CefTRIAXone

Dosage Forms

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 [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)

Pharmacology

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.

Pharmacokinetics/Pharmacodynamics

Absorption

IM: Well absorbed

Distribution

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

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

Excretion

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

Time to Peak

Serum: IM: 2 to 3 hours

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

Protein Binding

85% to 95%

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, community-acquired (mild to moderate infection in low-risk patients): 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, 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 (including pyelonephritis): Caused by E. coli, P. mirabilis, Proteus vulgaris, M. morganii, or K. pneumoniae.

Use: Off Label

Actinomycosis, severe or extensivec

Data from a limited number of patients suggest ceftriaxone may be beneficial for the treatment of severe or extensive actinomycosis McCann 2019, Onal 2009; clinical experience also suggests the utility of ceftriaxone in the treatment of severe or extensive actinomycosis Brook 2019.

Bite wound infection, treatment, animal or human biteyes

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections, ceftriaxone, in combination with clindamycin or metronidazole for anaerobic coverage, is an effective and recommended alternative for treatment of animal or human bite wounds.

Chancroidyes

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is effective and recommended for the treatment of chancroid due to Haemophilus ducreyi.

Chronic obstructive pulmonary disease, acute exacerbation (without risk factors for Pseudomonas aeruginosa)b

Data from a randomized, open-label, multicenter study and from a post-hoc analysis of 2 randomized, double-blind, multicenter studies support the use of ceftriaxone in the treatment of acute exacerbations of COPD Friedland 2004, Wilson 2003.

Diabetic foot infectioncyes

Data from a randomized, open-label, single-center study suggest the utility of ceftriaxone, in combination with metronidazole, in the treatment of diabetic foot infection Clay 2004.

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, ceftriaxone, in combination with other appropriate agents, is an effective and recommended treatment option for diabetic foot infection.

Empiric treatment (of sexually transmitted infections) following sexual assaultyes

Based on the CDC sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with azithromycin plus metronidazole (or tinidazole), is a recommended regimen for empiric treatment against sexually transmitted diseases following sexual assault.

Endocarditis, prophylaxis (dental or invasive respiratory tract procedures)yes

Based on the American Heart Association (AHA) guidelines for the prevention of infective endocarditis, ceftriaxone is an effective and recommended alternative agent for prophylaxis against infective endocarditis associated with dental or respiratory tract procedures in patients with certain cardiac conditions who have a nonsevere, non-IgE-mediated allergy to penicillins and are unable to take oral medication.

Endocarditis, treatmentyes

Based on the AHA scientific statement on infective endocarditis in adults, ceftriaxone, either as monotherapy or in combination with other antibiotics, is effective and recommended for the treatment of infective endocarditis caused by Enterococcus, HACEK organisms (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.), S. bovis, or viridans group streptococci (VGS). Recommendations regarding duration of therapy and use of concomitant antibiotics vary depending on the bacterial cause of the infection.

Epididymitisyes

Based on the CDC sexually transmitted diseases treatment guidelines, ceftriaxone is an effective and recommended agent in the treatment of acute epididymitis likely caused by sexually transmitted chlamydia and gonorrhea (in combination with doxycycline) or likely caused by sexually transmitted chlamydia and gonorrhea and enteric organisms in men who practice insertive anal sex (in combination with levofloxacin or ofloxacin).

Erysipeloid, diffuse cutaneous disease or systemic infectionc

Clinical experience suggests the utility of ceftriaxone in the treatment of diffuse cutaneous or systemic Erysipelothrix infection Reboli 2019.

Gonococcal infection, disseminated (arthritis and arthritis-dermatitis syndrome)yes

Based on the CDC sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with azithromycin, is effective and recommended in the treatment of disseminated gonococcal infections including arthritis and arthritis-dermatitis syndrome.

Gonococcal infection, uncomplicated (conjunctivitis)yes

Based on the CDC sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with azithromycin, is an effective and recommended treatment for patients with conjunctivitis due to gonorrhea.

Intracranial abscess (brain abscess or intracranial epidural abscess)c

Data from a limited number of patients studied suggest that ceftriaxone may be beneficial for the empiric treatment of brain abscess. Clinical experience also suggests the utility of ceftriaxone as definitive therapy in the treatment of brain abscess caused by Enterobacteriaceae or Haemophilus spp. Combination therapy may be needed when Enterobacteriaceae or Haemophilus spp. are isolated, as they are often a component of a mixed infection Brouwer 2014, de Louvois 2000.

Lyme disease (Borrelia spp. infection)yes

Based on the IDSA guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, ceftriaxone is effective and recommended for the treatment of Lyme disease with early disseminated neurologic disease (eg, meningitis, radiculopathy), Lyme carditis (severe disease), Lyme arthritis with evidence of neurologic disease, and late Lyme disease with central or peripheral nervous system disease IDSA [Wormser 2006].

Meningococcal disease, invasive, chemoprophylaxis after close contact with high-risk patientyes

Based on the Advisory Committee on Immunization Practices prevention and control of meningococcal disease guidelines and American Academy of Pediatrics recommendations for individuals with close exposure to patients with invasive meningococcal disease, ceftriaxone is effective and recommended for the chemoprophylaxis of meningococcal disease ACIP [Bilukha 2005], Red Book [AAP 2015].

Neurosyphilisyes

Based on the CDC sexually transmitted diseases treatment guidelines, limited data suggest ceftriaxone may be effective as an alternative agent in penicillin-allergic patients who cannot be desensitized to penicillin for the treatment of neurosyphilis.

Proctitis, acuteyes

Based on the CDC sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with doxycycline, is effective and recommended in the treatment of acute proctitis.

Salmonella species infection (nontyphoidal Salmonella GI and bloodstream infections and typhoid [enteric] fever [Salmonella typhi and paratyphi])cyes

Based on the HHS guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, ceftriaxone is a recommended alternative agent for treatment of salmonellosis. Clinical experience also suggests the utility of ceftriaxone in the treatment of Salmonella species infection (GI and bloodstream) Hohmann 2019a, Hohmann 2019b.

Based on the World Health Organization (WHO) guidelines for the treatment of typhoid fever WHO 2003 and the IDSA clinical practice guidelines for the diagnosis and management of infectious diarrhea, ceftriaxone is effective and recommended for the treatment of typhoid fever. It is usually reserved for fluoroquinolone-resistant cases.

Clinical experience also suggests the utility of ceftriaxone in the management/treatment of typhoid fever Ryan 2019.

Spontaneous bacterial peritonitis, prevention and treatmentyes

Based on the American Association for the Study of Liver Diseases (AASLD) guidelines for the management of adult patients with ascites due to cirrhosis, ceftriaxone is an effective and recommended alternative to prevent spontaneous bacterial peritonitis in patients with cirrhosis and gastrointestinal hemorrhage as well as for treatment of spontaneous bacterial peritonitis.

Toxic shock syndrome, streptococcalc

Clinical experience suggests the utility of ceftriaxone in combination with clindamycin for the treatment of streptococcal toxic shock syndrome Stevens 2019.

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.

Dosage and Administration

Dosing: Adult

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 2019; Onal 2009).

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: 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 (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 2018; Wilson 2003). Note: Some experts reserve ceftriaxone for patients with moderate to severe exacerbations of complicated COPD (eg, age ≥65 years, significant comorbidities, FEV₁ <50% predicted, frequent exacerbations) (Bartlett 2019).

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 2019). Note: Do not use for empiric therapy of patients at risk for Pseudomonas (eg, significant water exposure, macerated wound) (Weintrob 2019).

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 (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 2019b).

IV: 2 g every 12 hours for 6 weeks in combination with ampicillin (AHA [Baddour 2015]; Fernández-Hidalgo 2013; Karchmer 2019).

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, community-acquired (mild to moderate infection in low-risk patients):

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 2019). Note: The addition of anaerobic therapy 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 oral step-down therapy) is 4 to 7 days following adequate source control (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019).

Intracranial abscess (brain abscess or intracranial 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 (Brouwer 2014; de Louvois 2000; Sexton 2019c; Southwick 2019). Note: For postoperative neurosurgical patients and those at risk for P. aeruginosa, other regimens with expanded gram-negative coverage are preferred (Southwick 2019).

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

Early disseminated, 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 28 days; some experts prefer 28 days for patients with more serious cardiac disease (Hu 2019; IDSA [Wormser 2006]).

Early disseminated, neurologic disease (eg, meningitis or radiculopathy):

IV: 2 g once daily for 14 days for patients with mild to moderate infection; some experts prefer 21 to 28 days for patients with severe infection (Hu 2019; IDSA [Wormser 2006]). Note: For patients who are not hospitalized and do not have parenchymal involvement, oral doxycycline is recommended instead of parenteral regimens by some experts (Hu 2019).

Late disease, neurologic disease:

IV: 2 g once daily for 28 days (Hu 2019; IDSA [Wormser 2006]).

Late disease, recurrent arthritis after adequate oral regimen:

IV: 2 g once daily for 14 to 28 days (IDSA [Wormser 2006]).

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 (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: 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).

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 2019; manufacturer's labeling).

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

IV: 1 to 2 g once daily in combination with other appropriate agent(s) (File 2011; Low 2011; Nicholson 2012; Segev 1995); 1 g once daily is sufficient for most hemodynamically stable hospitalized patients with CAP (Segev 1995); for critically ill patients, some experts favor the 2 g dose (File 2019). Total duration (which may include oral step-down therapy) is for a minimum of 5 days and varies based on disease severity and response to therapy; patients should be afebrile for ≥48 hours and clinically stable prior to discontinuation (IDSA [Mandell 2007]).

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 (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 2019; 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] 2019); 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] 2019; Hohmann 2019b).

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:

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: 250 mg as a single dose in combination with azithromycin (plus metronidazole or tinidazole) (CDC [Workowski 2015]).

Epididymitis (off-label use):

IM: 250 mg as a single dose in combination with doxycycline. Note: An alternative combination regimen is recommended in patients who practice insertive anal sex (CDC [Workowski 2015]).

Gonococcal infection:

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: 250 mg in combination with azithromycin, each as a single dose (CDC [Workowski 2015]).

Treatment failure: Note: Reinfections 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 [Workowski 2015]).

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

IM: 1 g in combination with azithromycin, each as a single dose (CDC [Workowski 2015]).

Disseminated gonococcal infection (arthritis and arthritis-dermatitis) (off-label use):

IV, IM: 1 g once daily in combination with single-dose azithromycin. For patients with arthritis-dermatitis, may switch to IM ceftriaxone 250 mg once daily (or an oral agent guided by antimicrobial susceptibility, if available) 24 to 48 hours after clinical improvement to complete a total of ≥7 days of therapy. Patients with septic arthritis often require ≥7 to 14 days of parenteral therapy; duration depends on clinical status and response to therapy (CDC [Workowski 2015]; Klausner 2019).

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: 250 mg as a single dose in combination with doxycycline (with or without metronidazole) (CDC [Workowski 2015]).

Proctitis, acute (off-label use): Empiric therapy or pathogen-directed therapy for gonorrhea:

IM: 250 mg as a single dose in combination with doxycycline (CDC [Workowski 2015]). Note: Additional coverage for herpes simplex virus is warranted in patients with perianal or mucosal ulcers (CDC [Workowski 2015]; Wilcox 2019).

Skin and soft tissue infection:

Erysipeloid, diffuse cutaneous disease or systemic infection (alternative agent):

IV: 2 g once daily. Optimal duration is uncertain; 7 days total (which may include oral step-down therapy) is likely sufficient for diffuse cutaneous disease; some experts suggest ≥4 weeks for systemic infection (14 days of parenteral therapy followed by appropriate oral therapy) (Reboli 2019).

Other skin and soft tissue infections (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 (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 2019).

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 (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 at least 14 days (Stevens 2019).

Urinary tract infection, complicated (including pyelonephritis): Note: Use empirically only in patients without risk factors for multidrug-resistant organisms who are not critically ill and do not have suspected urinary tract obstruction.

Inpatients:

IV: 1 g once daily. Switch to an appropriate oral regimen once patient has improvement in symptoms, if culture and susceptibility results allow. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019).

Outpatients:

IV, IM: 1 g once, followed by 5 to 14 days of appropriate oral therapy (Hooton 2019; IDSA [Gupta 2011]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

General dosing, susceptible infection (Red Book [AAP 2018]): Infants, Children, and Adolescents: IM, IV:

Mild to moderate infection: 50 to 75 mg/kg/dose once daily; maximum daily dose: 1,000 mg/day

Severe infection (eg, meningitis, penicillin-resistant pneumococcal pneumonia): 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 4,000 mg/day

Chancroid: Infants, Children, and Adolescents: IM: 50 mg/kg as a single dose; maximum dose: 250 mg/dose (Red Book [AAP 2018])

Endocarditis, bacterial (non-gonococcal):

Prophylaxis for dental and upper respiratory procedures (patients allergic to penicillins and/or unable to take oral): Infants, Children, and Adolescents: IM, IV: 50 mg/kg 30 to 60 minutes prior to procedure; maximum dose: 1,000 mg/dose (Red Book [AAP 2018]; Wilson 2007). Note: AHA guidelines (Baltimore 2015) limit the use of prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or adverse outcomes (eg, prosthetic heart valves, patients with previous IE, 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, and heart transplant recipients with cardiac valvulopathy).

Treatment: Children and Adolescents: IV: 100 mg/kg/day divided 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 at least 4 weeks; longer durations may be necessary; may use in combination with other antibiotics based on organism (AHA [Baltimore 2015])

Enteric infection, bacteria, empiric therapy pending diagnostic studies (HIV-exposed/-positive): Adolescents: IV: 1,000 mg every 24 hours (HHS [OI adult 2018])

Gonococcal infections, treatment:

Bacteremia (CDC [Workowski 2015]):

Infants and Children weighing ≤45 kg: IM, IV: 50 mg/kg/dose once daily for 7 days; maximum dose: 1,000 mg/dose

Children weighing >45 kg and Adolescents: IM, IV: 1,000 mg once daily for 7 days

Epididymitis, acute: Adolescents: IM: 250 mg in a single dose in combination with oral doxycycline (CDC [Workowski 2015])

Uncomplicated cervicitis, pharyngitis, proctitis, urethritis, and vulvovaginitis (CDC [Workowski 2015]):

Infants and Children weighing ≤45 kg: IM, IV: 25 to 50 mg/kg as a single dose; maximum dose: 125 mg/dose

Children weighing >45 kg and Adolescents: IM: 250 mg as a single dose in combination with single oral dose of azithromycin

Disseminated infection (arthritis or arthritis-dermatitis syndrome) (CDC [Workowski 2015]):

Infants and Children: IM, IV: 50 mg/kg/dose once daily for 7 days; maximum dose: 1,000 mg/dose

Adolescents: IM, IV: 1,000 mg once daily for 7 days; use in combination with a single oral dose of azithromycin

Conjunctivitis: Adolescents: IM: 1,000 mg in a single dose in combination with a single oral dose of azithromycin (CDC [Workowski 2015])

Meningitis:

Infants and Children weighing <45 kg: IV, IM: 50 mg/kg/day divided every 12 to 24 hours for 10 to 14 days; maximum daily dose: 2,000 mg/day (Red Book [AAP 2018])

Children weighing ≥45 kg and Adolescents: IV: 1,000 to 2,000 mg every 12 to 24 hours for 10 to 14 days; use in combination with a single dose of oral azithromycin (CDC [Workowski 2015]; Red Book [AAP 2018])

Endocarditis:

Infants and Children weighing <45 kg: IV, IM: 50 mg/kg/day divided every 12 to 24 hours for at least 28 days; maximum daily dose: 2,000 mg/day (Red Book [AAP 2018])

Children weighing ≥45 kg and Adolescents: IV: 1,000 to 2,000 mg every 12 to 24 hours for at least 28 days; use in combination with a single dose of oral azithromycin (CDC [Workowski 2015]; Red Book [AAP 2018])

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 50 to 75 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 2,000 mg/day (IDSA [Solomkin 2010])

Lyme disease, neurologic involvement, persistent/recurrent arthritis, heart block, or carditis: Infants, Children, and Adolescents: IV: 50 to 75 mg/kg/dose once daily; maximum dose: 2,000 mg/dose; duration dependent on symptoms and response (AAN [Halperin 2007]; IDSA [Wormser 2006])

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

Acute bacterial 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 infection, chemoprophylaxis for high-risk contacts (close exposure to patients with invasive meningococcal disease) (Red Book [AAP 2018]):

Infants, Children, and Adolescents <15 years: IM: 125 mg in a single dose

Adolescents ≥15 years: IM: 250 mg in a single dose

Otitis media, acute (AAP [Lieberthal 2013]; Red Book [AAP 2018]): Infants, Children, and Adolescents:

Acute bacterial: IM, IV: 50 mg/kg/dose once daily for 1 or 3 days; maximum dose: 1,000 mg/dose

Persistent or relapsing: IM, IV: 50 mg/kg/dose once daily 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) (IDSA/PIDS [Bradley 2011]): Infants >3 months, Children, and Adolescents: IV: 50 to 100 mg/kg/day divided every 12 to 24 hours; usual maximum daily dose: 2,000 mg/day; higher maximum daily doses as high as 4,000 mg/day have been recommended for HIV-exposed/-positive patients (HHS [OI pediatric 2018]). Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. Use the higher end of the range for penicillin-resistant S. pneumoniae; in children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out; preferred in patients not fully immunized for H. influenzae type b and S. pneumoniae, or significant local resistance to penicillin in invasive pneumococcal strains.

Prophylaxis against sexually transmitted diseases following sexual assault (CDC [Workowski 2015]): Adolescents: IM: 250 mg as a single dose in combination with a single dose of oral azithromycin and oral metronidazole (or oral tinidazole)

Rhinosinusitis, acute bacterial:

Ambulatory patients: Children and Adolescents: IM, IV: 50 mg/kg as a single dose; usual 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])

Severe infection requiring hospitalization: Infants, Children, and Adolescents: IV: 50 mg/kg/day divided every 12 hours for 10 to 14 days; maximum daily dose: 2,000 mg/day (IDSA [Chow 2012])

Salmonellosis: Note: Salmonella in healthy patients typically does not require antibiotic treatment as it generally resolves in 5 to 7 days (CDC 2015).

Infants <6 months of age or Infants, Children, and Adolescents who have severe infection, prostheses, valvular heart disease, severe atherosclerosis, malignancy, or uremia: Non-typhi species diarrhea: IM, IV: 100 mg/kg/day divided every 12 to 24 hours for 14 days; or longer if relapsing. Note: Not recommended for routine use (Guerrant 2001).

HIV-exposed/-positive: Adolescents: IV: 1,000 mg every 24 hours; duration dependent upon CD4 counts and presence of bacteremia (HHS [OI adult 2018])

If CD4 count ≥200 cells/mm³: 7 to 14 days; if bacteremia present: At least 14 days; longer durations if bacteremia or if infection is complicated

If CD4 count <200 cells/mm³: 2 to 6 weeks

Shigellosis: Infants, Children, and Adolescents: IM, IV: 50 to 100 mg/kg/dose once daily; maximum daily dose: 4,000 mg/day; usual duration 5 days; may shorten duration to 2 days if clinical response good and no extraintestinal involvement (Red Book [AAP 2018]; WHO 2005)

Skin/skin structure infections: Infants, Children, and Adolescents: IM, IV: 50 to 75 mg/kg/day in 1 to 2 divided doses; maximum daily dose: 2,000 mg/day

S. pneumoniae infection, invasive (Red Book [AAP 2018]): Infants, Children, and Adolescents: IV:

CNS infection: 100 mg/kg/day divided every 12 to 24 hours; maximum dose: 2,000 mg/dose; maximum daily dose: 4,000 mg/day

Non-CNS infection: 50 to 75 mg/kg/day divided every 12 to 24 hours; maximum dose: 2,000 mg/dose; maximum daily dose: 4,000 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: Note: Not considered first-line therapy and use should be reserved for special circumstances with close monitoring and follow-up:

Congenital syphilis, treatment (CDC [Workowski 2015]): Note: There is insufficient data regarding the use of ceftriaxone for treatment of congenital syphilis (penicillin is recommended); use should be reserved for situations of penicillin shortage.

Infants ≥30 days: IM, IV: 75 mg/kg/dose once daily for 10 to 14 days

Children: IM, IV: 100 mg/kg/dose once daily for 10 to 14 days

Postexposure prophylaxis (HIV-exposed/-positive): Adolescents: IM, IV: 1,000 mg once daily for 10 to 14 days (HHS [OI adult 2018])

Treatment:

Early syphilis (independent of HIV status): Adolescents: IM, IV: 1,000 to 2,000 mg once daily for 10 to 14 days; optimal dose and duration have not been defined (CDC [Workowski 2015]; HHS [OI adult 2018])

Neurosyphillis, otic, ocular disease (HIV-exposed/-positive; penicillin-allergic): Adolescents: IM, IV: 2,000 mg once daily for 10 to 14 days (CDC [Workowski 2015). Note: Penicillin desensitization is the preferred approach; use should be reserved when desensitization is not feasible (HHS [OI adult 2018]).

Typhoid fever: Infants, Children, and Adolescents: IV: 80 mg/kg/dose once daily for 14 days (Stephens 2002). Note: Ceftriaxone is reserved for patients who have failed oral therapy or who have severe disease, intestinal complications, or obtundation and cannot take oral medications.

Urinary tract infections: Infants, Children, and Adolescents: IM, IV: 50 mg/kg/dose once daily; usual maximum dose: 2,000 mg/dose (AAP 2016; Bradley 2018)

Reconstitution

IM injection: Vials should be reconstituted with appropriate volume of diluent (including D₅W, NS, SWFI, bacteriostatic water, or 1% lidocaine) to make a final concentration of 250 mg/mL or 350 mg/mL.

Volume to add to create a 250 mg/mL solution:

250 mg vial: 0.9 mL

500 mg vial: 1.8 mL

1 g vial: 3.6 mL

2 g vial: 7.2 mL

Volume to add to create a 350 mg/mL solution:

500 mg vial: 1.0 mL

1 g vial: 2.1 mL

2 g vial: 4.2 mL

IV infusion: Infusion is prepared in two stages: Initial reconstitution of powder, followed by dilution to final infusion solution.

Vials: Reconstitute powder with appropriate IV diluent (including SWFI, D₅W, D₁₀W, NS) to create an initial solution of ~100 mg/mL. Recommended volume to add:

250 mg vial: 2.4 mL

500 mg vial: 4.8 mL

1 g vial: 9.6 mL

2 g vial: 19.2 mL

Note: After reconstitution of powder, further dilution into a volume of compatible solution (eg, 50-100 mL of D₅W or NS) is recommended.

Piggyback bottle: Reconstitute powder with appropriate IV diluent (D₅W or NS) to create a resulting solution of ~100 mg/mL. Recommended initial volume to add:

1 g bottle:10 mL

2 g bottle: 20 mL

Note: After reconstitution, to prepare the final infusion solution, further dilution to 50 mL or 100 mL volumes with the appropriate IV diluent (including D₅W or NS) is recommended.

Administration

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.

Dietary Considerations

Some products may contain sodium.

Storage

Powder for injection: Prior to reconstitution, store at ≤25°C (≤77°F). Protect from light.

Premixed solution (manufacturer premixed): Store at -20°C; once thawed, solutions are stable for 48 hours at 25°C (77°F) or for 21 days at 5°C (41°F). Do not refreeze.

Stability of reconstituted solutions:

10 to 40 mg/mL: Reconstituted in D₅W, D₁₀W, NS, or SWFI: Stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F). Stable for 26 weeks when frozen at -20°C when reconstituted with D₅W or NS. Once thawed (at room temperature), solutions are stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F); does not apply to manufacturer's premixed bags. Do not refreeze. If D₅NS or D₅¹/₂NS are used, solutions are only stable for 2 days at of 25°C (77°F).

100 mg/mL:

Reconstituted in D₅W, SWFI, or NS: Stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F).

Reconstituted in lidocaine 1% solution or bacteriostatic water: Stable for 24 hours at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F).

250 to 350 mg/mL: Reconstituted in D₅W, NS, lidocaine 1% solution, bacteriostatic water, or SWFI: Stable for 24 hours at room temperature of 25°C (77°F) or for 3 days when refrigerated at 4°C (39°F).

Drug Interactions

Aminoglycosides: Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

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

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. 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. Avoid combination

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

Probenecid: May increase the serum concentration of Cephalosporins. 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. 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. 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 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

Positive direct Coombs', false-positive urinary glucose test using nonenzymatic methods, false-positive galactosemia tests.

Adverse Reactions

>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%), thrombocythemia (5%), leukopenia (2%)

Hepatic: Increased serum transaminases (3%)

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

Renal: Increased blood urea nitrogen (1%)

<1%, postmarketing and/or case reports: Abdominal pain, acute generalized exanthematous pustulosis, acute renal failure (post-renal), agranulocytosis, allergic dermatitis, anaphylactoid reaction, anaphylaxis, anemia, basophilia, blood coagulation disorder, bronchospasm, candidiasis, casts in urine, chills, choledocholithiasis, cholelithiasis, Clostridioides (formerly Clostridium) difficile-associated diarrhea, colitis, decreased prothrombin time, diaphoresis, dizziness, dysgeusia, dyspepsia, edema, epistaxis, erythema multiforme, fever, flatulence, flushing, gallbladder sludge, glossitis, glycosuria, granulocytopenia, headache, hematuria, hemolytic anemia, hypersensitivity pneumonitis, increased monocytes, increased serum alkaline phosphatase, increased serum bilirubin, increased serum creatinine, jaundice, kernicterus, leukocytosis, lymphocytopenia, lymphocytosis, nausea, nephrolithiasis, neutropenia, oliguria, palpitations, pancreatitis, phlebitis, prolonged prothrombin time, pruritus, pseudomembranous colitis, seizure, serum sickness, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, toxic epidermal necrolysis, ureteral obstruction, urogenital fungal infection, urolithiasis, urticaria, vaginitis, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Serious and sometimes fatal hypersensitivity has been reported. Use caution in patients with a history of any allergy (particularly drugs), penicillin allergy or beta-lactam sensitivity. If severe hypersensitivity occurs, discontinue immediately and institute supportive emergency measures.
• 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.
• 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. Most patients had biliary stasis or sludge risk factors (eg, preceding major surgery, severe illness, TPN).
• 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 pseudolithiasis: Abnormal gallbladder sonograms have been reported, possibly due to ceftriaxone-calcium precipitates; probability is greatest in pediatric patients. Discontinue in patients who develop signs and symptoms and/or sonographic evidence 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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). 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 exhibit incompatibility 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.

Monitoring Parameters

Prothrombin time/INR. Observe for signs and symptoms of anaphylaxis.

Pregnancy

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Ceftriaxone crosses the placenta. 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 women for the treatment of gonococcal infections, Lyme disease, and may be used in certain situations prior to vaginal delivery in women at high risk for endocarditis (consult current guidelines) (ACOG 120, 2011; CDC [Workowski 2015]; Wormser 2006).

Patient Education

What is this drug used for?

• It is used to treat or prevent bacterial infections.

Frequently reported side effects of this drug

• Injection site irritation
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Hemolytic anemia like severe loss of strength and energy, dark urine, or yellow skin.
• Kidney stone like back pain, abdominal pain, or blood in the urine.
• Seizures
• Clostridium difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.