Dosage Form: injection, powder, for solution
Ceftriaxone Injection, USP
(In Dextrose)
in GALAXY Container
(PL 2040 Plastic)
Rx Only
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ceftriaxone Injection, USP and other antibacterial drugs, Ceftriaxone Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Ceftriaxone Description
Ceftriaxone Injection, USP is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous administration. Ceftriaxone sodium is (6R,7R) - 7 - [2 - (2 - Amino - 4 - thiazolyl)glyoxylamido] - 8 - oxo - 3 - [[(1,2,5,6 - tetrahydro - 2 - methyl - 5,6 - dioxo - as - triazin - 3 - yl)thio]methyl] - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - ene - 2 - carboxylic acid, 7²-(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.
The chemical formula of Ceftriaxone sodium is C18H16N8Na2O7S3•7/2 H2O. It has a calculated molecular weight of 661.60 and the following structural formula:
Ceftriaxone Sodium, USP is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol.
Ceftriaxone Injection, USP contains approximately 83 mg (3.6 mEq) of sodium per gram of Ceftriaxone activity.
Ceftriaxone Injection, USP is supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution premixed in a dextrose diluent. Dextrose, USP has been added to adjust the osmolality (approximately 1.9 g and 1.2 g as dextrose hydrous to the 1 g and 2 g dosages, respectively). The pH may be adjusted with sodium hydroxide and/or hydrochloric acid. Solutions of premixed Ceftriaxone Injection, USP may range from light yellow to amber in color. After thawing, the solution is intended for intravenous use. The pH of thawed solutions may range from 6.0 to 8.0. See HOW SUPPLIED for package description.
The plastic container for the frozen solution is fabricated from a specially designed multilayer plastic, PL 2040. Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers as well as by tissue culture toxicity studies.
Ceftriaxone - Clinical Pharmacology
Average plasma concentrations of Ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0.5, 1 or 2 gm dose in healthy subjects are presented in Table 1.
| |||||||||
| Ceftriaxone Plasma Concentrations After Single Dose Administration | |||||||||
| Dose/Route | Average Plasma Concentrations (mcg/mL) | ||||||||
| 0.5 hr | 1 hr | 2 hr | 4 hr | 6 hr | 8 hr | 12 hr | 16 hr | 24 hr | |
| 0.5 gm IV* | 82 | 59 | 48 | 37 | 29 | 23 | 15 | 10 | 5 |
| 1 gm IV* | 151 | 111 | 88 | 67 | 53 | 43 | 28 | 18 | 9 |
| 2 gm IV* | 257 | 192 | 154 | 117 | 89 | 74 | 46 | 31 | 15 |
Multiple IV doses ranging from 0.5 to 2 gm at 12- to 24-hour intervals resulted in 15% to 36% accumulation of Ceftriaxone above single dose values.
Ceftriaxone concentrations in urine are high, as shown in Table 2.
| Urinary Concentrations of Ceftriaxone After Single Dose Administration | ||||||
| Dose/Route | Average Urinary Concentrations (mcg/mL) | |||||
| 0-2 hr | 2-4 hr | 4-8 hr | 8-12 hr | 12-24 hr | 24-48 hr | |
| 0.5 gm IV | 526 | 366 | 142 | 87 | 70 | 15 |
| 1 gm IV | 995 | 855 | 293 | 147 | 132 | 32 |
| 2 gm IV | 2692 | 1976 | 757 | 274 | 198 | 40 |
Thirty-three percent to 67% of a Ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 gm IV dose, average concentrations of Ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/gm in the gallbladder wall and 62.1 mcg/mL in the concurrent plasma.
Over a 0.15 to 3 gm dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to 1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of <25 mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta barrier.
The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table 3. Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table 3.
| Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients With Meningitis | ||
| 50 mg/kg IV | 75 mg/kg IV | |
| Maximum Plasma Concentrations (mcg/mL) | 216 | 275 |
| Elimination Half-life (hr) | 4.6 | 4.3 |
| Plasma Clearance (mL/hr/kg) | 49 | 60 |
| Volume of Distribution (mL/kg) | 338 | 373 |
| CSF Concentration - inflamed meninges (mcg/mL) | 5.6 | 6.4 |
| Range (mcg/mL) | 1.3-18.5 | 1.3-44 |
| Time after dose (hr) | 3.7 (± 1.6) | 3.3 (± 1.4) |
Compared to that in healthy adult subjects, the pharmacokinetics of Ceftriaxone were only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (Table 4); therefore, dosage adjustments are not necessary for these patients with Ceftriaxone dosages up to 2 gm per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis. In 6 of 26 dialysis patients, the elimination rate of Ceftriaxone was markedly reduced.
| |||
| Average Pharmacokinetic Parameters of Ceftriaxone in Humans | |||
| Subject Group | Elimination Half-life (hr) | Plasma Clearance (L/hr) | Volume of Distribution (L) |
| Healthy Subjects | 5.8-8.7 | 0.58-1.45 | 5.8-13.5 |
| Elderly Subjects (mean age, 70.5 yr) | 8.9 | 0.83 | 10.7 |
| Patients With Renal Impairment | |||
| Hemodialysis Patients (0-5 mL/min)* | 14.7 | 0.65 | 13.7 |
| Severe (5-15 mL/min) | 15.7 | 0.56 | 12.5 |
| Moderate (16-30 mL/min) | 11.4 | 0.72 | 11.8 |
| Mild (31-60 mL/min) | 12.4 | 0.70 | 13.3 |
| Patients With Liver Disease | 8.8 | 1.1 | 13.6 |
The elimination of Ceftriaxone is not altered when Ceftriaxone Injection, USP is co-administered with probenecid.
Interaction with Calcium
Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood, have been carried out to assess interaction of Ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 grams Ceftriaxone infused over 30 minutes) were used in combination with calcium concentrations up to 12 mM (48 mg/dL). Recovery of Ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in neonatal plasma. This may be reflective of Ceftriaxone-calcium precipitation.
Microbiology
The bactericidal activity of Ceftriaxone results from inhibition of cell wall synthesis. Ceftriaxone has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.
In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and Ceftriaxone.
Ceftriaxone has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections described in the INDICATIONS AND USAGE section.
Aerobic gram-negative microorganisms:
Acinetobacter calcoaceticus
Enterobacter aerogenes
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae (including ampicillin-resistant and beta-lactamase producing strains)
Haemophilus parainfluenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Moraxella catarrhalis (including beta-lactamase producing strains)
Morganella morganii
Neisseria gonorrhoeae (including penicillinase- and nonpenicillinase-producing strains)
Neisseria meningitidis
Proteus mirabilis
Proteus vulgaris
Serratia marcescens
Ceftriaxone is also active against many strains of Pseudomonas aeruginosa.
NOTE: Many strains of the above organisms that are resistant to multiple antibiotics, e.g., penicillins, cephalosporins, and aminoglycosides, are susceptible to Ceftriaxone.
Aerobic gram-positive microorganisms:
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group streptococci
NOTE: Methicillin-resistant staphylococci are resistant to cephalosporins, including Ceftriaxone. Most strains of Group D streptococci and enterococci, e.g., Enterococcus (Streptococcus) faecalis, are resistant.
Anaerobic microorganisms:
Bacteroides fragilis
Clostridium species
Peptostreptococcus species
NOTE: Most strains of Clostridium difficile are resistant.
The following in vitro data are available, but their clinical significance is unknown. Ceftriaxone exhibits in vitro minimal inhibitory concentrations (MICs) of ≤8 mcg/mL or less against most strains of the following microorganisms, however, the safety and effectiveness of Ceftriaxone in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Aerobic gram-negative microorganisms:
Citrobacter diversus
Citrobacter freundii
Providencia species (including Providencia rettgeri)
Salmonella species (including Salmonella typhi)
Shigella species
Aerobic gram-positive microorganisms:
Streptococcus agalactiae
Anaerobic microorganisms:
Prevotella (Bacteroides) bivius
Porphyromonas (Bacteroides) melaninogenicus
Susceptibility Tests
Dilution Techniques
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure.1 Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of Ceftriaxone powder. The MIC values should be interpreted according to the following criteria2 for aerobic organisms other than Haemophilus spp, Neisseria gonorrhoeae, and Streptococcus spp, including Streptococcus pneumoniae:
| MIC (mcg/mL) | Interpretation |
| ≤8 | (S) Susceptible |
| 16-32 | (I) Intermediate |
| ≥64 | (R) Resistant |
The following interpretive criteria2 should be used when testing Haemophilus species using Haemophilus Test Media (HTM).
| MIC (mcg/mL) | Interpretation |
| ≤2 | (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 criteria2 should be used when testing Neisseria gonorrhoeae when using GC agar base and 1% defined growth supplement.
| MIC (mcg/mL) | Interpretation |
| ≤0.25 | (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 criteria2 should be used when testing Streptococcus spp including Streptococcus pneumoniae using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.
| MIC (mcg/mL) | Interpretation |
| ≤0.5 | (S) Susceptible |
| 1 | (I) Intermediate |
| ≥2 | (R) Resistant |
A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the results should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standardized Ceftriaxone powder should provide the following MIC values:2
| ||
| Microorganism | ATCC # | MIC (mcg/mL) |
| Escherichia coli | 25922 | 0.03-0.12 |
| Staphylococcus aureus | 29213 | 1-8* |
| Pseudomonas aeruginosa | 27853 | 8-32 |
| Haemophilus influenzae | 49247 | 0.06-0.25 |
| Neisseria gonorrhoeae | 49226 | 0.004-0.015 |
| Streptococcus pneumoniae | 49619 | 0.03-0.12 |
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 procedure3 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 Streptococcus spp:
| Zone Diameter (mm) | Interpretation |
| ≥21 | (S) Susceptible |
| 14-20 | (I) Intermediate |
| ≤13 | (R) Resistant |
The following interpretive criteria3 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 criteria3 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 criteria3 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:3
| Microorganism | ATCC # | Zone Diameter Ranges (mm) |
| Escherichia coli | 25922 | 29 - 35 |
| Staphylococcus aureus | 25923 | 22 - 28 |
| Pseudomonas aeruginosa | 27853 | 17 - 23 |
| Haemophilus influenzae | 49247 | 31 - 39 |
| Neisseria gonorrhoeae | 49226 | 39 - 51 |
| Streptococcus pneumoniae | 49619 | 30 - 35 |
Anaerobic Techniques
For anaerobic bacteria, the susceptibility to Ceftriaxone as MICs can be determined by standardized test methods.4 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 microorganisms 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 dilution4 testing method:
| Method | Microorganism | ATCC®# | MIC (mcg/mL) |
| Agar | Bacteroides fragilis | 25285 | 32 - 128 |
| Bacteroides thetaiotaomicron | 29741 | 64 - 256 | |
| Broth | Bacteroides thetaiotaomicron | 29741 | 32 - 128 |
Indications and Usage for Ceftriaxone
Before instituting treatment with Ceftriaxone Injection, USP, 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 Injection, USP and other antibacterial drugs, Ceftriaxone Injection, USP 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 Injection, USP 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 compared to 10 days of oral therapy. In a second study comparable cure rates were observed between single dose Ceftriaxone and the comparator. The potentially lower clinical cure rate of Ceftriaxone should be balanced against the potential advantages of parenteral therapy.
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 morganii,* Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis* 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, 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* and Escherichia coli.*
*Efficacy for this organism in this organ system was studied in fewer than ten infections.
SURGICAL PROPHYLAXIS: The preoperative administration of a single 1 gm dose of Ceftriaxone 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 provides protection from most infections due to susceptible organisms throughout the course of the procedure.
Contraindications
Ceftriaxone Injection, USP is contraindicated in patients with known allergy to the cephalosporin class of antibiotics. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.
Neonates (≤28 days)
Hyperbilirubinemic neonates, especially prematures, should not be treated with Ceftriaxone Injection, USP. In vitro studies have shown that Ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop in these patients.
Ceftriaxone Injection, USP 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 INJECTION, USP 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.
Interaction with Calcium-Containing Products
No data are available on potential interaction between Ceftriaxone and oral calcium-containing products or interaction between intramuscular Ceftriaxone and calcium-containing products (IV or oral).
Do not further dilute Ceftriaxone injection with products containing calcium, such as Ringer’s solution or Hartmann’s solution, because a precipitate can form. Precipitation of Ceftriaxone-calcium 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 Injection, USP, 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 media
No comments:
Post a Comment