CEFBACT-S Injection (Ceftriaxone & Sulbactam)

Table of Content

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

Qualitative and Quantitative Composition

CEFBACT-S Injection

Each vial contains:

Ceftriaxone Sodium IP (Sterile)

Eq. to anhydrous ceftriaxone………….1g

Sulbactam Sodium IP (Sterile)

Eq. to Sulbactam………………..500 mg

Dosage Form and Strength

Dry powder for reconstitution

Clinical Particulars

Therapeutic Indications

CEFBACT-S is indicated in the treatment of the following infections in adults and children including term neonates (from birth):

  • Bacterial Meningitis
  • Community acquired pneumonia
  • Hospital acquired pneumonia
  • Acute otitis media
  • Intra-abdominal infections
  • Complicated urinary tract infections (including pyelonephritis)
  • Infections of bones and joints
  • Complicated skin and soft tissue infections
  • Gonorrhoea
  • Syphilis
  • Bacterial endocarditis

CEFBACT-S may be used:

For treatment of acute exacerbations of chronic obstructive pulmonary disease in adults

For treatment of disseminated Lyme borreliosis (early (stage II) and late (stage III)) in adults and children including neonates from 15 days of age.

For Pre-operative prophylaxis of surgical site infections

In the management of neutropenic patients with fever that is suspected to be due to a bacterial infection

In the treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above

Ceftriaxone should be co-administered with other antibacterial agents whenever the possible range of causative bacteria would not fall within its spectrum.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Posology and Method of Administration

The dose depends on the severity, susceptibility, site and type of infection and on the age and hepato-renal function of the patient.

The doses recommended in the tables below are the generally recommended doses in these indications. In particularly severe cases, doses at the higher end of the recommended range should be considered.

Adults and children over 12 years of age (≥ 50 kg)

Ceftriaxone

Dosage*

Treatment frequency**

Indications

1-2 g

Once daily

Community acquired pneumonia

Acute exacerbations of chronic obstructive pulmonary disease

Intra-abdominal infections

Complicated urinary tract infections (including pyelonephritis)

2 g

Once daily

Hospital acquired pneumonia

Complicated skin and soft tissue infections

Infections of bones and joints

2-4 g

Once daily

Management of neutropenic patients with fever that is suspected to be due to a bacterial infection

Bacterial endocarditis

Bacterial meningitis

* In documented bacteraemia, the higher end of the recommended dose range should be considered.

** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.

Indications for adults and children over 12 years of age (≥ 50 kg) that require specific dosage schedules:

Acute otitis media

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 given as an intramuscular dose of 1-2 g daily for 3 days.

Pre-operative prophylaxis of surgical site infections

2 g as a single pre-operative dose.

Gonorrhoea

500 mg as a single intramuscular dose.

Syphilis

The generally recommended doses are 500 mg - 1g once daily increased to 2g once daily for neurosyphilis for 10-14days. The dose recommendations in syphilis, including neurosyphilis, are based on limited data. National or local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early and late )

2g once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Paediatric population

Neonates, infants and children 15 days to 12 years of age (< 50 kg)

For children with body weight of 50 kg or more, the usual adult dosage should be given.

Ceftriaxone dosage*

Treatment frequency**

Indications

50-80 mg/kg

Once daily

Intra-abdominal infections

Complicated urinary tract infections (including pyelonephritis)

Community acquired pneumonia

Hospital acquired pneumonia

50-100 mg/kg (Max 4 g)

Once daily

Complicated skin and soft tissue infections

Infections of bones and joints

Management of neutropenic patients with fever that is suspected to be due to a bacterial infection

80-100 mg/kg (max 4 g)

Once daily

Bacterial meningitis

100 mg/kg (max 4 g)

Once daily

Bacterial endocarditis

* In documented bacteraemia, the higher end of the recommended dose range should be considered.

** Twice daily (12 hourly) administration may be considered where doses greater than 2 g daily are administered.

Indications for neonates, infants and children 15 days to 12 years (< 50 kg) that require specific dosage schedules:

Acute otitis media

For initial treatment of acute otitis media, a single intramuscular dose of ceftriaxone 50 mg/kg can be given. Limited data suggest that in cases where the child is severely ill or initial therapy has failed, ceftriaxone may be effective when given as an intramuscular dose of 50 mg/kg daily for 3 days.

Pre-operative prophylaxis of surgical site infections

50-80 mg/kg as a single pre-operative dose.

Syphilis

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 local guidance should be taken into consideration.

Disseminated Lyme borreliosis (early and late )

50–80 mg/kg once daily for 14-21 days. The recommended treatment durations vary and national or local guidelines should be taken into consideration.

Neonates 0-14 days

Ceftriaxone is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age +chronological age).

Ceftriaxone dosage*

Treatment frequency**

Indications

20-50 mg/kg

 

Once daily

Intra-abdominal infections

Complicated urinary tract infections (including pyelonephritis)

Community acquired pneumonia

Hospital acquired pneumonia

Complicated skin and soft tissue infections

Infections of bones and joints

Management of neutropenic patients with fever that is suspected to be due to a bacterial infection

50 mg/kg

Once daily

 

Bacterial meningitis

Bacterial endocarditis

* In documented bacteraemia, the higher end of the recommended dose range should be considered.

A maximum daily dose of 50 mg/kg should not be exceeded.

Indications for neonates 0-14 days that require specific dosage schedules:

Acute otitis media

For initial treatment of acute otitis media, a single intramuscular dose of ceftriaxone 50 mg/kg can be given.

Pre-operative prophylaxis of surgical site infections

20-50 mg/kg as a single pre-operative dose.

Syphilis

The generally recommended dose is 50 mg/kg once daily for 10-14 days. The dose recommendations in syphilis, including neurosyphilis, are based on very limited data. National or local guidance should be taken into consideration.

Duration of therapy

The duration of therapy varies according to the course of the disease. As with antibiotic therapy in 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.

Older people

The dosages recommended for adults require no modification in older people provided that renal and hepatic function is satisfactory.

Patients with hepatic impairment

Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment provided renal function is not impaired.

There are no study data in patients with severe hepatic impairment.

Patients with renal impairment:

In patients with impaired renal function, there is no need to reduce the dosage of ceftriaxone provided hepatic function is not impaired. Only in cases of preterminal renal failure (creatinine clearance < 10 ml/min) should the ceftriaxone dosage not exceed 2 g daily.

In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. 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

Intramuscular administration

1.5 g ceftriaxone and sulbactam for injection should be dissolved in 5ml water for injections IP. The solution should be administered by deep intramuscular injection.

Intramuscular injections should be injected well within the bulk of a relatively large muscle and not more than 1 g should be injected at one site.

Dosages greater than 1g should be divided and injected at more than one site.

As the solvent used is lidocaine, the resulting solution should never be administered intravenously.

Intravenous administration

For IV injection 1.5 g ceftriaxone and sulbactam for Injection is dissolved in 9.6ml of water for injections IP. The injection should be administered over 5 minutes, directly into the vein or via the tubing of an intravenous infusion.

Ceftriaxone can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes. Intravenous intermittent injection should be given over 5 minutes preferably in larger veins. Intravenous doses of 50 mg/kg or more in infants and children up to 12 years of age should be given by infusion. In neonates, intravenous doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy. Intramuscular administration should be considered when the intravenous route is not possible or less appropriate for the patient. For doses, greater than 2 g intravenous administration should be used.

Ceftriaxone is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) treatment with calcium containing intravenous solutions, including continuous calcium-containing infusions such as parenteral nutrition, because of the risk of precipitation of ceftriaxone-calcium.

Diluents containing calcium, (e.g. Ringer's solution or Hartmann's solution), should not be used to reconstitute ceftriaxone 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 is mixed with calcium-containing solutions in the same IV administration line. Therefore, ceftriaxone and calcium-containing solutions must not be mixed or administered simultaneously.

For pre-operative prophylaxis of surgical site infections, ceftriaxone should be administered 30-90 minutes prior to surgery.

Contraindications

Hypersensitivity

Ceftriaxone 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.

Neonates

Premature neonates: Ceftriaxone is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age).

Hyperbilirubinemic neonates: Hyperbilirubinemic neonates should not be treated with ceftriaxone. Ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a risk of bilirubin encephalopathy in these patients.

Neonates Requiring Calcium Containing IV Solutions

Ceftriaxone 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.

Cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium-containing fluids and in some a precipitate was observed in the intravenous infusion line. 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.

Special Warnings and Precautions for Use

Hypersensitivity Reactions

Before therapy with ceftriaxone 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.e., anaphylaxis) have been reported. In case of severe hypersensitivity reactions, treatment with ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated.

Interaction with Calcium-Containing Products

Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to reconstitute ceftriaxone bottles or to further dilute a reconstituted bottle for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with calcium containing solutions in the same IV administration line. Ceftriaxone must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium.

Clostridium difficile -Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Hemolytic Anemia

An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin 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 while on ceftriaxone, the diagnosis of a cephalosporin associated anemia should be considered and ceftriaxone stopped until the etiology is determined.

Precautions

Development of Drug-resistant Bacteria

Prescribing ceftriaxone in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Prolonged use of ceftriaxone may result in overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Patients with Renal or Hepatic Impairment

Ceftriaxone is excreted via both biliary and renal excretion. Therefore, patients with renal failure normally require no adjustment in dosage when usual doses of ceftriaxone are administered.

Dosage adjustments should not be necessary in patients with hepatic dysfunction; however, in patients with both hepatic dysfunction and significant renal disease, caution should be exercised and the ceftriaxone dosage should not exceed 2 g daily.

Ceftriaxone is not removed by peritoneal or hemodialysis. In patients undergoing dialysis no additional supplementary dosing is required following the dialysis. In patients with both severe renal and hepatic dysfunction, close clinical monitoring for safety and efficacy is advised.

Effect on Prothrombin Time

Alterations in prothrombin times have occurred in patients treated with ceftriaxone. Monitor prothrombin time during ceftriaxone treatment in patients with impaired vitamin K synthesis or low 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.

Concomitant use of ceftriaxone with Vitamin K antagonists may increase the risk of bleeding. Coagulation parameters should be monitored frequently, and the dose of the anticoagulant adjusted accordingly, both during and after treatment with ceftriaxone.

Gallbladder Pseudolithiasis

Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving ceftriaxone. These precipitates appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. The probability of such precipitates appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop symptoms of gallbladder disease. The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of conservative management. Discontinue ceftriaxone sodium in patients who develop signs and symptoms suggestive of gallbladder disease and/or the sonographic findings described above.

Urolithiasis and Post-Renal Acute Renal Failure

Ceftriaxone-calcium precipitates in the urinary tract have been observed in patients receiving ceftriaxone and may be detected as sonographic abnormalities. The probability of such precipitates appears to be greatest in pediatric patients. Patients may be asymptomatic or may develop symptoms of urolithiasis, and ureteral obstruction and post-renal acute renal failure. The condition appears to be reversible upon discontinuation of ceftriaxone sodium and institution of appropriate management. Ensure adequate hydration in patients receiving ceftriaxone. Discontinue ceftriaxone in patients who develop signs and symptoms suggestive of urolithiasis, oliguria or renal failure and/or the sonographic findings described above.

Pancreatitis

Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients treated with ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of ceftriaxone related biliary precipitation cannot be ruled out.

Drug Interactions

Calcium-containing diluents, such as Ringer's solution or Hartmann's solution, should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for intravenous administration because a precipitate can form.

Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed with calcium-containing solutions in the same intravenous administration line.

Ceftriaxone must not be administered simultaneously with calcium-containing intravenous solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially of one another if the infusion lines are thoroughly flushed between infusions with a compatible fluid.

In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium.

Concomitant use with oral anticoagulants may increase the anti-vitamin K effect and the risk of bleeding. It is recommended that the International Normalised Ratio (INR) is monitored frequently and the posology of the anti-vitamin K drug adjusted accordingly, both during and after treatment with ceftriaxone.

There is conflicting evidence regarding a potential increase in renal toxicity of aminoglycosides when used with cephalosporins. The recommended monitoring of aminoglycoside levels (and renal function) in clinical practice should be closely adhered to in such cases.

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.

There have been no reports of an interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (intravenous or oral). In patients treated with ceftriaxone, the Coombs' test may lead to false-positive test results.

Ceftriaxone, like other antibiotics, may result in false-positive tests for galactosaemia.

Likewise, non-enzymatic methods for glucose determination in urine may yield false-positive results. For this reason, glucose level determination in urine during therapy with ceftriaxone should be carried out enzymatically.

No impairment of renal function has been observed after concurrent administration of large doses of ceftriaxone and potent diuretics (e.g. furosemide).

Simultaneous administration of probenecid does not reduce the elimination of ceftriaxone.

Use in Special Populations

Pregnancy:

Teratogenic Effects: Pregnancy Category B. Reproductive studies have been performed in mice and rats at doses up to 20 times the usual human dose and have no evidence of embryotoxicity, fetotoxicity or teratogenicity. In primates, no embryotoxicity or teratogenicity was demonstrated at a dose approximately 3 times the human dose.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects: In rats, in the Segment I (fertility and general reproduction) and Segment III (perinatal and postnatal) studies with intravenously administered ceftriaxone, no adverse effects were noted on various reproductive parameters during gestation and lactation, including postnatal growth, functional behavior and reproductive ability of the offspring, at doses of 586 mg/kg/day or less.

Nursing Mothers:

Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness of ceftriaxone in neonates, infants and pediatric patients have been 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 to hyperbilirubinemic neonates, especially premature.

Geriatric Use:

Of the total number of subjects in clinical studies of ceftriaxone, 32% were 60 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

The pharmacokinetics of ceftriaxone were only minimally altered in geriatric patients compared to healthy adult subjects and dosage adjustments are not necessary for geriatric patients with ceftriaxone dosages up to 2 grams per day provided there is no severe renal and hepatic impairment.

Effects on Ability to Drive and Use Machines

During treatment with ceftriaxone, undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use machines. Patients should be cautious when driving or operating machinery.

Undesirable Effects

CEFBACT-S is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone therapy or of uncertain etiology, were observed:

Local reactions: Pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL.

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site pain (0.6%).

Hypersensitivity: Rash (1.7%). Less frequently reported (<1%) were pruritus, fever or chills.

Infections and infestations: Genital fungal infection (0.1%).

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.

Blood and lymphatic disorders: Granulocytopenia (0.9%), coagulopathy (0.4%).

Gastrointestinal: Diarrhea/loose stools (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 aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) (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%).

Investigations: Blood creatinine increased (0.6%).

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: In addition to the adverse reactions reported during clinical trials, the following adverse experiences have been reported during clinical practice in patients treated with ceftriaxone. Data are generally insufficient to allow an estimate of incidence or to establish causation.

A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom ceftriaxone and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.

Gastrointestinal: Pancreatitis, stomatitis and glossitis.

Genitourinary: Oliguria, ureteric obstruction, post-renal acute renal failure.

Dermatologic: Exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) have been reported.

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.

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: Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, a plastic anemia, hemorrhage, and superinfection.

Altered Laboratory Tests: Positive direct Coombs' test, false-positive test for urinary glucose, and elevated LDH.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com.You can also report side effects directly via the National Pharmacovigilance Programme of India by calling on 18002677779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product.

Overdose

In the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of over dosage should be symptomatic.

Pharmacological Properties

Pharmacodynamics

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.

Sulbactam, a penicillanic acid sulfone with beta lactamase inhibitory properties has weak antibacterial activity but is an irreversible inhibitor of many plasmid mediated and some chromosomal beta lactamase. It has similar spectrum of beta lactamase inhibition to clavulanic acid, although it is less potent. It enhances the activity of penicillins and cephalosporins.

Mechanism of 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.

Antibacterial Activity

Ceftriaxone has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections:

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 data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible break point for ceftriaxone. However, the efficacy of ceftriaxone in treating clinical infections due to these microorganisms has not been established in adequate and well controlled clinical trials.

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

Pharmaceutical Particulars

Incompatibilities

Based on literature reports, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole and aminoglycosides and labetalol.

Solutions containing ceftriaxone should not be mixed with or added to other agents except those mentioned.

In particular, diluents containing calcium, (e.g. Ringer's solution, Hartmann's solution) should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Ceftriaxone must not be mixed or administered simultaneously with calcium containing solutions including total parenteral nutrition.

If treatment with a combination of another antibiotic with ceftriaxone is intended, administration should not occur in the same syringe or in the same infusion solution.

This medicinal product must not be mixed with other medicinal products except those mentioned.

Pharmacokinetics Properties

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.

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*

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

2 g IM

40

68

76

68

56

44

29

ND

ND

2 g IV*

257

192

154

117

89

74

46

31

15

*IV doses were infused at a constant rate over 30 minutes.

ND = Not determined.

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 2g at 12 to 24 hours intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.

Ceftriaxone concentrations in urine are shown in Table

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

0.5 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

ND = Not determined

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, 898mcg/mL in the cystic duct bile, 78.2 mcg/g in the gallbladder wall and 62.1 mcg/mL in the concurrent plasma.

Over a 0.15 to 3 g dose range in healthy adult subjects, the values of elimination half-life ranged from 5.8 to 8.7 hours; apparent volume of distribution from 5.78 to 13.5 L; plasma clearance from 0.58 to1.45 L/hour; and renal clearance from 0.32 to 0.73 L/hour. Ceftriaxone is reversibly bound to human plasma proteins, and the binding decreased from a value of 95% bound at plasma concentrations of < 25mcg/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. Ceftriaxone penetrated the inflamed meninges of infants and pediatric patients; CSF concentrations after a 50 mg/kg IV dose and after a 75 mg/kg IV dose are also shown in Table.

Average Pharmacokinetic Parameters of Ceftriaxone in Pediatric Patients With

Meningitis

 

50 mg/kg IV

75 mg/kg IV

Maximum Plasma Concentrations (mcg/mL)

216

275

Elimination Half-life (hr)

4.6

4.3

Plasma Clearance (mL/hr/kg)

49

60

Volume of Distribution (mL/kg)

338

373

CSF Concentration – inflamed meninges (mcg/mL)

Range (mcg/mL)

Time after dose (hr)

5.6

6.4

1.3 to 18.5

1.3 to 4.4

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

Subject Group

Elimination Half-

Life (hr)

Plasma Clearance

(L/hr)

Volume of

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.

After a 30-minute infusion of 500 mg of sulbactam, a peak serum concentration of approximately 20 µg/ml was obtained; 1,000 mg produced a peak of 43µg/ml. The half - life for elimination was about 1.0 hour. The data were interpreted as a two-compartment pharmacokinetic model. The 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 = 1.4 h-1). The apparent volume of distribution for the central compartment (serum and rapidly equilibrating tissues) was between 9 and 16 liters, and the total apparent volume of distribution was between 19 and 28 liters. Approximately 51% of the drug was in the central compartment in the post-distributive phase.

Calculated steady-state serum concentration were proportional to dose. These pharmacokinetic 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 infused over 33 minutes.

The results show that parenteral sulbactam acts like a typical penicillin in humans. Sulbactam has also been administered to humans by bolus IV injection: 500mg produced a peak serum concentration of approximately 32 µg/ml. After IM administration of 500 mg of sulbactam, the mean peak serum concentration was 6 – 24 mcg/ml. The elimination half-life was approximately 1.2 hour.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Carcinogenesis: Considering the maximum duration of treatment and the class of the compound, carcinogenicity studies with ceftriaxone in animals have not been performed. The maximum duration of animal toxicity studies was 6 months.

Mutagenesis: Genetic toxicology tests included the Ames test, a micronucleus test and a test for chromosomal aberrations in human lymphocytes cultured in vitro with ceftriaxone. Ceftriaxone showed no potential for mutagenic activity in these studies.

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 of 2 g/day.

Description

Ceftriaxone Sodium for Injection is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is (6R,7R)-7--8-oxo-3-methyl]-5-thia-1azabicyclooct-2-ene-2-carboxylic acid, 7 -(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.

Ceftriaxone Sodium is a white to yellowish-orange crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The pH of a 1% aqueous solution is approximately 6.7. The color of ceftriaxone and sulbactam for Injection, solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used.

Sulbactam sodium a beta-lactamase inhibitor, is a derivative of the basic penicillin nucleus. When combined with ceftriaxone, the sulbactam broadens the spectrum of the former agent to include many beta lactamase producing organisms, including those that are resistant to ceftriaxone alone.

Shelf-Life

See on pack

Packaging Information

Cefbact-s…………………. Vial of 20 ml

Storage and Handling Instructions

Store Below 25°C. Protect from light. Do not freeze.

Patient Counselling Information

What CEFBACT-S for injection is and what it is used for?

CEFBACT-S is an antibiotic given to adults and children (including new born babies). It works by killing bacteria that cause infections. It belongs to a group of medicines called cephalosporins. Ceftriaxone is used to treat infections of

  • the brain (meningitis).
  • the lungs.
  • the middle ear.
  • the abdomen and abdominal wall (peritonitis).
  • the urinary tract and kidneys.
  • bones and joints.
  • the skin or soft tissues.
  • the blood.
  • the heart.

It can be given:

  • to treat specific sexually transmitted infections (gonorrhoea and syphilis).
  • to treat patients with low white blood cell counts (neutropenia) who have fever due to bacterial infection.
  • to treat infections of the chest in adults with chronic bronchitis.
  • to treat Lyme disease (caused by tick bites) in adults and children including new born babies from 15 days of age.
  • to prevent infections during surgery.

What you need to know before you are given CEFBACT-S for Injection?

You must not been given CEFBACT-S for injection:

  • if you are allergic to ceftriaxone or any of the other ingredients of this medicine.
  • if you have had a sudden or severe allergic reaction to penicillin or similar antibiotics (such as cephalosporins, carbapenems or monobactams). The signs include sudden swelling of the throat or face which might make it difficult to breath or swallow, sudden swelling of the hands, feet and ankles, and a severe rash that develops quickly.
  • if you are allergic to lidocaine and you are to be given Ceftriaxone for injection as an injection into a muscle.

Ceftriaxone and Sulbactam for injection must not be given to babies if:

  • The baby is premature.
  • The baby is new born (up to 28 days of age) and has certain blood problems or jaundice (yellowing of the skin or the whites of the eyes) or is to be given a product that contains calcium into their vein.

Warnings and precautions

Talk to your doctor or pharmacist or nurse before you are given Ceftriaxone and Sulbactam for injection if:

• You have recently received or are about to receive products that contain calcium.

• You have recently had diarrhoea after having an antibiotic medicine. You have ever had problems with your gut, in particular colitis (inflammation of the bowel).

• You have liver or kidney problems.

• You have gall stones or kidney stones.

• You have other illnesses, such as haemolytic anaemia (a reduction in your red blood cells that may make your skin pale yellow and cause weakness or breathlessness).

• You are on a low sodium diet.

• You experience or have previously experienced a combination of any of the following symptoms: rash, red skin, blistering of the lips, eyes and mouth, skin peeling, high fever, flu-like symptoms, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (signs of severe skin reactions, see “Possible side effects”).

If you need a blood or urine test

If you are given Ceftriaxone and Sulbactam for injection for a long time, you may need to have regular blood tests. Ceftriaxone for injection can affect the results of urine tests for sugar and a blood test known as the Coombs test. If you are having tests:

• Tell the person taking the sample that you have been given Ceftriaxone for injection.

If you are diabetic or need to have your blood glucose level monitored, you should not use certain blood glucose monitoring systems which may estimate blood glucose incorrectly while you are receiving ceftriaxone. If you use such systems check the instructions for use and tell your doctor, pharmacist or nurse. Alternative testing methods should be used if necessary.

Children

Talk to your doctor or pharmacist or nurse before your child is administered ceftriaxone and sulbactam for injection if:

• He/she has recently been given or is to be given a product that contains calcium into their vein.

Other medicines and Ceftriaxone and Sulbactam for injection

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

• A type of antibiotic called an aminoglycoside.

• An antibiotic called chloramphenicol (used to treat infections, particularly of the eyes).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

The doctor will consider the benefit of treating you with Ceftriaxone against the risk to your baby.

Driving and using machines

Ceftriaxone and Sulbactam for injection may cause dizziness. If you feel dizzy, do not drive or use any tools or machines. Talk to your doctor if you experience these symptoms.

How to take Ceftriaxone and Sulbactam for injection

Ceftriaxone and Sulbactam for injection is usually given by a doctor or nurse. It can be given as:

• a drip (intravenous infusion) or

• as an injection directly into a vein or into a muscle.

Ceftriaxone and sulbactam for injection is made up by the doctor, pharmacist or nurse and will not be mixed with or given to you at the same time as calcium-containing injections.

The recommended dose

Your doctor will decide the correct dose of ceftriaxone and sulbactam for injection for you. The dose will depend on the severity and type of infection; whether you are on any other antibiotics; your weight and age; how well your kidneys and liver are working. The number of days or weeks that you are given ceftriaxone and sulbactam for injection depends on what sort of infection you have.

Adults, older people and children aged 12 years and over with a body weight greater than or equal to 50 kilograms (kg):

• 1 to 2 g once a day depending on the severity and type of infection. If you have a severe infection, your doctor will give you a higher dose (up to 4 g once a day). If your daily dose is higher than 2 g, you may receive it as a single dose once a day or as two separate doses.

New born babies, infants and children aged 15 days to 12 years with a body weight of less than 50 kg:

• 50-80 mg ceftriaxone for each kg of the child’s body weight once a day depending on the severity and type of infection. If you have a severe infection, your doctor will give you a higher dose up to100 mg for each kg of body weight to a maximum of 4 g once a day. If your daily dose is higher than 2 g, you may receive it as a single dose once a day or as two separate doses.

• Children with a body weight of 50 kg or more should be given the usual adult dose.

New born babies (0-14 days)

• 20 – 50 mg ceftriaxone for each kg of the child’s body weight once a day depending on the severity and type of infection.

• The maximum daily dose is not to be more than 50 mg for each kg of the baby’s weight.

People with liver and kidney problems

You may be given a different dose to the usual dose. Your doctor will decide how much CEFBACT-S for injection you will need and will check you closely depending on the severity of the liver and kidney disease.

If you are given more CEFBACT-S for injection than you should

If you accidentally receive more than your prescribed dose, contact your doctor or nearest hospital straight away.

If you forget to use CEFBACT-S for injection

If you miss an injection, you should have it as soon as possible. However, if it is almost time for your next injection, skip the missed injection. Do not take a double dose (two injections at the same time) to make up for a missed dose.

If you stop using CEFBACT-S for injection

Do not stop taking ceftriaxone and sulbactam for injection unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor or nurse.

Possible side effects?

CEFBACT-S is generally well tolerated. In clinical trials, the following adverse reactions, which were considered to be related to ceftriaxone therapy or of uncertain etiology, were observed:

Local reactions: Pain, induration and tenderness was 1% overall. Phlebitis was reported in <1% after IV administration. The incidence of warmth, tightness or induration was 17% (3/17) after IM administration of 350 mg/mL and 5% (1/20) after IM administration of 250 mg/mL.

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Injection site pain (0.6%).

Hypersensitivity: Rash (1.7%). Less frequently reported (<1%) were pruritus, fever or chills.

Infections and infestations: Genital fungal infection (0.1%).

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.

Blood and lymphatic disorders: Granulocytopenia (0.9%), coagulopathy (0.4%).

Gastrointestinal: Diarrhea/loose stools (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 aspartate aminotransferase (AST) (3.1%) or alanine aminotransferase (ALT) (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%).

Investigations: Blood creatinine increased (0.6%).

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: In addition to the adverse reactions reported during clinical trials, the following adverse experiences have been reported during clinical practice in patients treated with ceftriaxone. Data are generally insufficient to allow an estimate of incidence or to establish causation.

A small number of cases of fatal outcomes in which a crystalline material was observed in the lungs and kidneys at autopsy have been reported in neonates receiving ceftriaxone and calcium-containing fluids. In some of these cases, the same intravenous infusion line was used for both ceftriaxone and calcium containing fluids and in some a precipitate was observed in the intravenous infusion line. At least one fatality has been reported in a neonate in whom ceftriaxone and calcium-containing fluids were administered at different time points via different intravenous lines; no crystalline material was observed at autopsy in this neonate. There have been no similar reports in patients other than neonates.

Gastrointestinal: Pancreatitis, stomatitis and glossitis.

Genitourinary: Oliguria, ureteric obstruction, post-renal acute renal failure.

Dermatologic: Exanthema, allergic dermatitis, urticaria, edema; acute generalized exanthematous pustulosis (AGEP) and isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) have been reported.

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.

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: Allergic reactions, drug fever, serum sickness-like reaction, renal dysfunction, toxic nephropathy, reversible hyperactivity, hypertonia, hepatic dysfunction including cholestasis, aplastic anemia, hemorrhage, and superinfection.

Altered Laboratory Tests: Positive direct Coombs' test, false-positive test for urinary glucose, and elevated LDH.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the National Pharmacovigilance Programme of India by calling on 1800 267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safety of this product.

Details of The Manufacturer

Innova Captab Ltd.

1281/1, Hilltop Industrial Estate,

Near EPIP Phase – I,

Jharmajri, Baddi – 173 202 (H.P.)

Details of Permission or Licence Number with Date

M.L. MB/09/803 Date: 02.05.2020

Date of Revision

01/04/2022