Special Warning : אזהרת שימוש

4.4.       Special warnings and precautions for use

As with other antibiotics, the use of cefotaxime, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. If superinfection occurs during therapy, appropriate measures should be taken (see section 4.8).


Anaphylactic reactions
Serious, including fatal hypersensitivity reactions have been reported in patients receiving cefotaxime (see sections 4.3 and 4.8).
If a hypersensitivity reaction occurs, treatment must be stopped.
The use of cefotaxime is strictly contra-indicated in subjects with a previous history of immediate- type hypersensitivity to cephalosporins.
Since cross allergy exists between penicillins and cephalosporins, use of the latter should be undertaken with extreme caution in penicillin sensitive subjects. Hypersensitivity reactions (anaphylaxis) occurring with these two antibiotic families may be serious or even fatal.


Severe skin reactions
Severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported post-marketing in association with cefotaxime treatment.
At the time of prescription patients should be advised of the signs and symptoms for skin reactions.
If signs and symptoms suggestive of these reactions appear, cefotaxime should be withdrawn immediately. If the patient has developed AGEP, SJS, TEN or DRESS with the use of cefotaxime, treatment with cefotaxime must not be restarted and should be permanently discontinued.
In children, the presentation of a rash can be mistaken for the underlying infection or an alternative infectious process, and physicians should consider the possibility of a reaction to cefotaxime in children that develop symptoms of rash and fever during therapy with cefotaxime.



Clostridium difficile associated disease (e.g. pseudomembranous colitis) Diarrhea, particularly if severe and/or persistent, occurring during treatment or in the initial weeks following treatment, may be symptomatic of Clostridium difficile associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudo- membranous colitis.
The diagnosis of this rare but possibly fatal condition can be confirmed by endoscopy and/or histology. It is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of cefotaxime.
If a diagnosis of pseudomembranous colitis is suspected, cefotaxime should be stopped immediately and appropriate specific antibiotic therapy should be started without delay. Clostridium difficile associated disease can be favoured by faecal stasis. Medicinal products that inhibit peristalsis should not be given.


Blood disorders
Leukopenia, neutropenia and, more rarely, bone marrow failure, pancytopenia or agranulocytosis may develop during treatment with cefotaxime. For treatment, courses lasting longer than 7-10 days, the blood white cell count should be monitored and treatment stopped in the event of neutropenia.
Some cases of eosinophilia and thrombocytopenia, rapidly reversible on stopping treatment, have been reported. Cases of haemolytic anemia have also been reported (see section 4.8).


Patients with renal insufficiency
The dosage should be modified according to the creatinine clearance calculated.

Caution should be exercised if cefotaxime is administered together with aminoglycosides or other nephrotoxic drugs (see section 4.5). Renal function must be monitored in these patients, the elderly, and those with pre-existing renal impairment.


Encephalopathy
Beta-lactams, including cefotaxime, predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment (see section 4.8).



Patients should be advised to contact their doctor immediately prior to continuing treatment if such reactions occur.


Precautions for administration
During post-marketing surveillance, potentially life-threatening arrhythmia has been reported in a very few patients who received rapid intravenous administration of cefotaxime through a central venous catheter. The recommended time for injection or infusion should be followed (see section 4.2).


See section 4.3 for contraindications for cefotaxime when reconstituted with lidocaine.

Effects on Laboratory Tests
As with other cephalosporins a positive Coombs' test has been found in some patients treated with cefotaxime. This phenomenon can interfere with the cross-matching of blood. Urinary glucose testing with non-specific reducing agents may yield false-positive results. This phenomenon is not seen when a glucose-oxydase specific method is used.


Sodium intake
Cefotaxime Medo 1 g vial contains approximately 48 mg (2.09 mmol) sodium per dose, equivalent to 2.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving