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Ceftriaxone
Ceftriaxone (Systemic)
47
junction with an aminoglycoside (amikacin, gentamicin, tobramycin) is one of several preferred regimens for initial treatment of life-threatening sepsis in adults.
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Skin and Skin Structure Infections
Treatment of skin and skin structure infections caused by susceptible S. aureus,
S. epidermidis, S. pyogenes (group A ␤-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.
Antibacterial; ␤-lactam antibiotic; third generation cephalosporin.
Class: Third Generation Cephalosporins 8:12.06.12 (AHFS primary);
AM103 (VA primary)
Brands*: Rocephin
Urinary Tract Infections (UTIs)
Treatment of complicated and uncomplicated UTIs caused by E. coli, K. pneumo-
*also available generically
niae, M. morganii, P. mirabilis, or P. vulgaris.
Considered a drug of choice for treatment of UTIs caused by susceptible Entero-
Uses
Acute Otitis Media (AOM)
Treatment of AOM caused by S. pneumoniae, H. inﬂuenzae (including ␤-lacta-
mase-producing strains), or Moraxella catarrhalis (including ␤-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 ⱖ3 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 endocarditis caused by penicillin-susceptible viridans
streptococci (e.g., S. milleri group, S. mitis, S. mutans, S. salivarius, S. sanguis) or
S. bovis (nonenterococcal group D streptococcus)†.
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, Actinobacillus actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, Kingella kingae).
Not indicated for treatment of enterococcal or staphylococcal endocarditis.
Intra-abdominal Infections
Treatment of intra-abdominal infections caused by susceptible E. coli, K. pneumoniae, Bacteroides fragilis, Clostridium (not C. difﬁcile), or Peptostreptococcus.
bacteriaceae, 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.
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.
Chancroid
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).
Treatment of chancroid† (genital ulcers caused by H. ducreyi).
CDC and others recommend azithromycin, ceftriaxone, ciproﬂoxacin or erythromy-
Respiratory Tract Infections
Treatment of respiratory tract infections (including pneumonia) caused by suscep-
cin 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 HIVnegative 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 sus
tible S. aureus, S. pneumoniae, H. inﬂuenzae, H. parainﬂuenzae, E. aerogenes, E.
coli, K. pneumoniae, P. mirabilis, or Serratia marcescens.
Septicemia
Treatment of septicemia caused by S. aureus, S. pneumoniae, E. coli, H. inﬂuenzae, or K. pneumoniae.
A parenteral cephalosporin (i.e., cefepime, cefotaxime, ceftriaxone) given in con-
ceptible 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 a regimen of choice for pharyngeal gonorrhea in adults,
adolescents, and children.
Initial treatment of disseminated gonococcal infections†. Recommended by CDC,
AAP, and others as a 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).
Treatment of proctitis† (in conjunction with doxycycline) in patients most likely to
have infections caused by N. gonorrhoeae and/or C. trachomatis.
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Ceftriaxone
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. Use with caution in neonates who are hyperbilirubinemic (especially
those born prematurely); AAP suggests that cefotaxime may be preferred in these
neonates.
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
Lyme Disease
Treatment of Whipple’s disease†, a progressive systemic infection caused by Tro-
Treatment of severe forms or late complications of Lyme disease†.
Although oral anti-infectives (e.g., doxycycline, amoxicillin) generally are effective
Empiric Therapy in Febrile Neutropenic Patients
for treatment of the early stages of the disease (e.g., erythema migrans, isolated
facial nerve palsy, mild arthritis, or carditis), more serious manifestations associated with early disseminated or late disease (e.g., severe carditis, meningitis, radiculoneuritis) generally require higher dosage, more prolonged therapy, and/or parenteral anti-infectives (e.g., IV ceftriaxone, cefotaxime, or penicillin G).
Treatment of Lyme arthritis and concomitant neurologic disease documented by
CSF analysis.
pheryma whippelii.
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
Neisseria meningitidis Infections
Perioperative prophylaxis to reduce the incidence of infection in patients undergo-
Treatment of invasive infections caused by N. meningitidis. (See Meningitis and
ing 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.
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).
Pelvic Inﬂammatory Disease (PID)
Treatment of PID caused by N. gonorrhoeae.
Not considered a drug of choice for PID. CDC states ceftriaxone may be effective
for PID, but is less active than cefotetan or cefoxitin against anaerobic bacteria.
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 data are insufﬁcient to recommend use of ceftriaxone for treatment of early syphilis in pregnant women or pediatric patients hypersensitive to
penicillin or for treatment 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 HIVinfected 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.
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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.
Ceftizoxime ADD-Vantage vials and the commercially available frozen ceftriaxone
injection in dextrose should be used only for IV infusion.
IV Infusion
The recommended concentration for IV infusion is 10– 40 mg of ceftriaxone/mL;
lower concentrations may be used if desired.
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.
Reconstitute ADD-Vantage vials containing 1 or 2 g of ceftriaxone according to
the manufacturer’s directions.
Piggyback units containing 1 or 2 g of ceftriaxone should be reconstituted with 10
or 20 mL, respectively, of a compatible IV solution and then further diluted with 50–
100 mL with a compatible IV solution.
Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; 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
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Ceftriaxone
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.
recommended by CDC and AAP. Manufacturer recommends a single dose
of 250 mg.
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.
Alternatively, reconstitute 500-mg or 1-g vials in the commercially available convenience kit according to the manufacturer’s instructions using the lidocaine hydrochloride diluent provided in the kit.
Dosage
Available as ceftriaxone sodium; dosage expressed in terms of ceftriaxone.
Pediatric Patients
General Pediatric Dosage
⬎Infections in Neonates ⱕ4 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.
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 ⱖ28 days for endocarditis.
⬎Disseminated Gonorrhea in Children ⱖ8 Years of Age or Weighing ⱖ45
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 ⱖ7 days of treatment.
Lyme Disease†
⬎Early Disseminated or Late Lyme Disease with Serious Neurologic,
Cardiac, and/or Arthritic Manifestations†
IV or IM: 75– 100 mg/kg once daily for 14– 28 days. Additional courses
generally are not recommended unless relapse of neurologic disease is
documented with reliable objective measures.
Neisseria meningitidis Infections
⬎Meningitis
IV: An initial dose of 100 mg/kg (ⱕ4 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: A single 125-mg dose for children ⱕ12 years of age or a single 250mg dose for older children recommended by AAP.
A single 125-mg dose in children ⬍15 years of age recommended by
CDC.
⬎Prophylaxis in Household or Other Close Contacts†
IV or IM: A single 125-mg dose for children ⱕ12 years of age or a single
250-mg dose for older children recommended by AAP.
A single 125-mg dose in children ⬍15 years of age recommended by
CDC.
⬎Mild to Moderate Infections in Children ⬎4 Weeks of Age
IV or IM: AAP recommends 50– 75 mg/kg given in 1 or 2 divided doses.
⬎Severe Infections in Children ⬎4 Weeks of Age
IV or IM: AAP recommends 80– 100 mg/kg 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).
Shigella Infections†
IV or IM: 50 mg/kg once daily for 2– 5 days.
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 ⱖ14 days to prevent relapse. A duration of ⱖ4– 6 weeks may be necessary in immunocompromised individuals (including those with HIV infection) or for treatment of
Salmonella meningitis.
Endocarditis†
⬎Treatment of Native Valve Endocarditis Caused by Penicillin-susceptible
Viridans Streptococci or S. bovis†
IV: 100 mg/kg once every 24 hours for 4 weeks recommended by AHA.
If the streptococci are relatively resistant to penicillin (MIC 0.1– 0.5 mcg/
mL), AHA recommends concomitant gentamicin during the ﬁrst 2 weeks
of treatment.
Meningitis
IV: An initial dose of 100 mg/kg (ⱕ4 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.
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
Skin and Skin Structure Infections
IV or IM: 50– 75 mg/kg once daily or in equally divided doses twice daily.
General Adult Dosage
IV or IM: 1– 2 g once daily or in equally divided doses twice daily.
Chancroid†
IM: Adolescents: a single dose of 250 mg recommended by CDC.
Endocarditis†
⬎Treatment of Native Valve Endocarditis Caused by Penicillin-susceptible
Viridans Streptococci or S. bovis†
IV or IM: 2 g once daily for 4 weeks recommended by AHA.
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 ⱖ8 years of age or weighing ⱖ45 kg: a single dose of 125 mg
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⬎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.
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.)
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Alternatively, a regimen of 2 g once daily for 2 weeks (given in conjunction with gentamicin) can be used in those with uncomplicated endocarditis. The 2-week regimen is not recommended by AHA for patients with
complications such as extracardiac foci of infection or intracardiac abscesses.
⬎Endocarditis Caused by HACEK Group (i.e., H. parainﬂuenzae, H.
aphrophilus, A. actinomycetemcomitans, C. hominis, E. corrodens, K.
kingae)†
IV or IM: 2 g once daily for 3– 4 weeks for native valve endocarditis or
for 6 weeks for prosthetic valve endocarditis recommended by AHA.
Meningitis
IV: 2 g every 12 hours.
While 7 days may be adequate for uncomplicated meningitis caused by
susceptible H. inﬂuenzae or N. meningitidis, ⱖ10– 14 days is suggested
for complicated cases or meningitis caused by S. pneumoniae and ⱖ21
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days is suggested for meningitis caused by susceptible Enterobacteriaceae
(e.g., E. coli, Klebsiella).
Respiratory Tract Infections
⬎Community-acquired Pneumonia
IV or IM: 1 g every 12 or 24 hours in conjunction with other anti-infectives. Twice daily regimen recommended for critically ill patients.
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. Manufacturer recommends a 250-mg single dose.
⬎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
an oral regimen to complete ⱖ1 week of treatment.
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.
Dosage should not exceed 2 g daily in patients with both hepatic and renal
impairment unless serum ceftriaxone concentrations are monitored closely.
Renal Impairment
Dosage adjustments not usually necessary in patients with only impaired renal
function. Closely monitor patients with severe renal impairment (e.g., dialysis patients) and patients with both renal and hepatic impairment. If evidence of drug
accumulation occurs, dosage should be adjusted accordingly.
Dosage should not exceed 2 g daily in patients with both hepatic and renal
impairment unless serum ceftriaxone concentrations are monitored closely.
For gonococcal meningitis or endocarditis, 1– 2 g IV every 12 hours. Continue for 10– 14 days in those with meningitis and for ⱖ4 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.
Lyme Disease†
⬎Early Disseminated or Late Lyme Disease with Serious Neurologic,
Cardiac, and/or Arthritic Manifestations†
IV: 2 g IV once daily for 14– 28 days. Additional courses of antibiotic therapy generally are not recommended unless relapse of neurologic disease
is documented with 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 ⱖ14 days to prevent relapse. A duration of ⱖ4– 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.
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Cautions
Contraindications
•
Known hypersensitivity to ceftriaxone or other cephalosporins.
Warnings/Precautions
Warnings
Superinfection/Clostridium difficile-associated Colitis
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 may permit overgrowth of clostridia. Consider Clostridium difﬁcile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.
Some mild cases of C. difﬁcile-associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with ﬂuid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or
vancomycin) recommended if colitis is severe.
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.
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 ␤-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
History of GI Disease
Use with caution in patients with a history of GI disease, particularly colitis. (See
Superinfection/Clostridium difﬁcile-associated Colitis under Cautions.)
Perioperative Prophylaxis
IV: 1 g given 0.5– 2 hours prior to surgery.
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.
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.
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
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(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.
Concomitant administration
of oral probenecid (500
mg daily) does not appear
to affect the pharmacokinetics of ceftriaxone, presumably because ceftriaxone is excreted principally
by glomerular filtration
and nonrenal mechanisms
Higher dosages of oral probenecid (1 or 2 g daily)
may partially block biliary
secretion of ceftriaxone as
well as displace the drug
from plasma proteins resulting in increased clearance and decreased halflife of ceftriaxone
Quinolones
In vitro evidence of synergistic antibacterial effect between ceftriaxone and trovafloxacin against
penicillin-susceptible and
penicillin-resistant S.
pneumoniae, including
some strains resistant to
ceftriaxone alone
Clinical importance unknown
Tests for glucose
Possible false-positive reactions in urine glucose
tests using Clinitest, Benedict’s solution, or Fehling’s solution
Use glucose tests based on
enzymatic glucose oxidase
reactions (e.g., Clinistix,
Tes-Tape)
Pregnancy
Category B.
Lactation
Distributed into milk in low concentrations; use with caution.
Pediatric Use
Ceftriaxone can displace bilirubin from serum albumin and should not be administered to hyperbilirubinemic neonates, particularly those who are premature.
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.
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.
Dosage should not exceed 2 g daily in patients with both hepatic and renal impairment unless serum ceftriaxone concentrations are monitored closely.
Renal Impairment
Since ceftriaxone is eliminated by both biliary and renal routes, dosage adjustments may not be necessary in patients with renal impairment alone. Monitor serum
ceftriaxone concentrations periodically in patients with severe renal impairment (e.g.,
dialysis patients) and in those with both renal and hepatic impairment; adjust dosage
if there is evidence of accumulation.
Dosage should not exceed 2 g daily in patients with both hepatic and renal impairment unless serum ceftriaxone concentrations are monitored closely.
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
Common Adverse Effects
Extent
Local reactions at the administration site (warmth, tightness, induration, phlebitis);
hematologic effects (eosinophilia, thrombocytosis, leukopenia); hypersensitivity reactions.
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.
Interactions
Speciﬁc Drugs and Laboratory Tests
Drug or Test
Interaction
Aminoglycosides
Nephrotoxicity reported with
concomitant use of some
cephalosporins and aminoglycosides
In vitro evidence of additive
or synergistic antibacterial
activity against some Enterobacteriaceae and
Pseudomonas aeruginosa
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Probenecid
Sodium Content
Contains approximately 83 mg (3.6 mEq) of sodium per g of ceftriaxone.
Specific Populations
51
Plasma Protein Binding
Comments
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
ⱕ58% 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
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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 halflife 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
⬎Y-Site Compatibility
Compatible
Acyclovir sodium
Allopurinol sodium
Amifostine
Amiodarone HCl
Aztreonam
Bivalirudin
Dexmedetomidine HCl
Diltiazem HCl
Docetaxel
Doxorubicin HCl liposome injection
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Fludarabine phosphate
Foscarnet sodium
Gatifloxacin
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Hetastarch in lactated electrolyte injection
(Hextend)
Linezolid
Melphalan HCl
Meperidine HCl
Methotrexate sodium
Morphine sulfate
Paclitaxel
Propofol
Remifentanil HCl
Sargramostim
Sodium bicarbonate
Tacrolimus
Teniposide
Theophylline
Thiotepa
Warfarin sodium
Zidovudine
Incompatible
Storage
Parenteral
Powder for Injection or Infusion
ⱕ25C; 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 25C or 10 days at 4C. Those
containing 10– 40 mg/mL prepared using 5% dextrose and 0.45 or 0.9% sodium chloride are stable for 3 days at 25C; 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 (25C) or 10 days
refrigerated at 4C; those containing 250 or 350 mg/mL are stable for 24 hours at
25C or 3 days at 4C.
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 25C or 10 days at 4C; those containing 250 or 350 mg/mL are
stable for 24 hours at 25C or 3 days at 4C.
Injection (Frozen) for Infusion
⫺20 C or lower. Thawed solutions of the commercial frozen injection stable for
72 hours at room temperature (25C) or 21 days at 5C.
Do not refreeze after thawing.
Alatrofloxacin mesylate
Amphotericin B cholesteryl sulfate complex
Amsacrine
Azithromycin
Filgrastim
For information on systemic interactions resulting from concomitant use, see Interactions.
Vancomycin HCl
Actions and Spectrum
•
•
•
•
•
Parenteral
Solution Compatibility
•
Compatible
Dextrose 5% in sodium chloride 0.45%
Dextrose 5 or 10% in water
Sodium chloride 0.9%
Variable
Ringer’s injection, lactated
Fluconazole
Labetalol HCl
Pentamidine isethionate
Vinorelbine tartrate
Variable
Compatibility
Dextrose 3.4% in sodium chloride 0.3%
Dextrose 5% with potassium chloride 10
mEq/L
Dextrose 5% in sodium chloride 0.2% with
potassium chloride 20 mEq/L
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Drug Compatibility
⬎Admixture Compatibility
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 ␤-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.
Spectrum of activity includes many gram-positive aerobic bacteria, many gramnegative 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 ␤-hemolytic streptococci), Staphylococcus
aureus (including penicillinase-producing strains), S. epidermidis, and viridans
streptococci. Also active in vitro against S. agalactiae (group B streptococci). Oxacillin-resistant (methicillin-resistant) staphylococci and most enterococci (e.g., Enterococcus faecalis) are resistant.
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 ␤-lactamaseproducing strains), H. parainﬂuenzae, Klebsiella pneumoniae, K. oxytoca, Moraxella
catarrhalis (including ␤-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 Peptostreptococus. Also active in vitro against
Prevotella bivius and Porphyromonas melaninogenicus.
Compatible
Amikacin sulfate
Metronidazole
Advice to Patients
Incompatible
Aminophylline
Clindamycin phosphate
Gentamicin sulfate
Variable
Metronidazole HCl
Linezolid
Theophylline
•
•
•
•
Importance of informing clinicians if an allergic reaction occurs.
Importance of women informing clinician if they are or plan to become pregnant
or plan to breast-feed.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information.
(See Cautions.)
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Preparations
Ceftriaxone Sodium
Parenteral
For injection
For injection, for
IM use
For injection, for
IV infusion
250 mg (of ceftriaxone)
Rocephin, Roche
500 mg (of ceftriaxone)
1 g (of ceftriaxone)
Rocephin, Roche
Rocephin, Roche
2 g (of ceftriaxone)
10 g (of ceftriaxone) pharmacy
bulk package
500 mg (of ceftriaxone)
Rocephin, Roche
Rocephin, Roche
Rocephin Intramuscular Convenience Kit (with 2.1 mL lidocaine hydrochloride [XylocaineMPF 1%], diluent, a disposable
syringe, 2 needles, and alcohol
swabs), Roche
1 g (of ceftriaxone)
Rocephin Intramuscular Convenience Kit (with 2.1 mL lidocaine hydrochloride [XylocaineMPF 1%], diluent, a disposable
syringe, 2 needles, and alcohol
swabs), Roche
1 g (of ceftriaxone)
Rocephin ADD-Vantage, Roche
2 g (of ceftriaxone)
Rocephin Piggyback, Roche
Rocephin ADD-Vantage,
Roche
Rocephin Piggyback, Roche
Ceftriaxone Sodium in Dextrose
Parenteral
Injection (frozen), for IV infusion
20 mg (of ceftriaxone) per mL
(1 g) in 3.8% Dextrose
40 mg (of ceftriaxone) per mL
(2 g) in 2.4% Dextrose
Rocephin in Iso-osmotic Dextrose Injection (Galaxy [Baxter]), Roche
Rocephin in Iso-osmotic Dextrose Injection (Galaxy [Baxter]), Roche
†Use is not currently included in the labeling approved by the US Food and Drug Administration
Selected Revisions July 2005, Copyright, May 2004, American Society of Health-System Pharmacists, Inc.
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