Cetafor (Ceftriaxone for Injection)

Cetafor (Ceftriaxone for Injection) Special warning and precautions for use

Special warning and precautions for use

Hypersensitivity reactions: As with all beta-lactam antibacterial agents, serious and occasionally fatalhypersensitivity reactions have been reported. In case of severe hypersensitivityreactions, treatment with ceftriaxone must be discontinued immediately andadequate emergency measures must be initiated. Before beginning treatment, itshould be established whether the patient has a history of severe hypersensitivityreactions to ceftriaxone, to other cephalosporins or to any other type of beta-lactamagent. Caution should be used if ceftriaxone is given to patients with a history of nonseverehypersensitivity to other beta-lactam agents. Severe cutaneous adversereactions (Stevens Johnson syndrome or Lyell’s syndrome/toxic epidermalnecrolysis) have been reported; however, the frequency of these events is not known.

Interaction with calcium containing products: Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and kidneys inpremature and full-term neonates aged less than 1 month have been described. Atleast one of them had received ceftriaxone and calcium at different times and throughdifferent intravenous lines. In the available scientific data, there are no reports ofconfirmed intravascular precipitations in patients, other than neonates, treated withceftriaxone and calcium-containing solutions or any other calcium- containing products.

Immune mediated haemolytic anaemia: An immune mediated haemolytic anaemia has been observed in patients receivingcephalosporin class antibacterials including Cetafor. Severe cases of haemolyticanaemia, including fatalities, have been reported during Cetafor treatment in bothadults and children. If a patient develops anaemia while on ceftriaxone, the diagnosisof 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 regularintervals.

Pseudo-membranous colitis: Antibacterial agent-associated colitis and pseudo-membranous colitis have beenreported with nearly all antibacterial agents, including ceftriaxone, and may range inseverity from mild to life-threatening. Therefore, it is important to consider thisdiagnosis in patients who present with diarrhoea during or subsequent to theadministration of ceftriaxone. Discontinuation of therapy with ceftriaxone and the administration of specific treatment for Clostridium difficile

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should be considered.

Medicinal products that inhibit peristalsis should not be given.

Overgrowth of non-susceptible microorganisms

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

Severe renal and hepatic insufficiency

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.

Use of lidocaine: In case a lidocaine solution is used as a solvent, ceftriaxone solutions must only beused for intramuscular injection. Contraindications to lidocaine, warnings and otherrelevant information as detailed in the Summary of Product Characteristics oflidocaine must be considered before use. The lidocaine solution should never beadministered intravenously.

Biliary lithiasis: When shadows are observed on sonograms, consideration should be given to thepossibility 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.

Biliary stasis: Cases of pancreatitis, possibly of biliary obstruction aetiology, have been reported inpatients treated with ceftriaxone. Most patients presented with risk factors for biliarystasis 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.

Pediatric population: Studies in neonates, infants and children have shown that ceftriaxone, like someother cephalosporins, can displace bilirubin from serum albumin. Cetafor iscontraindicated in premature and full-term neonates at risk of developing bilirubin encephalopathy.

Interactions with other medicinal products and other forms of interactions

  • Calcium-containing diluents, such as Ringer’s solution or Hartmann’s solution, should not be used to reconstitute Cetafor 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 calciumcontaining 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.
  • 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.

Contraindications

  • Hypersensitivity to ceftriaxone, 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).
  • Premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age).
  • 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, leading to a possible risk of bilirubin encephalopathy.
  • Contraindications to lidocaine must be excluded before intramuscular injection of ceftriaxone when lidocaine solution is used as a solvent in patients who have hypersensitivity to local anaesthetics and who have heart block. Ceftriaxone solutions containing lidocaine should never be administered intravenously.

Pregnancy, lactation and fertility

Pregnancy: Ceftriaxone crosses the placental barrier. There are limited amounts of data from theuse of ceftriaxone in pregnant women. Animal studies do not indicate direct or indirectharmful effects with respect to embryonal, foetal, perinatal and postnataldevelopment. Ceftriaxone should only be administered during pregnancy and inparticular in the first trimester of pregnancy if the benefit outweighs the risk.

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Lactation: Ceftriaxone is excreted into human milk in low concentrations but at therapeutic dosesof ceftriaxone no effects on the breastfed infants are anticipated. However, a risk ofdiarrhoea and fungal infection of the mucous membranes cannot be excluded. Thepossibility of sensitization should be taken into account. A decision must be madewhether to discontinue breast-feeding or to discontinue the treatment with ceftriaxone,taking into account the benefit of breast feeding for the child and the benefit of therapyfor the woman.

Fertility: Reproductive studies have shown no evidence of adverse effects on male or femalefertility.

Effects on the 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,leucopenia, thrombocytopenia, diarrhoea, rash, and hepatic enzymes increased.

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 of overdose should be symptomatic.

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