CEFTRIAXONE SODIUM injection, powder, for solution

Ceftriaxone Sodium by

Drug Labeling and Warnings

Ceftriaxone Sodium by is a Prescription medication manufactured, distributed, or labeled by Rebel Distributors Corp. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure7 requires the use of standardized inoculum concentrations. This procedure uses paper discs impregnated with 30 mcg of ceftriaxone to test the susceptibility of microorganisms to ceftriaxone.

Reports from the laboratory providing results of the standard single-disc susceptibility test with a 30 mcg ceftriaxone disc should be interpreted according to the following criteria for aerobic organisms other than Haemophilus spp, Neisseria gonorrhoeae, and Streptoccocus spp:

Zone diameter (mm)Interpretation
≥ 21(S) Susceptible
14-20(I) Intermediate
≤ 13(R) Resistant

The following interpretive criteria8 should be used when testing Haemophilus species when using Haemophilus Test Media (HTM).

Zone diameter (mm)Interpretation
≥ 26(S) Susceptible

The absence of resistant strains precludes defining any categories other than "Susceptible". Strains yielding results suggestive of a "Nonsusceptible" category should be submitted to a reference laboratory for further testing.

The following interpretive criteria9 should be used when testing Neisseria gonorrhoeae when using GC agar base and 1 % defined growth supplement.

Zone diameter (mm)Interpretation
≥ 35(S) Susceptible

The absence of resistant strains precludes defining any categories other than "Susceptible". Strains yielding results suggestive of a "Nonsusceptible" category should be submitted to a reference laboratory for further testing.

The following interpretive criteria10 should be used when testing Streptococcus spp other than Streptococcus pneumoniae when using Mueller-Hinton agar supplemented with 5% sheep blood incubated in 5% CO2.

Zone diameter (mm)Interpretation
≥ 27(S) Susceptible
25-26(I) Intermediate
≤ 24(R) Resistant

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disc test with the MIC for ceftriaxone.

Disc diffusion interpretive criteria for ceftriaxone discs against Streptococcus pneumoniae are not available, however, isolates of pneumococci with oxacillin zone diameters of > 20 mm are susceptible (MIC ≤ 0.06 mcg/mL) to penicillin and can be considered susceptible to ceftriaxone. Streptococcus pneumoniae isolates should not be reported as penicillin (ceftriaxone) resistant or intermediate based solely on an oxacillin zone diameter of ≤ 19 mm. The ceftriaxone MIC should be determined for those isolates with oxacillin zone diameters ≤ 19 mm.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg ceftriaxone disc should provide the following zone diameters in these laboratory test quality control strains:11

MicroorganismATCC® #Zone Diameter Ranges (mm)
Escherichia coli2592229-35
Staphylococcus aureus2592322-28
Pseudomonas aeruginosa2785317-23
Haemophilus influenzae4924731-39
Neisseria gonorrhoeae4922639-51
Streptococcus pneumoniae4961930-35

  • 7

    National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.

  • 8

    National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.

  • 9

    National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.

  • 10

    National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.

  • 11

    National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition. NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.

  • Anaerobic Techniques

    For anaerobic bacteria, the susceptibility to ceftriaxone as MICs can be determined by standardized test methods.12 The MIC values obtained should be interpreted according to the following criteria:

    MIC (mcg/mL)Interpretation
    ≤ 16(S) Susceptible
    32(I) Intermediate
    ≥ 64(R) Resistant

    As with other susceptibility techniques, the use of laboratory control microorganism is required to control the technical aspects of the laboratory standardized procedures. Standardized ceftriaxone powder should provide the following MIC values for the indicated standardized anaerobic dilution13 testing method:

    MethodMicroorganismATCC ® #MIC (mcg/mL)
    AgarBacteroides fragilis2528532 -128
     Bacteroides thetaiotaomicron2974164 -256
    BrothBacteroides thetaiotaomicron 2974132 -128

    ATCC® is a registered trademark of the American Type Culture Collection.


  • 12

    National Committee for Clinical Laboratory Standards, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard-Fourth Edition. NCCLS document M11-A4 (ISBN 1-56238-210-1). NCCLS, Wayne, PA 19087-1898, 1997.

  • 13

    National Committee for Clinical Laboratory Standards, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard-Fourth Edition. NCCLS document M11-A4 (ISBN 1-56238-210-1). NCCLS, Wayne, PA 19087-1898, 1997.

  • INDICATIONS & USAGE

    Before instituting treatment with ceftriaxone, appropriate specimens should be obtained for isolation of the causative organism and for determination of its susceptibility to the drug. Therapy may be instituted prior to obtaining results of susceptibility testing.

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftriaxone for injection and other antibacterial drugs, ceftriaxone for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

    Ceftriaxone sodium is indicated for the treatment of the following infections when caused by susceptible organisms:

    Lower Respiratory Tract Infections caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or Serratia marcescens.

    Acute Bacterial Otitis Media caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase producing strains) or Moraxella catarrhalis (including beta-lactamase producing strains).

    NOTE: In one study lower clinical cure rates were observed with a single dose of ceftriaxone sodium compared to 10 days of oral therapy. In a second study comparable cure rates were observed between single dose ceftriaxone sodium and the comparator. The potentially lower clinical cure rate of ceftriaxone should be balanced against the potential advantages of parenteral therapy (see CLINICAL STUDIES).

    Skin And Skin Structure Infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Viridans group streptococci, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii14, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis 15 or Peptostreptococcus species.

    Urinary Tract Infections (complicated and uncomplicated) caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae.

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

    Pelvic Inflammatory Disease caused by Neisseria gonorrhoeae. Ceftriaxone sodium, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and Chlamydia trachomatis is one of the suspected pathogens, appropriate antichlamydial coverage should be added.

    Bacterial Septicemia caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae or Klebsiella pneumoniae.

    Bone And Joint Infections caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae or Enterobacter species.

    Intra-Abdominal Infections caused by Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridium species (Note: most strains of Clostridium difficile are resistant) or Peptostreptococcus species.

    Meningitis caused by Haemophilus influenzae, Neisseria meningitidis or Streptococcus pneumoniae. Ceftriaxone has also been used successfully in a limited number of cases of meningitis and shunt infection caused by Staphylococcus epidermidis 16 and Escherichia coli 17.

    Surgical Prophylaxis: The preoperative administration of a single 1 gm dose of ceftriaxone sodium may reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated (e.g., vaginal or abdominal hysterectomy or cholecystectomy for chronic calculous cholecystitis in high-risk patients, such as those over 70 years of age, with acute cholecystitis not requiring therapeutic antimicrobials, obstructive jaundice or common duct bile stones) and in surgical patients for whom infection at the operative site would present serious risk (e.g., during coronary artery bypass surgery). Although ceftriaxone has been shown to have been as effective as cefazolin in the prevention of infection following coronary artery bypass surgery, no placebo-controlled trials have been conducted to evaluate any cephalosporin antibiotic in the prevention of infection following coronary artery bypass surgery.

    When administered prior to surgical procedures for which it is indicated, a single 1 gm dose of ceftriaxone sodium provides protection from most infections due to susceptible organisms throughout the course of the procedure.


  • 14

    Efficacy for this organism in this organ system was studied in fewer than ten infections.

  • 15

    Efficacy for this organism in this organ system was studied in fewer than ten infections.

  • 16

    Efficacy for this organism in this organ system was studied in fewer than ten infections.

  • 17

    Efficacy for this organism in this organ system was studied in fewer than ten infections.

  • CONTRAINDICATIONS

    Ceftriaxone is contraindicated in patients with known allergy to the cephalosporin class of antibiotics.

    Nonates ( ≤28 days)

    Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a possible risk of bilirubin encephalopathy in these patients.

    Ceftriaxone is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium (see CLINICAL PHARMACOLOGY, WARNINGS and DOSAGE AND ADMINISTRATION).

    A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom ceftriaxone and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.

  • WARNINGS

    Hypersensitivity

    BEFORE THERAPY WITH CEFTRIAXONE IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE USE OF SUBCUTANEOUS EPINEPHRINE AND OTHER EMERGENCY MEASURES.

    As with other cephalosporins, anaphylactic reactions with fatal outcome have been reported, even if a patient is not known to be allergic or previously exposed.

    Interaction with Calcium-Containing Products

    Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone­calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

    Clostridium difficile

    Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

    If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

    Hemolytic Anemia

    An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including ceftriaxone. Severe cases of hemolytic anemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anemia while on ceftriaxone, the diagnosis of a cephalosporin associated anemia should be considered and ceftriaxone stopped until the etiology is determined.

  • PRECAUTIONS

    General

    Prescribing ceftriaxone for injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

    Although transient elevations of BUN and serum creatinine have been observed, at the recommended dosages, the nephrotoxic potential of ceftriaxone is similar to that of other cephalosporins.

    Ceftriaxone is excreted via both biliary and renal excretion (see CLINICAL PHARMACOLOGY). Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of ceftriaxone are administered.

    Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the ceftriaxone dosage should not exceed 2 gm daily.

    Alterations in prothrombin times have occurred rarely in patients treated with ceftriaxone. Patients with impaired vitamin K synthesis or low vitamin K stores (e.g., chronic hepatic disease and malnutrition) may require monitoring of prothrombin time during ceftriaxone treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.

    Prolonged use of ceftriaxone may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

    Ceftriaxone should be prescribed with caution in individuals with a history of gastrointestinal disease, especially colitis.

    There have been reports of sonographic abnormalities in the gallbladder of patients treated with ceftriaxone; some of these patients also had symptoms of gallbladder disease. These abnormalities appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. The chemical nature of the sonographically detected material has been determined to be predominantly a ceftriaxone-calcium salt. The condition appears to be transient and reversible upon discontinuation of ceftriaxone and institution of conservative management. Therefore, ceftriaxone should be discontinued in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.

    Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported rarely in patients treated with ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of ceftriaxone-related biliary precipitation cannot be ruled out.

    Information for Patients

    Patients should be counseled that antibacterial drugs including ceftriaxone for injection should only be used to treat bacterial infections. They do not treat viral infections (e.g., common cold). When ceftriaxone for injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by ceftriaxone for injection or other antibacterial drugs in the future.

    Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis

    Considering the maximum duration of treatment and the class of the compound, carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum duration of animal toxicity studies was 6 months.

    Mutagenesis

    Genetic toxicology tests included the Ames test, a micronucleus test and a test for chromosomal aberrations in human lymphocytes cultured in vitro with ceftriaxone. Ceftriaxone showed no potential for mutagenic activity in these studies.

    Impairment of Fertility

    Ceftriaxone produced no impairment of fertility when given intravenously to rats at daily doses up to 586 mg/kg/day, approximately 20 times the recommended clinical dose of 2 gm/day.

    Pregnancy

    Teratogenic Effects

    Pregnancy Category B

    Reproductive studies have been performed in mice and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at a dose approximately 3 times the human dose.

    There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

    Nonteratogenic Effects

    In rats, in the Segment I (fertility and general reproduction) and Segment III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior and reproductive ability of the offspring, at doses of 586 mg/kg/day or less.

    Nursing Mothers

    Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a nursing woman.

    Pediatric Use

    Safety and effectiveness of ceftriaxone in neonates, infants and pediatric patients have been established for the dosages described in the DOSAGE AND ADMINISTRATION section. In vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone should not be administered to hyperbilirubinemic neonates, especially prematures (see CONTRAINDICATIONS).

    Geriatric Use

    Of the total number of subjects in clinical studies of ceftriaxone, 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

    The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients  compared to healthy adult subjects and dosage adjustments are not necessary for geriatric  patients with ceftriaxone dosages up to 2 grams per day (see CLINICAL  PHARMACOLOGY).

  • ADVERSE REACTIONS

    Ceftriaxone is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone therapy or of uncertain etiology, were observed:

    Local Reactions - pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL.

    Hypersensitivity - rash (1.7%). Less frequently reported (<1 %) were pruritus, fever or chills.

    Hematologic - eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently reported (<1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time.

    Gastrointestinal - diarrhea (2.7%). Less frequently reported (<1%) were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment (see WARNINGS).

    Hepatic - elevations of SGOT (3.1%) or SGPT (3.3%). Less frequently reported (<1 %) were elevations of alkaline phosphatase and bilirubin.

    Renal - elevations of the BUN (1.2%). Less frequently reported (<1 %) were elevations of creatinine and the presence of casts in the urine.

    Central Nervous System - headache or dizziness were reported occasionally (<1 %).

    Genitourinary - moniliasis or vaginitis were reported occasionally (<1%).

    Miscellaneous - diaphoresis and flushing were reported occasionally (< 1%).

    Other rarely observed adverse reactions (< 0.1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness.

    Postmarketing Experience: In addition to the adverse reactions reported during clinical  trials, the following adverse experiences have been reported during clinical practice in patients treated with ceftriaxone. Data are generally insufficient to allow an estimate of incidence or to establish causation.

    A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom ceftriaxone and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.

    Gastrointestinal - stomatitis and glossitis.

    Genitourinary - oliguria.

    Dermatologic exanthema, allergic dermatitis, urticaria, edema. As with many   medications, isolated cases of severe cutaneous adverse reactions (erythema multiforme,  Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been  reported.

    Cephalosporin Class Adverse Reactions

    In addition to the adverse reactions listed above which have been observed in patients  treated with ceftriaxone, the following adverse reactions and altered laboratory test results have been reported for cephalosporin class antibiotics:

    Adverse Reactions: Allergic reactions, drug fever, serum sickness-like reaction, renal  dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction  including cholestasis, aplastic anemia, hemorrhage, and superinfection.

    Altered Laboratory Tests: Positive direct Coombs’ test, false-positive test for urinary glucose, and elevated LDH.

    Several cephalosporins have been implicated in triggering seizures, particularly in  patients with renal impairment when the dosage was not reduced (see DOSAGE AND  ADMINISTRATION). If seizures associated with drug therapy occur, the drug should  be discontinued. Anticonvulsant therapy can be given if clinically indicated.

  • OVERDOSAGE

    In the case of over dosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.

  • DOSAGE & ADMINISTRATION

    Ceftriaxone sodium may be administered intravenously or intramuscularly.

    Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone­calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid (see WARNINGS).

    There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

    Neonates

    Hyperbilirubinemic neonates, especially prematures, should not be treated with ceftriaxone (see CONTRAINDICATIONS).

    Ceftriaxone is contraindicated in neonates if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone- calcium (see CONTRAINDICATIONS).

    Pediatric Patients

    For the treatment of skin and skin structure infections, the recommended total daily dose is 50 to 75 mg/kg given once a day (or in equally divided doses twice a day). The total daily dose should not exceed 2 grams.

    For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 gram) is recommended (see INDICATIONS AND USAGE).

    For the treatment of serious miscellaneous infections other than meningitis, the recommended total daily dose is 50 to 75 mg/kg, given in divided doses every 12 hours. The total daily dose should not exceed 2 grams.

    In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 grams). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 grams daily) is recommended. The daily dose may be administered once a day (or in equally divided doses every 12 hours). The usual duration of therapy is 7 to 14 days.

    Adults

    The usual adult daily dose is 1 to 2 grams given once a day (or in equally divided doses twice a day) depending on the type and severity of infection. The total daily dose should not exceed 4 grams.

    If Chlamydia trachomatis is a suspected pathogen, appropriate antichlamydial coverage should be added, because ceftriaxone sodium has no activity against this organism.

    For the treatment of uncomplicated gonococcal infections, a single intramuscular dose of 250 mg is recommended.

    For preoperative use (surgical prophylaxis), a single dose of 1 gram administered intravenously 1/2 to 2 hours before surgery is recommended.

    Generally, ceftriaxone therapy should be continued for at least 2 days after the signs and symptoms of infection have disappeared. The usual duration of therapy is 4 to 14 days; in complicated infections, longer therapy may be required.

    When treating infections caused by Streptococcus pyogenes, therapy should be continued for at least 10 days.

    No dosage adjustment is necessary for patients with impairment of renal or hepatic function.

    DIRECTIONS FOR USE

    Intramuscular Administration

    Reconstitute ceftriaxone sodium powder with the appropriate diluent (see COMPATIBILITY AND STABILITY).

    Inject diluent into vial, shake vial thoroughly to form solution. Withdraw entire contents of vial into syringe to equal total labeled dose.

    After reconstitution, each 1 mL of solution contains approximately 250 mg or 350 mg equivalent of ceftriaxone according to the amount of diluent indicated below. If required, more dilute solutions could be utilized. A 350 mg/mL concentration is not recommended for the 250 mg vial since it may not be possible to withdraw the entire contents. 

    As with all intramuscular preparations, ceftriaxone sodium should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel.

    Vial Dosage SizeAmount of Diluent to be Added
     250 mg/mL350 mg/mL
    250 mg0.9 mL-
    500 mg1.8 mL1 mL
    1 gm3.6 mL2.1 mL
    2 gm7.2 mL4.2 mL

    Intravenous Administration

    Ceftriaxone sodium should be administered intravenously by infusion over a period of 30 minutes. Concentrations between 10 mg/mL and 40 mg/mL are recommended; however, lower concentrations may be used if desired. Reconstitute vials or “piggyback” bottles with an appropriate IV diluent (see COMPATIBILITY AND STABILITY).

    Vial Dosage SizeAmount of Diluent to be Added
    250 mg2.4 mL
    500 mg4.8 mL
    1 gm9.6 mL
    2 gm19.2 mL

    After reconstitution, each 1 mL of solution contains approximately 100 mg equivalent of ceftriaxone. Withdraw entire contents and dilute to the desired concentration with the appropriate IV diluent.

    Piggyback Bottle Dosage SizeAmount of Diluent to be Added
    1 gm10 mL
    2 gm20 mL

    After reconstitution, further dilute to 50 mL or 100 mL volumes with the appropriate IV diluent.

    COMPATIBILITY AND STABILITY

    Ceftriaxone has been shown to be compatible with Flagyl ®18 IV (metronidazole hydrochloride). The concentration should not exceed 5 to 7.5 mg/mL metronidazole hydrochloride with ceftriaxone 10 mg/mL as an admixture. The admixture is stable for 24 hours at room temperature only in 0.9% sodium chloride injection or 5% dextrose in water (D5W). No compatibility studies have been conducted with the Flagyl® IV RTU® (metronidazole) formulation or using other diluents. Metronidazole at concentrations greater than 8 mg/mL will precipitate. Do not refrigerate the admixture as precipitation will occur.

    Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.

    Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration. Particulate formation can result.

    Ceftriaxone sodium solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or into diluent solutions other than those listed above, due to possible incompatibility (see WARNINGS).

    Ceftriaxone sodium sterile powder should be stored at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature] and protected from light. After reconstitution, protection from normal light is not necessary. The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

    Ceftriaxone sodium intramuscular solutions remain stable (loss of potency less than 10%) for the following time periods:

       Storage
    Diluent
     
    Concentration
    mg/mL
    Room Temp.
    (25°C)
    Refrigerated
    (4°C)
    Sterile Water for Injection1002 days10 days
     250, 35024 hours3 days
    0.9% Sodium Chloride
        Solution
    1002 days10 days
     250, 35024 hours3 days
    5% Dextrose Solution 1002 days10 days
     250, 35024 hours3 days
    Bacteriostatic Water + 0.9%
    Benzyl Alcohol
    10024 hours10 days
     250, 35024 hours3 days
    1% Lidocaine Solution
        (without epinephrine)
    10024 hours10 days
     250, 35024 hours3 days

    Ceftriaxone sodium intravenous solutions, at concentrations of 10, 20 and 40 mg/mL, remain stable (loss of potency less than 10%) for the following time periods stored in glass or PVC containers:

     Storage
  • * Data available for 10 to 40 mg/mL concentrations in this diluent in PVC containers only.
  • Diluent
     
    Room Temp.
    (25°C)
    Refrigerated
    (4°C)
    Sterile Water2 days10 days
    0.9% Sodium Chloride Solution2 days10 days
    5% Dextrose Solution2 days10 days
    10% Dextrose Solution2 days10 days
    5% Dextrose + 0.9% Sodium Chloride Solution*2 daysIncompatible
    5% Dextrose + 0.45% Sodium Chloride Solution2 daysIncompatible

    Similarly, ceftriaxone sodium intravenous solutions, at concentrations of 100 mg/mL, remain stable in the IV piggyback glass containers for the above specified time periods.

    The following intravenous ceftriaxone sodium solutions are stable at room temperature (25°C) for 24 hours, at concentrations between 10 mg/mL and 40 mg/mL: Sodium Lactate (PVC container), 10% Invert Sugar (glass container), 5% Sodium Bicarbonate (glass container), Freamine III (glass container), Normosol-M in 5% Dextrose (glass and PVC containers), Ionosol-B in 5% Dextrose (glass container), 5% Mannitol (glass container), 10% Mannitol (glass container).

    After the indicated stability time periods, unused portions of solutions should be discarded.

    NOTE: Parenteral drug products should be inspected visually for particulate matter before administration.

    Ceftriaxone sodium reconstituted with 5% Dextrose or 0.9% Sodium Chloride solution at concentrations between 10 mg/mL and 40 mg/mL, and then stored in frozen state (-20°C) in PVC or polyolefin containers, remains stable for 26 weeks.

    Frozen solutions of ceftriaxone sodium should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.


  • 18

    Registered trademark of G.D. Searle & Co.

  • ANIMAL PHARMACOLOGY

    Concretions consisting of the precipitated calcium salt of ceftriaxone have been found in the gallbladder bile of dogs and baboons treated with ceftriaxone.

    These appeared as a gritty sediment in dogs that received 100 mg/kg/day for 4 weeks. A similar phenomenon has been observed in baboons but only after a protracted dosing period (6 months) at higher dose levels (335 mg/kg/day or more). The likelihood of this occurrence in humans is considered to be low, since ceftriaxone has a greater plasma half-life in humans, the calcium salt of ceftriaxone is more soluble in human gallbladder bile and the calcium content of human gallbladder bile is relatively low.

  • HOW SUPPLIED

    Ceftriaxone sodium is supplied as a sterile crystalline powder in glass vials and piggyback bottles. The following packages are available:

    Vials containing 500 mg equivalent of ceftriaxone. Box of 10 (NDC: 21695-202-10) . 

    Vials containing 1 gm equivalent of ceftriaxone. Box of 1 (NDC: 21695-352-01).

    Vials containing 1 gm equivalent of ceftriaxone. Box of 10 (NDC: 21695-352-10).

    NOTE: Ceftriaxone sodium sterile powder should be stored at 20° - 25°C (68° - 77°F) [See USP Controlled Room Temperature] and protected from light.

  • CLINICAL STUDIES

    Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media

    In two adequate and well-controlled U.S. clinical trials a single IM dose of ceftriaxone was compared with a 10 day course of oral antibiotic in pediatric patients between the ages of 3 months and 6 years. The clinical cure rates and statistical outcome appear in the table below:

    Clinical Efficacy in Evaluable Population
  • * Barnett ED, Teele DW, Klein JO, et al. Comparison of Ceftriaxone and Trimethoprim- Sulfamethoxazole for Acute Otitis Media. Pediatrics. Vol .99, No. 1, January 1997.
  • Study DayCeftriaxone Single DoseComparator- 10 Days of Oral Therapy95 % Confidence IntervalStatistical Outcome
    Study 1 - U.S. amoxicillin/clavulanate  
    1474% (220/296)82% (247/302)(-14.4%, -0.5%)Ceftriaxone is lower than control at study day 14 and 28.
    2858% (167/288)67% (200/297)(-17.5%, -1.2%) 
    Study 2 - U.S.* TMP-SMZ  
    1454% (113/210)60% (124/206)(-16.4%, 3.6%)Ceftriaxone is equivalent to control at study day 14 and 28.
    2835% (73/206)45% (93/205)(-19.9%, 0.0%) 

    An open-label bacteriologic study of ceftriaxone without a comparator enrolled 108 pediatric patients, 79 of whom had positive baseline cultures for one or more of the common pathogens. The results of this study are tabulated as follows:

    Week 2 and 4 Bacteriologic Eradication Rates in the Per Protocol Analysis in the Roche Bacteriologic Study by pathogen:

     Study Day
    13-15
     Study Day
    30+2
     
    OrganismNo. AnalyzedNo. Erad. (%)No. AnalyzedNo. Erad. (%)
    Streptococcus pneumoniae3832 (84)3525 (71)
    Haemophilus influenzae3328 (85)3122 (71)
    Moraxella catarrhalis1512 (80)159 (60)
  • REFERENCES

    1. National Committee for Clinical Laboratory Standards, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Fifth Edition. NCCLS document M7-A5 (ISBN 1-56238-309-9).NCCLS, Wayne, PA 19087-1898, 2000.
    2. National Committee for Clinical Laboratory Standards, Supplemental Tables.  NCCLS document M100-S10 (M7) (ISBN 1-56238-309-9).  NCCLS, Wayne, PA 19087-1898, 2000.
    3. National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Disc Susceptibility Tests; Approved Standard - Seventh Edition.  NCCLS document M2-A7 (ISBN 1-56238-393-0). NCCLS, Wayne, PA 19087-1898, 2000.
    4. National Committee for Clinical Laboratory Standards, Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard- Fourth Edition.  NCCLS document M11-A4 (ISBN 1- 56238-210-1). NCCLS, Wayne, PA 19087-1898, 1997.
    5. Barnett ED, Teele DW, Klein JO, et al. Comparison of Ceftriaxone and Trimethoprim- Sulfamethoxazole for Acute Otitis Media. Pediatrics. Vol. 99, No. 1, January 1997.

    Mfg. by:

    Hospira Healthcare India Pvt. Ltd.                                                              

    Irungattukottai - 602 105, India

    Mfg. for:

    Apotex Corp.

    Weston, FL 33326 

    DATE OF REVISION: JUNE 2010

    948026018

    Repackaged by:

    Rebel Distributors Corp

    Thousand Oaks, CA 91320

      

  •     Principal Display Panel

    Ceftriaxone 1gm

  • INGREDIENTS AND APPEARANCE
    CEFTRIAXONE SODIUM 
    ceftriaxone sodium injection, powder, for solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-202(NDC: 60505-751)
    Route of AdministrationINTRAVENOUS, INTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    CEFTRIAXONE SODIUM (UNII: 023Z5BR09K) (CEFTRIAXONE - UNII:75J73V1629) CEFTRIAXONE500 mg
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-202-1010 in 1 BOX
    11 in 1 VIAL
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06523008/02/2005
    CEFTRIAXONE SODIUM 
    ceftriaxone sodium injection, powder, for solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 21695-352(NDC: 60505-752)
    Route of AdministrationINTRAVENOUS, INTRAMUSCULAR
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    CEFTRIAXONE SODIUM (UNII: 023Z5BR09K) (CEFTRIAXONE - UNII:75J73V1629) CEFTRIAXONE1 g
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 21695-352-1010 in 1 BOX
    11 in 1 VIAL
    2NDC: 21695-352-011 in 1 BOX
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06523008/02/2005
    Labeler - Rebel Distributors Corp (118802834)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rebel Distributors Corp118802834RELABEL, REPACK

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