Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Hypersensitivity reactions
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported (see section 4.8). 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 cephalosporins 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 (Stevens Johnson syndrome or Lyell's syndrome/toxic epidermal necrolysis) and drug reaction with eosinophilia and systemic symptoms (DRESS)) which can be life-threatening or fatal, have been reported in association of ceftriaxone treatment; however, the frequency of these events is not known (see section 4.8).

Interaction with calcium containing products
Cases of fatal reactions with calcium-ceftriaxone precipitates in 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 intravenous 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 to other age groups.

In patients of any age ceftriaxone must not be mixed or administered simultaneously with any calcium- containing intravenous 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 which 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 (see sections 4.3, 4.8, 5.2 and 6.2).

Paediatric population
Safety and effectiveness of Ceftriaxone in neonates, infants and children have been established for the dosages described under Posology and Method of Administration (see section 4.2). 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 of developing bilirubin encephalopathy (see section 4.3).

Immune mediated haemolytic anaemia
An immune mediated haemolytic anaemia has been observed in patients receiving cephalosporin class antibacterials including ceftriaxone (see section 4.8). 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 pseudo-membranous 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 (see section 4.8). 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 insufficiency
In severe renal and hepatic insufficiency, close clinical monitoring for safety and efficacy is advised (see section 4.2).

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 (see section 4.8). Non- enzymatic methods for the glucose determination in urine may false- positive results. Urine glucose determination during therapy with Ceftriaxone should be done enzymatically (see section 4.8).

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

This medicinal product contains 3.6 mmol (or 83 mg) of sodium in a vial. 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 (see section 4.2). In polymicrobial infections, where suspected pathogens include organisms resistant to ceftriaxone, administration of an additional antibiotic should be considered.

Use of lidocaine
In case a lidocaine solution is used as a solvent, ceftriaxone solutions must only be used for intramuscular injection. Contraindications to lidocaine, warnings and other relevant information as detailed in the Physician's Information of lidocaine must be considered before use (see section 4.3). The lidocaine solution should never be administered intravenously.

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 (see section 4.8).

Biliary stasis
Cases of pancreatitis, possibly of biliary obstruction aetiology, have been reported in patients treated with ceftriaxone (see section 4.8). 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 (see section 4.8). 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.


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

Encephalopathy
Encephalopathy has been reported with the use of ceftriaxone (see section 4.8), particularly in elderly patients with severe renal impairment (see section 4.2) or central nervous system disorders. If ceftriaxone-associated encephalopathy is suspected (e.g. decreased level of consciousness, altered mental state, myoclonus, convulsions), discontinuation of ceftriaxone should be considered.

Effects on Driving

4.7 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 (see section 4.8). Patients should be cautious when driving or operating machinery.