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CefTRIAXone

Pronunciation

Pronunciation

(sef trye AKS one)

Index Terms

  • Ceftriaxone Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

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

Solution Reconstituted, Injection:

Rocephin: 500 mg (1 ea [DSC]); 1 g (1 ea [DSC])

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

Brand Names: U.S.

  • Rocephin [DSC]

Pharmacologic Category

  • Antibiotic, Cephalosporin (Third Generation)

Pharmacology

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.

Absorption

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: 0.3 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

Children (age not specified): 4.1 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

Acute bacterial otitis media: Caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), or Moraxella catarrhalis (including beta-lactamase-producing strains).

Bacterial septicemia: Caused by Staphylococcus aureus, S. pneumoniae, Escherichia coli, H. influenzae, or Klebsiella pneumoniae.

Bone and joint infections: Caused by S. aureus, S. pneumoniae, E. coli, Proteus mirabilis, K. pneumoniae, or Enterobacter spp.

Intra-abdominal infections: Caused by E. coli, K. pneumoniae, Bacteroides fragilis, Clostridium spp., or Peptostreptococcus spp.

Lower respiratory tract infections: Caused by S. pneumoniae, S. aureus, H. influenzae, Haemophilus parainfluenzae, K. pneumoniae, E. coli, Enterobacter aerogenes, P. mirabilis, or Serratia marcescens.

Meningitis: 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).

Pelvic inflammatory disease: 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 skin structure 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), Pseudomonas aeruginosa, S. marcescens, Acinetobacter calcoaceticus, or B. fragilis (efficacy for this organism in this organ system was studied in fewer than 10 infections), or Peptostreptococcus spp.

Surgical prophylaxis: Reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated (eg, vaginal or abdominal hysterectomy or cholecystectomy for chronic calculous cholecystitis in high-risk patients, such as those older than 70 years, with acute cholecystitis not requiring therapeutic antimicrobials, obstructive jaundice, or common duct bile stones) and in surgical patients for whom infection at the operative site would present serious risk (eg, during coronary artery bypass surgery).

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

Urinary tract infections (complicated and uncomplicated): Caused by E. coli, P. mirabilis, Proteus vulgaris, M. morganii, or K. pneumoniae.

Off Label Uses

Acute bacterial rhinosinusitis

Based on the Infectious Diseases Society of America (IDSA) guidelines for acute bacterial rhinosinusitis (ABRS) in children and adults, ceftriaxone is effective and recommended for the treatment of severe ABRS requiring hospitalization.

Arthritis, septic (adults)

Data from a limited number of patients studied suggest that ceftriaxone may be beneficial for the treatment of septic arthritis in adults [Coiffier 2014], [Dalla Vestra 2008], [Harwood 2008], [Raad 2004]. Additional data may be necessary to further define the role of ceftriaxone in this condition. Clinical experience also suggests the utility of ceftriaxone for the treatment of septic arthritis.

Bacterial enteric infections in HIV-infected patients (empiric treatment) (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, cefotaxime is a recommended agent for empiric treatment of bacterial enteric infection in adolescent and adult HIV-infected patients with advanced HIV (CD4 count <200 cells/mm3 or concomitant AIDS-defining illness) and severe diarrhea (≥6 stools/day or bloody stool) and/or fever or chills.

Bite wounds (animal)

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

Brain abscess (adults)

Data from a limited number of patients studied suggest that ceftriaxone may be beneficial in adults 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]. Additional data may be necessary to further define the role of ceftriaxone in these conditions.

Chancroid

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

Community-acquired pneumonia (children)

Following clinical guideline recommendations on the management of CAP reduces the incidence of morbidity and mortality related to pneumonia. Ceftriaxone is a parenteral option for empirical treatment of suspected bacterial CAP in children not fully immunized in areas where local penicillin resistance in pneumococcal strains is high, and for pathogen-directed therapy aimed at GAS in children older than 3 months of age.

Epididymitis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is an effective and recommended agent in the treatment 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).

Epiglottitis (children)

Data from case reports and a prospective, randomized trial in children support the use of ceftriaxone for the treatment of epiglottitis [Low 2003], [Sawyer 1994]. Additional trials may be necessary to further define the role of ceftriaxone in this condition.

Gonococcal bacteremia, meningitis and endocarditis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is effective and recommended in the treatment of bacteremia (children), meningitis (adolescents and adults), and endocarditis (adolescents and adults); should be combined with azithromycin when given to adolescents and adults for meningitis or endocarditis.

Gonococcal conjunctivitis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is an effective and recommended treatment for patients with conjunctivitis due to gonorrhea; should be combined with azithromycin when given to adolescents and adults.

Gonorrhea, disseminated infections (including arthritis and arthritis-dermatitis syndrome)

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is effective and recommended in the treatment of disseminated gonococcal infections in infants and disseminated gonococcal infections including arthritis (children, adolescents, and adults) and arthritis-dermatitis syndrome (adolescents and adults); should be combined with azithromycin when given to adolescents and adults.

Gonorrhea, infant prophylaxis (due to untreated maternal gonococcal infection)

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is effective and recommended for prophylactic treatment of gonorrhea in infants born to mothers with untreated maternal gonococcal infection.

Gonorrhea, uncomplicated infections of the pharynx and vulvovaginitis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone is effective and recommended in the treatment of uncomplicated gonococcal infections of the pharynx (children, adolescents, and adults) and vulvovaginitis (children); should be combined with azithromycin when given to adolescents and adults.

Infective endocarditis, treatment (adults)

Based on the AHA Scientific Statement for 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.

Infective endocarditis, treatment (children/adolescents)

The AHA recommends ceftriaxone as an alternative to treatment with penicillin, either as monotherapy or in combination with gentamicin. Recommendations for the use of ceftriaxone to treat endocarditis depend on the bacterial cause of the infection.

Infective endocarditis, prophylaxis

Based on the American Heart Association (AHA) guidelines for the prevention of infective endocarditis, ceftriaxone is effective and recommended for administration to patients with certain cardiac conditions who are unable to take oral medication or are allergic to penicillins or ampicillin and unable to take oral medication to provide prophylaxis against infective endocarditis associated with dental or respiratory tract procedures.

Lyme disease

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 neurologic disease (eg, meningitis, radiculopathy), Lyme carditis requiring hospitalization, Lyme arthritis with evidence of neurologic disease, and late Lyme disease with central or peripheral nervous system disease.

Meningococcal disease, invasive, high-risk patient contacts (chemoprophylaxis)

Based on the American Academy of Pediatrics recommendations for children and adults with close exposure to patients with invasive meningococcal disease, ceftriaxone is effective and recommended for the chemoprophylaxis of meningococcal disease [CDC 2005], [Red Book [AAP 2015]].

Neurosyphilis in penicillin-allergic patients

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, limited data suggest ceftriaxone may be effective as an alternative agent in penicillin allergic patients for the treatment of neurosyphilis.

Osteomyelitis, native vertebral

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, ceftriaxone is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to beta-hemolytic streptococci, Cutibacterium acnes, or Salmonella species (if nalidixic acid resistant).

Proctitis, proctocolitis, enteritis

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with doxycycline, is effective and recommended in the treatment of acute proctitis, proctocolitis, or enteritis.

Prophylaxis against sexually transmitted diseases following sexual assault

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, ceftriaxone, in combination with azithromycin plus metronidazole (or tinidazole), is a recommended regimen for prophylaxis against sexually transmitted diseases following sexual assault in adolescents and adults.

Prosthetic joint infection (adults)

Based on the Infectious Diseases Society of America (IDSA) guidelines for prosthetic joint infection in adults, ceftriaxone is effective and recommended for the treatment of prosthetic joint infection due to beta-hemolytic streptococci [Osmon 2013].

Salmonellosis in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, ceftriaxone is a recommended alternative agent for treatment of salmonellosis in adolescent and adult HIV-infected patients.

Shigellosis

Based on the World Health Organization guidelines for the treatment of shigellosis including epidemics due to Shigella dysenteriae type 1 in children and adults, ceftriaxone (second-line) is effective and recommended for the treatment of shigellosis.

Skin and soft tissue necrotizing infections due to Aeromonas hydrophilia or Vibrio vulnificus

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), ceftriaxone, in combination with doxycycline, is an effective and recommended treatment for necrotizing infections of the skin, fascia, and muscle caused by Aeromonas hydrophilia or Vibrio vulnificus.

Spontaneous bacterial peritonitis (prevention)

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 effective and recommended to prevent spontaneous bacterial peritonitis in patients with cirrhosis and gastrointestinal hemorrhage. Parenteral antibiotic therapy is recommended for use while patient is bleeding; patient may be transitioned to an oral antibiotic after oral intake is resumed.

Surgical site infections

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), ceftriaxone, in combination with metronidazole, is an effective and recommended option for treatment of surgical site infections occurring after intestinal or genitourinary tract surgery or surgery of the axilla or perineum. Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3).

Syphilis (primary and secondary) in penicillin allergic patients

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, limited data suggest ceftriaxone may be effective as an alternative agent in penicillin allergic patients for the treatment for early (primary and secondary) syphilis; however, optimal dose and duration have not been established.

Typhoid fever

Based on the World Health Organization guidelines for the treatment of typhoid fever in children and adults, 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 managing/the treatment of typhoid fever in children [Stephens 2002].

Whipple disease

Data from randomized studies support the use of ceftriaxone in the initial treatment of Whipple disease [Feurle 2010], [Feurle 2013]. Additional trials may be necessary to further define the role of ceftriaxone in this condition.

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.

Dosing: Adult

Dosage range: IM, IV: Usual dose: 1 to 2 g every 12 to 24 hours, depending on the type and severity of infection

Acute bacterial rhinosinusitis, severe infection requiring hospitalization (off-label use): IV: 1 to 2 g every 12 to 24 hours (Chow 2012)

Arthritis, septic (off-label use): IV: 1 to 2 g once daily (Coiffier 2014; Dalla Vestra 2008; Harwood 2008; Raad 2004). Additional data may be necessary to further define the role of ceftriaxone in this condition.

Bacterial enteric infections in HIV-infected patients (empiric treatment) (off-label use): IV: 1 g every 24 hours (HHS [OI adult 2016])

Bite wounds (animal) (off-label use): IV: 1 g every 12 hours in combination with clindamycin or metronidazole for anaerobic coverage (IDSA [Stevens 2014])

Brain abscess (off-label use): IV: 2 g every 12 hours in combination with other antibiotics (Brouwer 2014; Louvois 2000). Additional data may be necessary to further define the role of ceftriaxone in this condition.

Chancroid (off-label use): IM: 250 mg as single dose (CDC [Workowski 2015])

Cholecystitis, mild-to-moderate: IV: 1 to 2 g every 12 to 24 hours for 4 to 7 days (provided source controlled) (Solomkin 2010). Note: The addition of anaerobic therapy is recommended if biliary-enteric anastomosis is present.

Cystitis (acute, complicated): IV: 1 to 2 g once daily (Stamm 1993)

Epididymitis, acute (off-label use) (CDC [Workowski 2015]):

Likely caused by sexually transmitted chlamydia and gonorrhea: IM: 250 mg in a single dose plus doxycycline

Likely caused by sexually transmitted chlamydia and gonorrhea and enteric organisms in men who practice insertive anal sex: IM: 250 mg in a single dose plus oral levofloxacin or oral ofloxacin

Gonococcal infections:

Conjunctivitis (off-label use): IM: 1 g in a single dose plus oral azithromycin; additionally, consider a one-time saline lavage of the infected eye. Data on treatment in adults are limited, consultation with an infectious-disease specialist should be considered (CDC [Workowski 2015])

Disseminated gonococcal infection (arthritis and arthritis-dermatitis syndrome) (off-label use): IM, IV: 1 g once daily plus single dose oral azithromycin; continue for 24 to 48 hours after clinical improvement, then may switch to an oral agent guided by antimicrobial susceptibility to complete a total of at least 7 days of therapy (CDC [Workowski 2015])

Endocarditis (off-label use): IV: 1 to 2 g every 12 to 24 hours plus oral azithromycin; continue ceftriaxone for at least 28 days (CDC [Workowski 2015])

Meningitis (off-label use): IV: 1 to 2 g every 12 to 24 hours plus oral azithromycin; continue ceftriaxone for 10 to 14 days (CDC [Workowski 2015])

Uncomplicated gonorrhea:

Cervicitis, proctitis, urethritis (off-label regimen): IM: 250 mg in a single dose plus oral azithromycin (CDC [Workowski 2015])

Pharyngitis (off-label use): IM: 250 mg in a single dose plus oral azithromycin (CDC [Workowski 2015])

Infective endocarditis, treatment (off-label use) (AHA [Baddour 2015]):

Enterococcus, native or prosthetic valve (penicillin-susceptible/gentamicin-susceptible or penicillin-susceptible/aminoglycoside resistant): IV: 2 g every 12 hours for 6 weeks with concomitant ampicillin

HACEK organisms, native or prosthetic valve: IV, IM: 2 g once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve)

Viridans group Streptococcus (VGS) and S. bovis: IV, IM:

Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g once daily for 4 weeks or for 2 weeks with concomitant gentamicin

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)

Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL): 2 g once daily with concomitant gentamicin for 6 weeks

Infective endocarditis, prophylaxis (off-label use): IM, IV: 1 g 30 to 60 minutes before procedure (Wilson 2007). Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.

Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (in combination with metronidazole): IV: 1 to 2 g every 12 to 24 hours for 4 to 7 days (provided source controlled) (IDSA [Solomkin 2010])

Lyme disease (off-label use): IV: 2 g once daily for 14 days (neurologic), or 21 to 28 days (carditis), or 28 days (arthritis with neurologic manifestations) (AAN [Halperin 2007]; IDSA [Wormser 2006])

Meningitis, community-acquired (empiric treatment): IV: 2 g every 12 hours for 7 to 14 days (longer courses may be necessary for selected organisms) in combination with other agents (eg, vancomycin) (IDSA [Tunkel 2004]).

Meningococcal disease, invasive, high-risk patient contacts (chemoprophylaxis) (off-label use): IM: 250 mg in a single dose (CDC 2005; Red Book [AAP 2015])

Osteomyelitis, native vertebral: IV:

Staphylococci, oxacillin-susceptible (off-label dose): 2 g every 24 hours for 6 weeks (IDSA [Berbari 2015]).

Streptococci (beta-hemolytic), Cutibacterium acnes or Salmonella spp (off-label use): IV: 2 g every 24 hours for 6 weeks. Note: In the treatment of Salmonella spp, a 6- to 8-week duration is recommended (IDSA [Berbari 2015]).

Pelvic inflammatory disease (mild to moderately severe): IM: 250 mg in a single dose plus oral doxycycline (with or without oral metronidazole) (CDC [Workowski 2015])

Pneumonia, community-acquired (in combination with other antibiotics):

Manufacturer’s labeling: IM, IV: 1 to 2 g/day in 1 or 2 divided doses.

Alternate dosing: IV: 1 g once daily (Roson 2001; Segev 1995)

Proctitis, proctocolitis, enteritis (off-label use): IM: 250 mg in a single dose plus oral doxycycline (CDC [Workowski 2015])

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): IM: 250 mg as a single dose in combination with azithromycin plus metronidazole (or tinidazole) (CDC [Workowski 2015])

Prosthetic joint infection: IV: Streptococci, beta-hemolytic: 2 g every 24 hours for 4 to 6 weeks (Osmon 2013)

Pyelonephritis (acute, uncomplicated): IV: 1 to 2 g once daily; after improvement, may be switched to an oral regimen to complete a 1- to 2-week treatment course (Grabe 2015 ). In females, some clinicians administer a single dose of 1 g before initiating oral outpatient empiric therapy (IDSA [Gupta 2011]).

Salmonellosis in HIV-infected patients (off-label use): IV: 1 g every 24 hours. Duration of therapy in patients with CD4 count ≥200 cells/mm3 is 7 to 14 days (without concurrent bacteremia) or ≥14 days (patients with concurrent bacteremia); patients with CD4 count <200 cells/mm3 should be treated for 2 to 6 weeks (regardless of presence of bacteremia) (HHS [OI adult 2016]).

Skin and soft tissue necrotizing infection (off-label use) (IDSA [Stevens 2014]): Note: Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours.

Due to Aeromonas hydrophilia: IV: 1 to 2 g once daily in combination with doxycycline

Due to Vibrio vulnificus: IV: 1 g once daily in combination with doxycycline

Spontaneous bacterial peritonitis (prevention) (off-label use): IV: 1 g once daily during active gastrointestinal bleeding (may be transitioned to an oral antibiotic after oral intake is resumed) for total duration of antibiotic therapy of 7 days (AASLD [Runyon 2012]).

Surgical (perioperative) prophylaxis: IV: 1 g 30 minutes to 2 hours before surgery

Manufacturer's labeling: 1 g 30 minutes to 2 hours before surgery

Alternate dosing: 1 to 2 g within 60 minutes prior to surgery (Bratzler 2013)

Alternate dosing for colorectal procedures: 2 g within 60 minutes prior to surgery with concomitant metronidazole (Bratzler 2013)

Cholecystectomy: 1 to 2 g every 12 to 24 hours, discontinue within 24 hours unless infection outside gallbladder suspected (Solomkin 2010)

Surgical site infections (intestinal or genitourinary tract surgery, surgery of axilla, or perineum) (off-label use): IV: 1 g every 24 hours, in combination with metronidazole (IDSA [Stevens 2014])

Syphilis in penicillin allergic patients (off-label use) (CDC [Workowski 2015]): IM, IV:

Primary or secondary: 1 to 2 g once daily for 10 to 14 days (limited study data; optimal dose and duration have not been defined)

Neurosyphilis: 2 g once daily for 10 to 14 days (limited study data)

Typhoid fever (off-label use): IV: 2 g every 12 to 24 hours for 10 to 14 days; Note: Usually reserved for fluoroquinolone resistant disease (WHO 2003).

Whipple disease (off-label use): IV: Initial: 2 g once daily for 10 to 14 days, then oral therapy (sulfamethoxazole and trimethoprim preferred) (Feurle 2010; Feurle 2013)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Dosage range: Infants, Children, and Adolescents: Usual dose: IM, IV:

Mild to moderate infections: 50 to 75 mg/kg/day in 1 to 2 divided doses every 12 to 24 hours (maximum: 2,000 mg daily); continue until at least 2 days after signs and symptoms of infection have resolved

Serious infections: 80 to 100 mg/kg/day in 1 to 2 divided doses (maximum: 4,000 mg daily)

Acute bacterial rhinosinusitis, severe infection requiring hospitalization (off-label use): IV: 50 mg/kg/day divided every 12 hours for 10 to 14 days (Chow 2012)

Bacterial enteric infections in HIV-infected patients (empiric treatment) (off-label use): Adolescents: IV: Refer to adult dosing.

Community-acquired pneumonia (CAP) (IDSA/PIDS [Bradley 2011]) (off-label dose): Infants >3 months and Children: IV: 50 to 100 mg/kg/day once daily or divided every 12 hours (maximum: 2,000 mg daily). 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.

Epiglottis (off-label use): IV: 100 mg/kg/day as a single dose on day 1, then 50 mg/kg as a single dose on day 2 (Sawyer 1994) or 75 mg/kg once daily for 10 to 14 days (Low 2003). Additional data may be necessary to further define the role of ceftriaxone in this condition.

Gonococcal infections:

Bacteremia (off-label use) (CDC [Workowski 2015]): IM, IV:

Children ≤45 kg: 50 mg/kg/dose once daily (maximum: 1,000 mg) for 7 days

Children >45 kg: 1,000 mg once daily for 7 days

Conjunctivitis (off-label use): IM, IV:

Neonates and Infants: 25 to 50 mg/kg/dose as a single dose (maximum dose: 125 mg) (CDC [Workowski 2015]). Note: Use contraindicated in hyperbilirubinemic neonates.

Adolescents: Refer to adult dosing.

Disseminated gonococcal infection (DGI) in infants including scalp abscess (off-label use): IM, IV:

Infants: 25 to 50 mg/kg/dose once daily for 7 days (10 to 14 days for meningitis) (CDC [Workowski 2015]); Note: Use contraindicated in hyperbilirubinemic neonates.

Disseminated gonococcal infection (arthritis, arthritis-dermatitis syndrome) (off-label use): IM, IV:

Children ≤45 kg: Arthritis: 50 mg/kg/dose once daily (maximum dose: 1,000 mg) for 7 days (CDC [Workowski 2015])

Children >45 kg: Arthritis: 1,000 mg once daily for 7 days (CDC [Workowski 2015])

Adolescents: Refer to adult dosing.

Endocarditis (off-label use):

Children ≤45 kg: IM, IV: 50 mg/kg/day divided every 12 or 24 hours (maximum: 2,000 mg daily) for at least 28 days (Red Book [AAP 2015])

Children >45 kg and Adolescents: Refer to adult dosing.

Meningitis (off-label use): IV, IM:

Infants: 25 to 50 mg/kg/day in a single daily dose for 10 to 14 days (CDC [Workowski 2015]); Note: Use contraindicated in hyperbilirubinemic neonates.

Children ≤45 kg: 50 mg/kg/day divided every 12 or 24 hours (maximum: 2,000 mg daily); usual duration of treatment is 10 to 14 days (Red Book [AAP 2015])

Children >45 kg and Adolescents: Refer to adult dosing.

Prophylactic treatment in neonates due to untreated maternal gonococcal infection (off-label use): Neonates: IM, IV: 25 to 50 mg/kg as a single dose (maximum: 125 mg) (CDC [Workowski 2015]). Note: Use contraindicated in hyperbilirubinemic neonates.

Uncomplicated gonorrhea (cervicitis, proctitis, or urethritis) (off-label population) CDC [Workowski 2015]):

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

Children >45 kg and Adolescents: Refer to adult dosing.

Uncomplicated gonorrhea: Pharyngitis or vulvovaginitis (off-label use) (CDC [Workowski 2015]):

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

Children >45 kg and Adolescents: IM: 250 mg in a single dose plus oral azithromycin

Infective endocarditis (off-label use): IM, IV:

Native valve: 100 mg/kg once daily (maximum: 2,000 mg daily) for 2 to 4 weeks; Note: If using 2-week regimen or for relatively penicillin-resistant streptococcus, concurrent gentamicin is recommended; for HACEK organisms, duration of therapy is 4 weeks (Baddour 2005)

Prosthetic valve: 100 mg/kg once daily (maximum: 2,000 mg daily) for 6 weeks (with or without gentamicin [dependent on penicillin MIC]); for HACEK organisms, duration of therapy is 4 weeks (Baddour 2005)

Enterococcus faecalis (resistant to penicillin, aminoglycoside, and vancomycin), native or prosthetic valve: 100 mg/kg/day divided every 12 hours for ≥8 weeks administered concurrently with ampicillin (Baddour 2005)

Prophylaxis: 50 mg/kg 30 to 60 minutes before procedure; maximum dose: 1,000 mg (Red Book [AAP 2015]; Wilson 2007). Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications.

Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA.

Lyme disease (off-label use): IM, IV:

Atrioventricular heart block or carditis: 50 to 75 mg/kg once daily (maximum: 2,000 mg) for 14 to 21 days (Red Book [AAP 2015])

Encephalitis or other late neurologic disease: 50 to 75 mg/kg once daily (maximum: 2,000 mg) for 14 to 28 days (Red Book [AAP 2015])

Neurologic: 50 to 75 mg/kg once daily (maximum: 2,000 mg) for 14 days (Halperin 2007)

Meningitis: 50 to 75 mg/kg once daily (maximum: 2,000 mg) for 14 to 21 days (Red Book [AAP 2015])

Recurrent arthritis: 50 to 75 mg/kg once daily (maximum: 2,000 mg) for 14 to 28 days (Red Book [AAP 2015])

Meningitis (empiric treatment): IM, IV: Loading dose of 100 mg/kg (maximum: 4,000 mg), followed by:

Manufacturer's labeling: 100 mg/kg/day divided every 12 to 24 hours (maximum: 4,000 mg daily); usual duration of treatment is 7 to 14 days

Alternate dosing: 80 to 100 mg/kg/day divided every 12 to 24 hours (maximum: 4,000 mg daily) (Tunkel 2004)

Meningococcal disease, invasive, high-risk patient contacts (chemoprophylaxis) (off-label use):

Children and Adolescents <15 years: IM: 125 mg in a single dose (CDC 2005; Red Book [AAP 2015]).

Adolescents ≥15 years: Refer to adult dosing.

Otitis media: IM:

Acute: 50 mg/kg in a single dose (maximum: 1,000 mg)

Persistent or relapsing (off-label dose): 50 mg/kg once daily for 3 days (AAP 2014; Lieberthal 2013)

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Adolescents: Refer to adult dosing.

Salmonellosis in HIV-infected patients (off-label use): Adolescents: IV: Refer to adult dosing.

Shigella dysentery type 1 (off-label dose): IM: 50 to 100 mg/kg/day for 2 to 5 days (WHO 2005)

Skin/skin structure infections: IM, IV: 50 to 75 mg/kg/day in 1 to 2 divided doses (maximum: 2,000 mg daily)

Surgical (perioperative) prophylaxis (off-label dose): Children ≥ 1 year: IV: 50 to 75 mg/kg within 60 minutes prior to surgery (maximum: 2,000 mg) (Bratzler 2013)

Typhoid fever (off-label use): IV: 80 mg/kg once daily for 14 days (Stephens 2002)

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, in patients with concurrent renal and hepatic impairment, maximum daily dose should not exceed 2 g.

ESRD requiring dialysis: Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD) (Aronoff 2007).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, in patients with concurrent renal and hepatic impairment, maximum daily dose should not exceed 2 g.

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

Do not coadminister with calcium-containing solutions.

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 in children ≥12 years, adolescents, and adults (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). 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).

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 3 days 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 with calcium-containing solutions within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. 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 with calcium-containing solutions (including LR) within 48 hours of one another is contraindicated in neonates (28 days of age or younger). In older patients, flush lines with compatible fluid between administration. 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% (Limited to important or life-threatening): 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, choledocholithiasis, cholelithiasis, clostridium difficile associated diarrhea, colitis, decreased prothrombin time, dysgeusia, dyspepsia, edema, epistaxis, erythema multiforme, fever, 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, nephrolithiasis, neutropenia, oliguria, palpitations, pancreatitis, phlebitis, prolonged prothrombin time, pseudomembranous colitis, seizure, serum sickness, Stevens-Johnson syndrome, stomatitis, thrombocytopenia, toxic epidermal necrolysis, ureteral obstruction, urogenital fungal infection, urolithiasis, vaginitis

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, sever 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 complex with calcium causing precipitation. Fatal lung and kidney damage associated with calcium-ceftriaxone precipitates has been observed in premature and term neonates. Due to reports of precipitation reaction in neonates, do not reconstitute, admix, or coadminister with calcium-containing solutions (eg, LR, Hartmann’s solution, parenteral nutrition), even via separate infusion lines/sites or at different times in any neonate. Ceftriaxone should not be diluted or administered simultaneously with any calcium-containing solution via a Y-site in any patient. However, ceftriaxone and calcium-containing solutions may be administered sequentially of one another for use in patients other than neonates if infusion lines are thoroughly flushed (with a compatible fluid) between infusions.

Monitoring Parameters

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

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 Fernandez 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation or diarrhea. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of gallstones (pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; jaundice; or fever with chills), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of hemolytic anemia (severe loss of strength and energy, dark urine, or jaundice), back pain, abdominal pain, hematuria, confusion, hallucinations, change in balance, passing out, extra muscle movement, seizures, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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