Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2017 Publisher: Villerton Invest SA, Rue Edward Steichen 14, 2540 Luxembourg
Known or suspected hypersensitivity to Cefotaxime or other cephalosporins. Allergic cross-reactions can exist between penicillins and cephalosporins (see section 4.4).
Cefotaxime constituted with Lidocaine Injection BP must never be used:
As with other antibiotics, the use of cefotaxime, especially if prolonged, may result in overgrowth of non-susceptible organisms. Repeated evaluation of the patients condition is essential. If superinfection occurs during treatment, appropriate measures should be taken.
Cefotaxime should be used with caution in persons with a history of allergies or asthma.
Preliminary enquiry about hypersensitivity to penicillin and other β-lactam antibiotics is necessary before prescribing cephalosporins since cross allergy occurs in 5-10% of cases. Use of cephalosporins should be undertaken with extreme caution in penicillin-sensitive subjects.
Hypersensitivity reactions (anaphylaxis) occurring with the two types of antibiotics can be serious and occasionally fatal (see sections 4.3 and 4.8). If a hypersensitivity reaction occurs, treatment must be stopped.
The use of cefotaxime is strictly contraindicated in subjects with a history of immediate-type hypersensitivity to cephalosporins.
Cases of serious bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with cefotaxime (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.
Diarrhoea, 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 pseudomembranous colitis.
The diagnosis of this rare but potentially 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.
Leucopenia, neutropenia and more rarely, agranulocytosis, may develop during treatment with cefotaxime, particularly if given over long periods. 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 case of eosinophilia and thrombocytopenia, rapidly reversible on stopping treatment, have been reported. Cases of haemolytic anaemia have also been reported (see section 4.8).
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.
High doses of beta lactam antibiotics including cefotaxime, particularly in patients with renal insufficiency, may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions) (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 formulations reconstituted with lidocaine.
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-oxidase specific method is used.
The sodium content of this product (48.2 mg/g) should be taken into account when prescribing to patients requiring sodium restriction.
As far as possible, Cefotaxime should not be combined with substances having a bacteriostatic action (e.g. tetracycline, erythromycin, chloramphenicol or sulfonamides), since antagonistic effect has been observed regarding the anti-bacterial effect in vitro. A synergistic effect can result with the combination with aminoglycosides.
An increased risk of oto- and nephrotoxicity has been reported when cefotaxime has been used concomitantly with cephalosporins or aminoglycosides. Dose adjustment may be necessary, and the kidney function must be watched (see 4.2 Posology).
The simultaneous administration of Probenecid leads to higher, more prolonged plasma concentrations of Cefotaxime by interfering with renal tubular transfer thereby delaying excretion.
In combination with potentially nephrotoxic drugs (such as, for example, aminoglycoside antibiotics, polymyxin B and colistin) and with potent diuretics, (e.g. furosemide) the kidney function should be monitored (see section 4.4), since the nephrotoxicity of the substances quoted may be accentuated.
False positives may occur in the Coombs-Test in rare cases during treatment with cefotaxime.
In glucose determinations in urine and blood, false positive as well as false negative results may also be obtained, depending on the method; these may be avoided by the use of enzymatic methods.
The safety of cefotaxime has not been established in human pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. There are however no adequate and well controlled studies in pregnant women.
Cefotaxime passes through the human placenta. Therefore, Cefotaxime should only be used during pregnancy if the anticipated benefit outweighs any potential risks.
Cefotaxime is excreted in human milk in low concentrations. Use during lactation can lead in infants to an effect on the physiological intestinal flora with diarrhoea, colonisation by yeast-like fungi and may also lead to sensitisation of the infant. Therefore a decision must be made whether to discontinue breast-feeding or to discontinue therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the mother.
There is no evidence that cefotaxime impairs the ability to drive or operate machinery.
High doses of cefotaxime, particularly in patients with renal insufficiency, may cause encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions) (see section 4.8). Patients should be advised not to drive or operate machinery if any such symptoms occur.
Adverse reactions to cefotaxime sodium have occurred relatively infrequently and have generally been mild and transient.
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from available data)*
Not known: Superinfection (see section 4.4)
Uncommon: Leucopoenia, Eosinophilia, Thrombocytopenia
Not known: Neutropenia, agranulocytosis (see section 4.4), haemolytic anaemia
Uncommon: Jarisch-Herxheimer reaction
Not known: Anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock
Uncommon: Convulsions (see section 4.4)
Not known: Headache, dizziness, encephalopathy (e.g. impairment of consciousness, abnormal movements) (see section 4.4)
Not known: Arrhythmia following rapid bolus infusion through central venous catheter
Uncommon: Diarrhoea
Not known: Nausea, vomiting, abdominal pain, pseudomembranous colitis (see section 4.4)
Uncommon: Increase in liver enzymes (ALAT, ASAT, LDH, gamma GT and or alkaline phosphatase) and/or bilirubin
Not known: Hepatitis* (sometimes with jaundice)
Uncommon: Rash, pruritis, urticaria
Not known: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (see section 4.4)
Uncommon: Decrease in renal function/increase of creatinine (particularly when co-prescribed with aminoglycosides)
Not known: Interstitial nephritis
Very common: Pain at the injection site
Uncommon: Fever, Inflammatory reactions at the injection site including phlebitis, thrombophlebitis
Not known: Systemic reactions to lidocaine (if reconstituted with lidocaine)
* post-marketing experience
For the treatment of borreliosis, a Jarisch-Herxheimer reaction may develop during the first days of treatment. The occurrence of one or more of the following symptoms has been reported after several weeks of treatment of borreliosis: skin rash, itching, fever, leucopenia, increase in liver enzymes, difficulty in breathing, joint discomfort
Increase in liver enzymes (ALAT, ASAT, LDH, gamma-GT and/or alkaline phosphatase) and/or bilirubin have been observed. These laboratory abnormalities may rarely exceed twice the upper limit of the normal range and elicit a pattern of liver injury, usually cholestatic and most often asymptomatic.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the yellow card scheme at: www.mhra.gov.uk/yellowcard
None known.
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