Generic Name: ceftriaxone

Brand Names: Ceftriaxone Sodium Novaplus, Ceftriaxone Sodium, Rocephin

Uses

Acute Otitis Media (AOM)

Treatment of AOM caused by S. pneumoniae, H. influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains). The single-dose IM ceftriaxone regimen has some practical advantages (ensures compliance, can be used in patients with nausea and vomiting), but manufacturer cautions that clinical cure rate with the single-dose regimen may be lower than that reported with multiple-dose regimens of oral anti-infectives usually used for AOM.

Treatment of persistent or recurrent AOM† in pediatric patients ≥3 months of age with infections that failed to respond to other anti-infectives (e.g., amoxicillin, amoxicillin and clavulanate potassium, cefaclor, cefuroxime).

Bone and Joint Infections

Treatment of bone and joint infections (e.g., osteomyelitis, septic arthritis) caused by susceptible Staphylococcus aureus, Streptococcus pneumoniae, Enterobacter, Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis.

Endocarditis

Treatment of native valve or prosthetic valve endocarditis caused by viridans streptococci (e.g., S. oralis, S. milleri group, S. mitis, S. mutans, S. salivarius, S. sanguis) or S. bovis (nonenterococcal group D streptococcus)†. Used for endocarditis caused by viridans streptococci or S. bovis highly susceptible to penicillin (penicillin MIC ≤0.12 mcg/mL) or relatively resistant to penicillin (penicillin MIC >0.12 mcg/mL but ≤0.5 mcg/mL). Should not be used for endocarditis caused by viridans streptococci or S. bovis highly resistant to penicillin (penicillin MIC >0.5 mcg/mL) or caused by Abiotrophia defectiva, Granulicatella, or Gamella.

Treatment of native valve or prosthetic valve endocarditis caused by slow-growing fastidious gram-negative bacilli termed the HACEK group† (i.e., Haemophilus parainfluenzae, H. aphrophilus, H. paraphrophilus, H. influenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae, K. denitrificans).

Not usually recommended for treatment of endocarditis caused by Enterococcus (e.g., E. faecalis, E. faecium). May be used in conjunction with ampicillin and sulbactam for treatment of native or prosthetic valve endocarditis caused by E. faecalis resistant to penicillin, aminoglycosides, and vancomycin when there are few therapeutic options. Since treatment of enterococcal endocarditis caused by vancomycin-resistant or multidrug-resistant enterococci is complex, consult specialists in infectious disease, cardiology, cardiac surgery, and microbiology.

Not indicated for treatment of staphylococcal endocarditis.

Alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk of endocarditis. Oral amoxicillin is usual drug of choice for such prophylaxis; ceftriaxone (or cefazolin) is an alternative in penicillin-allergic individuals or when an oral anti-infective cannot be used. Should not be used in those with immediate-type penicillin hypersensitivity (see Cross-hypersensitivity under Cautions). Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with highest risk of endocarditis and which procedures require prophylaxis.

Intra-abdominal Infections

Treatment of intra-abdominal infections caused by susceptible E. coli, K. pneumoniae, Bacteroides fragilis, Clostridium (not C. difficile), or Peptostreptococcus.

Treatment of mixed aerobic-anaerobic intra-abdominal infections; should not be used alone when B. fragilis may be present.

Meningitis and Other CNS Infections

Treatment of meningitis caused by susceptible H. influenzae, N. meningitidis, or S. pneumoniae in neonates, children, or adults. A drug of choice for meningitis caused by penicillin-resistant S. pneumoniae, but consider that S. pneumoniae with reduced susceptibility to cephalosporins have been reported with increasing frequency and susceptibility can no longer be assumed.

Treatment of meningitis and other CNS infections caused by susceptible Enterobacteriaceae† (e.g., E. coli, Klebsiella).

Should not be used alone for empiric treatment of meningitis when Listeria monocytogenes, enterococci, staphylococci, or Pseudomonas aeruginosa may be involved.

Empiric treatment of bacterial brain abscesses and other CNS infections (e.g., subdural empyema, intracranial epidural abscesses) caused by gram-positive aerobic cocci, Enterobacteriaceae (e.g., E. coli, Klebsiella), and/or anaerobic bacteria (e.g., Bacteroides, Fusobacterium).

Respiratory Tract Infections

Treatment of respiratory tract infections (including pneumonia) caused by susceptible S. aureus, S. pneumoniae, H. influenzae, H. parainfluenzae, E. aerogenes, E. coli, K. pneumoniae, P. mirabilis, or Serratia marcescens.

Treatment of community-acquired pneumonia (CAP). Recommended by ATS and IDSA as an alternative for treatment of CAP caused by penicillin-susceptible S. pneumoniae and as a preferred drug for treatment of CAP caused by penicillin-resistant S. pneumoniae, provided in vitro susceptibility has been demonstrated. Also recommended in certain combination regimens used for empiric treatment of CAP. Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).

For empiric outpatient treatment of CAP when risk factors for drug-resistant S. pneumoniae are present (e.g., comorbidities such as chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancies, asplenia, immunosuppression, use of anti-infectives within the last 3 months), ATS and IDSA recommend monotherapy with a fluoroquinolone active against S. pneumoniae (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.

For empiric inpatient treatment of CAP in patients not requiring treatment in an intensive care unit (non-ICU patients), IDSA and ATS recommend monotherapy with a fluoroquinolone (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin). For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).

Septicemia

Treatment of septicemia caused by S. aureus, S. pneumoniae, E. coli, H. influenzae, or K. pneumoniae.

Select anti-infective for treatment of sepsis syndrome based on probable source of infection, gram-stained smears of appropriate clinical specimens, immune status of the patient, and current patterns of bacterial resistance within the hospital and local community. Some clinicians suggest that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) are good choices for treatment of gram-negative sepsis.

For initial treatment of life-threatening sepsis in adults, some clinicians suggest that a third or fourth generation cephalosporin (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime), fixed combination of piperacillin and tazobactam, or a carbapenem (imipenem or meropenem) be used in conjunction with vancomycin with or without an aminoglycoside (amikacin, gentamicin, tobramycin).

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible S. aureus, S. epidermidis, S. pyogenes (group A β-hemolytic streptococci), viridans streptococci, E. coli, E. cloacae, K. oxytoca, K. pneumoniae, P. mirabilis, Morganella morganii, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, B. fragilis, or Peptostreptococcus.

Urinary Tract Infections (UTIs)

Treatment of complicated and uncomplicated UTIs caused by E. coli, K. pneumoniae, M. morganii, P. mirabilis, or P. vulgaris.

Considered a drug of choice for treatment of UTIs caused by susceptible Enterobacteriaceae, including susceptible strains of E. coli, K. pneumoniae, P. rettgeri, M. morganii, P. vulgaris, or P. stuartii; an aminoglycoside usually used concomitantly in severe infections.

Ceftriaxone (like other third generation cephalosporins) generally should not be used for treatment of uncomplicated UTIs when other anti-infectives with a narrower spectrum of activity could be used.

Actinomycosis

Has been used for treatment of infections caused by Actinomyces†. Not considered a drug of choice; penicillin G generally preferred for initial treatment of all forms of actinomycosis, including thoracic, abdominal, CNS, and cervicofacial infections.

Bartonella Infections

Treatment of bacteremia caused by Bartonella quintana† (in conjunction with oral erythromycin or oral azithromycin).

The possible role of ceftriaxone in the treatment of infections caused by Bartonella henselae† (e.g., cat scratch disease, bacillary angiomatosis, peliosis hepatitis) has not been determined. Cat scratch disease generally is self-limited in immunocompetent individuals and may resolve spontaneously in 2–4 months; some clinicians suggest that anti-infective therapy be considered for acutely or severely ill patients with systemic symptoms, particularly those with hepatosplenomegaly or painful lymphadenopathy, and such therapy probably is indicated in immunocompromised patients. Anti-infectives also are indicated in patients with B. henselae infections who develop bacillary angiomatosis, neuroretinitis, or Parinaud’s oculoglandular syndrome.

Optimum regimens for treatment of infections caused by B. quintana or for treatment of cat scratch disease or other B. henselae infections have not been identified.

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga.

Optimum regimens for treatment of infections caused by Capnocytophaga have not been identified; some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem and cilastatin sodium, meropenem), vancomycin, a fluoroquinolone, or clindamycin.

Chancroid

Treatment of chancroid† (genital ulcers caused by H. ducreyi).

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin or erythromycin as drugs of choice for treatment of chancroid. HIV-infected patients and uncircumcised patients may not respond to treatment as well as those who are HIV-negative or circumcised. CDC recommends that the single-dose ceftriaxone regimen be used in HIV patients only if follow-up can be ensured.

Gonorrhea and Associated Infections

Treatment of uncomplicated cervical, urethral, or rectal infections caused by susceptible N. gonorrhoeae. Recommended by CDC, AAP, and others as a drug of choice for uncomplicated gonorrhea in adults, adolescents, and children.

Treatment of pharyngeal infections caused by N. gonorrhoeae. Recommended by CDC, AAP, and others as the regimen of choice for pharyngeal gonorrhea in adults, adolescents, and children.

Initial treatment of disseminated gonococcal infections†. Recommended by CDC, AAP, and others as the regimen of choice for initial parenteral treatment in adults, adolescents, and children, especially when meningitis, endocarditis, or conjunctivitis is involved.

Treatment of epididymitis† (in conjunction with doxycycline) in patients most likely to have infections caused by N. gonorrhoeae and/or C. trachomatis (e.g., in those <35 years of age). Drug of choice for empiric treatment.

Treatment of proctitis† (in conjunction with doxycycline) in patients most likely to have infections caused by N. gonorrhoeae and/or C. trachomatis.

Parenteral prophylaxis† in neonates born to mothers with documented peripartum gonococcal infection. Considered drug of choice by CDC and AAP.

Treatment of ophthalmia neonatorum† caused by N. gonorrhoeae. The single-dose ceftriaxone regimen is adequate therapy for gonococcal conjunctivitis, but infants with ophthalmia neonatorum should be hospitalized and evaluated for signs of disseminated infection (e.g., sepsis, arthritis, meningitis).

Treatment of disseminated gonococcal infections (e.g., sepsis, arthritis, meningitis) in neonates. Should not be used in neonates who are hyperbilirubinemic (especially those born prematurely) (see Pediatric Use under Cautions); AAP suggests cefotaxime is preferred in these neonates.

Leptospirosis

Treatment of severe leptospirosis† caused by Leptospira.

Leptospirosis is a spirochete infection that may range in severity from a self-limited systemic illness to a severe, life-threatening illness that includes jaundice, renal failure, hemorrhage, cardiac arrhythmias, pneumonitis, and hemodynamic collapse (Weil syndrome).

Penicillin G generally has been considered the drug of choice for treatment of moderate to severe leptospirosis, and doxycycline has been used in less severe infections. Cephalosporins (ceftriaxone, cefotaxime), aminopenicillins (ampicillin, amoxicillin), tetracyclines (doxycycline, tetracycline), or macrolides (azithromycin) also have been recommended for severe infections.

Lyme Disease

Treatment of early neurologic Lyme disease† with acute neurologic manifestations such as meningitis or radiculopathy. IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G. Although an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) may be effective for early localized or early disseminated Lyme disease associated with erythema migrans in the absence of specific neurologic manifestations or advanced atrioventricular (AV) heart block, a parenteral regimen usually is recommended when there are acute neurologic manifestations.

Treatment of Lyme carditis† when a parenteral regimen is indicated. IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G. Although a parenteral regimen usually is recommended for initial treatment of hospitalized patients, an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) can be used to complete therapy and for the treatment of outpatients.

Treatment of Lyme arthritis† when a parenteral regimen is indicated. IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G. Although the comparative safety and efficacy of oral versus IV anti-infectives for treatment of Lyme arthritis has not been fully evaluated, those with concomitant neurologic disease generally should receive a parenteral regimen.

Treatment of late neurologic Lyme disease† affecting the CNS or peripheral nervous system (e.g., encephalopathy, neuropathy). IV ceftriaxone is the drug of choice; alternatives are IV cefotaxime or IV penicillin G.

Neisseria meningitidis Infections

Treatment of invasive infections caused by N. meningitidis. (See Meningitis and Other CNS Infections under Uses.)

Elimination of nasopharyngeal carriage of N. meningitidis†. CDC and AAP consider rifampin, ceftriaxone, or ciprofloxacin the drugs of choice for such carriers.

Postexposure prophylaxis to prevent meningococcal disease in household or other close contacts of patients with invasive meningococcal disease†.

Outbreak control of meningococcal disease when outbreaks involve small populations (e.g., a small organization such as a single school).

Nocardiosis

Treatment of nocardiosis† caused by Nocardia.

Co-trimoxazole (fixed combination of sulfamethoxazole and trimethoprim) generally is the drug of choice for treatment of nocardiosis. Other drugs that have been used alone or in combination regimens for treatment of nocardiosis include a sulfonamide alone (sulfamethoxazole [not commercially available in the US], sulfadiazine), amikacin, tetracyclines (minocycline), cephalosporins (ceftriaxone, cefotaxime, cefuroxime), cefoxitin, carbapenems (imipenem or meropenem), fixed combination of amoxicillin and clavulanate, clarithromycin, cycloserine, or linezolid.

For treatment of invasive nocardiosis or when sulfonamides cannot be tolerated, select anti-infectives based on results of in vitro susceptibility tests. If nocardiosis involves the CNS or if the infection is disseminated or overwhelming, some clinicians suggest that amikacin and ceftriaxone be included in the treatment regimen during the first 4–12 weeks of therapy or until there is clinical improvement. A regimen of amikacin and ceftriaxone has been effective for the treatment of disseminated N. asteroides infection complicated by cerebral abscess.

Pelvic Inflammatory Disease (PID)

Treatment of PID caused by N. gonorrhoeae.

Not considered a drug of choice for parenteral regimens used for treatment of PID. CDC states ceftriaxone may be effective for PID, but is less active than cefotetan or cefoxitin against anaerobic bacteria.

When an oral regimen is used for treatment of mild to moderately severe acute PID, CDC recommends a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or other parenteral third-generation cephalosporin (e.g., cefotaxime, ceftizoxime) given in conjunction with oral doxycycline (with or without oral metronidazole).

Because ceftriaxone (like other cephalosporins) is not active against Chlamydia, concomitant use of a drug active against Chlamydia (e.g., doxycycline) is necessary when these organisms are suspected pathogens.

Pseudomonas aeruginosa Infections

May be effective for treatment of some infections caused by Ps. aeruginosa (see Skin and Skin Structure Infections under Uses).

Because many strains of Ps. aeruginosa are only susceptible to high concentrations of ceftriaxone in vitro and because resistant strains of the organism have developed during therapy with the drug, ceftriaxone generally should not be used alone in the treatment of any infection where Ps. aeruginosa may be present.

Relapsing Fever

Treatment of relapsing fever† caused by Borrelia recurrentis; other drugs (e.g., tetracyclines, penicillin G) usually considered drugs of choice.

Shigella Infections

Treatment of shigellosis† in children caused by susceptible Shigella sonnei or S. flexneri.

Anti-infectives generally indicated in addition to fluid and electrolyte replacement for severe shigellosis. Ceftriaxone is considered a drug of choice for shigellosis when the susceptibility of the isolate is unknown, especially in areas where ampicillin-resistant Shigella have been reported.

Syphilis

Alternative for treatment of early syphilis† in patients hypersensitive to penicillin; CDC cautions that optimal dosage and duration of ceftriaxone for this use have not been defined.

Alternative for treatment of neurosyphilis† in patients hypersensitive to penicillin.

CDC states that IM or IV ceftriaxone may be considered for treatment of infants with clinical evidence of congenital syphilis if there is a penicillin shortage and penicillin G sodium and penicillin G procaine are unavailable. However, the drug should be used in consultation with a specialist in treatment of infants with congenital syphilis and with careful clinical and serologic follow-up.

CDC states that data are insufficient to recommend use of ceftriaxone for treatment of early syphilis in pregnant women or pediatric patients hypersensitive to penicillin or for prevention of congenital syphilis and the only acceptable alternatives to penicillin G for patients with late latent syphilis, syphilis of unknown duration, or tertiary syphilis are doxycycline or tetracycline. Use of ceftriaxone in HIV-infected individuals with syphilis has not been adequately studied and such therapy should be undertaken with caution.

Because of limited experience with penicillin alternatives, close follow-up is essential if ceftriaxone is used in the treatment of syphilis. If compliance with an alternative regimen cannot be ensured in patients hypersensitive to penicillin, the CDC recommends desensitization and treatment with penicillin G.

Typhoid Fever and Other Salmonella Infections

Treatment of typhoid fever (enteric fever) or septicemia caused by Salmonella typhi or S. paratyphi†, including multidrug-resistant strains.

Treatment of infections caused by nontyphi Salmonella, including bacteremia or osteomyelitis caused by S. typhimurium.

Treatment of gastroenteritis caused by Salmonella (e.g., S. enteritidis, S. typhimurium) in individuals with severe Salmonella gastroenteritis and in those who are at increased risk of invasive disease.

Whipple's Disease

Treatment of Whipple’s disease†, a progressive systemic infection caused by Tropheryma whippelii.

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic adults or pediatric patients†; used in conjunction with an aminoglycoside.

Ceftriaxone monotherapy may not provide adequate coverage against some potential pathogens (e.g., Ps. aeruginosa) and such monotherapy generally is not recommended for empiric anti-infective therapy in febrile neutropenic patients.

Perioperative Prophylaxis

Perioperative prophylaxis to reduce the incidence of infection in patients undergoing contaminated or potentially contaminated surgical procedures, including cholecystectomy, intra-abdominal surgery, or vaginal or abdominal hysterectomy, and in those undergoing clean surgical procedures in which the development of infection at the surgical site would represent a serious risk, including coronary artery bypass, open heart surgery, thoracic surgery, or orthopedic surgery. The drug also has been used perioperatively in patients undergoing transurethral resection of the prostate†.

Other cephalosporins or cephamycins (cefazolin, cefuroxime, cefotetan, cefoxitin) are the preferred drugs for perioperative prophylaxis. Ceftriaxone and other third generation cephalosporins usually not used for perioperative prophylaxis since they are expensive, some are less active against staphylococci than cefazolin, they have a spectrum of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis promotes emergence of resistant organisms.

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims†; used in conjunction with oral metronidazole and oral azithromycin or doxycycline.

Prophylaxis Following Bite Wounds

Prophylaxis following a bite wound† (human or animal).

Dosage and Administration

Administration

Administer by IV infusion or deep IM injection.

The commercially available premixed ceftriaxone injection (frozen) should be used only for IV infusion.

Do not use diluents containing calcium (e.g. Ringer's/lactated Ringer's injection, Hartmann's injection) to reconstitute or further dilute ceftriaxone because a precipitate can form.

Because precipitation of ceftriaxone-calcium can occur, ceftriaxone must not be admixed with calcium-containing solutions and must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age). (See Interaction with Calcium-containing Products under Cautions.)

Ceftriaxone is contraindicated in neonates (≤28 days of age) if they are receiving (or expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition. In adults and pediatric patients older than 28 days of age, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid.

IV Infusion

The recommended concentration for IV infusion is 10–40 mg of ceftriaxone/mL; lower concentrations may be used if desired.

Do not use diluents containing calcium (e.g., Ringer's/lactated Ringer's injection, Hartmann's injection) to reconstitute or further dilute ceftriaxone because a precipitate can form.

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution and Dilution

Reconstitute vials containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone with 2.4, 4.8, 9.6, or 19.2 mL, respectively, of a compatible IV solution to provide solutions containing approximately 100 mg/mL. Then, further dilute in a compatible IV solution.

Reconstitute 10-g pharmacy bulk package by adding 95 mL of a compatible IV solution to provide a solution containing approximately 100 mg/mL and then further dilute in a compatible IV infusion solution.

The commercially available Duplex^® drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection, respectively, in separate chambers should be reconstituted (activated) according to the manufacturer's directions.

Thaw the commercially available premixed injection (frozen) at room temperature (25°C) or in a refrigerator (5°C); do not force thaw by immersion in a water bath or by exposure to microwave radiation. A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature. Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact. The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.

Rate of Administration

Intermittent IV infusions should be infused over 30 minutes.

In clinical studies, doses have been infused over 15–30 minutes in adults or over 10–30 minutes in neonates or children.

IM Administration

Inject IM deeply into a large muscle mass. Use aspiration to ensure that the needle is not in a blood vessel.

IM solutions prepared using bacteriostatic water containing benzyl alcohol should not be used in neonates. (See Pediatric Use under Cautions.)

Do not use diluents containing calcium (e.g., Ringer's/lactated Ringer's injection, Hartmann's injection) to reconstitute or further dilute ceftriaxone because a precipitate can form.

Reconstitution

Prepare IM injections by adding 0.9, 1.8, 3.6, or 7.2 mL of sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, bacteriostatic water for injection containing 0.9% benzyl alcohol, or 1% lidocaine hydrochloride (without epinephrine) to a vial containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 250 mg/mL or by adding 1, 2.1, or 4.2 mL of one of these diluents to a vial containing 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 350 mg/mL.

Vials containing 250 mg should not be reconstituted to a concentration of 350 mg/mL since it will be impossible to withdraw the entire contents of the vial.

Dosage

Available as ceftriaxone sodium; dosage expressed in terms of ceftriaxone.

Pediatric Patients

General Pediatric Dosage

Infections in Neonates ≤4 Weeks of Age

IV or IM

AAP recommends 50 mg/kg once daily in neonates <1 week of age; 50 mg/kg once daily in those 1–4 weeks of age weighing <2 kg; and 50–75 mg/kg once daily in those 1–4 weeks of age weighing >2 kg.

Mild to Moderate Infections in Children >4 Weeks of Age

IV or IM

AAP recommends 50–75 mg/kg daily given in 1 or 2 divided doses.

Severe Infections in Children >4 Weeks of Age

IV or IM

AAP recommends 80–100 mg/kg daily given in 1 or 2 divided doses.

Manufacturer recommends 50–75 mg/kg daily (maximum 2 g daily) given in 2 equally divided doses every 12 hours.

Acute Otitis Media (AOM)

IM

A single dose of 50 mg/kg (maximum 1 g).

50 mg/kg daily given for 3 days† has been recommended for retreatment and may be more effective than a single-dose regimen in these patients.

Endocarditis

Treatment of Native Valve Endocarditis Caused by Viridans Streptococci or S. bovis

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 100 mg/kg once daily for 4 weeks recommended by AHA and IDSA for most patients.†

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 100 mg/kg once daily for 2 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA for selected patients. May be considered in patients with uncomplicated infections who are at low risk for gentamicin adverse effects; do not use in those with known cardiac or extracardiac abscess, Cl_cr <20 mL/minute, impaired eighth cranial nerve function, or infections caused by Abiotrophia, Granulicatella, or Gemella.†

Strains relatively resistant to penicillin (penicillin MIC >0.12 mcg/mL but ≤0.5 mcg/mL): 100 mg/kg once daily for 4 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA.†

Treatment of Prosthetic Valve Endocarditis Caused by Viridans Streptococci or S. bovis

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 100 mg/kg once daily for 6 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA.†

Strains relatively or highly resistant to penicillin (penicillin MIC >0.12 mcg/mL): 100 mg/kg once daily for 6 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 6 weeks) recommended by AHA and IDSA.†

Treatment of Native or Prosthetic Valve Endocarditis Caused by the HACEK Group

IV or IM

100 mg/kg once daily for 4 weeks recommended by AHA and IDSA.†

Treatment of Native or Prosthetic Valve Endocarditis Caused by E. faecalis Resistant to Penicillin, Aminoglycosides, and Vancomycin

IV or IM

100 mg/kg daily in 2 equally divided doses for ≥8 weeks in conjunction with IV ampicillin (300 mg/kg daily in 4–6 equally divided doses) recommended by AHA and IDSA.†

Prevention of Endocarditis in Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures

IV or IM

A single dose of 50 mg/kg given 0.5–1 hour prior to the procedure.†

Meningitis

IV

An initial dose of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily given as a single daily dose or in equally divided doses every 12 hours. Usual duration is 7–21 days.

Skin and Skin Structure Infections

IV or IM

50–75 mg/kg once daily or in equally divided doses twice daily.

Chancroid

IM

Adolescents: A single dose of 250 mg recommended by CDC.†

Gonorrhea and Associated Infections

Disseminated Gonococcal Infection or Gonococcal Scalp Abscess in Neonates

IV or IM

25–50 mg/kg once daily for 7 days recommended by CDC and AAP; if meningitis is documented, continue for 10–14 days.†

Parenteral Prophylaxis in Neonates Born to Mothers with Gonococcal Infections

IV or IM

A single dose of 25–50 mg/kg (maximum 125 mg) recommended by CDC and AAP.†

Gonococcal Ophthalmia Neonatorum

IV or IM

A single dose of 25–50 mg/kg (maximum 125 mg) recommended by CDC and AAP.†

Uncomplicated Urethral, Cervical, Rectal, or Pharyngeal Gonorrhea in Children

IM

Prepubertal children weighing <45 kg: A single dose of 125 mg recommended by CDC and AAP.

Children ≥8 years of age or weighing ≥45 kg: A single dose of 125 mg recommended by CDC and AAP. Manufacturer recommends a single dose of 250 mg.

Disseminated Gonorrhea in Prepubertal Children Weighing <45 kg

IV or IM

50 mg/kg (maximum 1 g) once daily for 7 days for disseminated infections with bacteremia or arthritis.†

50 mg/kg (maximum 2 g) daily in equally divided doses every 12 hours for disseminated infections with endocarditis or meningitis. Duration of treatment is 10–14 days for meningitis or ≥28 days for endocarditis.†

Disseminated Gonorrhea in Children ≥8 Years of Age or Weighing ≥45 kg

IV or IM

1 g once daily recommended by CDC and AAP. Continue for 7 days or discontinue 24–48 hours after improvement occurs and switch to an oral regimen to complete ≥7 days of treatment.†

Lyme Disease

Early Neurologic Lyme Disease

IV

50–75 mg/kg (up to 2 g) once daily for 14 days (range: 10–28 days) recommended by IDSA for early Lyme disease in children with acute neurologic manifestations (e.g., meningitis, radiculopathy). AAP and other clinicians recommend 75–100 mg/kg once daily for 14–28 days.†

Lyme Carditis

IV or IM

50–75 mg/kg (up to 2 g) IV once daily for 14 days (range: 14–21 days) recommended by IDSA and others for those with AV heart block and/or myopericarditis associated with early Lyme disease when a parenteral regimen is indicated (e.g., hospitalized patients). AAP and others recommend 75–100 mg/kg (up to 2 g) IV or IM once daily for 14–28 days.†

Parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy when clinically indicated.†

Lyme Arthritis

IV or IM

50–75 mg/kg (up to 2 g) IV once daily for 14 days (range: 14–28 days) recommended by IDSA for children with evidence of neurologic disease or when arthritis has not responded to an oral regimen. AAP and others recommend 75–100 mg/kg (up to 2 g) IV or IM once daily for 14–28 days.†

Late Neurologic Lyme Disease

IV

50–75 mg/kg (up to 2 g) once daily for 14 days (range: 14–28 days) recommended by IDSA for children with late neurologic disease affecting the CNS or peripheral nervous system. AAP recommends 75–100 mg/kg IV once daily for 28 days.†

Response to anti-infective treatment usually is slow and may be incomplete in such patients. IDSA states that retreatment is not recommended unless relapse is shown by reliable objective measures.†

Neisseria meningitidis Infections

Meningitis

IV

An initial dose of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily given as a single daily dose or in equally divided doses every 12 hours. Usual duration is 7–14 days.

Elimination of Pharyngeal Carrier State

IM

Children <15 years of age: A single 125-mg dose recommended by CDC and AAP.†

Prophylaxis in Household or Other Close Contacts

IV or IM

Children <15 years of age: A single 125-mg dose recommended by CDC and AAP.†

Shigella Infections

IV or IM

50 mg/kg once daily for 2–5 days.†

Syphilis

Congenital Syphilis

IV or IM

Infants with clinical evidence of congenital syphilis: CDC recommends 75 mg/kg once daily for 10–14 days in those ≤30 days of age and 100 mg/kg once daily for 10–14 days in older infants. Dosage adjustments may be necessary based on birthweight; use with caution in infants with jaundice.†

Use for treatment of congenital syphilis only when necessary (i.e., during a penicillin shortage) and consult with a specialist in the treatment of infants with congenital syphilis.†

†

Typhoid Fever and Other Salmonella Infections

Typhoid Fever or Septicemia caused by S. typhi or S. paratyphi

IV or IM

50–75 mg/kg once daily.†

May be effective for treatment of typhoid fever when given for 3–7 days, but anti-infective treatment usually continued for ≥14 days to prevent relapse. A duration of ≥4–6 weeks may be necessary in immunocompromised individuals (including those with HIV infection) or for treatment of Salmonella meningitis.†

Empiric Therapy in Febrile Neutropenic Patients

IV

80 mg/kg (up to 2 g) once daily in conjunction with IV amikacin (20 mg/kg daily) has been used.†

Prophylaxis in Sexual Assault Victims

IM

Prepubertal children: A single dose of 125 mg given in conjunction with doxycycline or a macrolide (azithromycin, erythromycin).†

Adolescents: A single dose of 125 mg given in conjunction with oral metronidazole and either oral azithromycin or oral doxycycline.†

Adults

General Adult Dosage

IV or IM

1–2 g once daily or in equally divided doses twice daily.

Endocarditis

Treatment of Native Valve Endocarditis Caused by Viridans Streptococci or S. bovis

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 4 weeks recommended by AHA and IDSA for most patients.†

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 2 weeks with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA for selected patients. May be considered in patients with uncomplicated infections who are at low risk for gentamicin adverse effects; do not use in those with known cardiac or extracardiac abscess, Cl_cr <20 mL/minute, impaired eighth cranial nerve function, or infections caused by Abiotrophia, Granulicatella, or Gemella.†

Strains relatively resistant to penicillin (penicillin MIC >0.12 mcg/mL but ≤0.5 mcg/mL): 2 g once daily for 4 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA.†

Treatment of Prosthetic Valve Endocarditis Caused by Viridans Streptococci or S. bovis

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 6 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 2 weeks) recommended by AHA and IDSA.†

Strains relatively or highly resistant to penicillin (penicillin MIC >0.12 mcg/mL): 2 g once daily for 6 weeks in conjunction with IV or IM gentamicin (3 mg/kg daily in 1 or 3 divided doses for 6 weeks) recommended by AHA and IDSA.†

Treatment of Native or Prosthetic Valve Endocarditis Caused by the HACEK Group

IV or IM

2 g once daily for 4 weeks recommended by AHA and IDSA.†

Treatment of Native or Prosthetic Valve Endocarditis Caused by E. faecalis Resistant to Penicillin, Aminoglycosides, and Vancomycin

IV or IM

4 g daily in 2 equally divided doses for ≥8 weeks in conjunction with IV ampicillin (12 g daily in 6 equally divided doses) recommended by AHA and IDSA.†

Prevention of Endocarditis in Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures

IV or IM

A single 1-g dose given 0.5–1 hour prior to the procedure.†

Meningitis

IV

2 g every 12 hours. Some clinicians suggest 50–100 mg/kg (up to 4 g) once daily; others suggest 4 g once daily.

While 7 days may be adequate for uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis, ≥10–14 days is suggested for complicated cases or meningitis caused by S. pneumoniae and ≥21 days is suggested for meningitis caused by susceptible Enterobacteriaceae (e.g., E. coli, Klebsiella).

Respiratory Tract Infections

Community-acquired Pneumonia (CAP)

IV or IM

1 g every 12 or 24 hours has been used for treatment of CAP caused by susceptible S. pneumoniae.

Used in conjunction with other anti-infectives for empiric treatment of CAP. (See Respiratory Tract Infections under Uses.)

Chancroid

IM

A single dose of 250 mg recommended by CDC.†

Gonorrhea and Associated Infections

Uncomplicated Cervical, Urethral, Rectal, or Pharyngeal Gonorrhea

IM

A single dose of 125 mg recommended by CDC and others.

Manufacturers recommend a 250-mg single dose, and this higher dosage is recommended by some experts.

Disseminated Gonococcal Infections

IV or IM

1 g once daily recommended by CDC and others. Continue for 24–48 hours after improvement begins; therapy may then be switched to oral cefixime or oral cefpodoxime to complete ≥1 week of treatment.†

For gonococcal meningitis or endocarditis, 1–2 g IV every 12 hours. Continue for 10–14 days in those with meningitis and for ≥4 weeks in those with endocarditis.†

Gonococcal Conjunctivitis

IM

A single dose of 1 g recommended by CDC and others.†

Epididymitis

IM

A single dose of 250 mg given in conjunction with a 10-day regimen of oral doxycycline.†

Proctitis

IM

A single dose of 125 mg given in conjunction with a 7-day regimen of oral doxycycline.†

Leptospirosis

IV

1 g once daily for 7 days has been used for the treatment of severe infections.†

Lyme Disease

Early Neurologic Lyme Disease

IV

2 g once daily for 14 days (range: 10–28 days) recommended by IDSA and others for adults with acute neurologic manifestations (e.g., meningitis, radiculopathy).†

Lyme Carditis

IV

2 g once daily for 14 days (range: 14–21 days) recommended by IDSA and others for adults with AV heart block and/or myopericarditis associated with early Lyme disease when a parenteral regimen is indicated (e.g., hospitalized patients).†

Parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, cefuroxime axetil) to complete therapy when clinically indicated.†

Lyme Arthritis

IV

2 g once daily for 14 days (range: 14–28 days) recommended by IDSA and others for adults with evidence of neurologic disease or when arthritis has not responded to an oral regimen.†

Late Neurologic Lyme Disease

IV

2 g once daily for 14 days (range: 14–28 days) recommended by IDSA and others for adults with late neurologic disease affecting the CNS or peripheral nervous system.†

Response to anti-infective treatment usually is slow and may be incomplete in such patients. IDSA states that retreatment is not recommended unless relapse is shown by reliable objective measures.†

Neisseria meningitidis Infections

Meningitis

IV

2 g every 12 hours.

Elimination of Pharyngeal Carrier State

IM

A single dose of 250 mg recommended by CDC and others.†

Prophylaxis in Household or Other Close Contacts

IM

A single dose of 250 mg recommended by CDC and others.†

Pelvic Inflammatory Disease

IM

A single dose of 250 mg; followed by a 14-day regimen of oral doxycycline (100 mg twice daily) with or without oral metronidazole (500 mg twice daily).

Syphilis

Early Syphilis in Penicillin-hypersensitive Patients

IV or IM

1 g daily for 8–10 days has been recommended. CDC cautions that the optimal dosage and duration of the drug for treatment of early syphilis have not been defined.†

Neurosyphilis in Penicillin-hypersensitive Patients

IV or IM

2 g daily for 10–14 days has been suggested. CDC cautions that the optimal dosage and duration of the drug for treatment of early syphilis have not been defined.†

Typhoid Fever and Other Salmonella Infections

Typhoid Fever or Septicemia caused by S. typhi or S. paratyphi

IV or IM

2–4 g once daily.†

May be effective for treatment of typhoid fever when given for 3–7 days, but anti-infective treatment usually continued for ≥14 days to prevent relapse. A duration of ≥4–6 weeks may be necessary in immunocompromised individuals (including those with HIV infection) or for the treatment of Salmonella meningitis.†

Empiric Therapy in Febrile Neutropenic Patients

IV

30 mg/kg (2 g) once daily in conjunction with IV amikacin.†

Perioperative Prophylaxis

IV

1 g given 0.5–2 hours prior to surgery.

Prophylaxis in Sexual Assault Victims

IV

A single 125-mg dose recommended by CDC and AAP; given in conjunction with oral metronidazole and either oral azithromycin or oral doxycycline.†

Prescribing Limits

Pediatric Patients

Maximum 2 g daily for treatment of most infections. Maximum 4 g daily for treatment of meningitis.

Adults

Maximum 4 g daily.

Special Populations

Hepatic Impairment

Dosage adjustments not usually necessary in patients with only impaired hepatic function.

In those with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed a dosage of 2 g daily. Some manufacturers and clinicians recommend monitoring serum concentrations. If evidence of drug accumulation occurs, adjust dosage accordingly.

Renal Impairment

Dosage adjustments not usually necessary in patients with impaired renal function.

In those with clinically significant renal impairment and hepatic dysfunction, do not exceed a dosage of 2 g daily.

Some manufacturers and clinicians recommend monitoring serum concentrations in patients with severe renal impairment (e.g., dialysis patients) or with both hepatic impairment and clinically important renal impairment. If evidence of drug accumulation occurs, adjust dosage accordingly.

Cautions

Contraindications

• Known hypersensitivity to ceftriaxone or other cephalosporins.
• Hyperbilirubinemic neonates, especially those who are premature. (See Pediatric Use under Cautions.)
• Neonates ≤28 days of age) receiving (or expected to require) treatment with calcium-containing IV solutions, including calcium-containing infusions such as parenteral nutrition. (See Pediatric Use under Cautions.)
• Commercially available premixed (frozen) injection in dextrose may be contraindicated in patients with known allergy to corn or corn products.

Warnings/Precautions

Warnings

Interaction with Calcium-containing Products

Fatalities reported in neonates receiving ceftriaxone and calcium-containing IV solutions; a crystalline material was observed in the lungs and kidneys at autopsy. In some cases, the same IV infusion line had been used for both ceftriaxone and the calcium-containing fluid and, in some, a precipitate was observed in the IV infusion line. At least 1 fatality occurred in a neonate who received ceftriaxone and calcium-containing fluids administered at different times and through different infusion lines; no crystalline material was observed at autopsy in this neonate.

No similar reports to date in patients other than neonates treated with ceftriaxone and calcium-containing IV solutions.

There is some evidence that neonates have an increased risk for precipitation of ceftriaxone-calcium. In vitro studies evaluating the combination of ceftriaxone and calcium in adult plasma and neonatal plasma from umbilical cord blood indicate that recovery of ceftriaxone from plasma was reduced with calcium concentrations ≥24 mg/dL in adult plasma or ≥16 mg/dL in neonatal plasma. This may reflect ceftriaxone-calcium precipitation.

Ceftriaxone must not be admixed with calcium-containing IV solutions and must not be administered simultaneously with calcium-containing IV solutions, including calcium-containing infusions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age). (See Administration under Dosage and Administration.)

No reports to date of an interaction between ceftriaxone and oral calcium-containing products or between IM ceftriaxone and calcium-containing products (IV or oral).

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy, especially Candida, enterococci, Bacteroides fragilis, or Pseudomonas aeruginosa. Resistant strains of Ps. aeruginosa and Enterobacter have developed during ceftriaxone therapy. Careful observation of the patient is essential. Institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis. Hypertoxin producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, may need to discontinue anti-infectives not directed against C. difficile. Some mild cases may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.

Hemolytic Anemia

Immune-mediated hemolytic anemia reported. Severe cases, including fatalities, have occurred in both adults and children. Some cases occurred shortly after administration of a ceftriaxone dose; some reactions have consisted of severe intravascular hemolysis and anemia, decreased hemoglobin concentrations, reticulocytosis, hemoglobinuria, and cardiac arrest.

Consider diagnosis of cephalosporin-associated anemia if anemia occurs in a patient receiving ceftriaxone. Discontinue ceftriaxone until etiology of the anemia is determined.

Sensitivity Reactions

Hypersensitivity Reactions

Possible hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

As with other cephalosporins, anaphylaxis cannot be ruled out despite a thorough patient history prior to administration of the drug.

If an allergic reaction occurs, discontinue drug and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).

Cross-hypersensitivity

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. Cautious use recommended in individuals hypersensitive to penicillins: avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftriaxone and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

History of GI Disease

Use with caution in patients with a history of GI disease, particularly colitis. (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Prolonged PT

Prolonged PT reported rarely.

Monitor PT in patients with impaired vitamin K synthesis or low vitamin K stores (e.g., chronic hepatic disease, malnutrition). Administer vitamin K when indicated.

Sonographic Abnormalities/Gallbladder Disease

Sonographic gallbladder abnormalities reported rarely; symptoms of gallbladder disease also reported in some patients.

Abnormalities appear on sonography as an echo without acoustical shadowing (suggesting sludge) or as an echo with acoustical shadowing and may be misinterpreted as gallstones. The chemical nature of the material detected has been determined to be predominantly a ceftriaxone-calcium salt.

Discontinue ceftriaxone in patients with manifestations suggestive of gallbladder disease and/or in those in whom characteristic sonographic abnormalities have been observed.

Because the condition appears to be transient and generally resolves following discontinuance of the drug, conservative management can be considered; surgery generally does not appear to be necessary. The time to resolution may range from a few days to several months.

Upper abdominal ultrasonography should be considered for patients who develop biliary colic while receiving ceftriaxone therapy; biliary precipitates of ceftriaxone may be detected by ultrasonography after only 4 days of ceftriaxone therapy. The risk of precipitation may depend on the dose and rate of IV administration of ceftriaxone, occurring more frequently with relatively high dosages and rapid (e.g., over several minutes) rates of administration.

Pancreatitis

Pancreatitis, possibly secondary to biliary obstruction, reported rarely. Most had preexisting risk factors for biliary stasis and biliary sludge (e.g., preceding major therapy, severe illness, total parenteral nutrition).

Co-factor role of ceftriaxone-related biliary precipitation cannot be ruled out.

Seizures

Seizures reported with some cephalosporins, particularly in patients with renal impairment who did not receive dosage adjustment based on renal function.

Discontinue ceftriaxone if seizures occur; administer anticonvulsant therapy if clinically indicated.

Patients with Diabetes

The commercially available Duplex^® delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection should be used with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.

Sodium Content

Contains approximately 83 mg (3.6 mEq) of sodium per g of ceftriaxone.

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk in low concentrations; use with caution.

Pediatric Use

Contraindicated in hyperbilirubinemic neonates, particularly those who are premature. Ceftriaxone can displace bilirubin from serum albumin; bilirubin encephalopathy can possibly develop.

Contraindicated in neonates (≤28 days of age) if they are receiving (or expected to require) treatment with calcium-containing IV solutions, including continuous infusions of calcium-containing solutions such as parenteral nutrition, because of risk of precipitation of ceftriaxone-calcium salt. Fatalities reported in neonates who received ceftriaxone and calcium-containing IV solutions. (See Interaction with Calcium-containing Products under Cautions.)

Ceftriaxone that has been reconstituted for IM use with bacteriostatic water for injection containing benzyl alcohol should not be used in neonates. Although a causal relationship has not been established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates. Toxicity appears to have resulted from administration of large amounts (i.e., about 100–400 mg/kg daily) of benzyl alcohol in these neonates.

To avoid overdosage, do not use the commercially available Duplex^® drug delivery system containing 1 or 2 g of ceftriaxone and 50 mL of dextrose injection in separate chambers in pediatric patients unless the entire 1- or 2-g dose is required.

Geriatric Use

No overall differences in safety and efficacy in those ≥60 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.

Pharmacokinetics only minimally altered in geriatric patients compared with healthy younger adults. Dosage adjustments based solely on age not necessary in those receiving up to 2 g daily.

Hepatic Impairment

Hepatic impairment generally does not affect pharmacokinetics of ceftriaxone and dosage adjustments not usually necessary unless both hepatic and renal function are impaired.

In those with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed a dosage of 2 g daily. Some manufacturers and clinicians suggest monitoring serum ceftriaxone concentrations periodically and adjusting dosage if there is evidence of accumulation.

Renal Impairment

Since ceftriaxone is eliminated by both biliary and renal routes, dosage adjustments may not be necessary in patients with renal impairment alone.

Some manufacturers and clinicians suggest monitoring serum ceftriaxone concentrations periodically in patients with severe renal impairment (e.g., dialysis patients) or with both renal and hepatic impairment; adjust dosage if there is evidence of accumulation.

In those with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed a dosage of 2 g daily.

Common Adverse Effects

Local reactions at the administration site (warmth, tightness, induration, phlebitis); hematologic effects (eosinophilia, thrombocytosis, leukopenia); hypersensitivity reactions.

Interactions

Specific Drugs and Laboratory Tests

Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed from GI tract; must be given parenterally.

Appears to be completely absorbed following IM administration in healthy adults; peak serum concentrations attained 1.5–4 hours after the dose.

Multiple-dose studies in healthy adults indicate serum concentrations at steady state on day 4 of therapy are 15–36% higher than serum concentrations attained with a single dose.

Distribution

Extent

Following IM or IV administration, widely distributed into body tissues and fluids including the gallbladder, lungs, bone, heart, bile, prostate adenoma tissue, uterine tissue, atrial appendage, sputum, tears, middle ear fluid, and pleural, peritoneal, synovial, ascitic, and blister fluids.

Generally diffuses into CSF following IM or IV administration; CSF concentrations are higher in patients with inflamed meninges.

Crosses the placenta and is distributed into amniotic fluid. Distributed into milk.

Plasma Protein Binding

Degree of protein binding is concentration dependent; decreases nonlinearly with increasing concentrations of the drug. Principally binds to albumin.

93–96% bound to plasma proteins at <70 mcg/mL, 84–87% at 300 mcg/mL, and ≤58% at 600 mcg/mL.

Protein binding is lower in neonates and children than in adults because of decreased plasma albumin concentrations in this age group. Also less protein bound in patients with renal or hepatic impairment as the result of decreased plasma albumin concentrations or displacement from protein binding sites by bilirubin and other endogenous compounds that may accumulate.

Elimination

Metabolism

Metabolized to a small extent in the intestines after biliary elimination.

Elimination Route

Eliminated by renal and nonrenal mechanisms.

33–67% eliminated in urine by glomerular filtration as unchanged drug; remainder eliminated in feces via bile as unchanged drug and microbiologically inactive metabolites.

Half-life

Adults with normal renal and hepatic function: Distribution half-life 0.12–0.7 hours and elimination half-life 5.4–10.9 hours.

Neonates: 16.2 hours in those 1–4 days of age and 9.2 hours in those 9–30 days of age.

Children 2–42 months of age: Distribution half-life 0.25 hours and elimination half-life 4 hours.

Special Populations

Patients with moderately impaired renal function: Elimination half-life averages 10–16 hours.

Elimination half-life averages 12.2–18.2 hours in patients with creatinine clearances <5 mL/min and 15–57 hours in uremic patients.

Stability

Storage

Parenteral

Powder for Injection or IV Infusion

≤25°C (usually 20–25°C); protect from light. No need to protect reconstituted solutions from normal light.

IV solutions containing 10–40 mg/mL prepared using sterile water, 0.9% sodium chloride, or 5 or 10% dextrose are stable for 3 days at 25°C or 10 days at 4°C. Those containing 10–40 mg/mL prepared using 5% dextrose and 0.45 or 0.9% sodium chloride are stable for 3 days at 25°C; do not refrigerate.

IM solutions containing 100 mg/mL prepared using sterile water, 0.9% sodium chloride, or 5% dextrose are stable for 3 days at room temperature (25°C) or 10 days refrigerated at 4°C; those containing 250 or 350 mg/mL are stable for 24 hours at 25°C or 3 days at 4°C.

IM solutions containing 100 mg/mL prepared using 1% lidocaine hydrochloride (without epinephrine) or bacteriostatic water (containing 0.9% benzyl alcohol) are stable for 24 hours at 25°C or 10 days at 4°C; those containing 250 or 350 mg/mL are stable for 24 hours at 25°C or 3 days at 4°C.

Store commercially available Duplex^® drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection at 20–25°C (may be exposed to 15–30°C). Following reconstitution (activation), use these IV infusions within 24 hours if stored at room temperature or within 7 days if stored in a refrigerator; do not freeze.

Injection (Frozen) for IV Infusion

-20° C or lower. Thawed solutions stable for 48 hours at room temperature (25°C) or 21 days under refrigeration (5°C).

Do not refreeze after thawing.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Do not use calcium-containing diluents to reconstitute or further dilute reconstituted ceftriaxone because a precipitate forms.

Drug Compatibility

Actions and Spectrum

• Based on spectrum of activity, classified as a third generation cephalosporin. Usually less active in vitro against susceptible staphylococci than first generation cephalosporins, but has expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.
• Usually bactericidal.
• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.
• Spectrum of activity includes many gram-positive aerobic bacteria, many gram-negative aerobic bacteria, and some anaerobic bacteria; inactive against Chlamydia, fungi, and viruses.
• Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci), Staphylococcus aureus (including penicillinase-producing strains), S. epidermidis, and viridans streptococci. Also active in vitro against S. agalactiae (group B streptococci). Methicillin-resistant (oxacillin-resistant) staphylococci and most enterococci (e.g., Enterococcus faecalis) are resistant.
• Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to ceftriaxone, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.
• Active in vitro against some strains of Nocardia, including some strains of N. asteroides and N. brasiliensis. Resistance to ceftriaxone reported in some environmental isolates of N. asteroides and clinical isolates of N. farcinica.
• Gram-negative aerobes: Active in vitro and in clinical infections against Acinetobacter calcoaceticus, Enterobacter (including E. aerogenes, E. cloacae), Escherichia coli, Haemophilus influenzae (including ampicillin-resistant and β-lactamase-producing strains), H. parainfluenzae, Klebsiella pneumoniae, K. oxytoca, Moraxella catarrhalis (including β-lactamase-producing strains), Morganella morganii, Neisseria gonorrhoeae, N. meningitidis, Proteus mirabilis, P. vulgaris, Pseudomonas aeruginosa, and Serratia marcescens. Also active in vitro against Capnocytophaga, Citrobacter, Providencia, Salmonella, and Shigella. Less active than ceftazidime against Ps. aeruginosa.
• Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, Clostridium (except C. difficile), and Peptostreptococcus. Also active in vitro against Prevotella bivius and Porphyromonas melaninogenicus.
• Spirochetes: Has some activity against Treponema pallidum when tested in a rabbit model. Active in vitro against Borrelia burgdorferi, causative agent of Lyme disease. Active in vitro against Leptospira, including L. interrogans and L. weilii.

Advice to Patients

• Advise patients that antibacterials (including ceftriaxone) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).
• Importance of completing full course of therapy, even if feeling better after a few days.
• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftriaxone or other antibacterials in the future.
• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.
• Advise patients that ceftriaxone and calcium-containing products can interact with each other and cause life-threatening reactions. Importance of informing clinicians of all medicines that have been given, especially those given IV within the past 2 days.
• Importance of informing clinicians if an allergic reaction occurs.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 11/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions November 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.