recommended for patients with cardiac conditions associated with the highest risk of an adverse outcome from endocarditis and who are undergoing a procedure likely to result in bacteremia with an organism that has the potential ability to cause endocarditis (AHA [Wilson 2007]).

Endocarditis, treatment

Endocarditis, treatment (off-label use):

Enterococcus faecalis, native or prosthetic valve (penicillin-susceptible): Note: Recommended regimen in patients with or at risk of renal insufficiency (eg, older age, concomitant nephrotoxins) or with aminoglycoside resistance (AHA [Baddour 2015]); some experts prefer this regimen for all patients with susceptible enterococcal native valve endocarditis (Sexton 2020b).

IV: 2 g every 12 hours for 6 weeks in combination with ampicillin (AHA [Baddour 2015]; Fernández-Hidalgo 2013; Karchmer 2020).

HACEK organisms, native or prosthetic valve: IV, IM: 2 g once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve) (AHA [Baddour 2015]).

Viridans group streptococci (VGS) and Streptococcus gallolyticus (Streptococcus bovis): IV, IM:

Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g once daily alone for 4 weeks or in combination with gentamicin for 2 weeks for patients with uncomplicated infection, rapid response to therapy, and no underlying renal disease (AHA [Baddour 2015]).

Native valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL), ceftriaxone-susceptible (alternative agent): 2 g once daily for 4 weeks (AHA [Baddour 2015]).

Native valve: Penicillin-resistant (MIC ≥0.5 mcg/mL), ceftriaxone-susceptible (alternative agent): 2 g once daily in combination with gentamicin. The duration of this regimen is not well established; infectious diseases consultation recommended (AHA [Baddour 2015]; Fujitani 2008).

Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g once daily for 6 weeks (with or without concomitant gentamicin for the first 2 weeks) (AHA [Baddour 2015]).

Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL), ceftriaxone-susceptible: 2 g once daily in combination with gentamicin for 6 weeks (AHA [Baddour 2015]).

Intra-abdominal infection, mild to moderate, community acquired in patients without risk factors for resistance or treatment failure

Intra-abdominal infection, mild to moderate, community acquired in patients without risk factors for resistance or treatment failure:

Cholecystitis, acute:

IV: 1 to 2 g once daily; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2021). Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (SIS/IDSA [Solomkin 2010]).

Other intra-abdominal infections (eg, perforated appendix, diverticulitis, intra-abdominal abscess):

IV: 1 to 2 g once daily in combination with metronidazole. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021).

Intracranial abscess or spinal epidural abscess

Intracranial abscess (brain abscess or intracranial epidural abscess) or spinal epidural abscess (off-label use):

IV: 2 g every 12 hours; for empiric therapy, use in combination with other appropriate agents. Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Brouwer 2014; de Louvois 2000; Sexton 2021; Sexton 2020d; Southwick 2020). Note: For postoperative neurosurgical patients and those at risk for P. aeruginosa, other regimens with expanded gram-negative coverage are preferred (Southwick 2020).

Lyme disease

Lyme disease (Borrelia spp. infection) (off-label use):

Carditis, severe disease (patients who are symptomatic, have second or third-degree AV block, or have first degree AV block with PR interval ≥300 msec):

IV: 2 g once daily until high-grade AV block resolved and PR interval <300 msec; may switch to oral therapy to complete a total of 14 to 21 days (Hu 2021; IDSA/AAN/ACR [Lantos 2021]).

Acute neurologic disease (eg, meningitis or radiculopathy), patients requiring hospitalization:

IV: 2 g once daily for 14 to 21 days (IDSA/AAN/ACR [Lantos 2021]).

Late disease, neurologic disease:

IV: 2 g once daily for 14 to 28 days (IDSA/AAN/ACR [Lantos 2021]); some experts favor a duration of 28 days (Hu 2021).

Recurrent arthritis after adequate oral regimen:

IV: 2 g once daily for 14 days; may extend to 28 days if inflammation is not resolving (IDSA/AAN/ACR [Lantos 2021]).

Meningitis, bacterial

Meningitis, bacterial: As a component of empiric therapy (community-acquired infections in immunocompetent patients) or pathogen-specific therapy (eg, Streptococcus pneumoniae [ceftriaxone MIC <1 mcg/mL], Neisseria meningitidis, Haemophilus influenzae, Cutibacterium acnes, and susceptible gram-negative bacilli; alternative agent for certain pathogens):

IV: 2 g every 12 hours; for empiric therapy, use in combination with other appropriate agents. Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Meningococcal disease, chemoprophylaxis after close contact with high-risk patient

Meningococcal disease, chemoprophylaxis after close contact with high-risk patient (off-label use):

IM: 250 mg as a single dose. Note: Prophylaxis should be initiated as soon as possible following exposure (ideally <24 hours after identification of index patient) (ACIP [Bilukha 2005]; Red Book [AAP 2015]). Close contacts include persons with prolonged exposure (≥8 hours) in close proximity (<3 feet) to index patient or direct exposure to oral secretions (eg, household contacts, childcare center contacts) (ACIP [Bilukha 2005]; Apicella 2019; Red Book [AAP 2015]).

Osteomyelitis and/or discitis

Osteomyelitis and/or discitis:

Treatment: As a component of empiric therapy or pathogen-specific therapy (eg, Streptococci [beta-hemolytic], C. acnes, susceptible gram-negative bacilli):

IV: 2 g every 24 hours, generally for ≥6 weeks depending on patient-specific factors such as organism, extent of infection, debridement, and clinical response. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation). For empiric therapy, use as part of an appropriate combination regimen (IDSA [Berbari 2015]; Osmon 2019).

Prevention, following open fractures (type III [severe contamination or comminution]): IV: 2 g every 24 hours as part of an appropriate combination regimen; ideally, administer within 6 hours of injury. Duration is 72 hours after injury or up to 24 hours after wound closure (Rodriguez 2014; Schmitt 2020). Note: For patients with risk for methicillin-resistant S. aureus (MRSA), potential water exposure, or fecal or clostridial contamination, alternative or additional antibiotics are recommended (Schmitt 2020).

Otitis media, acute

Otitis media, acute (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy):

IM, IV: 1 to 2 g once daily for 3 days (Limb 2021; manufacturer's labeling).

Pneumonia, community-acquired

Pneumonia, community-acquired: Inpatients without risk factors for P. aeruginosa:

IV: 1 to 2 g once daily in combination with other appropriate agent(s) (ATS/IDSA [Metlay 2019]; File 2011; Low 2011; Nicholson 2012; Segev 1995); 1 g once daily is sufficient for most hemodynamically stable hospitalized patients with community-acquired pneumonia (Segev 1995); for critically ill patients, some experts favor the 2 g dose (File 2021). Total duration (which may include oral step-down therapy) is for a minimum of 5 days; patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]).

Prosthetic joint infection

Prosthetic joint infection: As a component of empiric therapy or pathogen-specific therapy (eg, Streptococci [beta-hemolytic], C. acnes, susceptible gram-negative bacilli):

IV: 2 g every 24 hours for 4 to 6 weeks; for empiric therapy, use as part of an appropriate combination regimen (IDSA [Osmon 2013]; Berbari 2019).

Salmonella species infection

Salmonella species infection (alternative agent) (off-label use):

Enteric fever (Salmonella typhi and paratyphi): Empiric therapy for severe disease or an alternative directed therapy for quinolone-nonsusceptible infection:

IV: 2 g every 12 to 24 hours for 10 to 14 days. Note: May be switched to an oral regimen based on susceptibility testing, if available. Geographic location at time of acquisition impacts risk of resistance; ceftriaxone is not recommended if there is concern for extensively drug-resistant Salmonella spp. (Arjyal 2016; Ryan 2021; WHO 2003).

Nontyphoidal Salmonella GI infection:

IV: 1 to 2 g every 24 hours for 3 to 14 days (7 to 14 days in HIV-infected patients with a CD4 count ≥200 cells/mm3). Immunosuppressed patients (eg, HIV-infected with CD4 count <200 cells/mm3) warrant a longer duration of treatment (eg, weeks to months). Note: Reserve antibiotic treatment for patients with severe illness or at high risk of invasive disease (eg, extremes of age, immunosuppression); reserve parenteral therapy for those who cannot tolerate oral agents (HHS [OI adult 2020]); Hohmann 2019a).

Nontyphoidal Salmonella bloodstream infection:

IV: 1 to 2 g every 24 hours for 14 days. Note: Immunosuppressed patients (eg, HIV-infected with CD4 count <200 cells/mm3) and those with an extraintestinal focus of infection warrant a longer duration of treatment (eg, weeks to months) (HHS [OI adult 2020]; Hohmann 2019b).

Septic arthritis

Septic arthritis (as a component of empiric therapy for traumatic bacterial arthritis without risk factors for P. aeruginosa; pathogen-directed therapy for gram-negative bacilli):

IV: 2 g once daily. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy. For empiric therapy, give as part of an appropriate combination regimen (Coiffier 2014; Goldenberg 2019).

Sexually transmitted infections

Sexually transmitted infections:

Chancroid (due to Haemophilus ducreyi) (off-label use):

IM: 250 mg as a single dose. Note: Efficacy data in patients with HIV are limited (CDC [Workowski 2015]).

Empiric treatment following sexual assault (off-label use):

IM: 500 mg (1 g in patients ≥150 kg) as a single dose, as part of an appropriate combination regimen (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Epididymitis (off-label use):

IM: 500 mg (1 g in patients ≥150 kg) as a single dose in combination with doxycycline. Note: An alternative combination regimen is recommended in patients who practice insertive anal sex (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Gonococcal infection:

Note: Reinfections with uncomplicated gonorrhea (eg, cervicitis, pharyngitis, proctitis, urethritis) are more likely to occur than actual treatment failures. Consult an infectious diseases specialist when treatment failure is suspected and report failures to the CDC through state and local health departments (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Uncomplicated gonorrhea (cervicitis, urethritis, pharyngitis): Note: Empiric treatment of cervicitis or urethritis should include coverage for gonococcal infection in patients at high risk for gonorrhea or if the community prevalence of gonorrhea is high (eg, >5%) (CDC [Workowski 2015]; Powell 2019):

IM: 500 mg as a single dose; 1 g is recommended for patients ≥150 kg. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen. A test-of-cure (culture or nucleic acid amplification test) is recommended 7 to 14 days after initial treatment of pharyngeal gonorrhea (CDC [St. Cyr 2020]).

Uncomplicated gonorrhea (proctitis, acute): Empiric therapy or pathogen-directed therapy for gonorrhea:

IM: 500 mg as a single dose; 1 g is recommended for patients ≥150 kg. If chlamydial infection has not been excluded, give in combination with doxycycline (CDC [St. Cyr 2020]). Note: Additional coverage for herpes simplex virus is warranted in patients with perianal or mucosal ulcers (CDC [Workowski 2015]; Wilcox 2020).

Uncomplicated gonorrhea (conjunctivitis [off-label use]):

IM: 1 g as a single dose; if chlamydial infection has not been excluded, give as part of an appropriate combination regimen (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Disseminated gonococcal infection (tenosynovitis, dermatitis, polyarthralgia; purulent arthritis) (off-label use):

IV (preferred), IM: 1 g once daily. For patients with triad of tenosynovitis, dermatitis, and arthralgia or synovitis, may switch to IM ceftriaxone 500 mg (1 g in patients ≥150 kg) once daily 24 to 48 hours after clinical improvement to complete a total of ≥7 days of therapy. Patients with purulent arthritis often require ≥7 to 14 days of parenteral therapy; duration depends on clinical status and response to therapy. Note: If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (CDC [Workowski 2015]; Klausner 2021).

Neurosyphilis (alternative agent for nonpregnant patients with nonsevere, non-IgE-mediated penicillin allergy) (off-label use): Note: Patients with penicillin allergy should be desensitized to penicillin whenever possible.

IM, IV: 2 g once daily for 10 to 14 days (CDC [Workowski 2015]).

Pelvic inflammatory disease (mild to moderate):

IM: 500 mg (1 g in patients ≥150 kg) as a single dose in combination with doxycycline (with or without metronidazole) (CDC [St. Cyr 2020]; CDC [Workowski 2015]).

Skin and soft tissue infection

Skin and soft tissue infection (eg, select surgical site or necrotizing infections):

IV: 1 to 2 g once daily, usually as part of an appropriate combination regimen. Duration varies by extent of infection, clinical response, and other patient factors; for necrotizing infection, continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (IDSA [Stevens 2014]).

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (alternative agent) (off-label use):

Prevention, patients with advanced cirrhosis and active GI bleeding:

IV: 1 g once daily (may be transitioned to an oral antibiotic when bleeding is controlled and after oral intake is resumed) for a total duration of 7 days (AASLD [Runyon 2012]; Fernández 2006; Runyon 2019).

Treatment:

IV: 2 g once daily for 5 days, as long as fever and pain have resolved (AASLD [Runyon 2012]; Runyon 2021).

Surgical prophylaxis, colorectal

Surgical prophylaxis, colorectal (alternative agent):

IV: 2 g within 60 minutes prior to surgical incision in combination with metronidazole. Note: Reserved for locations where gram-negative resistance to first- and second-generation cephalosporins is high (ASHP/IDSA/SIS/SHEA [Bratzler 2013]). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berríos-Torres 2017]).

Toxic shock syndrome, streptococcal

Toxic shock syndrome, streptococcal (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy) (off-label use):

IV: 1 to 2 g every 12 hours in combination with clindamycin. Duration of therapy depends on extent and severity of infection and response to treatment; treat patients who are bacteremic for ≥14 days (Stevens 2019).

Urinary tract infection, complicated

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):

Note: Use empirically only in patients who do not have risk factors for multidrug-resistant organisms, critical illness, or suspected urinary tract obstruction (Hooton 2021).

Inpatients: IV: 1 g once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; IDSA/ESCMID [Gupta 2011]; Wells 2004).

Outpatients: IV, IM: 1 g once, followed by 5 to 14 days of appropriate oral therapy (Hooton 2021; IDSA/ESCMID [Gupta 2011]). Note: For patients who are systemically ill or at risk for more severe illness, some experts continue daily parenteral therapy pending culture and susceptibility testing results (Hooton 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney impairment: IM, IV:

CrCl >15 mL/minute: No dosage adjustment necessary.

CrCl <15 mL/minute: No dosage adjustment necessary (Aronoff 2007). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Joos 1984; Patel 1984; Stoeckel 1984).

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): IV: Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without organ dysfunction and with normal serum creatinine levels. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematological malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010). Note: Dosing based on Monte Carlo simulation.

CrCl ≥150 mL/minute (empiric therapy or organism with minimum inhibitory concentration [MIC] = 2): 2 g twice daily (Ollivier 2019).

Hemodialysis, intermittent (thrice weekly): IM, IV: Poorly dialyzed; no dosage adjustment necessary (Aronoff 2007). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Joos 1984; Patel 1984; Stoeckel 1984). Alternatively, 2 g thrice weekly post dialysis achieves pharmacodynamic goals when the MIC ≤1 mcg/mL (Simon 2006).

Peritoneal dialysis: IM, IV: Poorly dialyzed; no dosage adjustment necessary (Aronoff 2007). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Joos 1984; Patel 1984; Stoeckel 1984).

CRRT: IM, IV: No dosage adjustment necessary (Heintz 2009).

PIRRT (eg, sustained, low-efficiency hemodiafiltration): IM, IV: No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, in patients with concurrent hepatic dysfunction (impaired biliary excretion) and severe kidney impairment, use of >2 g/day should be done with caution and close monitoring for toxicity (Joos 1984; Stoeckel 1984).

Dosing: Pediatric

(For additional information see "Ceftriaxone: Pediatric drug information")

General dosing: Infants, Children, and Adolescents: IM, IV: 50 to 75 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose; higher doses are recommended in certain infections (eg, endocarditis, meningitis) (Red Book [AAP 2021]).

Chancroid: Infants, Children, and Adolescents: IM: 50 mg/kg as a single dose; maximum dose: 250 mg/dose (Red Book [AAP 2021]).

Endocarditis, bacterial:

Prophylaxis before invasive dental or respiratory tract procedures (alternative agent for patients with nonsevere, non-IgE-mediated allergy to penicillin who cannot take oral therapy):

Note: Recommended only in patients who are at highest risk for infective endocarditis (IE) or adverse outcomes (eg, history of IE, prosthetic heart valves, or prosthetic material used to repair valves, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, heart transplant recipients with cardiac valvulopathy) (AHA [Baltimore 2015]; AHA [Wilson 2021]; AHA/ACC [Nishimura 2017]).

Infants, Children, and Adolescents: IM, IV: 50 mg/kg 30 to 60 minutes prior to procedure; maximum dose: 1,000 mg/dose (AHA [Wilson 2021]).

Treatment: Children and Adolescents: IV: 50 mg/kg/dose every 12 hours or 80 mg/kg/dose every 24 hours; maximum daily dose: 4,000 mg/day; daily doses over 2,000 mg should be divided into 2 doses. Treat for ≥4 weeks depending on pathogen and valve type; longer durations may be necessary; use in combination with other antibiotics depending on pathogen (AHA [Baltimore 2015]).

Epididymitis, acute; empiric treatment: Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended for patients weighing ≥150 kg. Use as part of an appropriate combination regimen (CDC [Workowski 2021]).

Gonococcal infections, treatment:

Uncomplicated gonococcal infection (cervicitis, pharyngitis, proctitis, and urethritis): Note: For pharyngeal gonorrhea, a test-of-cure is recommended 7 to 14 days following treatment (CDC [Workowski 2021]).

Infants and Children weighing ≤45 kg: IM, IV: 25 to 50 mg/kg as a single dose; maximum dose: 250 mg/dose (CDC [Workowski 2021]).

Children weighing >45 kg and Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended for patients weighing ≥150 kg. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (CDC [St. Cyr 2020]; CDC [Workowski 2021]).

Disseminated gonococcal infection (arthritis or arthritis-dermatitis syndrome):

Infants and Children: IM, IV: 50 mg/kg/dose every 24 hours for 7 days; maximum dose: 2,000 mg/dose (CDC [Workowski 2021]).

Adolescents: IM, IV: 1,000 mg every 24 hours; may switch to an oral agent (per susceptibility testing) 24 to 48 hours after clinical improvement and treat for a total of ≥7 days. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (CDC [Workowski 2021]).

Gonococcal bacteremia:

Infants and Children weighing ≤45 kg: IM, IV: 50 mg/kg/dose every 24 hours for 7 days; maximum dose: 2,000 mg/dose (CDC [Workowski 2021]).

Children weighing >45 kg and Adolescents: IM, IV: 1,000 mg every 24 hours for 7 days (CDC [Workowski 2021]).

Gonococcal conjunctivitis: Adolescents: IM: 1,000 mg in a single dose. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (CDC [Workowski 2021]).

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 50 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 2,000 mg/day (IDSA [Solomkin 2010]; SIS [Mazuski 2017]).

Lyme disease (Borrelia spp. infection): Limited data available: Infants, Children, and Adolescents: IV: 50 to 75 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose. Duration of therapy depends on clinical syndrome; treat meningitis, radiculopathy, or carditis for 14 to 21 days, and recurrent or refractory arthritis for 14 to 28 days depending on clinical response (IDSA/AAN/ACR [Lantos 2021]).

Meningitis, bacterial: Note: Per the manufacturer's labeling, doses may be administered IM.

Community-acquired meningitis: Infants, Children, and Adolescents: IV: 80 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 4,000 mg/day (IDSA [Tunkel 2004]).

Health care-associated meningitis/ventriculitis: Infants, Children, and Adolescents: IV: 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 4,000 mg/day (IDSA [Tunkel 2017]).

Meningococcal disease, chemoprophylaxis for high-risk contacts (following close exposure to patients with invasive meningococcal disease):

Infants, Children, and Adolescents <15 years: IM: 125 mg in a single dose (Red Book [AAP 2021]).

Adolescents ≥15 years: IM: 250 mg in a single dose (Red Book [AAP 2021]).

Otitis media, acute (AAP [Lieberthal 2013]; Red Book [AAP 2021]): Infants, Children, and Adolescents:

Acute bacterial: IM, IV: 50 mg/kg/dose every 24 hours for 1 or 3 days; maximum dose: 1,000 mg/dose.

Persistent or relapsing: IM, IV: 50 mg/kg/dose every 24 hours for 3 days; maximum dose: 1,000 mg/dose.

Peritonitis (peritoneal dialysis), prophylaxis for patients receiving peritoneal dialysis who require dental procedures: Infants, Children, and Adolescents: IM, IV: 50 mg/kg administered 30 to 60 minutes before dental procedure; maximum dose: 1,000 mg/dose (ISPD [Warady 2012]).

Pneumonia, community-acquired (CAP): Infants >3 months, Children, and Adolescents: IV: 50 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 2,000 mg/day (IDSA/PIDS [Bradley 2011]; manufacturer's labeling); higher maximum daily doses of 4,000 mg/day are recommended for HIV-exposed/-infected patients (HHS [OI pediatric 2021]). Note: Use as part of appropriate combination therapy if methicillin-resistant Staphylococcus aureus (MRSA) or atypical pathogens are of concern. Use doses on the higher end of the range for penicillin-resistant S. pneumoniae (IDSA/PIDS [Bradley 2011]).

Rhinosinusitis, acute bacterial:

Ambulatory patients (alternative agent): Children and Adolescents: IM, IV: 50 mg/kg as a single dose; maximum dose: 2,000 mg/dose; use for patients who are unable to tolerate oral medication, or unlikely to be adherent to the initial doses of antibiotic (AAP [Wald 2013]; IDSA [Chow 2012]).

Severe infection requiring hospitalization: Infants, Children, and Adolescents: IV: 25 mg/kg/dose every 12 hours for 10 to 14 days; maximum dose: 2,000 mg/dose (IDSA [Chow 2012]).

Salmonella species infection, treatment:

Nontyphoidal Salmonella infection (alternative agent): Note: Antibiotic treatment is typically not needed for uncomplicated nontyphoidal Salmonella infection; consider treating infants <3 months of age and persons with immunosuppression, chronic GI tract disease, and significant cardiac or joint disease (IDSA [Shane 2017]); Red Book [AAP 2021]).

Non-HIV-infected: Infants, Children, and Adolescents: IM, IV: 75 to 100 mg/kg/day divided every 12 to 24 hours; treat GI infections for 5 to 14 days (Bradley 2021; Guerrant 2001; Wen 2017); maximum dose: 2,000 mg/dose.

HIV-infected: Adolescents: IV: 1,000 mg every 24 hours for ≥7 to 14 days; bacteremia should be treated for ≥14 days (longer if bacteremia persists or infection is complicated); treat patients with CD4 counts <200 cells/mm3 for 2 to 6 weeks (HHS [OI adult 2021]).

Typhoid fever (Salmonella typhi): Note: Reserve for patients who have failed oral therapy or who have severe disease, intestinal complications, or obtundation and cannot take oral medications (Stephens 2002).

Infants, Children, and Adolescents: IV: 75 to 80 mg/kg/dose every 24 hours for 5 to 14 days (Bradley 2021; Stephens 2002); maximum dose: 2,000 mg/dose (manufacturer's labeling).

Sexually transmitted infections, prophylaxis following sexual assault: Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended in patients weighing ≥150 kg. Use as part of an appropriate combination regimen (CDC [Workowski 2021]).

Shigellosis: Infants, Children, and Adolescents: IM, IV: 50 to 100 mg/kg/dose every 24 hours for 2 to 5 days; maximum dose: 2,000 mg/dose (Bradley 2021; WHO 2005; manufacturer's labeling). Note: Mild infections typically do not require antibiotic treatment; antibiotics are recommended for patients with severe disease or immunosuppression (Red Book [AAP 2021]).

Skin and soft tissue infection: Infants, Children, and Adolescents: IM, IV: 50 to 75 mg/kg/day in divided doses every 12 to 24 hours; maximum daily dose: 2,000 mg/day.

Surgical prophylaxis: Children and Adolescents: IV: 50 to 75 mg/kg within 60 minutes prior to the procedure; maximum dose: 2,000 mg/dose (ASHP/IDSA [Bratzler 2013]).

Syphilis (alternative agent): Note: Not considered first-line therapy; use should be reserved for special circumstances with close monitoring and follow-up.

Congenital syphilis (CDC [Workowski 2021]): Note: Only for use when aqueous and procaine penicillin are unavailable (eg, shortage) due to insufficient data for use; if used, close monitoring and follow-up in consultation with an expert are required (CDC [Workowski 2021]).

Infants: IM, IV: 75 mg/kg/dose every 24 hours for 10 to 14 days; maximum dose: 2,000 mg/dose.

Children: IM, IV: 100 mg/kg/dose every 24 hours for 10 to 14 days; maximum dose: 2,000 mg/dose.

Acquired syphilis (nonpregnant patients with penicillin allergy):

Early syphilis (primary, secondary, and early-latent): Adolescents: IM, IV: 1,000 mg every 24 hours for 10 to 14 days; optimal dose and duration have not been defined (CDC [Workowski 2021]; HHS [OI adult 2021]). Note: If adherence or follow-up cannot be ensured, patients with penicillin allergy should be desensitized to penicillin (CDC [Workowski 2021]).

Neurosyphilis: Adolescents: IM, IV: 1,000 to 2,000 mg every 24 hours for 10 to 14 days; patients infected with HIV should receive 2,000 mg once daily. Note: Patients with penicillin allergy should be desensitized to penicillin whenever possible (CDC [Workowski 2021]; HHS [OI adult 2021]).

Urinary tract infection: Infants, Children, and Adolescents: IM, IV: 50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose. Treatment duration dependent on age of patient, response to therapy, and extent of involvement (Balighian 2018; Bradley 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

No dosage adjustment is generally necessary in renal impairment; Note: If concurrent renal and hepatic dysfunction, a reduced maximum daily dose should be considered; in adults a maximum daily dose ≤2,000 mg/day is suggested.

Not dialyzable; no supplemental dose is necessary following hemodialysis or peritoneal dialysis; patients with concomitant hepatic dysfunction must be monitored closely for safety and efficacy.

Dosing: Hepatic Impairment: Pediatric

No adjustment is generally necessary in hepatic impairment; Note: If concurrent renal and hepatic dysfunction, a reduced maximum daily dose should be considered; in adults a maximum daily dose ≤2,000 mg/day is suggested.

Dosing: Geriatric

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Generic: 20 mg/mL (50 mL); 40 mg/mL (50 mL)

Solution Reconstituted, Injection:

Generic: 1 g (1 ea); 2 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea); 100 g (1 ea)

Solution Reconstituted, Intravenous [preservative free]:

Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 20 mg/mL (50 mL); 40 mg/mL (50 mL)

Solution Reconstituted, Injection:

Generic: 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea); 100 g (1 ea)

Solution Reconstituted, Intravenous:

Generic: 10 g (1 ea)

Administration: Adult

IM: Inject deep IM into large muscle mass; a concentration of 250 mg/mL or 350 mg/mL is recommended for all vial sizes except the 250 mg size (250 mg/mL is suggested); can be diluted with 1:1 water or 1% lidocaine for IM administration only.

IV: Infuse as an intermittent infusion over 30 minutes. IV push administration over 1 to 4 minutes has been reported (concentration: 100 mg/mL), primarily in patients outside the hospital setting (Baumgartner 1983; Garrelts 1988; Poole 1999), although a 2 g dose administered IV push over 5 minutes resulted in tachycardia, restlessness, diaphoresis, and palpitations in one patient (Lossos 1994). Do not coadminister with calcium-containing solutions.

Administration: Pediatric

Parenteral: Do not coadminister with calcium-containing solutions.

IM: Administer IM injections deep into a large muscle mass.

Intermittent IV infusion:

Neonates: Administer over 60 minutes to decrease risk of bilirubin encephalopathy.

Infants, Children, and Adolescents: Administer over 30 minutes; shorter infusion times (15 minutes) have been reported (Yogev 1986).

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.

IV Push: Administration over 2 to 4 minutes has been reported in pediatric patients >11 years and adults primarily in the outpatient setting (Baumgartner 1983; Garrelts 1988; Poole 1999) and over 5 minutes in pediatric patients ages newborn to 15 years with meningitis (Grubbauer 1990; Martin 1984). Rapid IVP injection over 5 minutes of a 2,000 mg dose resulted in tachycardia, restlessness, diaphoresis, and palpitations in an adult patient (Lossos 1994). IV push administration in young infants may also have been a contributing factor in risk of cardiopulmonary events occurring from interactions between ceftriaxone and calcium (Bradley 2009).

Use: Labeled Indications

Bloodstream infection: Caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, or Klebsiella pneumoniae.

Bone and joint infections (osteomyelitis and/or discitis, prosthetic joint infection, septic arthritis): Caused by S. aureus, S. pneumoniae, E. coli, Proteus mirabilis, K. pneumoniae, or Enterobacter spp.

Gonococcal infection, uncomplicated (cervical/urethral, rectal, and pharyngeal): Caused by Neisseria gonorrhoeae, including both penicillinase- and nonpenicillinase-producing strains, and pharyngeal gonorrhea caused by nonpenicillinase-producing strains of N. gonorrhoeae.

Intra-abdominal infection, mild to moderate, community acquired in patients without risk factors for resistance or treatment failure: Caused by E. coli, K. pneumoniae, Bacteroides fragilis, Clostridium spp. (Note: Most strains of C. difficile are resistant), or Peptostreptococcus spp.

Lower respiratory tract infections (pneumonia, community-acquired): Caused by S. pneumoniae, S. aureus, H. influenzae, Haemophilus parainfluenzae, K. pneumoniae, E. coli, Klebsiella aerogenes (formerly Enterobacter aerogenes), P. mirabilis, or Serratia marcescens.

Meningitis, bacterial: Caused by H. influenzae, Neisseria meningitidis, or S. pneumoniae. Ceftriaxone has also been used successfully in a limited number of cases of meningitis and shunt infection caused by Staphylococcus epidermidis and E. coli (efficacy for these 2 organisms in this organ system was studied in fewer than 10 infections).

Otitis media, acute : Caused by S. pneumoniae, H. influenzae (including beta-lactamase-producing strains), or Moraxella catarrhalis (including beta-lactamase-producing strains).

Pelvic inflammatory disease (mild to moderate): Caused by N. gonorrhoeae. Ceftriaxone, like other cephalosporins, has no activity against Chlamydia trachomatis; therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

Skin and soft tissue infections: Caused by S. aureus, S. epidermidis, Streptococcus pyogenes, viridans group streptococci, E. coli, Enterobacter cloacae, Klebsiella oxytoca, K. pneumoniae, P. mirabilis, Morganella morganii (efficacy for this organism in this organ system was studied in fewer than 10 infections), S. marcescens, Acinetobacter calcoaceticus, B. fragilis (efficacy for this organism in this organ system was studied in fewer than 10 infections), or Peptostreptococcus spp.

Surgical prophylaxis, colorectal: To reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated.

Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Caused by E. coli, P. mirabilis, Proteus vulgaris, M. morganii, or K. pneumoniae.

Use: Off-Label: Adult

Actinomycosis, severe or extensive; Bite wound infection, treatment, animal or human bite; Chancroid; Chronic obstructive pulmonary disease, acute exacerbation (hospitalized patients without risk factors for Pseudomonas aeruginosa); Diabetic foot infection; Empiric treatment (of sexually transmitted infections) following sexual assault; Endocarditis, prophylaxis (dental or invasive respiratory tract procedures); Endocarditis, treatment; Epididymitis; Gonococcal infection, disseminated (tenosynovitis, dermatitis, polyarthralgia; purulent arthritis); Gonococcal infection, uncomplicated (conjunctivitis); Intracranial abscess (brain abscess or intracranial epidural abscess) or spinal epidural abscess; Lyme disease (Borrelia spp. infection); Meningococcal disease, invasive, chemoprophylaxis after close contact with high-risk patient; Neurosyphilis; Salmonella species infection (nontyphoidal Salmonella GI and bloodstream infections and typhoid [enteric] fever [Salmonella typhi and paratyphi]); Spontaneous bacterial peritonitis, prevention and treatment; Toxic shock syndrome, streptococcal

Medication Safety Issues
Sound-alike/look-alike issues:

CefTRIAXone may be confused with ceFAZolin, cefoTEtan, cefOXitin, cefTAZidime, Cetraxal

Rocephin may be confused with Roferon

Pediatric patients: High-risk medication:

KIDs List: Ceftriaxone, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of kernicterus (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Adverse Reactions (Significant): Considerations
Ceftriaxone-calcium precipitation

Ceftriaxone-calcium precipitation has occurred, leading to fatal lung and kidney damage in premature and term neonates. Urinary sludge (hypercalciuria), nephrolithiasis, urolithiasis, and acute renal failure have been reported (Ref). Gallbladder sludge, cholelithiasis, and pseudolithiasis (choledocholithiasis), as well as subsequent pancreatitis, have also occurred. Most reports have occurred in pediatric patients; however, there are reports in adults (Ref).

Mechanism : Incompatibility with calcium, resulting in ceftriaxone-calcium precipitates; pancreatitis occurs subsequent to biliary obstruction.

Onset: Varied; 2 to 18 days after last dose for detection via ultrasound of gallbladder sludge, cholelithiasis, or pseudolithiasis in pediatric patients (Ref).

Risk factors:

• Pediatric patients (Ref); age ≥12 to 24 months (for biliary precipitation) (Ref)

• High doses (>40 mg/kg/day or ≥2 g) (Ref)

• Longer durations of treatment (>5 days) (Ref)

• Impaired gallbladder emptying (Ref)

• Biliary stasis risk factors (eg, major surgery, severe illness, TPN)

Clostridioides difficile infection

Clostridioides difficile infection has occurred, including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis.

Onset: Variable; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Type of antibiotic (third-/fourth-generation cephalosporins among the highest risk) (Ref)

• Long durations in a hospital or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)

• Chemotherapy (Ref)

Hemolytic anemia

Immune hemolytic anemia has occurred in patients receiving cephalosporins, including ceftriaxone (Ref).

Mechanism: Non dose-related; immunologic (ie, induces complement activating drug-dependent antibodies [mainly IgM-type] resulting in immune-complexes) (Ref).

Onset: Varied; occurs several minutes to 7 days after the first dose (Ref).

Risk factors:

• Pediatric patients (Ref)

• Sickle cell disease (Ref)

• Cross-reactivity with other cephalosporins (Ref)

Hypersensitivity reactions (immediate and delayed)

Hypersensitivity reactions (immediate and delayed) range from maculopapular skin rash to rare cases of anaphylaxis. Severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported. (Ref). Urticaria and serum sickness-like reaction have also occurred (Ref).

Mechanism: Non dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) are IgE-mediated. Delayed hypersensitivity reactions, including maculopapular rash and SCARs, are T-cell-mediated (Ref).

Onset: Immediate hypersensitivity reactions: rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Maculopapular reactions: intermediate; occur 7 to 10 days after initiation. Other reactions (including SCARs): varied; occur after 7 to 14 days up to 3 months (Ref).

Risk factors:

• Cross-reactivity between penicillins and cephalosporins and among cephalosporins is mostly related to side chain similarity (Ref)). A meta-analysis showed negligible cross-reactivity between penicillins and third-generation cephalosporins, such as ceftriaxone (Ref).

Kernicterus

Kernicterus has been reported in neonates, resulting from hyperbilirubinemia (increased serum bilirubin).

Mechanism: Displaces bilirubin from albumin, resulting in higher concentrations of free unconjugated bilirubin, leading to kernicterus (Ref).

Risk factors:

• Neonates, especially premature infants

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Skin tightness (IM: ≤5% to ≤17%; local)

Local: Induration at injection site (≤5% to ≤17%; incidence higher with IM), warm sensation at injection site (IM: ≤5% to ≤17%)

1% to 10%:

Dermatologic: Skin rash (2%)

Gastrointestinal: Diarrhea (3%)

Hematologic & oncologic: Eosinophilia (6%), leukopenia (2%), thrombocythemia (5%)

Hepatic: Increased serum transaminases (3%)

Local: Pain at injection site (≤1%), tenderness at injection site (≤1%)

Renal: Increased blood urea nitrogen (1%)

<1%:

Cardiovascular: Flushing, palpitations, phlebitis

Dermatologic: Diaphoresis, pruritus

Endocrine & metabolic: Glycosuria

Gastrointestinal: Abdominal pain, choledocholithiasis, cholelithiasis, Clostridioides difficile colitis, dysgeusia, dyspepsia, flatulence, gallbladder sludge, nausea, pancreatitis, vomiting

Genitourinary: Casts in urine, hematuria, vaginitis

Hematologic & oncologic: Agranulocytosis, anemia, basophilia, decreased prothrombin time, granulocytopenia, hemolytic anemia, lymphocytopenia, lymphocytosis, monocytosis, neutropenia, prolonged prothrombin time, thrombocytopenia

Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, jaundice

Hypersensitivity: Anaphylaxis, serum sickness

Infection: Candidiasis

Nervous system: Chills, dizziness, headache, seizure

Renal: Increased serum creatinine, nephrolithiasis

Respiratory: Bronchospasm, epistaxis, hypersensitivity pneumonitis

Postmarketing:

Dermatologic: Acute generalized exanthematous pustulosis (Salman 2019), allergic dermatitis, erythema multiforme, Stevens-Johnson syndrome (Liberopoulos 2003), toxic epidermal necrolysis (Atanaskovic-Markovic 2013; Lam 2008), urticaria (Baniasadi 2007)

Gastrointestinal: Clostridioides difficile associated diarrhea, glossitis, kernicterus, stomatitis

Genitourinary: Hypercalciuria (Zeng 2020), oliguria (Shen 2014), ureteral obstruction (Lu 2012), urolithiasis (Shen 2014)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Hansel 2017)

Renal: Acute kidney injury (post-renal) (Li 2014; Shen 2014)

Contraindications

Hypersensitivity to ceftriaxone, 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); IV use of ceftriaxone solutions containing lidocaine.

Warnings/Precautions

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. Monitor INR during treatment if patient has impaired synthesis or low stores of vitamin K; supplementation may be needed if clinically indicated.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Renal/hepatic impairment (concurrent): Use with caution in patients with concurrent hepatic dysfunction (impaired biliary excretion) and severe kidney disease; dosing adjustments may be recommended.

Special populations:

• Neonates: Use extreme caution in neonates due to risk of hyperbilirubinemia, particularly in premature infants (contraindicated in hyperbilirubinemic neonates and neonates <41 weeks postmenstrual age).

Metabolism/Transport Effects

None known.

Drug Interactions

Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Calcium Salts (Intravenous): May enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions. In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

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 is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions (ie, LR). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. 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: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. 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 Considerations

Ceftriaxone crosses the placenta.

Based on available data, cephalosporin antibiotics are generally considered compatible for use during pregnancy.

Pregnancy was found to influence the single dose pharmacokinetics of ceftriaxone when administered prior to delivery (Popović 2007). The pharmacokinetics of ceftriaxone following multiple doses in the third trimester are similar to those of nonpregnant patients (Bourget 1993).

Ceftriaxone is recommended for use in pregnant patients for the treatment of gonococcal infections, Lyme disease, and may be used in certain situations prior to vaginal delivery in patients at high risk for endocarditis (consult current guidelines) (ACOG 2018; CDC [St. Cyr 2020]; CDC [Workowski 2015]; IDSA/AAN/ACR [Lantos 2021]; Lambert 2020).

Breast-Feeding Considerations

Ceftriaxone is present in breast milk.

The relative infant dose (RID) of ceftriaxone is 1.2% to 2.4% when calculated using the highest breast milk concentration located and compared to a therapeutic infant dose of 50 to 100 mg/kg/day.

In general, breastfeeding is considered acceptable when the relative infant dose is <10% (Anderson 2016; Ito 2000).

The RID of ceftriaxone was calculated using a milk concentration of 7.89 mcg/mL providing an estimated daily infant dose via breast milk of 1.2 mg/kg/day. This milk concentration was obtained following a maternal dose of IV ceftriaxone 2 g/day on postpartum day 2 (day 7 of antimicrobial therapy) (Bourget 1993).

The elimination half-life in breast milk following administration of a single dose of ceftriaxone 1 g was 12.8 hours and 17.3 hours with IV and IM administration, respectively (Kafetzis 1983).

In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Ceftriaxone is considered compatible with breastfeeding when used in usual recommended doses (WHO 2002).

Dietary Considerations

Some products may contain sodium.

Monitoring Parameters

Prothrombin time/INR. Observe for signs and symptoms of anaphylaxis. Test-of-cure 7 to 14 days after initial treatment of pharyngeal gonorrhea (CDC [St. Cyr 2020]).

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 and Pharmacokinetics

Absorption: IM: Well absorbed.

Distribution: Widely throughout the body including gallbladder, lungs, bone, bile, CSF (higher concentrations achieved when meninges are inflamed).

Vd:

Neonates: 0.34 to 0.55 L/kg (Richards 1984).

Infants and Children: 0.32 to 0.4 L/kg (Richards 1984).

Adults: ~6 to 14 L.

CSF:blood ratio: ~14% (range: 6% to 66%) (Grégoire 2019).

Pleural fluid:serum ratio: ~27% to 29% (range: 1% to 63%) (Goonetilleke 1996).

Protein binding: 85% to 95%.

Half-life elimination:

Neonates (Martin 1984): 1 to 4 days: 16 hours; 9 to 30 days: 9 hours.

Infants and Children: 4 to 6.6 hours (Richards 1984).

Adults: Normal renal and hepatic function: ~5 to 9 hours.

Adults: Renal impairment (mild to severe): ~12 to 16 hours.

Time to peak, serum: IM: 2 to 3 hours.

Excretion: Urine (33% to 67% as unchanged drug); feces (as inactive drug).

Pharmacodynamics and Pharmacokinetics: Additional Considerations

Anti-infective considerations:

Parameters associated with efficacy:

Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC):

Organism specific:

Enterobacterales: Goal: ≥ ~38% fT > MIC (bacteriostatic); ≥ ~60% to 70% fT > MIC (bactericidal) (Craig 1995; Turnidge 1998).

S. pneumoniae: ≥ ~40% fT > MIC (bacteriostatic) (Craig 1995; Craig 1998; Turnidge 1998).

Population specific:

Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Roberts 2014); some experts favor ≥100% fT >4 times the MIC (Guilhaumou 2019).

Expected drug exposure in normal renal function:

Neonates and Infants: Cmax (peak): IV: 50 mg/kg, single dose: ~136 to 184 mg/L (Chadwick 1983; McCracken 1983).

Infants and Children ≤3 years of age: Cmax (peak): IV:

50 mg/kg, single dose: 207 mg/L (range: 120 to 375 mg/L) (Del Rio 1982).

50 mg/kg every 12 hours, steady state: 263 mg/L (range: 150 to 410 mg/L) (Del Rio 1982).

Adults: Cmax (peak): IV:

1 g once daily, steady state: ~136.4 ± 21.2 mg/L (Chiu 2002).

1 g every 12 hours, steady state: 168 ± 25 mg/L (Pollock 1982).

2 g every 12 hours, steady state: 280 ± 39 mg/L (Pollock 1982).

Postantibiotic effect: Generally <1 hour; varies based on organism (Aldridge 2002; Buxbaum 1996; Craig 1993).

Pricing: US

Solution (cefTRIAXone Sodium in Dextrose Intravenous)

20 mg/mL (per mL): $0.34

40 mg/mL (per mL): $0.81

Solution (reconstituted) (cefTRIAXone Sodium Injection)

1 g (per each): $1.49 - $46.75

2 g (per each): $2.65 - $91.72

100 g (per each): $270.00

250 mg (per each): $0.90 - $15.94

500 mg (per each): $1.15 - $27.99

Solution (reconstituted) (cefTRIAXone Sodium Intravenous)

1 g (per each): $4.92 - $46.75

2 g (per each): $9.47 - $91.72

10 g (per each): $19.06 - $448.43

Solution (reconstituted) (cefTRIAXone Sodium-Dextrose Intravenous)

1GM 3.74%(50ML) (per each): $20.43

2GM 2.22%(50ML) (per each): $29.21

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • 3 Gen-1000 (PH);
  • Acantex (AR, CL);
  • Aciphin (BD);
  • Acrocef (EC);
  • Actaxon (ID);
  • Alcizon (ET);
  • Alcizone (UA);
  • Alvobak (UA);
  • Amcef (MX);
  • Amplospec (BR);
  • Aumax (VN);
  • Aurofox (MX);
  • Axobat (IT);
  • Axone (AE, CY, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Axtar (CR, DO, GT, HN, MX, NI, PA, SV);
  • Benaxona (MX);
  • Biotriax (ID);
  • Broadced (ID);
  • Brospec (ID);
  • Cafalogen (PE);
  • Carotan (PE);
  • Cef-S (PH);
  • Cef-Zone (TH);
  • Cefacrol (PE);
  • Cefaxona (MX);
  • Cefaxone (MY, SG, UA);
  • Cefilan (PL);
  • Cefin (SG);
  • Cefizon (LK);
  • Cefkizon (KR);
  • Cefogram (UA);
  • Cefort (RO);
  • Cefotrix (AT);
  • Cefraden (MX);
  • Ceftash (ET);
  • Ceftral (LK);
  • Ceftrax (EG);
  • Ceftrex (MX, TH);
  • Ceftrian (EC);
  • Ceftrianol (MX);
  • Ceftriax-1 (PH);
  • Ceftrifil (PH);
  • Ceftrilem (MX);
  • Ceftritina (VN);
  • Ceftron (LK);
  • Cefxon (ID);
  • Celltriaxon (MY);
  • Ceptaxone (KR);
  • Cerixon (KR);
  • Cetriaf (DO);
  • Chef (TW);
  • Cikedrix (PH);
  • Diacef (UA);
  • Ecotrixon (ID);
  • Elpicef (ID);
  • Epicephin (BH);
  • Eroxet (PH);
  • Erphacef (ID);
  • Excephin (ET);
  • Exempla (AR);
  • Ferfacef (ID);
  • Forgram (PH);
  • Gomcephin (KR);
  • Infecef (BD);
  • Ivixone (TZ);
  • Keptrix (PH);
  • Kocef (ZA);
  • Lendacin (HU);
  • Longacef (AE, CY, EG, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Lyceft (IN);
  • Megion (AE, BH, CR, GT, HN, JO, KW, LB, MX, NI, PA, PH, QA, SA, SV);
  • Mesporin (AE, BF, BJ, CI, CY, EE, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN, TT, TZ, UG, YE, ZM, ZW);
  • Mesporin IM (BB, BM, BS, BZ, GY, HK, JM, PR, SR);
  • Mesporin IV (BB, BM, BS, BZ, GY, HK, JM, PR, SR);
  • Monocef (IN);
  • Nectram (TH);
  • Newcef (KR);
  • Novosef (AE, CY, IQ, IR, JO, KW, LY, OM, PH, RU, SA, SY, TR, YE);
  • Oframax (BF, BJ, CI, EG, ET, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SG, SL, SN, TN, TZ, UG, VN, ZA, ZM, ZW);
  • Oncef (PH);
  • Pan-Ceftriaxone (IL);
  • Pantrixon (PH);
  • Powergef (TZ);
  • Ragex (IT);
  • Retrokor (PH);
  • Riaxon (GR);
  • Rocefin (BR, CO, IT);
  • Rocefort (CR, DO, GT, HN, NI, PA, SV);
  • Rocephalin (DK, FI, IS, NO, SE);
  • Rocephin (AE, AT, AU, BH, CH, CN, CU, CY, DE, EC, EG, GB, GH, HK, HU, IE, IQ, IR, JO, JP, KE, KR, KW, LB, LV, LY, MT, MX, OM, PE, PH, PK, PL, PT, PY, QA, RO, SA, SG, SY, TH, TW, TZ, UG, UY, VE, VN, YE, ZM);
  • Rocephine (BE, FR, LU);
  • Rocidar (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Roxcef (BF, BH, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Samixon (AE, BH, CY, IQ, IR, JO, KW, LY, OM, QA, SA, SY, YE);
  • Sintrex (TW);
  • Socef (ID);
  • Tacex (MX);
  • Terbac (MX);
  • Tercef (BG);
  • Tiaxone (AU);
  • Traxef (BD);
  • Traxol (ZW);
  • Trexofin (SG);
  • Triaken (MX);
  • Triax-1 (PH);
  • Triaxon (BR);
  • Triaxone (AE, BH, ET, KR, KW, LB, SA, SG);
  • Tricef (TW);
  • Tricefin (SG);
  • Trijec (ID);
  • Triox (MX);
  • Trixone (MY);
  • Trizon (BD);
  • U-Ron (TW);
  • Unocef (MY);
  • Utrixone (ZW);
  • Vaxcel (LK);
  • Veracol (GR, NZ);
  • Viatrex (PH);
  • Xone (ZW);
  • Xtenda (PH);
  • Zefone 250 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Zeftrox (LK);
  • Zeptri (PH);
  • Zontrixone (TH)


For country abbreviations used in Lexicomp (show table)

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