For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Ceftriaxone & Sulbactam for Injection IP

JB Zone SB*
Composition: Ceftriaxone Treatment
Indications
Each combipack contains: Dosage* frequency**

(A) Ceftriaxone & Sulbactam for Injection Community acquired pneumonia

Each vial contains: Acute exacerbations of chronic obstructive pulmonary disease
1-2g Oncedaily
Sterile Ceftriaxone Sodium IP Intra-abdominal infections
Equivalent to Complicate durinary tract infections (including pyelonephritis)
Anhydrous Ceftriaxone........................ 1000 mg Hospital acquired pneumonia
Sterile Sulbactam Sodium IP 2g Oncedaily Complicated skin and soft tissue infections
Equivalent to Infections of bones and joints
Anhydrous Sulbactam........................... 500 mg Management of neutropenic patients with fever that is suspected to be due
(B) Sterile water for injections IP 10 ml to a bacterial infection
2-4g Oncedaily
Bacterial endocarditis
Dosage Form and Strength
Bacterial meningitis
Dry powder for reconstitution
* In documented bacteraemia, the higher end of the recommended dose range should be considered.
Therapeutic Indications ** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.
JB Zone SB is indicated in the treatment of the following infections in adults and children including Indications for neonates, infants and children 15 days to 12 years (< 50 kg) that require specific dosage schedules:
term neonates (from birth): Acute otitis media
Bacterial Meningitis For initial treatment of acute otitis media, a single intramuscular dose of ceftriaxone 50 mg/kg
Community acquired pneumonia can be given. Limited data suggest that in cases where the child is severely ill or initial therapy
Hospital acquired pneumonia has failed, ceftriaxone may be effective when given as an intramuscular dose of 50 mg/kg daily
Acute otitis media for 3 days.
Intra-abdominal infections Pre-operative prophylaxis of surgical site infections
Complicated urinary tract infections (including pyelonephritis) 50-80 mg/kg as a single pre-operative dose.
Infections of bones and joints Syphilis
Complicated skin and soft tissue infections The generally recommended doses are 75-100 mg/kg (max 4 g) once daily for 10-14 days. The dose
recommendations in syphilis, including neurosyphilis, are based on very limited data. National or
Gonorrhoea
local guidance should be taken into consideration.
Syphilis
Disseminated Lyme borreliosis (early [Stage II] and late [Stage III])
Bacterial endocarditis
50–80 mg/kg once daily for 14-21 days. The recommended treatment durations vary and national
Posology and Method of Administration or local guidelines should be taken into consideration.
The dose depends on the severity, susceptibility, site and type of infection and on the age and Neonates 0-14 days
hepato-renal function of the patient. Ceftriaxone is contraindicated in premature neonates up to a postmenstrual age of 41 weeks
The doses recommended in the tables below are the generally recommended doses in these (gestational age + chronological age).
Indications. In particularly severe cases, doses at the higher end of the recommended range should
be considered. Ceftriaxone Treatment
Indications
Dosage* frequency**
Adults and children over 12 years of age (≥ 50 kg) Community acquired pneumonia
Acute exacerbations of chronic obstructive pulmonary disease
Ceftriaxone Treatment 1-2g Oncedaily
Indications Intra-abdominal infections
Dosage* frequency**
Complicate durinary tract infections (including pyelonephritis)
Community acquired pneumonia
Hospital acquired pneumonia
Acute exacerbations of chronic obstructive pulmonary disease
2g Oncedaily Complicated skin and soft tissue infections
1-2g Oncedaily
Intra-abdominal infections Infections of bones and joints
Management of neutropenic patients with fever that is suspected to be due
Complicate durinary tract infections (including pyelonephritis)
to a bacterial infection
Hospital acquired pneumonia 2-4g Oncedaily
Bacterial endocarditis

2g Oncedaily Complicated skin and soft tissue infections Bacterial meningitis

*In documented bacteraemia, the higher end of the recommended dose range should be considered.
Infections of bones and joints
A maximum daily dose of 50 mg/kg should not be exceeded.
Management of neutropenic patients with fever that is suspected to be due Indications for neonates 0-14 days that require specific dosage schedules:
to a bacterial infection
Acute otitis media
2-4g Oncedaily
Bacterial endocarditis For initial treatment of acute otitis media, a single intramuscular dose of ceftriaxone 50 mg/kg can
Bacterial meningitis be given.
Pre-operative prophylaxis of surgical site infections
* In documented bacteraemia, the higher end of the recommended dose range should be considered. 20-50 mg/kg as a single pre-operative dose.
** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.
Syphilis
Indications for adults and children over 12 years of age (≥ 50 kg) that require specific dosage The generally recommended dose is 50 mg/kg once daily for 10-14 days. The dose recommendations
schedules: in syphilis, including neurosyphilis, are based on very limited data. National or local guidance
should be taken into consideration.
Acute otitis media
Duration of therapy
A single intramuscular dose of ceftriaxone 1-2 g can be given. Limited data suggest that in cases
where the patient is severely ill or previous therapy has failed, ceftriaxone may be effective when The duration of therapy varies according to the course of the disease. As with antibiotic therapy in
given as an intramuscular dose of 1-2 g daily for 3 days. general, administration of ceftriaxone should be continued for 48 - 72 hours after the patient has
become a febrile or evidence of bacterial eradication has been achieved.
Pre-operative prophylaxis of surgical site infections
Older people
2 g as a single pre-operative dose.
The dosages recommended for adults require no modification in older people provided that renal
Gonorrhoea
and hepatic function is satisfactory.
500 mg as a single intramuscular dose.
Patients with hepatic impairment
Syphilis
Available data do not indicate the need for dose adjustment in mild or moderate liver function
The generally recommended doses are 500 mg - 1g once daily increased to 2g once daily for Impairment provided renal function is not impaired.
neurosyphilis for 10-14days. The dose recommendations in syphilis, including neurosyphilis, are
There are no study data in patients with severe hepatic impairment.
based on limited data. National or local guidance should be taken into consideration.
Patients with renal impairment:
Disseminated Lyme borreliosis (early [Stage II] and late [Stage III])
In patients with impaired renal function, there is no need to reduce the dosage of ceftriaxone
2g once daily for 14-21 days. The recommended treatment durations vary and national or local
provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine
guidelines should be taken into consideration.
clearance < 10 ml/min) should the ceftriaxone dosage not exceed 2 g daily.
Paediatric population
In patients undergoing dialysis no additional supplementary dosing is required following the
Neonates, infants and children 15 days to 12 years of age (< 50 kg) dialysis.
For children with body weight of 50 kg or more, the usual adult dosage should be given. Ceftriaxone is not removed by peritoneal or haemodialysis. Close clinical monitoring for safety
and efficacy is advised.
Patients with severe hepatic and renal impairment
In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and
efficacy is advised.
Method of Administration If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may
Intramuscular administration need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation,
antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
1.5 g ceftriaxone and sulbactam for injection should be dissolved in 3.6ml Sterilewater for injections
IP. Thesolution should be administered by deep intramuscular injection. Hemolytic Anemia
Intramuscular injections should be injected well within the bulk of a relatively large muscle and not An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin
more than 1 g should be injected at one site. class antibacterial including ceftriaxone. Severe cases of hemolytic anemia, including fatalities,
have been reported during treatment in both adults and children. If a patient develops anemia
Dosages greater than 1g should be divided and injected at more than one site.
while on ceftriaxone, the diagnosis of a cephalosporin associated anemia should be considered and
As the solvent used is lidocaine, the resulting solution should never be administered intravenously. ceftriaxone stopped until the etiology is determined.
Intravenous administration
Precautions
For IV injection 1.5 g ceftriaxone and sulbactam for Injection is dissolved in 9.6ml of Sterilewater
for injections IP. The injection should be administered over 5 minutes, directly into the vein or via Development of Drug-resistant Bacteria
the tubing of an intravenous infusion. Prescribing ceftriaxone in the absence of a proven or strongly suspected bacterial infection or a
Ceftriaxone can be administered by intravenous infusion over at least 30 minutes (preferred route) prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the
or by slow intravenous injection over 5 minutes. Intravenous intermittent injection should be given development of drug-resistant bacteria. Prolonged use of ceftriaxone may result in overgrowth of
over 5 minutes preferably in larger veins. Intravenous doses of 50 mg/kg or more in infants and non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs
children up to 12 years of age should be given by infusion. In neonates, intravenous doses should during therapy, appropriate measures should be taken.
be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy. Intramuscular Patients with Renal or Hepatic Impairment
administration should be considered when the intravenous route is not possible or less appropriate Ceftriaxone is excreted via both biliary and renal excretion. Therefore, patients with renal failure
for the patient. For doses, greater than 2 g intravenous administration should be used. normally require no adjustment in dosage when usual doses of ceftriaxone are administered.
Ceftriaxone is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in
treatment with calcium containing intravenous solutions, including continuous calcium-containing patients with both hepatic dysfunction and significant renal disease, caution should be exercised
infusions such as parenteral nutrition, because of the risk of precipitation of ceftriaxone-calcium. and the ceftriaxone dosage should not exceed 2 g daily.
Diluents containing calcium, (e.g. Ringer&#39;s solution or Hartmann &#39;s solution), Ceftriaxone is not removed by peritoneal or hemodialysis. In patients undergoing dialysis no
should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for additional supplementary dosing is required following the dialysis. In patients with both severe
IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.
occur when ceftriaxone is mixed with calcium-containing solutions in the same IV administration
line. Therefore, ceftriaxone and calcium-containing solutions must not be mixed or administered Effect on Prothrombin Time
simultaneously. Alterations in prothrombin times have occurred in patients treated with ceftriaxone. Monitor
For pre-operative prophylaxis of surgical site infections, ceftriaxone should be administered 30-90 prothrombin time during ceftriaxone treatment in patients with impaired vitamin K synthesis or low
minutes prior to surgery. vitamin K stores (e.g., chronic hepatic disease and malnutrition). Vitamin K administration (10 mg
weekly) may be necessary if the prothrombin time is prolonged before or during therapy.
Contraindications Concomitant use of ceftriaxone with Vitamin K antagonists may increase the risk of bleeding.
Hypersensitivity Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted
Ceftriaxone is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its accordingly, both during and after treatment with ceftriaxone.
excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to Gallbladder Pseudolithiasis
penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to
Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving
ceftriaxone.
ceftriaxone. These precipitates appear on sonography as an echo without acoustical shadowing
Neonates suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as
Premature neonates: Ceftriaxone is contraindicated in premature neonates up to a postmenstrual age gallstones. The probability of such precipitates appears to be greatest in pediatric patients. Patients
of 41 weeks (gestational age + chronological age). may be asymptomatic or may develop symptoms of gallbladder disease. The condition appears to be
Hyperbilirubinemic neonates: Hyperbilirubinemic neonates should not be treated with ceftriaxone. reversible upon discontinuation of ceftriaxone sodium and institution of conservative management.
Ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a risk of bilirubin Discontinue ceftriaxone sodium in patients who develop signs and symptoms suggestive of
encephalopathy in these patients. gallbladder disease and/or the sonographic findings described above.
Neonates Requiring Calcium Containing IV Solutions Urolithiasis and Post-Renal Acute Renal Failure
Ceftriaxone is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) Ceftriaxone-calcium precipitates in the urinary tract have been observed in patients receiving
treatment with calcium-containing IV solutions, including continuous calcium-containing infusions ceftriaxone and may be detected as sonographic abnormalities. The probability of such precipitates
such as parenteral nutrition because of the risk of precipitation of ceftriaxone-calcium. appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop
Cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at symptoms of urolithiasis, and ureteral obstruction and post-renal acute renal failure. The condition
autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In appears to be reversible upon discontinuation of ceftriaxone sodium and institution of appropriate
some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium management. Ensure adequate hydration in patients receiving ceftriaxone. Discontinue ceftriaxone
containing fluids and in some a precipitate was observed in the intravenous infusion line. There in patients who develop signs and symptoms suggestive of urolithiasis, oliguria or renal failure and/
have been no similar reports in patients other than neonates. or the sonographic findings described above.
Lidocaine Pancreatitis
Intravenous administration of ceftriaxone solutions containing lidocaine is contraindicated. When Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients
lidocaine solution is used as a solvent with ceftriaxone for intramuscular injection, exclude all treated with ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary
contraindications to lidocaine. sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of
ceftriaxone related biliary precipitation cannot be ruled out.
Special Warnings and Preautions for Use
Drug Interactions
Hypersensitivity Reactions
Calcium-containing diluents, such as Ringer&#39;s solution or Hartmann&#39;s solution, should
Before therapy with ceftriaxone is instituted, careful inquiry should be made to determine whether not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for intravenous
the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other administration because a precipitate can form.
betalactam agents or other drugs. This product should be given cautiously to penicillin and other
Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with
betalactam agent-sensitive patients. Antibacterial drugs should be administered with caution
calciumcontaining solutions in the same intravenous administration line.
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 Ceftriaxone must not be administered simultaneously with calcium-containing intravenous
measures. solutions, including continuous calcium-containing infusions such as parenteral nutrition via a
Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions
be administered sequentially of one another if the infusion lines are thoroughly flushed between
(i.e., anaphylaxis) have been reported. In case of severe hypersensitivity reactions, treatment with
infusions with a compatible fluid.
ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated.
In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that
Interaction with Calcium-Containing Products neonates have an increased risk of precipitation of ceftriaxone-calcium.
Do not use diluents containing calcium, such as Ringer&#39;s solution or Hartmann&#39;s Concomitant use with oral anticoagulants may increase the anti-vitamin K effect and the risk of
solution, to reconstitute ceftriaxone bottles or to further dilute a reconstituted bottle for IV bleeding. It is recommended that the International Normalised Ratio (INR) is monitored frequently
administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur and the posology of the anti-vitamin K drug adjusted accordingly, both during and after treatment
when ceftriaxone is mixed with calcium containing solutions in the same IV administration line. with ceftriaxone.
Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, There is conflicting evidence regarding a potential increase in renal toxicity of aminoglycosides
including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. when used with cephalosporins. The recommended monitoring of aminoglycoside levels (and renal
However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be function) in clinical practice should be closely adhered to in such cases.
administered sequentially of one another if the infusion lines are thoroughly flushed between In an in-vitro study antagonistic effects have been observed with the combination of chloramphenicol
infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical and ceftriaxone. The clinical relevance of this finding is unknown.
cord blood demonstrated that neonates have an increased risk of precipitation of plasma from There have been no reports of an interaction between ceftriaxone and oral calcium-containing
umbilical cord blood demonstrated that neonates have an increased risk of precipitation of products or interaction between intramuscular ceftriaxone and calcium-containing products
ceftriaxone-calcium. (intravenous or oral). In patients treated with ceftriaxone, the Coombs&#39; test may lead to
Clostridium difficile - Associated Diarrhea falsepositive test results.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all Ceftriaxone, like other antibiotics, may result in false-positive tests for galactosaemia.
antibacterial agents, including ceftriaxone, and may range in severity from mild diarrhea to Likewise, non-enzymatic methods for glucose determination in urine may yield false-positive
fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to results.
overgrowth of C. difficile.
For this reason, glucose level determination in urine during therapy with ceftriaxone should be
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin carried out enzymatically.
producing strains of C. difficile cause increased morbidity and mortality, as these infections can be
No impairment of renal function has been observed after concurrent administration of large doses
refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all
of ceftriaxone and potent diuretics (e.g. furosemide).
patients who present with diarrhea following antibiotic use. Careful medical history is necessary
since CDAD has been reported to occur over two months after the administration of antibacterial Simultaneous administration of probenecid does not reduce the elimination of ceftriaxone.
agents.
Use in Special Populations Cephalosporin Class Adverse Reactions
Pregnancy: In addition to the adverse reactions listed above which have been observed in patients treated with
Teratogenic Effects: Pregnancy Category B. Reproductive studies have been performed in mice ceftriaxone, the following adverse reactions and altered laboratory test results have been reported
and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, for cephalosporin class antibiotics:
fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at Adverse Reactions: Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction,
a dose approximately 3 times the human dose. toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis,
There are, however, no adequate and well-controlled studies in pregnant women. Because animal a plastic anemia, hemorrhage, and superinfection.
reproductive studies are not always predictive of human response, this drug should be used during Altered Laboratory Tests: Positive direct Coombs&#39; test, false-positive test for urinary glucose,
pregnancy only if clearly needed. and elevated LDH.
Nonteratogenic Effects: In rats, in the Segment I (fertility and general reproduction) and Segment Several cephalosporins have been implicated in triggering seizures, particularly in patients with
III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur,
were noted on various reproductive parameters during gestation and lactation, including postnatal the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.
growth, functional behavior and reproductive ability of the offspring, at doses of 586 mg/kg/day Reporting of suspected adverse reactions:
or less. Reporting suspected adverse reactions after authorisation of the medicine is important. It allows
Nursing Mothers: continued monitoring of the benefit/risk balance of the medicine. Kindly report any suspected
Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when adverse reactions to [email protected]
ceftriaxone is administered to a nursing woman. Overdose
Pediatric Use: In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal
Safety and effectiveness of ceftriaxone in neonates, infants and pediatric patients have been dialysis. There is no specific antidote. Treatment of over dosage should be symptomatic.
established for the dosages. In vitro studies have shown that ceftriaxone, like some other
cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone should not be administered Pharmacological Properties
to hyperbilirubinemic neonates, especially premature. Pharmacodynamics
Geriatric Use: Mechanism of Action
Of the total number of subjects in clinical studies of ceftriaxone, 32% were 60 and over. No overall Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone
differences in safety or effectiveness were observed between these subjects and younger subjects, has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of
and other reported clinical experience has not identified differences in responses between the Gram-negative and Gram-positive bacteria.
elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Sulbactam, a penicillanic acid sulfone with beta lactamase inhibitory properties has weak
The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared antibacterial activity but is an irreversible inhibitor of many plasmid mediated and some
to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with chromosomal beta lactamase. It has similar spectrum of beta lactamase inhibition to clavulanic
ceftriaxone dosages up to 2 grams per day provided there is no severe renal and hepatic impairment. acid, although it is less potent. It enhances the activity of penicillins and cephalosporins.
Effects on Ability to Drive and Use Machines Mechanism of Resistance
During treatment with ceftriaxone, undesirable effects may occur (e.g. dizziness), which may Resistance to ceftriaxone is primarily through hydrolysis by beta-lactamase, alteration of penicillin
influence the ability to drive and use machines. Patients should be cautious when driving or binding proteins (PBPs), and decreased permeability.
operating machinery.
Interaction with Other Antimicrobials
Undesirable Effects In an in vitro study, antagonistic effects have been observed with the combination of chloramphenicol
JB Zone SB is generally well tolerated. In clinical trials, the following adverse reactions, which and ceftriaxone.
were considered to be related to ceftriaxone therapy or of uncertain etiology, were observed: Antibacterial Activity
Local reactions: Pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in
after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM vitro and in clinical infections:
administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL. Gram-negative bacteria
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site pain Acinetobacter calcoaceticus
(0.6%). Enterobacter aerogenes
Hypersensitivity: Rash (1.7%). Less frequently reported (<1%) were pruritus, fever or chills. Enterobacter cloacae
Infections and infestations: Genital fungal infection (0.1%). Escherichia coli
Haemophilus influenzae
Hematologic: Eosinophilia (6%), thrombocytosis (5.1%) and leukopenia (2.1%). Less frequently
Haemophilusparainfluenzae
reported (<1%) were anemia, hemolytic anemia, neutropenia, lymphopenia, thrombocytopenia and
Klebsiella oxytoca
prolongation of the prothrombin time.
Klebsiella pneumoniae
Blood and lymphatic disorders: Granulocytopenia (0.9%), coagulopathy (0.4%). Moraxella catarrhalis
Gastrointestinal: Diarrhea/loose stools (2.7%). Less frequently reported (<1%) were nausea or Morganella morganii
vomiting, and dysgeusia. The onset of pseudomembranous colitis symptoms may occur during or Neisseria gonorrhoeae
after antibacterial treatment. Neisseria meningitidis
Hepatic: Elevations of aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) Proteus mirabilis
(3.3%). Less frequently reported (<1%) were elevations of alkaline phosphatase and bilirubin. Proteus vulgaris
Renal: Elevations of the BUN (1.2%). Less frequently reported (<1%) were elevations of creatinine Pseudomonas aeruginosa
and the presence of casts in the urine. Serratia marcescens
Central nervous system: Headache or dizziness were reported occasionally (<1%). Gram-positive bacteria
Staphylococcus aureus
Genitourinary: moniliasis or vaginitis were reported occasionally (<1%).
Staphylococcus epidermidis
Miscellaneous: Diaphoresis and flushing were reported occasionally (<1%). Streptococcus pneumoniae
Investigations: Blood creatinine increased (0.6%). Streptococcus pyogenes
Other rarely observed adverse reactions (<0.1%) include abdominal pain, agranulocytosis, allergic Viridans group streptococci
pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, Anaerobic bacteria
flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, Bacteroides fragilis
monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, Clostridium species
seizures, and serum sickness. Peptostreptococcus species
Postmarketing Experience: In addition to the adverse reactions reported during clinical trials, The following in vitro data are available, but their clinical significance is unknown. At least 90
the following adverse experiences have been reported during clinical practice in patients treated percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration
with ceftriaxone. Data are generally insufficient to allow an estimate of incidence or to establish (MIC) less than or equal to the susceptible break point for ceftriaxone. However, the efficacy of
causation. ceftriaxone in treating clinical infections due to these microorganisms has not beenestablished in
A small number of cases of fatal outcomes in which a crystalline material was observed in the adequate and well controlled clinical trials.
lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium- Gram-negative bacteria
containing fluids. In some of these cases, the same intravenous infusion line was used for both Citrobacter diversus
ceftriaxone and calcium containing fluids and in some a precipitate was observed in the intravenous Citrobacter freundii
infusion line. At least one fatality has been reported in a neonate in whom ceftriaxone and calcium- Providencia species (including Providencia rettgeri)
containing fluids were administered at different time points via different intravenous lines; no Salmonella species (including Salmonella typhi)
crystalline material was observed at autopsy in this neonate. There have been no similar reports in Shigella species
patients other than neonates. Gram-positive bacteria
Gastrointestinal: Pancreatitis, stomatitis and glossitis. Streptococcus agalactiae
Genitourinary: Oliguria, ureteric obstruction, post-renal acute renal failure. Anaerobic bacteria
Dermatologic: Exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous Porphyromonas (Bacteroides) melaninogenicus
pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Prevotella (Bacteroides) bivius
Stevens-Johnson syndrome or syndrome/toxic epidermal necrolysis) have beenreported.
Hematological changes: Isolated cases of agranulocytosis (< 500/mm) have been reported, most of
them after 10 days of treatment and following total doses of 20 g or more.
Nervous system disorders: Convulsion
Other Adverse Reactions: symptomatic precipitation of ceftriaxone calcium salt in the gallbladder,
kernicterus, oliguria, and anaphylactic or anaphylactoid reactions.
Pharmacokinetics Properties After a 30-minute infusion of 500 mg of sulbactam, a peak serum concentration of approximately
Average plasma concentrations of ceftriaxone following a single 30-minute intravenous (IV) 20 μg/ml was obtained; 1,000 mg produced a peak of 43μg/ml. The half - life for elimination
infusion of a 0.5, 1 or 2 g dose and intramuscular (IM) administration of a single 0.5 (250 mg/mL or was about 1.0 hour. The data were interpreted as a two-compartment pharmacokinetic model. The
350 mg/mL concentrations) or 1 g dose in healthy subjects are presented in Table. results are compatible with IV infusion followed by moderate rates of distribution into and out
of the peripheral compartment (k = 0.9 h-1; k21= 1.8 h-1) and a moderate elimination rate (k10
Dose/Route Average Plasma Concentrations (mcg/mL) = 1.4 h-1). The apparent volume of distribution for the central compartment (serum and rapidly
0.5 hr 1 hr 2 hr 4 hr 6 hr 8 hr 12 hr 16 hr 24 hr equilibrating tissues) was between 9 and 16 liters, and the total apparent volume of distribution was
between 19 and 28 liters.
0.5 g IV* 82 59 48 37 29 23 15 10 5
Approximately 51% of the drug was in the central compartment in the post-distributive phase.
0.5 g IM 250 mg/mL 22 33 38 35 30 26 16 ND 5 Calculated steady-state serum concentration were proportional to dose. These pharmacokinetic
0.5 g IM 350 mg/mL 20 32 38 34 31 24 16 ND 5 parameters are very close to those of amoxicillin for which the following parameters have been
reported: t1/2 = 1.05; Vb = 22.3 liters; fc = 0.46; Vc = 13.9 liters; and C = 14.6 μg/ml for 250 mg
1 g IV* 151 111 88 67 53 43 28 18 9
infused over 33 minutes.
2 g IM 40 68 76 68 56 44 29 ND ND
The results show that parenteral sulbactam acts like a typical penicillin in humans. Sulbactam
2 g IV* 257 192 154 117 89 74 46 31 15 has also been administered to humans by bolus IV injection: 500mg produced a peak serum
*IV doses were infused at a constant rate over 30 minutes. concentration of approximately 32 μg/ml. After IM administration of 500 mg of sulbactam, the
ND = Not determined. mean peak serum concentration was 6 – 24 mcg/ml. The elimination half-life was approximately
1.2 hour.
Ceftriaxone was completely absorbed following IM administration with mean maximum plasma
Non-Clinical Properties
concentrations occurring between 2 and 3 hours post-dose. Multiple IV or IM doses ranging from
0.5 to 2g at 12 to 24 hours intervals resulted in 15% to 36% accumulation of ceftriaxone above Animal Toxicology or Pharmacology
single dose values. Carcinogenesis: Considering the maximum duration of treatment and the class of the compound,
Ceftriaxone concentrations in urine are shown in Table carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum
Urinary Concentrations of Ceftriaxone After Single Dose Administration duration of animal toxicity studies was 6 months.
Mutagenesis: Genetic toxicology tests included the Ames test, a micronucleus test and a test for
Dose/Route Average Urinary Concentrations (mcg/mL) chromosomal aberrations in human lymphocytes cultured in vitro with ceftriaxone. Ceftriaxone
0 to 2 hr 2 to 4 hr 4 to 8 hr 8 to 12 hr 12 to 24 hr 24 to 48 hr showed no potential for mutagenic activity in these studies.
0.5 g IV 526 366 142 87 70 15
Impairment of Fertility: Ceftriaxone produced no impairment of fertility when given intravenously
to rats at daily doses up to 586 mg/kg/day, approximately 20 times the recommended clinical dose
0.5 g IM 115 425 308 127 96 28 of 2 g/day.
1 g IV 995 855 293 147 132 32
Description
1 g IM 504 628 418 237 ND ND
Ceftriaxone Sodium is a white to yellowish-orange crystalline powder which is readily soluble in
2 g IV 2692 1976 757 274 198 40 water, sparingly soluble in methanol and very slightly soluble in ethanol.
ND = Not determined
Pharmaceutical Particulars
Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug Incompatibilities
and the remainder was secreted in the bile and ultimately found in the feces as microbiologically Based on literature reports, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole
inactive compounds. After a 1 g IV dose, average concentrations of ceftriaxone, determined from and aminoglycosides and labetalol.
1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common Solutions containing ceftriaxone should not be mixed with or added to other agents except those
duct bile, 898mcg/mL in the cystic duct bile, 78.2 mcg/g in the gallbladder wall and 62.1 mcg/mL mentioned.
in the concurrent plasma.
In particular, diluents containing calcium, (e.g. Ringer&#39;s solution, Hartmann&#39;s solution)
Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV
from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance administration because a precipitate can form. Ceftriaxone must not be mixed or administered
from 0.58 to1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly simultaneously with calcium containing solutions including total parenteral nutrition.
bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma
If treatment with a combination of another antibiotic with ceftriaxone is intended, administration
concentrations of < 25mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the
should not occur in the same syringe or in the same infusion solution.
blood placenta barrier.
This medicinal product must not be mixed with other medicinal products except those mentioned.
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 Shelf-Life
suffering from bacterial meningitis are shown in Table. Ceftriaxone penetrated the inflamed
See on pack
meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a
75 mg/kg IV dose are also shown in Table. Packaging Information
Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients with Meningitis 1 vial + 10 ml SWFI

50 mg/kg IV 75 mg/kg IV Storage and Handling Instructions

Maximum Plasma Concentrations (mcg/mL) 216 275 Store protected from light at a temperature not exceeding 30°C.
Elimination Half-life (hr) 4.6 4.3 Marketed by & ® Regd. Trade Mark of :
Plasma Clearance (mL/hr/kg) 49 60 J. B. CHEMICALS & PHARMACEUTICALS LTD.
Volume of Distribution (mL/kg) 338 373 Neelam Centre, ‘B’ Wing, Hind Cycle Road,
Worli, Mumbai - 400 030. India.
CSF Concentration – inflamed meninges (mcg/mL) Range (mcg/mL) 5.6 6.4
Time after dose (hr) 1.3 to 18.5 1.3 to 4.4 Note: This prescribing information is applicable for India Market only
3.7 (±1.6) 3.3 (±1.4)

Compared to that in healthy adult subjects, the pharmacokinetics of ceftriaxone were only
minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction;
therefore, dosage adjustments are not necessary for these patients with ceftriaxone dosages up to 2
g per day. Ceftriaxone was not removed to any significant extent from the plasma by hemodialysis;
in six of 26 dialysis patients, the elimination rate of ceftriaxone was markedly reduced.
Average Pharmacokinetic Parameters of Ceftriaxone in Humans

Elimination Half- Plasma Clearance Volume of

Subject Group
Life (hr) (L/hr) Distribution (L)
Healthy Subjects 5.8 to 8.7 0.58 to 1.45 5.8 to 13.5
Elderly Subjects (mean age, 70.5 yr) 8.9 0.83 10.7
Patients with Renal Impairment
Hemodialysis Patients (0 to 5 mL/min)* 14.7 0.65 13.7
Severe (5 to 15 mL/min) 15.7 0.56 12.5
Moderate (16 to 30 mL/min) 11.4 0.72 11.8
Mild (31 to 60 mL/min) 12.4 0.70 13.3
Patients with Liver Disease 8.8 1.1 13.6

The elimination of ceftriaxone is not altered when ceftriaxone is co-administered with probenecid.
Sulbactam
Sulbactam, a new beta lactamase inhibitor, has pharmacokinetic characteristics in humans
similar to those of ampicillin and amoxicillin. Its half-life in humans is approximately 1 hour. In
a two compartment, pharmacokinetic model, the apparent volume of distribution for the central
compartment is approximately 12 liters, and half of the dose is found in the central compartment in
the post-distributive phase. Approximately 75% of a parenteral dose is excreted unchanged in urine.
The co-administration of sulbactam with ampicillin, penicillin G, or cefoperazone has essentially no
effect upon the kinetics of either the beta- lactam antibiotic or sulbactam.