Product Index

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

Composition

CEFBACT

Each vial contains:

Ceftriaxone Sodium IP (Sterile)

equivalent to anhydrous Ceftriaxone ………1000 mg

Dosage Form(s) and Strength(s)

Powder for solution for injection containing Ceftriaxone sodium 1000mg

Clinical Particulars

Therapeutic Indications

CEFBACT for injection (Ceftriaxone sodium) is indicated in the treatment of the following infections in adults and children, including term neonates (from birth):

Indicated in the treatment of UTI, lower respiratory tract infections, bacteraemia, septicaemia, meningitis, abdominal infections and infections caused by pseudomonas species.

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

Consideration should be given to the 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	Treatment Frequency**	Indications
Dosage*
1–2 g	Once daily	Community-acquired pneumonia
		Acute exacerbations of COPD
		Intra-abdominal infections
		Complicated urinary tract infections (including pyelonephritis)
2 g	Once daily	Hospital-acquired pneumonia
		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.

Paediatric Patients

Neonates, Infants and Children 15 Days to 12 Years of Age (<50 kg)

For children with bodyweight of ≥50 kg, 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
80–100 mg/kg (max 4 g)	Once daily	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.

Neonates 0–14 Days of Age

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
50 mg/kg	Once daily	Bacterial meningitis

*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.

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 afebrile or evidence of bacterial eradication has been achieved.

Geriatric Patients

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 that hepatic 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 that renal function is not impaired. Only in cases of preterminal renal failure (creatinine clearance <10 mL/minute) 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 dialysis 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

Intravenous (IV) Administration

For IV injection, 1 g Ceftriaxone is dissolved in 9.6 mL of sterile Water for Injections. The injection should be administered over 5 minutes, directly into the vein or via the tubing specified for an IV infusion. Ceftriaxone can be administered by IV infusion over at least 30 minutes or by slow IV injection over 5 minutes. IV intermittent injection should be given over 5 minutes preferably in larger veins. IV doses of 50 mg/kg or more in infants and children up to 12 years of age should be given by infusion. In neonates, IV doses should be given over 60 minutes to reduce the potential risk of bilirubin encephalopathy.

Intravenous (IM) Administration

For IM injection, dissolve the contents of the vial in 3.6 ml Sterile Water for injection for IM administration. IM administration should be considered when the IV route is not possible or less appropriate for the patient. For doses greater than 2 g, IV administration should be used.

Ceftriaxone is contraindicated in neonates (≤28 days of age) 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.

Ceftriaxone is contraindicated in neonates (≤28 days of age) 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.

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 to the active substance, to any other cephalosporin or to any of the excipients.
• History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).

Ceftriaxone is also contraindicated in the following:

• Premature neonates upto a postmenstrual age of 41 weeks (gestationalage+chronologicalage).*
• Full-term neonates (up to 28 days of age):
  • with hyperbilirubinaemia, Jaundice, or who are hypoalbuminaemic or acidotic because these are conditions in which bilirubin binding is likely to be impaired*
  • if they require (or are expected to require) IV calcium treatment, or calcium-containing infusions due to the risk of precipitation of a Ceftriaxone-calcium salt

* In vitro studies have shown that Ceftriaxone can displace bilirubin from its serum albumin-binding sites, leading to a possible risk of bilirubin encephalopathy in these patients.

Special Warnings and Precautions for Use

Hypersensitivity Reactions

As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with Ceftriaxone must be discontinued immediately and adequate emergency measures must be initiated. Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to Ceftriaxone, to other cephalosporin or to any other type of beta-lactam agent. Caution should be used if Ceftriaxone is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.

Severe cutaneous adverse reactions , which can be life-threatening or fatal, have been reported in association with Ceftriaxone treatment; however, the frequency of these events is not known.

Jarisch-Herxheimer Reaction

Some patients with spirochete infections may experience a Jarisch-Herxheimer reaction shortly after Ceftriaxone treatment is started. A Jarisch-Herxheimer reaction is usually a self-limiting condition or can be managed by symptomatic treatment. The antibiotic treatment should not be discontinued if such reaction occurs.

Interaction with Calcium-containing Products

Cases of fatal reactions with Ceftriaxone-calcium precipitates in the lungs and kidneys in premature and full-term neonates aged less than 1 month have been described. At least one of them had received Ceftriaxone and calcium at different times and through different IV lines. In the available scientific data, there are no reports of confirmed intravascular precipitations in patients, other than neonates, treated with Ceftriaxone and calcium-containing solutions or any other calcium-containing products. In vitro studies demonstrated that neonates have an increased risk of precipitation of Ceftriaxone-calcium compared with other age groups.

In patients of any age, Ceftriaxone must not be mixed or administered simultaneously with any calcium-containing IV solutions, even via different infusion lines or at different infusion sites. However, in patients older than 28 days of age, Ceftriaxone and calcium-containing solutions may be administered sequentially one after another if infusion lines at different sites are used or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt-solution to avoid precipitation. In patients requiring continuous infusion with calcium-containing total parenteral nutrition (TPN) solutions, healthcare professionals may wish to consider the use of alternative antibacterial treatments that do not carry a similar risk of precipitation. If the use of Ceftriaxone is considered necessary in patients requiring continuous nutrition, TPN solutions and Ceftriaxone can be administered simultaneously ,albeit via different infusion lines at different sites. Alternatively, infusion of TPN solution could be stopped for the period of Ceftriaxone infusion and the infusion lines flushed between solutions.

Paediatric Patients

Safety and effectiveness of ceftriaxone in neonates, infants and children have been established for the dosages described under Posology and Method of Administration Studies have shown that Ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin.

Ceftriaxone is contraindicated in premature and full-term neonates at risk for developing bilirubin encephalopathy.

Immune-mediated Haemolytic Anaemia

An immune-mediated haemolytic anaemia has been observed in patients receiving cephalosporin class anti-bacterial, including Ceftriaxone. Severe cases of haemolytic anaemia, including fatalities, have been reported during Ceftriaxone treatment in both adults and children.

If a patient develops anaemia while on Ceftriaxone, the diagnosis of a cephalosporin-associated anaemia should be considered and Ceftriaxone discontinued until the aetiology is determined.

Long-term Treatment

During prolonged treatment, complete blood count should be performed at regular intervals.

Colitis/Overgrowth of Non-Susceptible Microorganisms

Antibacterial agent-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial agents, including Ceftriaxone, and may range in severity from mild to life-threatening. Therefore, it is important to   consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of Ceftriaxone.  Discontinuation of therapy with Ceftriaxone and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.

Superinfections with non-susceptible microorganisms may occur as with other antibacterial agents.

Severe Renal and Hepatic Impairment

In severe renal and hepatic insufficiency, close clinical monitoring for safety and efficacy is advised.

Interference with Serological Testing

Interference with Coombs’ tests may occur, as Ceftriaxone may lead to false-positive test results. Ceftriaxone can also lead to false-positive test results for galactosaemia

Non-enzymatic methods for the glucose determination in urine may give false-positive results. Urine glucose determination during therapy with Ceftriaxone should be done enzymatically

The presence of Ceftriaxone may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Please refer to instructions for use for each system. Alternative testing methods should be used if necessary.

Sodium

Each gram of Ceftriaxone sodium contains sodium. This should be taken into consideration in patients on a controlled sodium diet.

Antibacterial Spectrum

Ceftriaxone has a limited spectrum of antibacterial activity and may not be suitable for use as a single agent for the treatment of some types of infections unless the pathogen has already been confirmed. In polymicrobial infections, where suspected pathogens include organisms resistant to Ceftriaxone, administration of an additional antibiotic should be considered.

Biliary Lithiasis

When shadows are observed on sonograms, consideration should be given to the possibility of precipitates of calcium Ceftriaxone. Shadows, which have been mistaken for gallstones, have been detected on sonograms of the gallbladder and have been observed more frequently at Ceftriaxone doses of 1 g per day and above. Caution should be particularly considered in the paediatric population. Such precipitates disappear after discontinuation of Ceftriaxone therapy. Rarely precipitates of calcium Ceftriaxone have been associated with symptoms. In symptomatic cases, conservative nonsurgical management is recommended and discontinuation of Ceftriaxone treatment should be considered by the physician based on specific benefit risk assessment.

Biliary Stasis

Cases of pancreatitis, possibly of biliary obstruction aetiology, have been reported in patients treated with Ceftriaxone. Most patients presented with risk factors for biliary stasis and biliary sludge, e.g. preceding major therapy, severe illness and total parenteral nutrition. A trigger or cofactor of Ceftriaxone-related biliary precipitation cannot be ruled out.

Renal Lithiasis

Cases of renal lithiasis have been reported, which is reversible upon discontinuation of Ceftriaxone. In symptomatic cases, sonography should be performed. Use in patients with history of renal lithiasis or with hypercalciuria should be considered by the physician based on specific benefit–risk assessment.

Clostridium difficile-associated Diarrhoea

Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including Ceftriaxone, and may range in severity from mild diarrhoea 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. Hyper-toxin 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 diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 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.

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 dialysis or haemodialysis. 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 paediatric 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 paediatric 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, and TPN). 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 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 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 IM Ceftriaxone and calcium-containing products (IV 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

Pregnant Women

Ceftriaxone crosses the placental barrier. There are limited amounts of data from the use of Ceftriaxone in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to embryonal/foetal, perinatal and postnatal development.  Ceftriaxone should only be administered during pregnancy and, in particular, in the first trimester of pregnancy if the benefit outweighs the risk.

Lactating Women

Ceftriaxone is excreted into human milk in low concentrations but, at therapeutic doses of Ceftriaxone, no effects on the breastfed infants are anticipated. However, a risk of diarrhoea and fungal infection of the mucous membranes cannot be excluded. The possibility of sensitisation should be taken into account. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Ceftriaxone therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Reproductive studies have shown no evidence of adverse effects on male or female fertility.

Paediatric Patients

Safety and effectiveness of Ceftriaxone in neonates, infants and paediatric patients have been established for the dosages described in the Posology and Method of Administration section. In vitro studies have shown that Ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Ceftriaxone should not be administered to hyperbilirubinaemic neonates, especially prematures.

Geriatric Patients

Of the total number of subjects in clinical studies of Ceftriaxone, 32% were 60 years of age 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 was only minimally altered in geriatric patients compared with healthy adult subjects, and dosage adjustments are not necessary for geriatric patients with Ceftriaxone dosages up to 2 g per day provided there is no severe renal and hepatic impairment.

Influence on Diagnostic Tests

In patients treated with Ceftriaxone, the Coombs' test may become positive. Ceftriaxone, like other antibacterial drugs, may result in positive test results for galactosaemia.

Non-enzymatic methods for the glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with Ceftriaxone should be done enzymatically.

The presence of Ceftriaxone may falsely lower estimated blood glucose values obtained with some blood glucose monitoring systems. Please refer to the instructions for use for each system. Alternative testing methods should be used if necessary.

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

The most frequently reported adverse reactions for Ceftriaxone are eosinophilia, leucopaenia, thrombocytopaenia, diarrhoea, rash, and hepatic enzymes increased.

Data to determine the frequency of Ceftriaxone adverse drug reactions was derived from clinical trials. The following convention has been used for the classification of frequency:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1000)

Not known (cannot be estimated from the available data)

System Organ Class	Common	Uncommon	Rare	Not Knowna
Infections and infestations		Genital fungal infection	Pseudo- membranous colitisb	Superinfectionb
Blood and lymphatic system disorders	Eosinophilia Leucopaenia Thrombocytopaenia	Granulocytopaenia Anaemia Coagulopathy		Haemolytic anaemiab Agranulocytosis
Immune system disorders				Anaphylactic shock Anaphylactic reaction Anaphylactoid reaction Hypersensitivityb Jarisch- Herxheimer reactionb
Nervous system disorders		Headache Dizziness		Convulsion
Ear and labyrinth disorders				Vertigo
Respiratory, thoracic and mediastinal disorders			Bronchospasm
Gastrointestinal disorders	Diarrhoeab Loose stools	Nausea Vomiting		Pancreatitisb Stomatitis Glossitis
Hepatobiliary disorders	Hepatic enzyme increased			Gallbladder precipitationb Kernicterus
Skin and subcutaneous tissue disorders	Rash	Pruritus	Urticaria	Stevens-Johnson syndromeb Toxic epidermal necrolysisb Erythema multiforme Acute generalised exanthematous pustulosis (AGEP) Drug reaction with eosinophilia and systemic symptoms (DRESS)b
Renal and urinary disorders			Haematuria Glycosuria	Oliguria Renal precipitation (reversible)
General disorders and administration site conditions		Phlebitis  Injection-site pain Pyrexia	Oedema Chills
Investigations		Blood creatinine increased		Coombs’ test false-positiveb
				Galactosaemia test false-positiveb
				Non-enzymatic methods for glucose determination false-positiveb

aBased on postmarketing reports. Since these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known.

b See Special Warnings and Precautions for Use section

Description of Selected Adverse Reactions

Infections and Infestations

Reports of diarrhoea following the use of Ceftriaxone may be associated with C. difficile. Appropriate fluid and electrolyte management should be instituted.

Ceftriaxone-Calcium Salt Precipitation

Rarely, severe, and in some cases, fatal, adverse reactions have been reported in pre-term and full-term neonates (age<28 days) who had been treated with IV Ceftriaxone and calcium. Precipitations of Ceftriaxone-calcium salt have been observed in lung and kidneys post-mortem. The high risk of precipitation in neonates is a result of their low blood volume and the longer half-life of Ceftriaxone compared with adults.

Cases of Ceftriaxone precipitation in the urinary tract have been reported, mostly in children treated with high doses (e.g.≥80 mg/kg/day or total doses exceeding 10 g) and who have other risk factors (e.g. dehydration, confinement to bed). This event may be asymptomatic or symptomatic, and may lead to ureteric obstruction and post-renal acute renal failure, but is usually reversible upon discontinuation of Ceftriaxone.

Precipitation of Ceftriaxone-calcium salt in the gallbladder has been observed, primarily in patients treated with doses higher than the recommended standard dose. In children, prospective studies have shown a variable incidence of precipitation with IV application–above 30% in some studies. The incidence appears to be lower with slow infusion (20–30 minutes). This effect is usually asymptomatic, but the precipitations have been accompanied by clinical symptoms such as pain, nausea and vomiting in rare cases. Symptomatic treatment is recommended in these cases.

Precipitation is usually reversible upon discontinuation of Ceftriaxone.

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 IV 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 IV 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 glossaries.

Genitourinary

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

Dermatologic

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

Haematological Changes

Isolated cases of agranulocytosis (<500/mm3) 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 that 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 anaemia, haemorrhage, 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.

Overdose

In overdose, the symptoms of nausea, vomiting and diarrhoea can occur. Ceftriaxone concentrations cannot be reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic.

Reporting of side effects

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 Pharma co vigilance Programme of India by calling on 1800 180 3024or you can report to Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more information on the safety of this product.

Pharmacological Properties

Pharmacotherapeutic Group

Antibacterials for systemic use, Third-generation cephalosporins.

Mechanism of Action

Ceftriaxone inhibits bacterial cell wall synthesis following attachment to penicillin-binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial celllysis and death.

Pharmacodynamic Properties

Average plasma concentrations of Ceftriaxone following a single 30-minute IV infusion of a 0.5, 1 or 2 g dose and 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 the table below.

Ceftriaxone Plasma Concentrations after Single-Dose Administration

Dose/Route	Average Plasma Concentrations (mcg/mL)
	0.5 hours	1 hour	2 hours	4 hours	6 hours	8 hours	12 hours	16 hours	24 hours
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
1 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 from0.5 to 2 g at 12- to 24-hour intervals resulted in 15–36% accumulation of Ceftriaxone above single-dose values.

Ceftriaxone concentrations in urine are shown in the table below.

Urinary Concentrations of Ceftriaxone after Single-Dose Administration

Dose/Route	Average Urinary Concentrations (mcg/mL)
	0–2 hours	2– 4 hours	4–8 hours	8–12 hours	12–24 hours	24–48 Hours
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.

Of the Ceftriaxone dose, 33–67% was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the faeces as microbiologically inactive compounds. After a 1 g IV dose, average concentrations of Ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gallbladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/g in the gallbladder wall, and 62.1 mcg/mL in the concurrent plasma.

Over a 0.15–3 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 to 1.45 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 <25 mcg/mL to a value of 85% bound at 300 mcg/mL. Ceftriaxone crosses the blood placenta barrier.

The average values of maximum plasma concentration, elimination half-life, plasma clearance and volume of distribution after a 50 mg/kg IV dose and after a 75 mg/kg IV dose in pediatric patients suffering from bacterial meningitis are shown in Table below. 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 is also shown in Table below.

Average Pharmacokinetic Parameters of Ceftriaxone in Paediatric 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 range (mcg/mL) Time after dose (hour)	5.6	6.4
	1.3–18.5	1.3–44
	3.7 (±1.6)	3.3 (±1.4)

Compared with that in healthy adult subjects, the pharmacokinetics of Ceftriaxone was only minimally altered in elderly subjects and in patients with renal impairment or hepatic dysfunction (see table below); therefore, dosage adjustments are not necessary for these patients with Ceftriaxone upto 2 g per day. Ceftriaxone was not removed to any significant extent from the plasma by haemodialysis; in 6 of 26 dialysis patients, the elimination rate of Ceftriaxone was markedly reduced.

Average Pharmacokinetic Parameters of Ceftriaxone in Humans

Subject Group	Elimination Half-Life (hour)	Plasma Clearance (L/hour)	Volume of Distribution (L)
Healthy subjects	5.8–8.7	0.58–1.45	5.8–13.5
Elderly subjects (mean age, 70.5 years)	8.9	0.83	10.7
Patients with renal impairment
Haemodialysis patients (0– 5 mL/min)*	14.7	0.65	13.7
Severe (5–15 mL/min)	15.7	0.56	12.5
Moderate (16– 30 mL/min)	11.4	0.72	11.8
Mild (31–60 mL/min)	12.4	0.70	13.3
Patients with liver disease	8.8	1.1	13.6

*Creatinine clearance

The elimination of Ceftriaxone is not altered when Ceftriaxone is co-administered with probenecid.

Pharmacokinetics in the Middle Ear Fluid

In one study, total Ceftriaxone concentrations (bound and unbound) were measured in middle ear fluid obtained during the insertion of tympanostomy tubes in 42 paediatric patients with otitis media. Sampling times were from 1 to 50 hours after a single IM injection of 50 mg/kg of Ceftriaxone. Mean (± SD) Ceftriaxone levels in the middle ear reached a peak of 35 (± 12) mcg/mL at 24 hours, and remained at 19 (± 7) mcg/mL at 48 hours. Based on middle ear fluid Ceftriaxone concentrations in the 23-to 25-hour and the 46-to 50-hour sampling time intervals, a half-life of 25 hours was calculated. Ceftriaxone is highly bound to plasma proteins. The extent of binding to proteins in the middle ear fluid is unknown.

Interaction with Calcium

Two in vitro studies, one using adult plasma and the other neonatal plasma from umbilical cord blood, have been carried out to assess interaction of Ceftriaxone and calcium. Ceftriaxone concentrations up to 1 mM (in excess of concentrations achieved in vivo following administration of 2 g Ceftriaxone infused over 30 minutes) were used in combination with calcium concentrations up to 12 mM (48 mg/dL). Recovery of Ceftriaxone from plasma was reduced with calcium concentrations of 6 mM (24 mg/dL) or higher in adult plasma or 4 mM (16 mg/dL) or higher in neonatal plasma. This may be reflective of Ceftriaxone-calcium precipitation.

Resistance

Bacterial resistance to Ceftriaxone may be due to one or more of the following mechanisms:

• Hydrolysis by beta-lactamases, including extended-spectrum beta-lactamases (ESBLs), carbapenemases and Amp C enzymesthatmaybeinducedorstablyde-repressedincertainaerobicgram-negativebacterialspecies.
• Reduced affinity of penicillin-binding proteins for Ceftriaxone.
• Outer membrane impermeability in gram-negative organisms.
• Bacterial efflux pumps.

Clinical Efficacy against Specific Pathogens

The prevalence of acquired resistance may vary geographically and with time for selected species and, hence, local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of Ceftriaxone in at least some

Commonly susceptible species

Gram-positive aerobes Staphylococcus aureus (methicillin-susceptible)£ Staphylococci coagulase-negative (methicillin-susceptible)£ Streptococcus pyogenes (Group A) Streptococcus agalactiae (Group B) Streptococcus pneumonia Viridans group Streptococci Gram-negative aerobes Borrelia burgdorferi Haemophilus influenzae Haemophilus parainfluenzae Moraxella catarrhalis Neisseria gonorrhoea Neisseria meningitidis Proteus mirabilis Providencia spp. Treponema pallidum

Species for which acquired resistance may be a problem

Gram-positive aerobes Staphylococcus epidermidis+ Staphylococcus haemolyticus+ Staphylococcus hominis+ Gram-negative aerobes Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli% Klebsiella pneumoniae% Klebsiella oxytoca% Morganella morganii Proteus vulgaris Serratia marcescens Anaerobes Bacteroides spp. Fusobacterium spp. Peptostreptococcus spp. Clostridium perfringens

Inherently resistant organisms

Gram-positive aerobes Enterococcus spp. Listeria monocytogenes Gram-negative aerobes Acinetobacter baumannii Pseudomonas aeruginosa Stenotrophomonas maltophilia Anaerobes Clostridium difficile Others Chlamydia spp. Chlamydophila spp. Mycoplasma spp. Legionella spp. Ureaplasma urealyticum

^£ All methicillin-resistant staphylococci are resistant to Ceftriaxone.

⁺ Resistance rates  >50% in  atleast one region

^% ESBL-producing strains are always resistant

Pharmacokinetic Properties

Absorption

After IV bolus administration of Ceftriaxone 500 mg and 1 g, mean peak plasma ceftriaxone levels are approximately 120 and 200 mg/L, respectively. After IV infusion of Ceftriaxone 500 mg, 1 g and 2 g, the plasma Ceftriaxone levels are approximately 80, 150 and 250 mg/L respectively.

Distribution

The volume of distribution of Ceftriaxone is 7–12 l. Concentrations well above the MICs of most relevant pathogens are detectable in tissue, including lungs, heart, biliary tract/liver, tonsil, middle ear and nasal mucosa, bone, and in cerebrospinal, pleural, prostatic and synovial fluids. An 8–15 % increase in mean peak plasma concentration (Cmax) is seen on repeated administration; steady state is reached in most cases within 48–72 hours depending on the route of administration.

Penetration into Particular Tissues

Ceftriaxone penetrates the meninges. Penetration is greatest when the meninges are inflamed. Mean peak Ceftriaxone concentrations in the cerebral spinal fluid (CSF) in patients with bacterial meningitis are reported to be up to 25% of plasma levels compared to 2% of plasma levels in patients with uninflamed meninges. Peak Ceftriaxone concentrations in the CSF are reached approximately 4–6 hours after IV injection. Ceftriaxone crosses the placental barrier and is excreted in the breast milk at low concentrations.

Protein-binding

Ceftriaxone is reversibly bound to albumin. Plasma protein-binding is about 95% at plasma concentrations below 100 mg/l. Binding is saturable and the bound portion decreases with rising concentration (up to 85% at a plasma concentration of 300 mg/L).

Biotransformation

Ceftriaxone is not metabolised systemically; it is converted to inactive metabolites by the gut flora.

Elimination

Plasma clearance of total Ceftriaxone (bound and unbound) is 10–22 ml/min. Renal clearance is 5–12 ml/min. Nearly 50–60% of Ceftriaxone is excreted unchanged in the urine, primarily by glomerular filtration, while 40–50% is excreted unchanged in the bile. The elimination half-life of total Ceftriaxone in adults is about 8 hours.

Patients with Renal or Hepatic Impairment

In patients with renal or hepatic dysfunction, the pharmacokinetics of Ceftriaxone is only minimally altered with the half-life slightly increased (less than twofold), even in patients with severely impaired renal function.

The relatively modest increase in half-life in renal impairment is explained by a compensatory increase in non-renal clearance, resulting from a decrease in protein-binding and corresponding increase in non-renal clearance of total Ceftriaxone.

In patients with hepatic impairment, the elimination half-life of Ceftriaxone is not increased, due to a compensatory increase in renal clearance. This is also due to an increase in plasma free fraction of Ceftriaxone contributing to the observed paradoxical increase in total drug clearance, with an increase in volume of distribution paralleling that of total clearance.

Geriatric Patients

In older people aged over 75 years, the average elimination half-life is usually two to three times that of young adults.

Paediatric Patients

The half-life of Ceftriaxone is prolonged in neonates. From birth to 14 days of age, the levels of free Ceftriaxone may be further increased by factors such as reduced glomerular filtration and altered protein-binding. During childhood, the half-life is lower than in neonates or adults.

The plasma clearance and volume of distribution of total Ceftriaxone are greater in neonates, infants and children than in adults.

Linearity/Non-Linearity

The pharmacokinetics of Ceftriaxone are non-linear and all basic pharmacokinetic parameters, except the elimination half-life, are dose-dependent if based on total drug concentrations, increasing less than proportionally with dose. Non-linearity is due to saturation of plasma protein-binding and is, therefore, observed for total plasma Ceftriaxone but not for free (unbound) Ceftriaxone.

Pharmacokinetic/Pharmacodynamic Relationship

As with other beta-lactams, the pharmacokinetic-pharmacodynamic index demonstrating the best correlation with in vivo efficacy is the percentage of the dosing interval that the unbound concentration remains above the MIC of Ceftriaxone for individual target species (i.e. %T > MIC).

Nonclinical Properties

Animal Toxicology or Pharmacology

There is evidence from animal studies that high doses of Ceftriaxone-calcium salt led to formation of concrements and precipitates in the gallbladder of dogs and monkeys, which proved to be reversible. Animal studies produced no evidence of toxicity to reproduction and genotoxicity. Carcinogenicity studies on Ceftriaxone were not conducted.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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 6months.

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 or mutagenic activity in these studies.

Impairment of Fertility

Ceftriaxone produced no impairment of fertility when given to rats at daily IV doses up to 586 mg/kg/day, approximately 20 times the recommended clinical dose of2 g/day.

Description

CEFBACT(Ceftriaxone) for injection is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for IV or IM administration.

Ceftriaxone sodium is chemically known as (6R,7R)-7--8-oxo-3-methyl]-5-thia-1 azabicyclooct-2-ene-2-carboxylic acid, 72-(Z)-(O-methyloxime), disodium salt, sesquaterhydrate.

The chemical formula of Ceftriaxone sodium is C₁₈H₁₆N₈Na₂O₇S₃•3.5H₂O.

CEFBACT(Ceftriaxone) for injection 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 colour of the ceftriaxone solution ranges from light-yellow to amber, depending on the length of storage, concentration and the diluent used.

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 TPN.

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.

Shelf-Life

As on the pack.

Packaging Information

Cefbact…………………..Vial of 10 ml

Storage & Handling Instruction

Store in a dry and dark place below 30°C. After reconstitution protection from normal light is not necessary.

Patient Counselling Information

● What CEFBACT (Ceftriaxone) for Injection is and what it is used for.

CEFBACT for injection contains Ceftriaxone, which is an antibiotic given to adults and children (including newborn babies). It works by killing bacteria that cause infections. It belongs to a group of medicines called cephalosporins.

Ceftriaxone for injection 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

• The bones and joints

• The skin or soft tissues

• The blood

• The heart

● What you need to know before you are given Ceftriaxone for injection.

You must not been given Ceftriaxone for injection in case of the following:

• You are allergic to Ceftriaxone or any of the other ingredients of this medicine.

• 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.

• You are allergic to Lidocaine and you are to be given Ceftriaxone for injection as an injection into a muscle.

Ceftriaxone for injection must not be given to babies if

• the baby is premature.

• the baby is newborn (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 for injection in case of the following:

• 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 gallstones 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.

• If you need a blood or urine test:
  • If you are given Ceftriaxone 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 that 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 for injection if

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

● Before taking Ceftriaxone for injection, tell your healthcare provider about other medicines.

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, breastfeeding and fertility

If you are pregnant or breastfeeding, 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 for injection against the risk to your baby.

Driving and using machines

Ceftriaxone 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 for injection

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

• a drip (IV infusion), or

• as an injection directly into a vein, or

• into a muscle.

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

Recommended dosage

Your doctor will decide the correct dose of Ceftriaxone 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 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)

• 1–2 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.

Newborn 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.

Newborn 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 Ceftriaxone 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 Ceftriaxone for injection than you should get

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

If you forget to take Ceftriaxone 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 taking Ceftriaxone for injection

Do not stop taking Ceftriaxone 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 of Ceftriaxone for injection.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects may happen with this medicine:

• Severe allergic reactions (not known, frequency cannot be estimated from the available data). If you have a severe allergic reaction, tell a doctor straight away. The signs may include the following:

- Sudden swelling of the face, throat, lips or mouth. This can make it difficult to breathe or swallow.

- Sudden swelling of the hands, feet and ankles.

• Severe skin reactions (not known, frequency cannot be estimated from the available data). If you get a severe skin reaction, tell a doctor straight away. The signs may include the following:

- A severe rash that develops quickly, with blisters or peeling of the skin and possibly blisters in the mouth. (Stevens-Johnson syndrome and toxic epidermal necrolysis, which are also known as SJS and TEN).

- A combination of any of the following symptoms: widespread rash, high body temperature, liver enzyme elevations, blood abnormalities (eosinophilia), enlarged lymph nodes and other body organs involvement (drug reaction with eosinophilia and systemic symptoms– also known as DRESS or drug hypersensitivity syndrome).

- Jarisch-Herxheimer reaction, which causes fever, chills, headache, muscle pain, and skin rash that is usually self-limiting. This occurs shortly after starting Ceftriaxone for injection treatment for infections with spirochete such as Lyme disease.

Other possible side effects

Common (may affect up to 1 in 10 people)

• Abnormalities with your white blood cells (such as a decrease of leucocytes and an increase of eosinophils) and platelets (decrease of thrombocytes).

• Loose stools or diarrhoea.

• Changes in the results of blood tests for liver functions.

• Rash.

Uncommon (may affect up to 1 in 100 people)

• Fungal infections (e.g. thrush).

• A decrease in the number of white blood cells (granulocytopenia).

• Reduction in number of red blood cells (anaemia).

• Problems with the way your blood clots. The signs may include bruising easily and pain and swelling of your joints.

• Headache.

• Dizziness.

• Feeling sick or being sick.

• Pruritus (itching).

• Pain or a burning feeling along the vein where Ceftriaxone for injection has been given. Pain at the site where the injection was given.

• A high temperature (fever).

• Abnormal kidney function test (blood creatinine increased).

Rare (may affect up to 1 in 1,000 people)

• Inflammation of the large bowel (colon). The signs include diarrhoea, usually with blood and mucus, stomach pain and fever.

• Difficulty in breathing (bronchospasm).

• A lumpy rash (hives) that may cover a lot of your body, feeling itchy and swelling.

• Blood or sugar in your urine.

• Oedema (fluid build-up).

• Shivering.

Not known (frequency cannot be estimated from the available data)

• A secondary infection that may not respond to the antibiotic previously prescribed

• Form of anaemia where red blood cells are destroyed (haemolytic anaemia).

• Severe decrease in white blood cells (agranulocytosis).

• Convulsions.

• Vertigo (spinning sensation).

• Inflammation of the pancreas (pancreatitis). The signs include severe pain in the stomach, which spreads to your back.

• Inflammation of the mucus lining of the mouth (stomatitis).

• Inflammation of the tongue (glossitis). The signs include swelling, redness and soreness of the tongue.

• Problems with your gallbladder, which may cause pain, feeling sick and being sick.

• A neurological condition that may occur in neonates with severe jaundice (kernicterus).

• Kidney problems caused by deposits of calcium Ceftriaxone. There may be pain when passing water (urine) or low output of urine.

• A false-positive result in a Coombs’ test (a test for some blood problems).

• A false-positive result for galactosaemia (an abnormal build-up of the sugar galactose).

• Ceftriaxone for injection may interfere with some types of blood glucose tests – please check with your doctor.

Reporting of side effects

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 180 3024or you can report to Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more information on the safety of this product.

● How to store Ceftriaxone for Injection.

• Keep this medicine out of the sight and reach of children.

• Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month

• The vials and bottles should not be stored above 30°C.

• Keep the vial or bottle in the outer carton in order to protect from light.

Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

Details of The Manufacturer:

Mfd. by: Zeiss Pharma Ltd.

Unit-II, IGC, SIDCO, Phase II,

Samba, Jammu -184121 (J&K)

Marketed by: Cipla Ltd.

Registered Office:

Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg,

Lower Parel, Mumbai 400013 INDIA.

Details of Licence Number:

JK/02/16-17/232

Date of Revision

19/04/2021