Ceftriaxone by is a Prescription medication manufactured, distributed, or labeled by Samson Medical Technologies, LLC. Drug facts, warnings, and ingredients follow.
PHARMACY BULK PACKAGE - NOT FOR DIRECT INFUSION |
To reduce the development of drug-resistant bacteria and maintain the effectiveness of ceftriaxone and other antibacterial drugs, ceftriaxone should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (12.4)
Ceftriaxone for Injection, USP is a cephalosporin antibacterial indicated for the treatment of the following infections caused by susceptible isolates of the designated bacteria: Lower Respiratory Tract Infections (1.1); Skin and Skin Structure Infections (1.2); Complicated and Uncomplicated Urinary Tract Infections (1.3); Pelvic Inflammatory Disease (1.4); Bacterial Septicemia (1.5); Bone and Joint infections (1.6); Intra-abdominal Infections (1.7); Meningitis (1.8); and Surgical Prophylaxis (1.9).
For intravenous use only over approximately 30 minutes. (2)
THIS IS A PHARMACY BULK PACKAGE – NOT FOR DIRECT INJECTION.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of ceftriaxone (2.1).
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Recommended Dosing Schedule for Ceftriaxone for Injection, USP | |||
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Site and Type of Infection | Dose | Frequency | Total Daily Dose |
Usual Adult Dose | 1 to 2 grams | Once a day or in equally divided doses every 12 hours | Should not exceed 4 grams* |
Surgical prophylaxis | 1 gram I.V. once | ½ to 2 hours before surgery | |
Meningitis | 100 mg per kg | Once a day or in equally divided doses every 12 hours | Should not exceed 4 grams* |
Skin and Skin Structure Infections | 50 mg per kg to 75 mg per kg | Once a day or in equally divided doses every 12 hours | Should not exceed 2 grams |
Serious Infections other than Meningitis | 50 mg per kg to 75 mg per kg | Every 12 hours | Should not exceed 2 grams |
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof. Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of ceftriaxone. (2.1)
The most common adverse reactions occurring in >2% of patients receiving ceftriaxone include diarrhea, eosinophilia, thrombocytosis, leukopenia, and elevations of SGOT and SGPT. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Samson Medical Technologies, L.L.C. at 1-877-418-3600 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 12/2019
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 for Injection is indicated for the treatment of the following infections when caused by susceptible bacteria:
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.
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 morganii1, Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis1 or Peptostreptococcus species.
Complicated and uncomplicated urinary tract infections caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae.
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 or Peptostreptococcus species.
Meningitis caused by Haemophilus influenzae, Neisseria meningitidis or Streptococcus pneumoniae. Ceftriaxone sodium has also been used successfully in a limited number of cases of meningitis and shunt infection caused by Staphylococcus epidermidis and Escherichia coli; however, the efficacy for these organisms in this organ system were studied in fewer than ten infections.
The preoperative administration of a single 1 gram 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 sodium 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 antibacterial in the prevention of infection following coronary artery bypass surgery.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of Ceftriaxone.
THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION WITH STERILE WATER FOR INJECTION, USP TO A CONCENTRATION OF 100 mg per mL AND FURTHER DILUTION IN 50 mL OF A COMPATIBLE SOLUTION.
THIS IS A PHARMACY BULK PACKAGE – NOT FOR DIRECT INJECTION |
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USE THIS FORMULATION OF CEFTRIAXONE ONLY IN PATIENTS WHO REQUIRE A 1 GRAM DOSE.
Ceftriaxone for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone for Injection USP Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of Ceftriaxone.
Ceftriaxone for Injection should be reconstituted with Sterile Water for Injection, USP to a concentration of 100 mg per mL and further diluted in 50 mL of a compatible solution.
The recommended adult dosages are outlined in Table 1. Ceftriaxone for Injection, USP, Pharmacy Bulk Package SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone should be administered intravenously (I.V.) over approximately 30 minutes.
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.
Site and Type of Infection | Dose | Frequency | Total Daily Dose |
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Usual Adult Dose | 1 gram to 2 grams | Once a day or in equally divided doses every 12 hours | Should not exceed 4 grams* |
Surgical prophylaxis | 1 gram I.V. once | ½ to 2 hours before surgery | |
Skin and Skin Structure Infections | 50 to 75 mg per kg | Once a day or in equally divided doses every 12 hours | Should not exceed 2 grams |
Meningitis | 100 mg per kg | Once a day or in equally divided doses every 12 hours | Should not exceed 4 grams* |
Serious Infections other than Meningitis | 50 to 75 mg per kg | Every 12 hours | Should not exceed 2 grams |
*Patients with hepatic impairment and significant renal impairment should not receive more than 2 grams per day of ceftriaxone. **This formulation of Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of ceftriaxone. |
To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the adult 1 gram dose of ceftriaxone. [see Use in Specific Populations (8.4)]
Ceftriaxone for Injection, USP Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone for Injection USP, Pharmacy Bulk Package SmartPak® bag should not be used in patients who require less than the 1 gram dose of ceftriaxone.
Directions for Proper Use of a Pharmacy Bulk Package
INSTRUCTION FOR RECONSTITUTION OF THE PHARMACY BULK PACKAGE BAG SmartPak®
The entire contents of the bag and the preparation process (reconstitution and dilution) should be completed within 4 hours of initial entry.
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Table 2: Reconstitution Table | ||
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SmartPak® Bag Size | Amount of Sterile Water* | Approximate Concentration |
100 grams | 950 mL | 100 mg/mL (1 g/10 mL) |
It should be noted that the spike placed into the transfer port of the Pharmacy Bulk Package SmartPak® is NEVER removed during this procedure and that the reconstitution port is self-sealing.
Dilution
Important Administration Instructions
Ceftriaxone for Injection, USP is contraindicated in patients who have a history of anaphylaxis to ceftriaxone or the cephalosporin class of antibacterials, penicillins, or other beta-lactam antibacterials [see Warnings and Precautions (5.1)].
Serious, occasionally fatal, hypersensitivity (anaphylactic) reactions have been reported with ceftriaxone. Before therapy with Ceftriaxone for Injection, USP is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to ceftriaxone, cephalosporins, penicillins, or other drugs. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterials has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Ceftriaxone for Injection, USP occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures including oxygen, corticosteroids, intravenous fluids, intravenous antihistamines, pressor amines, and airway management, as clinically indicated.
Precipitation of ceftriaxone-calcium can occur when Ceftriaxone for Injection, USP is mixed with calcium-containing solutions in the same intravenous administration line. Ceftriaxone for Injection must not be administered simultaneously with calcium-containing intravenous solutions, including continuous calcium-containing infusions, such as parenteral nutrition via a Y-site. However, in patients other than neonates, Ceftriaxone for Injection, USP and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with 0.9% Sodium Chloride Injection or D5W. 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 Drug Interactions (7.2)]
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 antibacterial 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
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 for Injection, USP, the diagnosis of a cephalosporin-associated anemia should be considered and Ceftriaxone for Injection, USP stopped until the etiology is determined.
There have been reports of sonographic abnormalities in the gallbladder of patients treated with ceftriaxone sodium; 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 sodium 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.
Hepatic Impairment: In patients with both hepatic and significant renal disease, Ceftriaxone for Injection dosage should not exceed 2 grams daily.
Renal Impairment: This formulation of Ceftriaxone for Injection USP – Pharmacy Bulk Package bags SmartPak® should not be used in renally impaired patients who require less than the 1 gram dose of ceftriaxone. In patients with both hepatic impairment and significant renal disease, Ceftriaxone for Injection dosage should not exceed 2 grams per day.
Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients treated with ceftriaxone sodium. 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.
Prescribing Ceftriaxone for Injection, USP 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. As with other antibacterial drugs, use of Ceftriaxone for Injection may result in overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Alterations in prothrombin times have occurred in patients treated with ceftriaxone sodium. 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 for Injection treatment. Vitamin K administration (10 mg weekly) may be necessary if the prothrombin time is prolonged before or during therapy.
The following serious adverse reactions to ceftriaxone are described below and elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following reactions occurred in ≤ 6% of the patients:
The following adverse reactions have been reported during postapproval use of ceftriaxone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to readily estimate their frequency or establish a causal relationship to drug exposure.
Cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis) have been reported.
Anaphylaxis (including anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia) has been reported.
In addition to the adverse reactions listed above that have been observed in patients treated with ceftriaxone, the following adverse reactions and altered laboratory tests have been reported for cephalosporin-class antibacterials:
Vancomycin, amsacrine, aminoglycosides, and fluconazole are physically incompatible with ceftriaxone in admixtures [see Dosage and Administration (2.3)].
Precipitation of ceftriaxone-calcium can occur when Ceftriaxone for Injection is mixed with calcium-containing solutions in the same intravenous administration line. Ceftriaxone for Injection, USP must not be administered simultaneously with calcium-containing intravenous solutions. Ceftriaxone for Injection and calcium-containing solutions can be administered sequentially [see Warnings and Precautions (5.2)]
Reproductive studies have been performed in mice, rats, and primates at intravenous doses of 625, 586, and 84 mg/kg/day, respectively without evidence of embryotoxicity, fetotoxicity, or teratogenicity. These doses are approximately 1.5, 2.8, and 0.8 times the recommended clinical dose of 2 grams/day based on body surface area comparisons.
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.
Ceftriaxone was tested in a Segment III (pre-postnatal) study in rats at intravenous doses of up to 586 mg/kg/day approximately 2.8 times (mg/m2 comparison) the recommended daily dose of 2 grams/day. No adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior, and reproductive ability of the offspring.
Ceftriaxone is excreted in human breast milk. Caution should be exercised when Ceftriaxone for Injection is administered to a nursing woman.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag, SmartPak® should not be used in pediatric patients who require less than the 1 gram dose of ceftriaxone. To prevent unintentional overdose, this product should not be used in pediatric patients who require less than the adult 1 gram dose of ceftriaxone.
Of the total number of subjects in clinical studies of ceftriaxone sodium, 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.
Ceftriaxone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
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 (12)].
Ceftriaxone for Injection, USP, Pharmacy Bulk Package bag SmartPak® should be used only in patients who require a 1 gram dose and not any fraction thereof.
Ceftriaxone for Injection USP, Pharmacy Bulk Package bag SmartPak® should not be used in patients who require less than the 1 gram dose of ceftriaxone.
Ceftriaxone for Injection, USP, is a sterile, semisynthetic, broad-spectrum cephalosporin antibacterial 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 C18H16N8Na2O7S33.5H2O. It has a calculated molecular weight of 661.60 and the following structural formula:
Ceftriaxone sodium is a white to yellowish-orange crystalline powder, which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of ceftriaxone sodium solutions ranges from light yellow to amber, depending on the length of storage and concentration. Each Pharmacy Bulk Package contains approximately 83 mg (3.6 mEq) of sodium per 1 gram of ceftriaxone activity. Ceftriaxone for Injection, USP is supplied in 100 grams SmartPak® Pharmacy Bulk Packages bags equivalent. Each SmartPak® Pharmacy Bulk Package bag contains ceftriaxone sodium, USP equivalent to 100 grams of ceftriaxone.
BEFORE ADMINISTRATION, THIS PHARMACY BULK PACKAGE REQUIRES RECONSTITUTION USING STERILE WATER FOR INJECTION, USP TO A CONCENTRATION OF 100 mg per mL AND FURTHER DILUTION IN 50 mL OF A COMPATIBLE SOLUTION AND INFUSED INTRAVENOUSLY OVER 30 MINUTES.
THIS PRODUCT IS NOT INTENDED TO BE USED IN PEDIATRIC PATIENTS AND RENALLY IMPAIRED PATIENTS WHO REQUIRE LESS THAN A 1 GRAM DOSE.
A Pharmacy Bulk Package is a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture service and are restricted to the preparation of admixtures for intravenous infusion.
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (I.V.) infusion of a 0.5, 1 or 2 g dose in healthy subjects are presented in Table 3. Multiple intravenous doses ranging from 0.5 to 2 g at 12- to 24-hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.
TABLE 3: Ceftriaxone Plasma Concentrations After Single Dose Administration
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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 gram I.V.* | 82 | 59 | 48 | 37 | 29 | 23 | 15 | 10 | 5 |
1 gram I.V.* | 151 | 111 | 88 | 67 | 53 | 43 | 28 | 18 | 9 |
2 grams I.V.* | 257 | 192 | 154 | 117 | 89 | 74 | 46 | 31 | 15 |
Over a 0.15 to 3 g dose range in healthy adult subjects, the mean elimination half-life ranged from 5.8 to 8.7 hours, plasma clearance ranged from 0.58 to 1.45 L/hour, and renal clearance ranged from 0.32 to 0.73 L/hour.
Ceftriaxone is reversibly bound to human plasma proteins and the binding of ceftriaxone decreases with increasing concentration from a value of 95% at plasma concentrations less than 25 mcg/mL to 85% at plasma concentration of 300 mcg/mL. Over a 0.15 to 3 g dose range in healthy adult subjects, the apparent volume of distribution ranged from 5.8 to 13.5 L.
Ceftriaxone crosses the blood placenta barrier.
Ceftriaxone penetrates the inflamed meninges of infants and pediatric patients. The average values of maximum plasma concentration, cerebrospinal fluid (CSF) concentrations, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg intravenous dose and after a 75 mg/kg intravenous dose in pediatric patients suffering from bacterial meningitis are shown in Table 4.
TABLE 4: Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients with Meningitis
50 mg/kg I.V. | 75 mg/kg I.V. | |
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) |
After a 1 gram intravenous 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/gram in the gallbladder wall compared to a corresponding concentration of 62.1 mcg/mL in plasma.
Ceftriaxone concentrations in urine are shown in Table 5.
TABLE 5: Urinary Concentrations of Ceftriaxone After Single Dose Administration
Average Urinary Concentrations (mcg/mL) | ||||||
Dose/Route | 0-2 hr | 2-4 hr | 4-8 hr | 8-12 hr | 12-24 hr | 24-48 hr |
0.5 gram I.V. | 526 | 366 | 142 | 87 | 70 | 15 |
1 gram I.V. | 995 | 855 | 293 | 147 | 132 | 32 |
2 grams I.V. | 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.
The elimination of ceftriaxone is not altered by probenecid.
Average pharmacokinetic parameters of ceftriaxone in healthy subjects, elderly subjects, subjects with renal impairment, and subjects with liver disease are summarized in Table 6. Compared to healthy adult subjects, the pharmacokinetics of ceftriaxone were only minimally altered in elderly subjects and in patients with renal or hepatic impairment; therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2 grams 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, suggesting that plasma concentrations of ceftriaxone should be monitored in these patients to determine if dosage adjustments are necessary [see Dosage and Administration (2.1) and Warnings and Precautions (5.6)].
TABLE 6: Average Pharmacokinetic Parameters of Ceftriaxone in Humans
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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 |
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.
Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
Resistance to ceftriaxone is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.
Interaction with Other Antimicrobials
In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone.
Antibacterial Activity
Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections described in the INDICATIONS AND USAGE (1) section.
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftriaxone. However, the efficacy of ceftriaxone in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC
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 test method. 1,3 . The MIC values should be interpreted according to the criteria provided in Table 7.
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 2,3 This procedure uses paper disks impregnated with 30 mcg ceftriaxone to test the susceptibility of microorganisms to ceftriaxone. The disk diffusion interpretive criteria are provided in Table 7.
For anaerobic bacteria, the susceptibility to ceftriaxone as MICs can be determined by a standardized agar test method.3,4 The MIC values obtained should be interpreted according to the criteria provided in Table 7.
Table 7: Susceptibility Test Interpretive Criteria for Ceftriaxone
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Pathogen | Minimum Inhibitory Concentrations (mcg/mL) | Disk Diffusion Zone Diameters (mm) |
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S Susceptible |
I Intermediate |
R Resistant |
S Susceptible |
I Intermediate |
R Resistant |
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Enterobacteriaceae* | ≤ 1 | 2 | ≥ 4 | ≥ 23 | 20-22 | ≤ 19 |
Haemophilus influenzae†‡ | ≤ 2 | - | - | ≥ 26 | - | - |
Neisseria gonorrhoeae‡ | ≤ 0.25 | - | - | ≥ 35 | - | - |
Neisseria meningitidis‡ | ≤ 0.12 | - | - | ≥ 34 | - | - |
Streptococcus pneumoniae§ meningitis isolates | ≤ 0.5 | 1 | ≥ 2 | - | - | - |
Streptococcus pneumoniae§ non-meningitis isolates | ≤ 1 | 2 | ≥ 4 | - | - | - |
Streptococcus species beta-hemolytic group‡ | ≤ 0.5 | - | - | ≥ 24 | - | - |
Viridans group streptococci | ≤ 1 | 2 | ≥ 4 | ≥ 27 | 25-26 | ≤ 24 |
Anaerobic bacteria (agar method) | ≤ 1 | 2 | ≥ 4 | - | - | - |
Susceptibility of staphylococci to ceftriaxone may be deduced from testing only penicillin and either cefoxitin or oxacillin. |
A report of Susceptible indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration at the site of infection. A report of Intermediate indicates that the result 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 a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test 1,2,3,4. Standard ceftriaxone powder should provide the following range of MIC values noted in Table 8. For the diffusion technique using the 30 mcg disk, the criteria in Table 8 should be achieved.
Table 8: Acceptable Quality Control Ranges for Ceftriaxone
QC Strain |
Minimum Inhibitory Concentrations | Disk Diffusion Zone Diameters (mm) |
Escherichia coli ATCC 25922 | 0.03 – 0.12 | 29 – 35 |
Staphylococcus aureus ATCC 25923 | - | 22 – 28 |
Staphylococcus aureus ATCC 29213 | 1 – 8 | - |
Haemophilus influenzae ATCC 49247 | 0.06 – 0.25 | 31 – 39 |
Neisseria gonorrhoeae ATCC 49226 | 0.004 – 0.015 | 39 – 51 |
Pseudomonas aeruginosa ATCC 27853 | 8 – 64 | 17 – 23 |
Streptococcus pneumoniae ATCC 49619 | 0.03 – 0.12 | 30 – 35 |
Bacteroides fragilis ATCC 25285 (agar method) | 32 – 128 | - |
Bacteroides thetaiotaomicron ATCC 29741 (agar method) | 64 – 256 | - |
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.
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).
Ceftriaxone for Injection, USP is available in the following SmartPak® Pharmacy Bulk Package bags:
100 grams* One Pharmacy Bulk Package bag Product No. 6100 NDC: 66288-6100-1.
*Each 100 gram Pharmacy Bulk Package bag contains sterile ceftriaxone sodium equivalent to 100 grams of ceftriaxone
SmartPak® system components are not made with natural rubber latex.
Precautions
As with other cephalosporins, reconstituted Ceftriaxone for Injection tends to darken depending on storage conditions within the stated recommendations. However, product potency is not adversely affected.
Use only if prepared solution is clear and free from particulate matter.
Storage Conditions
Prior to reconstitution, store Ceftriaxone for Injection sterile powder at room temperature 20º-25ºC (68º-77ºF) [see USP Controlled Room Temperature] and protected from light.
Patients should be advised that allergic reactions, including serious allergic reactions could occur and that serious reactions require immediate treatment and discontinuation of ceftriaxone. Patients should report to their health care provider any previous allergic reactions to ceftriaxone, cephalosporins, penicillins, or other similar antibacterials.
Advise patients of neurological adverse reactions that could occur with Ceftriaxone for Injection, USP use. Instruct patients to inform a healthcare provider at once of any neurological signs and symptoms, including encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures, for immediate treatment, dosage adjustment, or discontinuation of Ceftriaxone for Injection, USP.
Patients should be advised that diarrhea is a common problem caused by antibacterials, which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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 antibacterial. If this occurs, patients should contact a physician as soon as possible.
Patients should be counseled that antibacterial drugs including ceftriaxone, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Ceftriaxone for Injection, USP 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 or other antibacterial drugs in the future.
Rx only
SmartPak is a registered trademark of Samson Medical Technologies, L.L.C.
C6100c
Manufactured for
SAMSON
MEDICAL TECHNOLOGIES L.L.C.
Cherry Hill, NJ 08003, USA
by
ACS Dobfar S.p.A.
20067 Tribiano (Milano) Italy
NDC 66288-6100-1 SMARxTPAK
CEFTRIAXONE FOR INJECTION, USP
PHARMACY BULK PACKAGE -
NOT FOR DIRECT INFUSION
100 grams [ONE HUNDRED GRAMS] per Pharmacy Bulk Package Bag
FOR INTRAVENOUS USE ONLY
NOT TO BE DISPENSED AS A UNIT
Rx Only
Sterile, Nonpyrogenic, Preservative-Free
Each 100 gram Pharmacy Bulk Package contains sterile ceftriaxone sodium equivalent to 100 grams of ceftriaxone. The sodium content is 83 mg (3.6 mEq) per gram of ceftriaxone activity.
Use this formulation only in patients who require a 1 gram dose. Contains 100 doses (1 gram per dose). See package insert. USUAL DOSAGE: See package insert.
Prior to reconstitution, store dry powder at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature] Protect from light. After reconstitution, dilute and use promptly. DISCARD BAG WITHIN 4 HOURS AFTER INITIAL ENTRY. See package insert for full information.
THIS PHARMACY BULK PACKAGE IS INTENDED FOR PREPARING MANY SINGLE DOSES IN A PHARMACY ADMIXTURE PROGRAM.
Approximate Concentration | Amount of Sterile Water for Injection |
1 gram/10 mL | 950 mL |
See package insert for detailed reconstitution, final dilution, and administration instructions.
PROTECT FROM LIGHT. THE INNER BAG SHOULD BE RETAINED IN THE OUTER BAG UNTIL TIME OF USE.
SmartPak® system components are not made with natural rubber latex.
Manufactured for
SAMSON
MEDICAL TECHNOLOGIES L.L.C.
Cherry Hill, NJ 08003,
Date entered | |
Time of entry | |
Discard within 4 hours |
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CEFTRIAXONE
ceftriaxone sodium injection, powder, for solution |
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Labeler - Samson Medical Technologies, LLC (102837429) |