Elores

Ceftriaxone sodium, sulbactam sodium.

ELORES is a novel antibiotic adjuvant entity (AAE) to combat antimicrobial resistance caused by multidrug resistance ESBL/MBL producing strains comprising of a third generation cephalosporin Ceftriaxone Sodium a beta lactam antibiotic, Sulbactam Sodium an irreversible β-lactamase inhibitor along with non antibiotic adjuvant Disodium Edetate for intravenous administration.
Ceftriaxone sodium is a third generation broad-spectrum cephalosporin with molecular formula C₁₈H₁₆N₈Na₂O₇S₃·3.5H₂O. It has a calculated molecular weight of 661.59 and contains 83 mg sodium per gram.
Sulbactam sodium is a derivative of basic penicillin nucleus. It is an irreversible β-lactamase inhibitor. Chemically it is Sodium penicillinate sulfone, chemical formula is C₈H₁₀NNaO₅S with a molecular weight of 255.22. It contains 92 mg sodium per gram.
Disodium Edetate is Sodium salt of Ethylene Diamine Tetra Acetate is a non antibiotic adjuvant entity. The chemical formula is C₁₀H₁₄N₂Na₂O₈·2H₂O and the molecular weight 372.24. It contains 114 microgram Sodium per milligram. Edetate is a cell membrane permeability enhancer, chelating agent, antioxidant and acts as a catalyst.
ELORES available in 1.5 g strength as a white to off-white sterile, dry powder consisting of Ceftriaxone Sodium/Disodium Edetate/Sulbactam Sodium packaged in tubular glass vials. The product does not contain any preservative and is for single use only. It is administered as intravenous injection. Each single dose 1.5 g vial of ELORES contains Ceftriaxone Sodium Ph. Eur. equivalent to Ceftriaxone 1000 mg, Sulbactam Sodium Ph. Eur. equivalent to Sulbactam 500 mg, Disodium Edetate Ph. Eur. 37 mg.

Pharmacology: Pharmacodynamics: Mechanism of Action: Ceftriaxone in ELORES acts by inhibiting the mucopeptide synthesis in the bacterial cell wall. The β-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, ceftriaxone causes the formation of defective cell walls resulting in cell death.
Disodium Edetate is a non-antibiotic adjuvant entity and membrane permeability enhancer, chelator with a high affinity for calcium, zinc & other divalent ions. It does not have antimicrobial property of its own but acts as a potentiator and makes ceftriaxone sulbactam combo effective in Metallo-beta-lactamase (MBL) and other ESBL strains (TEM, SHV, AMP-C, CTX-M). It alters the porosity of bacterial cell membrane and enhances the penetration of ceftriaxone and sulbactam. It also inhibits Efflux pump by altering genes expression responsible for OMPs expression. Due to its chelation property it chelates divalent ions of lipopolysaccharide layer and makes biofilm porous and thus breaks existing biofilm and prevents biofilm formation.
Sulbactam sodium is a β-lactamase inhibitor with weak antibacterial action. Sulbactam is an irreversible inhibitor of β-lactamase; it binds the enzyme and does not allow it to interact with the antibiotic, thus extending their spectrum activity. It has maximum activity against CTX-M type of class A β-lactamases, which is the most common β-lactamases of this class. It has also got moderate activity against other class A β-lactamases including TEM & SHV. It does not induce the production of AmpC type class C beta lactamases.
ELORES, a novel antibiotic adjuvant entity comprising Ceftriaxone, Sulbactam & Disodium edetate powder for solution for injection/Infusion is a synergistic antimicrobial antibiotic adjuvant entity with marked in-vitro antibacterial activity against a broad spectrum of ESBL producing microorganisms. Presence of Disodium Edetate synergizes the activity of ceftriaxone and sulbactam as it helps in opening porin channels and allows more drug to enter periplasmic space resulting in enhanced killing. ELORES alters the membrane potential, resulting in disturbing ATP balance required for efflux pump activity and hence is effective in bacterial strains where efflux is overactive such as in P. aeruginosa and E.coli.
Clinical Studies: An open label, randomized, comparative, Phase III study conducted to compare the efficacy and safety of ELORES with ceftriaxone in patients with various bacterial infections like Lower respiratory tract infection, Urinary tract infection, Skin and Skin Structure Infection, Otitis Media, Bone and Joint infection, Bacterial septicemia and Surgical prophylaxis in 654 patients.
Study drugs: ELORES 3 g (ceftriaxone 2000 mg with sulbactam 1000 mg and disodium edetate 74 mg) or monotherapy with Ceftriaxone, given IV, once daily, (n = 654).
The clinical cure, treatment failures and bacteriological response of ELORES and Ceftriaxone were as follows, (see Figures 1 and 2.)

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ELORES 3 g is safe and effective option in the treatment of various ESBL/MBL resistant bacteriological infections.
PK-PD Correlation: The pharmacodynamic effect of ceftriaxone depends on the time above which plasma concentration remains above MIC. Whereas, as per the reported data on Time kill curve (TKC) and beta lactamase inhibition potential of beta lactamase inhibitors (BLI), the plasma concentration of BLI above MIC is required only up to 90 minutes, and the inhibition is maintained up to the time, the plasma concentration of beta lactam antibiotic is maintained above MIC to a maximum of 8 to 12 hrs. Based on 30 min infusion pharmacokinetic data of ELORES in human volunteers, 60 min and 90 min infusion PK data are simulated based on In-house software. It is evident from simulations that compared to 30 min and 60 min infusion, 90 minutes infusion will maintain the required Sulbactam concentration for more time. Hence, 90 min infusion regimen could be preferred for ELORES in case of treating infections where the clinical isolate exhibit intermediate sensitivity.
Pharmacokinetics: Absorption: ELORES is to be administered intravenously.
Following intravenous administration, peak serum concentrations of Ceftriaxone and Sulbactam are seen after 30 minutes. The maximum plasma conc of Ceftriaxone after a single IV dose of 1.5 g is about 148.762 µg/ml (SD ± 14.826) and is reached 0.563 hours (SD ± 0.1 69) after the dose, while that of Sulbactam sodium is 19.287 (SD ± 5.685 µg/ml) and is reached approximately 0.521 hour (SD ± 0.102) in healthy volunteers after the dose.
Distribution: Ceftriaxone distributes well in various compartments include extravascular spaces, tissue fluid, synovial fluid of inflamed joints and also passes the placental barrier. The volume of distribution of Ceftriaxone sodium is 7-12 L and Sulbactam is 18-27.6 L. Ceftriaxone is reversibly bound to albumin. The binding is 95% at plasma concentrations less than 100 mg/l with the binding percentage decreasing as the concentration increases (to 85 % at ceftriaxone plasma concentrations of 300 µg/ml). The ceftriaxone is distributed in 5.2 hours approximately in blood stream, while sulbactam reaches its half life in 0.94 hours. Sulbactam has been found to be approximately 38% reversibly bound to human serum protein.
Metabolism: Ceftriaxone does not undergo systemic metabolism but it is broken down in the small intestine by bacterial action.
Disodium Edetate molecule is not metabolized in the body, it thus passes very rapidly into the urine carrying its metallic ion with it. Disodium Edetate molecule leave the body intact.
Sulbactam is not metabolised, but is excreted primarily in the urine (glomerular filtration and tubular secretion) with a small amount being recovered in bile and faeces.
Elimination: Over 1.5 to 3 g dose range, the values of elimination half-life range from 6 to 9 hours, total plasma clearance from 0.6-1.4 l/h and renal clearance from 0.3-0.7 l/h.
Approximately 50-60 % of ceftriaxone and 70-80% of Sulbactam is eliminated as an unchanged active substance in the urine whilst the remainder is excreted via the bile into the faeces as microbiologically inactive metabolites.
ELORES concentrates in the urine arc 5-10 times higher than those found in the plasma.
ELORES cannot be removed by dialysis. This applies to both haemodialysis and peritoneal dialysis.
Urinary excretion is via glomerular filtration. No tubular secretion takes place. For this reason, no increase in the serum levels is to be expected in coincident administration of probenecid and is actually - even at higher dosage e.g. with 1-2 g probenecid - not found. (See Table 1.)

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Microbiology: ELORES, the combination of Ceftriaxone sodium, Sulbactam sodium and Disodium Edetate is active against wide range of Gram-positive and Gram-negative aerobic ESBL pathogens, carbapenemase producing (MBL), efflux overexpressed and biofilm producing pathogens. ELORES exhibits synergistic activity against TEM, SHV, Amp C, VIM, IMP, KPC, NDM-1, Van A, Mec A, AcrAB, and Tol C genes expressing strains.
Gram-negative aerobes: Acinetobacter spp⁴, Enterobacter spp.³, Neisseria meningitidis*, Citrobacter koseri¹, Escherichia coli*^1,4, Haemophilus influenzae*, Haemophilus parainfluenzae*, Klebsiella pneumoniae*^1,4, Klebsiella oxytoca*^1,4, Moraxella catarrhalis*, Morganella morganii¹, Proteus mirabilis^*1, Proteus vulgaris¹, Providencia spp.¹, Salmonella spp.¹, Serratia spp.¹ , Shigella spp., Neisseria gonorrhoeae, Pseudomonas spp².
Gram-positive aerobes: Staphylococcus aureus* (MSSA), Streptococcus agalactiae, Streptococcus bovis, Streptococcus pyogenes*, Streptococcus pneumoniae*.
Elores exhibits mild to moderate activity against species with acquired resistance.
Gram-positive aerobes: Staphylococcus epidermidis^* (MSSE).
Gram-negative aerobes: Enterobacter spp.^1,3, Citrobacter freundii¹.
Inherently resistant species: Gram-positive aerobes: Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes, Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE).
Gram-positive anaerobes: Clostridium difficile, Peptococcus niger, Peptostreptococcus spp.
Gram-negative aerobes: Achromobacter spp., Aeromonas spp., Alcaligenes spp., Flavobacterium spp., Legionella gormanii.
Gram-negative anaerobes: Bacteroides spp.
Others: Chlamydia spp., Chlamydophila spp., Mycobacterium spp., Mycoplasma spp., Rickettsia spp., Ureaplasma urealyticum.
*Clinical efficacy has been demonstrated for ESBL producing resistant and susceptible isolates species with natural intermediate susceptibility to carbapenems.
1. Some strains produce inducible or stably derepressed chromosomally-encoded cephalosporinases and ESBLs (extended spectrum beta-lactamases) and thus are clinically resistant to cephalosporins.
2. In suspected or proven Pseudomonas infection with NDM-1.
3. Clinical efficacy has been demonstrated for susceptible isolates of Enterobacter cloacae and Enterobacter aerogenes in approved clinical indications.
4. KPC and/or MBL producing strains found resistant to carbapenems.
Susceptibility testing methods: As is recommended with all antimicrobials, the results of in vitro susceptibility tests, when available, should be provided to the physician as a periodic reports, which describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Techniques: Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure.
Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of Ceftriaxone Sodium, Disodium Edetate, Sulbactam sodium powders. MIC values should be determined using serial dilutions of ceftriaxone sodium, sulbactam sodium combined with disodium edetate. MIC interpretive criteria is based on a dosage regimen of 1.5 g ELORES every 24 hrs.
Diffusion technique: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations.
This procedure uses paper disks impregnated with 30 µg of Ceftriaxone and 15 µg of Sulbactam and 10 µg of disodium edetate to test the susceptibility of microorganisms to ELORES. The disk diffusion interpreted criteria are provided in Table 2. (See Table 2.)

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A report of Susceptible (S) indicates that the pathogen is likely to respond to therapy. A report of Intermediate (I) indicates that the organism would be susceptible if the infection were confined to tissues and fluids (e.g., urine), in which high antibiotic levels were attained. A report of Resistant (R) suggests that the pathogen is not likely to respond to the therapy.

Mono-Therapy: ELORES (Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) is indicated for the treatment of the following infections when caused by susceptible organisms, which could include ESBL/MBL producing multidrug resistant pathogens: Lower Respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter aerogenes, Proteus mirabilis or Serratia marcescens, Pseudomonas aeruginosa, A. baumanii.
Urinary Tract Infections caused by Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii or Klebsiella pneumoniae, E. faecalis, A. baumanii, P. aeruginosa.
Acute bacterial septicemia caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Staphylococcus albus, Haemophilus influenzae or Klebsiella pneumoniae, A. baumanii, P. aeruginosa.
Infections of bones and joints caused by Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Citrobacter spp, Klebsiella pneumoniae or Enterobacter species, P. aeruginosa, A. baumanii.
Infections of skin and Soft-tissue 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, P. aeruginosa.
Chronic suppurative otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis, Klebsiella pneumoniae, A. baumanii, P. aeruginosa, Staphylococcus aureus.
Surgical prophylaxis: Reduce the incidence of postoperative infections in patients undergoing surgical procedures classified as contaminated or potentially contaminated.
Combination Therapy: Because of broad spectrum of activity of Ceftriaxone sodium, Sulbactam sodium, and Disodium edetate, most infections can be treated adequately with ELORES alone. However, in some cases ELORES may be combined with other antibiotics like vancomycin, amsacrine, aminoglycosides, and fluconazole. 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, as they are physically incompatible with ELORES in admixtures. If an aminoglycoside is used renal function should be monitored during the course of therapy (see use in Renal Dysfunction under Precautions).
Culture sensitivity studies should be performed to identify the causative organism and their susceptibility tests to ELORES.
ELORES is useful as presumptive therapy in the indicated conditions prior to the identification of causative organisms because of its broad spectrum bactericidal activity against gram-positive and gram-negative aerobic and anaerobic organisms. Clinical trials demonstrated that ELORES is effective against ESB/MBL producing Gram-negative and gram positive pathogens. The decision to continue therapy with the drug should be based on results of susceptibility tests, the severity of infection, the response of the patient, and the important additional considerations contained in the Warnings section.

Mode of administration: ELORES (Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) is to be administered intravenously after reconstitution, over a period of 30 minutes. The PK-PD simulation study done for ELORES on 30, 60 and 90 min infusions recommends 90 minutes infusion regimen for better clinical response in case of clinical isolate exhibiting intermediate sensitivity.
Diluents containing calcium (e.g. Ringer's solution or Hartmann's solution) must not be used to reconstitute ELORES 1.5 g/vial powder for infusion or to further dilute a reconstituted vial for IV administration because precipitates can form at higher calcium concentration. Therefore, ELORES and calcium-containing solutions must not be mixed or administered simultaneously.
Dosage and rate of administration should be determined by the severity of the infection, susceptibility of the causative organism and the patient's condition.
Adults (18 years and above): The usual adult daily dose is 1.5 g to 3 g every 24 hours or in two divided doses, which could be increased as per severity of infection (in severe septicemic cases) to a maximum dosage of 6 g per day in divided doses.
The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of ELORES should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or evidence of bacterial eradication has been obtained.
Elderly: These dosages do not require modification in elderly patients provided that renal and hepatic functions are satisfactory (see below).
Renal and hepatic impairment: In patients with impaired renal function, there is no need to reduce the dosage of ELORES. Only in cases of pre-terminal renal failure (creatinine clearance <10 ml per minute) should the daily dosage be limited to 3 g or less.
In patients with liver damage there is no need for the dosage to be reduced provided renal function is intact.
In severe renal impairment accompanied by hepatic insufficiency, the plasma concentration of ELORES should be determined at regular intervals and dosage adjusted.
In patients undergoing dialysis, no additional supplementary dosing is required following the dialysis. Serum concentrations should be monitored, however, to determine whether dosage adjustments are necessary, since the elimination rate in these patients may be reduced.
Duration of Therapy: The usual duration of ELORES treatment is from 5 to 14 days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress.

In the case of overdose, nausea, vomiting and diarrhoea can occur. Ceftriaxone/disodium edetate/sulbactam concentration cannot be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic. The drug is safe up to 6 g/day.

ELORES is contraindicated in patients with known hypersensitivity to β-lactam antibiotics. In patients hypersensitive to penicillin, the possibility of allergic cross-reactions should be borne in mind. Elores 1.5 g strength is not recommended for patients below 18 years specially Hyperbilirubinaemic newborns and preterm newborns should not be treated with ceftriaxone-Sulbactam powder for infusion. 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, though studies with Ceftriaxone have proved improved safety with significantly lesser encephalopathy. But, as a precautionary measure ELORES should be avoided or taken with extra caution.

Hypersensitivity: As with other cephalosporins, anaphylactic reactions with fatal outcome were also reported, even if a patient is not known to be allergic or previously exposed.
Before therapy with Elores is instituted, careful inquiry should be made to determine whether the patient has had any previous hypersensitivity reactions to Ceftriaxone, any other Cephalosporin, or to any Penicillin or other β-lactam drug. This product should be given cutaneously to test Penicillin-sensitive patients or to any patients who have demonstrated some form of allergy. If an allergic reaction occurs, Elores should be discontinued and the appropriate therapy instituted.
Interaction with Calcium-Containing Products: In patients other than neonates, ELORES and calcium-containing solutions may be administered sequentially to one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. Diluents containing calcium, such as Ringer's solution or Hartmann's solution, are not to be used to reconstitute ELORES vials or to further dilute a reconstituted vial for intravenous administration because a precipitate can form. ELORES must not be administered simultaneously with calcium-containing intravenous solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site because precipitation of ceftriaxone-calcium can occur.
Pseudomembranous colitis has been reported with the use of cephalosporins (and other broad spectrum antibiotics), therefore it is important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use. As per the published in-vivo data on ELORES in animal model of C. difficile induced Pseudomembranous colitis, it does not induce colitis, as ELORES neutralizes the toxin produced by C. difficile, still it is advised to be cautious in low immunity patients.
Hemolytic Anemia: An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials. 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 Elores is stopped until the etiology is determined.

Drug interactions: No impairment of renal function has so far been observed after concurrent administration of large doses of Elores and potent diuretics (e.g. Furosemide).
No interference with the action or increase in nephrotoxicity of aminoglycosides has been observed during simultaneous administration with Ceftriaxone/disodium edetate/ sulbactam powder for infusion. Probenecid decreases the renal tubular secretion of sulbactam. Concurrent use of probenecid with ELORES may result in increased and prolonged blood levels of sulbactam.
In an in-vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone. The clinical relevance of this finding is unknown, but caution is advised if concurrent administration of ceftriaxone with chloramphenicol is proposed.
In patients treated with Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion, the Coombs' test may rarely become false-positive. Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion, like other antibiotics, may result in false-positive tests for galactosaemia. Likewise, non-enzymatic methods for glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with Elores should be done enzymatically.
Ceftriaxone may adversely affect the efficacy of oral hormonal contraceptives. Consequently, it is advisable to use supplementary (non-hormonal) contraceptive measures during treatment and in the month following treatment.
Effects on ability to drive and use machines: Since ceftriaxone sometimes induces dizziness the ability to drive and use machines can be impaired with Elores.
Carcinogenesis, mutagenesis, Impairment of fertility: Long-term studies in animals have not been performed to evaluate carcinogenic or mutagenic potential. Ceftriaxone produced no impairment in fertility when given intravenously to rats at daily doses up to 586 mg/kg/day, approximately 20 times the recommended dose of 3 g/day of Elores.
Use in Pregnancy: Pregnancy Category B. For Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion, limited clinical data on Elores exposed pregnancies are available. Ceftriaxone crosses the placental barrier. Reproductive studies in animals have shown no evidence of embryotoxicity, foetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed. Since safety in human pregnancy is not established, Elores should be used with caution.
Use in Lactation: Low concentrations of ceftriaxone and sulbactam are excreted in the milk; therefore, caution should be exercised when ELORES is administered to a nursing woman.
Use in Elderly: The pharmacokinetics of Elores were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with Elores dosages up to 3 g/day.

Pregnancy: Pregnancy Category B. For Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion, limited clinical data on Elores exposed pregnancies are available. Ceftriaxone crosses the placental barrier. Reproductive studies in animals have shown no evidence of embryotoxicity, foetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed. Since safety in human pregnancy is not established, Elores should be used with caution.
Lactating women/Nursing mother: Low concentrations of ceftriaxone and sulbactam are excreted in the milk; therefore, caution should be exercised when ELORES is administered to a nursing woman.

Postmarketing experience: In phase III clinical trial and post marketing surveillance study, few adverse events were observed of which details are given below: Summary of safety profile: There were no serious adverse event observed in the studies conducted so far on Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion. In these studies, the most common adverse effect following administration of Ceftriaxone sodium, Sulbactam sodium, and Disodium edetate are pain at the site of injection, nausea, vomiting, headache, and dizziness. These adverse events were related to ceftriaxone/sulbactam.
Description of selected adverse reactions: Out of the above adverse events, pain at site of injection was most common adverse event observed during the trial. This adverse event was of mild to moderate intensity and last for 2 to 3 days after the intravenous administration of Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion.
Frequently reported adverse events: Elores is generally well tolerated. Other frequently reported adverse events related to ceftriaxone/sulbactam which were considered to be related to Cephalosporin therapy or of uncertain etiology, may occur.
Local reactions: Pain, induration and tenderness was 1% overall. Phlebitis was reported in < 1% after IV administration.
Hypersensitivity: Rash (1.7%). Less frequently reported (<1% ) were pruritus, fever or chills.
Hematologic: Eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently reported (<1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and prolongation of the prothrombin time.
Gastrointestinal: Diarrhea (2.7%). Less frequently reported (<1%) were nausea or vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment.
Hepatic: Elevations of SGOT (3.1%) or SGPT (3.3%). Less frequently reported (<1%) were elevations of alkaline phosphatase and bilirubin.
Renal: Elevations of the BUN (1.2%). Less frequently reported (<1%) were elevations of creatinine and the presence of casts in the urine.
Central nervous system: Headache or dizziness were reported occasionally (<1%).
Genitourinary: Moniliasis or vaginitis were reported occasionally (<1%).
Miscellaneous: Diaphoresis and flushing were reported occasionally (<1%).
Other rarely observed adverse reactions (<0.1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness.

Incompatibility and Stability: Solutions containing Ceftriaxone sodium, Sulbactam sodium, and Disodium edetate should not be mixed with or added to solutions containing other agents. In particular, diluents containing calcium, (e.g. Ringer's solution, Hartmann's solution) should not be used to reconstitute Ceftriaxone sodium, Sulbactam sodium, and Disodium edetate vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Ceftriaxone sodium, Sulbactam sodium, and Disodium edetate must not be mixed or administered simultaneously with calcium-containing solutions. Based on literature reports, Ceftriaxone/disodium edetate/sulbactam is not compatible with amsacrine, fluconazole, and labetalol. When any of these drugs are to be administered concomitantly with ceftriaxone by intermittent intravenous infusion, it is recommended that they must be given sequentially, with thorough flushing of the intravenous lines (with one of the compatible fluids) between the administrations.
Compatible Reconstitution Diluents: ELORES has been shown to be compatible with following infusion solutions at given concentrations, however, reducing drug concentrations increase the stability. (See Table 3.)

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The use of freshly prepared solutions is recommended. Protect from direct sun light.
Reconstitution: Reconstitute ELORES (Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) with the 10 ml WFI or any of the solvents defined above and agitate the vial gently until the powder dissolves completely and administer immediately. Though the reconstituted solution is stable up to >16 hrs at 25°C ( except 10% Dextrose) and up to >24 hrs under 2°C-8°C, however it is advisable to use the solution immediately after reconstitution.
The color of solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.
Instructions for use: The procedures below are provided as general guidelines for the reconstitution and administration of ELORES.
Always work on a clean surface and wash the hands before performing the following procedures.
Reconstitution, product administration and handling of the administration set must be done with caution.
Reconstitution procedure: Reconstitute ELORES (Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) with the 10 ml WFI or any of the solvents mentioned above.
1. Bring the ELORES (powder) and diluent (sterile Water for Injection, etc) to room temperature if refrigerated.
2. Remove caps from the ELORES and diluent vials to expose the center part of the rubber stopper.
3. Use an alcohol swab to cleanse the metal ring and rubber stopper, allow it to dry before use. Place each vial on a flat surface.
4. Remove outer wrapping from one syringe.
5. Uncover & do not touch the needle.
6. Pull the syringe plunger back until its tip is at the proper mark.
7. Place the diluent vial on a clean, flat surface and push the needle through the center of the rubber stopper on the bottle. Push the plunger all the way in to inject air into the bottle.
8. Keep the needle in the bottle containing diluent. Lift the bottle and tum it straight upside down. Check to see that the needle tip is in the liquid.
9. With the needle tip in the liquid, slowly pull back the plunger until syringe fills to the proper mark. If any bubbles appear in the syringe, remove them by pushing the plunger up slowly.
10. Transfer the diluent (10 ml WFI for 1.5 g vial or 20 ml for 3 g vial) from the needle to the vial containing ELORES powder.
11. Agitate the vial gently until the powder dissolves completely.
12. Withdraw all of the dissolved solution from the powder vial into the syringe and then inject in an infusion bag. Mix the solution, DO NOT USE if it has particles in it.
13. Administer the solution via intravenous route. Cleanse the injection site with a new alcohol swab prior to administration.
Handling Disposal: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration when ever the solution and container permit. Any unused product or waste material should be disposed of in accordance with local requirements.

ELORES (Ceftriaxone/Sulbactam 1.5 g/Vial Powder for Solution for Injection/Infusion) is to be stored below 30°C. Protect from direct sunlight.
Shelf-life: 24 months.

Cephalosporins

J01DD63 - ceftriaxone and beta-lactamase inhibitor ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

POM

Powd for soln for inj/infusion (white to off-white sterile, crystalline in vial) 1.5 g x 1's.