CEFTRIAXONE SODIUM- ceftriaxone sodium_injection, powder, for solution

CLINICAL PHARMACOLOGY
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) infusion of a 0. 5, 1 or 2 g dose and intramuscular (IM) administration of a single 0. 5 (250 mg/mL or 350 mg/mL concentrations) or 1 g dose in healthy subjects are presented in Table 1 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 g IV IV doses were infused at a constant rate over 30 minutes. ND = Not determined. 82 59 48 37 29 23 15 10 5 0. 5 g IM 250 mg/mL 22 33 38 35 30 26 16 ND 5 0. 5 g IM 350 mg/mL 20 32 38 34 31 24 16 ND 5 1 g IV 151 111 88 67 53 43 28 18 9 1 g IM 40 68 76 68 56 44 29 ND ND 2 g IV 257 192 154 117 89 74 46 31 15 Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM 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. Ceftriaxone concentrations in urine are shown in Table 2 Table 2 Urinary Concentrations of Ceftriaxone After Single Dose Administration Dose/Route Average Urinary Concentrations (mcg/mL) 0 to 2 hr 2 to 4 hr 4 to 8 hr 8 to 12 hr 12 to 24 hr 24 to 48 hr ND = Not determined. 5 g IV 526 366 142 87 70 15 0. 5 g IM 115 425 308 127 96 28 1 g IV 995 855 293 147 132 32 1 g IM 504 628 418 237 ND ND 2 g 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 g 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/g in the gallbladder wall and 62. 1 mcg/mL in the concurrent plasma. 15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5. 7 hours; apparent volume of distribution from 5. 5 L; plasma clearance from 0. 45 L/hour; and renal clearance from 0. 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 Table 3 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. 3 Plasma Clearance (mL/hr/kg) 49 60 Volume of Distribution (mL/kg) 338 373 CSF Concentrationem dashinflamed meninges (mcg/mL) 5. 4 Range (mcg/mL) 1. 3 to 44 Time after dose (hr) 3. 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 Table 4 Average Pharmacokinetic Parameters of Ceftriaxone in Humans Subject Group Elimination Half-Life Plasma Clearance Volume of Distribution Healthy Subjects 5. 5 Elderly Subjects (mean age, 70. 7 Patients With Renal Impairment Hemodialysis Patients (0 to 5 mL/min) Creatinine clearance. 7 Severe (5 to 15 mL/min) 15. 5 Moderate (16 to 30 mL/min) 11. 8 Mild (31 to 60 mL/min) 12. 3 Patients With Liver Disease 8. 6 The elimination of ceftriaxone is not altered when Ceftriaxone for injection is co-administered with probenecid. Pharmacokinetics in the Middle Ear Fluid: Interaction with Calcium: Microbiology: Mechanism of Action 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 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. Antimicrobial Activity Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE (1) section: Gram-negative bacteria Acinetobacter calcoaceticus Enterobacter aerogenes Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Neisseria meningitidis Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens Gram-positive bacteria Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus pyogenes Viridans group streptococci Anaerobic bacteria Bacteroides fragilis Clostridium species Peptostreptococcus species The following in vitro Gram-negative bacteria Citrobacter diversus Citrobacter freundii Providencia species (including Providencia rettgeri) Salmonella species (including Salmonella typhi) Shigella species Gram-positive bacteria Streptococcus agalactiae Anaerobic bacteria Porphyromonas (Bacteroides) melaninogenicus Prevotella (Bacteroides) bivius 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.
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.

Before instituting treatment with Ceftriaxone for 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 for injection, USP and other antibacterial drugs, Ceftriaxone for 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 for injection, USP is indicated for the treatment of the following infections when caused by susceptible organisms: LOWER RESPIRATORY TRACT INFECTIONS Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis Serratia marcescens. ACUTE BACTERIAL OTITIS MEDIA Streptococcus pneumoniae, Haemophilus influenzae Moraxella catarrhalis NOTE: In one study lower clinical cure rates were observed with a single dose of Ceftriaxone for injection, USP compared to 10 days of oral therapy. In a second study comparable cure rates were observed between single dose Ceftriaxone for injection, USP and the comparator. The potentially lower clinical cure rate of Ceftriaxone for injection, USP should be balanced against the potential advantages of parenteral therapy (see CLINICAL STUDIES SKIN AND SKIN STRUCTURE INFECTIONS Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Morganella morganii,* Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus, Bacteroides fragilis* Peptostreptococcus URINARY TRACT INFECTIONS (complicated and uncomplicated) Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii Klebsiella pneumoniae. UNCOMPLICATED GONORRHEA (cervical/urethral and rectal) Neisseria gonorrhoeae, Neisseria gonorrhoeae. PELVIC INFLAMMATORY DISEASE Neisseria gonorrhoeae. Chlamydia trachomatis Chlamydia trachomatis BACTERIAL SEPTICEMIA Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae Klebsiella pneumoniae. BONE AND JOINT INFECTIONS Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae Enterobacter INTRA-ABDOMINAL INFECTIONS Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis, Clostridium Clostridium difficile Peptostreptococcus MENINGITIS Haemophilus influenzae, Neisseria meningitidis Streptococcus pneumoniae. Staphylococcus epidermidis* Escherichia coli. * * Efficacy for this organism in this organ system was studied in fewer than ten infections.  SURGICAL PROPHYLAXIS: , , When administered prior to surgical procedures for which it is indicated, a single 1 g dose of Ceftriaxone for injection, USP provides protection from most infections due to susceptible organisms throughout the course of the procedure.

Ceftriaxone for injection may be administered intravenously or intramuscularly. Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection 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 for injection 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: CONTRAINDICATIONS Ceftriaxone for injection is contraindicated in neonates (<= 28 days) 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 Intravenous doses should be given over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy. PEDIATRIC PATIENTS: For the treatment of acute bacterial otitis media, a single intramuscular dose of 50 mg/kg (not to exceed 1 g) 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 g. In the treatment of meningitis, it is recommended that the initial therapeutic dose be 100 mg/kg (not to exceed 4 g). Thereafter, a total daily dose of 100 mg/kg/day (not to exceed 4 g 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: If Chlamydia trachomatis 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 g administered intravenously 1/2 to 2 hours before surgery is recommended. Generally, Ceftriaxone for injection 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 No dosage adjustment is necessary for patients with impairment of renal or hepatic function (see PRECAUTIONS The dosages recommended for adults require no modification in elderly patients, up to 2 g per day, provided there is no severe renal and hepatic impairment (see PRECAUTIONS DIRECTIONS FOR USE: COMPATIBILITY AND STABILITY Inject diluent into vial, shake vial thoroughly to form solution. 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 for injection should be injected well within the body of a relatively large muscle; aspiration helps to avoid unintentional injection into a blood vessel. Vial Dosage Size Amount of Diluent to be Added 250 mg/mL 350 mg/mL 250 mg 0. 9 mL - 500 mg 1. 2 mL Intravenous Administration: COMPATIBILITY AND STABILITY Vial Dosage Size Amount of Diluent to be Added 250 mg 2. 4 mL 500 mg 4. 6 mL 2 g 19. 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. COMPATIBILITY AND STABILITY: Ceftriaxone has been shown to be compatible with Flagyl registered registered registered 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. Ceftriaxone for injection 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 for injection sterile powder should be stored at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect 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 for injection intramuscular Storage Diluent Concentration Room Temp. Refrigerated Sterile Water for Injection 100 2 days 10 days 0. 9% Sodium Chloride Solution 100 2 days 10 days 5% Dextrose Solution 100 2 days 10 days Bacteriostatic Water + 0. 9% Benzyl Alcohol 100 24 hours 10 days 1% Lidocaine Solution (without epinephrine) 100 24 hours 10 days Ceftriaxone for injection intravenous Storage Diluent Room Temp. Refrigerated Sterile Water 2 days 10 days 0. 9% Sodium Chloride Solution 2 days 10 days 5% Dextrose Solution 2 days 10 days 10% Dextrose Solution 2 days 10 days 5% Dextrose + 0. 9% Sodium Chloride Solution Data available for 10 to 40 mg/mL concentrations in this diluent in PVC containers only. 2 days Incompatible 5% Dextrose + 0. 45% Sodium Chloride Solution 2 days Incompatible The following intravenous 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 for injection 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 for injection should be thawed at room temperature before use. After thawing, unused portions should be discarded. DO NOT REFREEZE.

Neurological Adverse Reactions
Serious neurological adverse reactions have been reported during postmarketing surveillance with ceftriaxone use. These reactions include encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and non-convulsive status epilepticus (see ADVERSE REACTIONS DOSAGE AND ADMINISTRATION
Hemolytic Anemia
An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including Ceftriaxone for injection. 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.
ADVERSE REACTIONS
Ceftriaxone for injection is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to Ceftriaxone for injection therapy or of uncertain etiology, were observed: LOCAL REACTIONS GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS em dash HYPERSENSITIVITY INFECTIONS AND INFESTATIONS HEMATOLOGIC BLOOD AND LYMPHATIC DISORDERSem dash GASTROINTESTINAL WARNINGS HEPATIC RENAL CENTRAL NERVOUS SYSTEM GENITOURINARY MISCELLANEOUS INVESTIGATIONS 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: 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 for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection 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 for injection 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 GENITOURINARY DERMATOLOGIC en dash HEMATOLOGICAL CHANGES: Isolated cases of agranulocytosis (< 500/mm 3 NEUROLOGIC WARNINGS AND PRECAUTIONS OTHER, Adverse Reactions: symptomatic precipitation of ceftriaxone calcium salt in the gallbladder, kernicterus, oliguria, and anaphylactic or anaphylactoid 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: Altered Laboratory Tests: PRECAUTIONS Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION.
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: Altered Laboratory Tests: PRECAUTIONS Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced (see DOSAGE AND ADMINISTRATION

CONTRAINDICATIONS
Ceftriaxone for injection is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone (see WARNINGS en dash Hypersensitivity Premature neonates Hyperbilirubinemic neonates Ceftriaxone for injection is contraindicated in neonates (<= 28 days) 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 DOSAGE AND ADMINISTRATION 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 for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. There have been no similar reports in patients other than neonates. Intravenous administration of ceftriaxone solutions containing lidocaine is contraindicated. When lidocaine solution is used as a solvent with ceftriaxone for intramuscular injection, exclude all contraindications to lidocaine. Refer to the prescribing information of lidocaine.
Hypersensitivity
Ceftriaxone for injection is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone (see WARNINGS en dash Hypersensitivity
Neonates Requiring Calcium Containing IV Solutions
Ceftriaxone for injection is contraindicated in neonates (<= 28 days) 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 DOSAGE AND ADMINISTRATION 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 for injection and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both Ceftriaxone for injection and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. There have been no similar reports in patients other than neonates.
Lidocaine
Intravenous administration of ceftriaxone solutions containing lidocaine is contraindicated. When lidocaine solution is used as a solvent with ceftriaxone for intramuscular injection, exclude all contraindications to lidocaine. Refer to the prescribing information of lidocaine.

Premature neonates Hyperbilirubinemic neonates

Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection 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 for injection 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 CLINICAL PHARMACOLOGY CONTRAINDICATIONS DOSAGE AND ADMINISTRATION

WARNINGS
Before therapy with Ceftriaxone for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other beta-lactam agents or other drugs. This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients. Antibacterial drugs 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 all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions (i. , anaphylaxis) have been reported. In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated. Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Ceftriaxone for injection vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Ceftriaxone for injection is mixed with calcium-containing solutions in the same IV administration line. Ceftriaxone for injection 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 for injection 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 CLINICAL PHARMACOLOGY CONTRAINDICATIONS DOSAGE AND ADMINISTRATION Serious neurological adverse reactions have been reported during postmarketing surveillance with ceftriaxone use. These reactions include encephalopathy (disturbance of consciousness including somnolence, lethargy, and confusion), seizures, myoclonus, and non-convulsive status epilepticus (see ADVERSE REACTIONS DOSAGE AND ADMINISTRATION Clostridium difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including Ceftriaxone for injection. 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.
Carcinogenesis,Mutagenesis, Impairment of Fertility:
Carcinogenesis: Mutagenesis: in vitro Impairment of Fertility:.
OVERDOSAGE
Ceftriaxone overdosage has been reported in patients with severe renal impairment. Reactions have included neurological outcomes, including encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus. In the event of overdosage, discontinue Ceftriaxone for Injection therapy and provide general supportive treatment (see DOSAGE AND ADMINISTRATION WARNINGS PRECAUTIONS In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic.
CLINICAL STUDIES
Clinical Trials in Pediatric Patients With Acute Bacterial Otitis Media: Table 7 Clinical Efficacy in Pediatric Patients with Acute Bacterial Otitis Media Clinical Efficacy in Evaluable Population Study Day Ceftriaxone Single Dose Comparator en dash 95% Statistical Study 1 en dash US amoxicillin/clavulanate 14 74% (220/296) 82% (247/302) (-14.4%, -0.5%) Ceftriaxone is lower than control at study day 14 and 28. Study 2 - US TMP-SMZ 14 54% (113/210) 60% (124/206) (-16.4%, 3.6%) Ceftriaxone is equivalent to control at study day 14 and 28. 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: Table 8 Bacteriologic Eradication Rates by Pathogen Study Day Study Day Organism No. No. No. No. Streptococcus pneumoniae 38 32 (84) 35 25 (71) Haemophilus influenzae 33 28 (85) 31 22 (71) Moraxella catarrhalis 15 12 (80) 15 9 (60)

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CEFTRIAXONE SODIUM- ceftriaxone sodium_injection, powder, for solution Product manual source documgent