Cefotaxime Other names: Cephotaxime

With patients with a creatinine clearance of 20 ml/minute or less, the maintenance dose is reduced to half the normal dose. With patients with a creatinine clearance of 5 ml/minute or less, a reduction of the maintenance dose to 1 g cefotaxime (divided into 2 individual administrations at 12 hour intervals), seems to be appropriate. The stated recommendations are based on experiences with adults.

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, since the nephrotoxicity of the substances quoted may be accentuated.

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.

The simultaneous administration of probenecid leads to higher, more prolonged plasma concentrations of cefotaxime by interfering with renal tubular transfer thereby delaying excretion.

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.

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

Since cefotaxime is to a large extent eliminated by haemodialysis, an additional dose should be administered to patients who are dialysed, after the dialysis procedure.

Cases of serious bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with cefotaxime. Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

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. 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.

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.

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). 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)*

Infections and infestation

Not known: Superinfection

Blood and the lymphatic system disorders

Uncommon: Leucopoenia, Eosinophilia, Thrombocytopenia

Not known: Neutropenia, agranulocytosis, haemolytic anaemia

Immune system disorders

Uncommon: Jarisch-Herxheimer reaction

Not known: Anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock

Nervous system disorders

Uncommon: Convulsions

Not known: Headache, dizziness, encephalopathy (e.g. impairment of consciousness, abnormal movements)

Cardiac disorders

Not known: Arrhythmia following rapid bolus infusion through central venous catheter

Gastro-intestinal disorders

Uncommon: Diarrhoea

Not known: Nausea, vomiting, abdominal pain, pseudomembranous colitis

Hepato-biliary disorders

Uncommon: Increase in liver enzymes (ALAT, ASAT, LDH, gamma GT and or alkaline phosphatase) and/or bilirubin

Not known: Hepatitis* (sometimes with jaundice)

Skin and subcutaneous tissue disorders

Uncommon: Rash, pruritis, urticaria

Not known: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis

Renal and urinary disorders

Uncommon: Decrease in renal function/increase of creatinine (particularly when co-prescribed with aminoglycosides)

Not known: Interstitial nephritis

General disorders and administration site conditions

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

Jarisch-Herxheimer reaction

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

Hepatobiliary disorders

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.