Anda di halaman 1dari 7

Ceftriaxone

47

Ceftriaxone (Systemic)
Antibacterial; -lactam antibiotic; third generation cephalosporin.

junction with an aminoglycoside (amikacin, gentamicin, tobramycin) is one of several preferred regimens for initial treatment of life-threatening sepsis in adults.

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.

Class: Third Generation Cephalosporins 8:12.06.12 (AHFS primary); AM103 (VA primary) Brands*: Rocephin
*also available generically

Urinary Tract Infections (UTIs)


Treatment of complicated and uncomplicated UTIs caused by E. coli, K. pneumo Considered a drug of choice for treatment of UTIs caused by susceptible Enteroniae, M. morganii, P. mirabilis, or P. vulgaris.

Uses
Acute Otitis Media (AOM)
Treatment of AOM caused by S. pneumoniae, H. inuenzae (including -lactamase-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 3 months of age with infections that failed to respond to other anti-infectives (e.g., amoxicillin, amoxicillin and clavulanate potassium, cefaclor, cefuroxime).

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 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 Parinauds 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 identied. erythromycin or oral azithromycin).

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 parainuenzae, 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. pneumo Treatment of mixed aerobic-anaerobic intra-abdominal infections; should not be
used alone when B. fragilis may be present. niae, Bacteroides fragilis, Clostridium (not C. difcile), or Peptostreptococcus.

Capnocytophaga Infections
Treatment of infections caused by Capnocytophaga. Optimum regimens for treatment of infections caused by Capnocytophaga have
not been identied; 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 uoroquinolone, or clindamycin.

Meningitis and Other CNS Infections


Treatment of meningitis caused by susceptible H. inuenzae, 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).

Chancroid
Treatment of chancroid (genital ulcers caused by H. ducreyi). CDC and others recommend azithromycin, ceftriaxone, ciprooxacin 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 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
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.

Respiratory Tract Infections


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

Septicemia
Treatment of septicemia caused by S. aureus, S. pneumoniae, E. coli, H. inuen A parenteral cephalosporin (i.e., cefepime, cefotaxime, ceftriaxone) given in conzae, or K. pneumoniae.

48

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 ty Treatment of infections caused by nontyphi Salmonella, including bacteremia or 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. osteomyelitis caused by S. typhimurium. phi or S. paratyphi, including multidrug-resistant strains.

Whipples Disease
Treatment of Whipples disease, a progressive systemic infection caused by Tropheryma whippelii.

Lyme Disease
Treatment of severe forms or late complications of Lyme disease. Although oral anti-infectives (e.g., doxycycline, amoxicillin) generally are effective
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.

Empiric Therapy in Febrile Neutropenic Patients


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

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.

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 ciprooxacin 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 Inammatory 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.

Prophylaxis in Sexual Assault Victims


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

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.

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 manufacturers 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

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.
exneri. Anti-infectives generally indicated in addition to uid 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 dened. Alternative for treatment of neurosyphilis in patients hypersensitive to penicillin. CDC states that data are insufcient 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.

Ceftriaxone from the primary container before administration of uid 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.) 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 manufacturers instructions using the lidocaine hydrochloride diluent provided in the kit.

49

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 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 (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: A single 125-mg dose for children 12 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 12 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. 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 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. 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 Penicillin-susceptible Viridans Streptococci or S. bovis IV or IM: 2 g once daily for 4 weeks recommended by AHA. 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. parainuenzae, 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. inuenzae or N. meningitidis, 10 14 days is suggested for complicated cases or meningitis caused by S. pneumoniae and 21

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 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). 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 rst 2 weeks of treatment. Meningitis IV: An initial dose of 100 mg/kg (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. 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

50

Ceftriaxone 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 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. 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 Inammatory 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 dened. 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 dened. 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. 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.

Cautions
Contraindications

Known hypersensitivity to ceftriaxone or other cephalosporins.

Warnings/Precautions
Warnings Superinfection/Clostridium difcile-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 difcile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly. Some mild cases of C. difcile-associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with uid, 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 difcile-associated 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

Ceftriaxone (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. Sodium Content Contains approximately 83 mg (3.6 mEq) of sodium per g of ceftriaxone. Specic Populations 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. Quinolones Probenecid 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 ltration 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 In vitro evidence of synergistic antibacterial effect between ceftriaxone and trovaoxacin against penicillin-susceptible and penicillin-resistant S. pneumoniae, including some strains resistant to ceftriaxone alone Possible false-positive reactions in urine glucose tests using Clinitest, Benedicts solution, or Fehlings solution

51

Clinical importance unknown

Tests for glucose

Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)

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 uids including the gallbladder, lungs, bone, heart, bile, prostate adenoma tissue, uterine tissue, atrial appendage, sputum, tears, middle ear uid, and pleural, peritoneal, synovial, ascitic, and blister uids. Generally diffuses into CSF following IM or IV administration; CSF concentrations are higher in patients with inamed meninges. Crosses the placenta and is distributed into amniotic uid. Distributed into milk. Plasma Protein Binding

Common Adverse Effects


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

Interactions
Specic Drugs and Laboratory Tests
Drug or Test Aminoglycosides Interaction 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 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 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 ltration as unchanged drug; remainder

52

Ceftriaxone 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 Gatioxacin Gemcitabine HCl Granisetron HCl Heparin sodium Incompatible Alatrooxacin mesylate Amphotericin B cholesteryl sulfate complex Amsacrine Azithromycin Filgrastim Variable Vancomycin HCl Fluconazole Labetalol HCl Pentamidine isethionate Vinorelbine tartrate 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

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
Storage
Parenteral Powder for Injection or Infusion 25C; 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.

Actions and Spectrum



Based on spectrum of activity, classied as a third generation cephalosporin. Usually less active in vitro against susceptible staphylococci than rst generation cephalosporins, but has expanded spectrum of activity against gram-negative bacteria compared with rst 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 inuenzae (including ampicillin-resistant and -lactamaseproducing strains), H. parainuenzae, 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. difcile), and Peptostreptococus. Also active in vitro against Prevotella bivius and Porphyromonas melaninogenicus.

Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility Compatible 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 Variable Ringers injection, lactated Drug Compatibility Admixture Compatibility Compatible Amikacin sulfate Metronidazole Incompatible Aminophylline Clindamycin phosphate Gentamicin sulfate Variable Metronidazole HCl Linezolid Theophylline Dextrose 5% in sodium chloride 0.45% Dextrose 5 or 10% in water Sodium chloride 0.9%

Advice to Patients

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.)

Ceftriaxone

53

Preparations
Ceftriaxone Sodium Parenteral For injection 250 mg (of ceftriaxone) 500 mg (of ceftriaxone) 1 g (of ceftriaxone) 2 g (of ceftriaxone) 10 g (of ceftriaxone) pharmacy bulk package 500 mg (of ceftriaxone) Rocephin, Roche Rocephin, Roche Rocephin, Roche 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 Rocephin Intramuscular Convenience Kit (with 2.1 mL lidocaine hydrochloride [XylocaineMPF 1%], diluent, a disposable syringe, 2 needles, and alcohol swabs), Roche Rocephin ADD-Vantage, Roche Rocephin Piggyback, Roche Rocephin ADD-Vantage, Roche Rocephin Piggyback, Roche

For injection, for IM use

1 g (of ceftriaxone)

For injection, for IV infusion

1 g (of ceftriaxone) 2 g (of ceftriaxone)

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.

Anda mungkin juga menyukai