STOPAREN Powder and solvent for solution for injection Ref.[4799] Active ingredients: Cefotaxime

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. Cefotaxime is contraindicated in patients who have had a previous hypersensitivity reaction to any cephalosporin. It is also contraindicated in patients who have had a previous immediate and/or any severe hypersensitivity reaction to any penicillin or to any other betalactam drug (see section 4.3, Contraindications). Cefotaxime should be given with caution to patients who have had any other type of hypersensitivity reaction to a penicillin or any other betalactam drug. Hypersensitivity reactions (anaphylaxis) occurring with the two types of antibiotics can be serious and occasionally fatal. Hypersensitivity requires that treatment be stopped.

Patients with severe renal dysfunction should be placed on the dosage schedule recommended under “Posology and Method of Administration”.

Since haematological abnormalities may develop during treatment with cefotaxime, blood count should be monitored if treatment lasts for longer than 7 days. In case of neutropenia (<1400 neutrophils/mm³), treatment should be interrupted.

As with other antibiotics, the use of cefotaxime, especially if prolonged, may result in overgrowth of non susceptible organisms, such as Enterococcus spp, candida, Pseudomonas aeruginosa. Repeated evaluation of the condition of the patient is essential. If super infection occurs during treatment with cefotaxime, specific antimicrobial therapy should be instituted if considered clinically necessary.

The sodium content of cefotaxime (2.09mmol/g) should be taken into account when prescribing to patients requiring sodium restriction.

Cefotaxime may predispose patients to pseudomembranous colitis. Although any antibiotic may predispose to pseudomembranous colitis, the risk is higher with broad spectrum drugs, such as cephalosporins. This side effect, which may occur more frequently in patients receiving higher doses for prolonged periods, should be considered as potentially serious. The presence of C. difficile toxin should be investigated, and treatment with cefotaxime stopped in cases of suspected colitis. Diagnosis can be confirmed by toxin detection and specific antibiotic therapy (e.g. oral vancomycin or metronidazole) should be initiated if considered clinically necessary. The administration of products which cause faecal stasis should be avoided.

Aminoglycoside antibiotics and diuretics

Cephalosporin antibiotics at high dosage should be given with caution to patients receiving aminoglycoside antibiotics or potent diuretics such as frusemide as these combinations are suspected to adversely affect renal function. However, at the recommended doses, enhancement of nephrotoxicity is unlikely to be a problem with cefotaxime.

Uricosurics

Probenecid interferes with renal tubular transfer of cefotaxime delaying its excretion and increasing the plasma concentration.

Interference with Laboratory Tests

A false positive Coombs test may be seen during treatment with cephalosporins. This phenomenon may occur during treatment with cefotaxime and can interfere with blood cross-matching.

A false positive reaction to urinary glucose may occur with copper reduction methods (Benedict’s, Fehling’s or Clinitest) but not with the use of specific glucose oxidase methods.

Pregnancy

It is known that cefotaxime crosses the placental barrier. Although studies in animals have not shown an adverse effect on the developing foetus, the safety of cefotaxime in human pregnancy has not been established. Consequently, cefotaxime should not be administered during pregnancy especially during the first trimester, without carefully weighing the expected benefit against possible risks.

Lactation

Cefotaxime is excreted in the milk in small amounts and is usually compatible with breast feeding, but careful monitoring of the infant is recommended. Consequently caution should be exercised when cefotaxime is administered to a nursing woman.

There is no evidence that cefotaxime affect the ability to drive or operate machinery.

Adverse reactions to cefotaxime have occurred relatively infrequently and have generally been mild and transient.

Effects reported include the following:

Genito urinary: Candidiasis

Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhoea (diarrhoea may sometimes be a symptom of pseudomembranous colitis see 4.4, Special Warnings and precautions for use).

Hepatobiliary: Transient rises in liver transaminases, alkaline phosphatase and/or bilirubin, transient hepatitis and cholestatic jaundice.

Renal: As with other cephalosporins, changes in renal function have been rarely observed with high doses of cefotaxime, particularly when co-prescribed with aminoglycosides. Rare cases of interstitial nephritis have been reported in patients treated with cefotaxime.

Nervous system: Headache, dizziness. Administration of high doses of cephalosporins, particularly in patients with renal insufficiency, may result in encephalopathy (e.g. impairment of consciousness, abnormal movements and convulsions).

Hypersensitivity: Hypersensitivity reactions have been reported. These include skin rashes, pruritus and less frequently urticaria, drug fever and very rarely anaphylaxis (e.g. angioedema and bronchospasm possibly culminating in shock). As with other cephalosporins, occasional cases of bullous reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme have also been reported. Serum levels of cefotaxime may be reduced by peritoneal dialysis or haemodialysis. In the case of overdosage, particularly in renal insufficiency, there is a risk of reversible encephalopathy.

Blood and lymphatic system: As with other beta-lactam antibiotics, granulocytopenia and more rarely agranulocytosis may develop during treatment with cefotaxime, particularly if given over long periods. A few cases of eosinophilia and neutropenia have been observed, reversible when treatment is ceased. Some cases of rapidly reversible eosinophilia and thrombocytopenia on stopping treatment, have been reported. Rare cases of haemolytic anaemia have been reported. For cases of treatment lasting longer than 10 days, blood count should therefore be monitored.

Cardiac: Avery small number of cases of arrhythmias have occurred following rapid bolus infusion through a central venous catheter.

Local effects: Transient pain may be experienced at the site of injection. This is more likely to occur with higher doses. Occasionally, phlebitis has been reported in patients receiving intravenous cefotaxime. However, this has rarely been a cause for discontinuation of treatment.

The following symptoms have occurred after several weeks of treatment for borreliosis (Lyme’s Disease): skin rash, itching, fever, leucopenia, increases in liver enzymes, difficulty of breathing, joint discomfort. To some extent these manifestations are consistent with the symptoms of the underlying disease, for which the patient is being treated.

Cefotaxime sodium should not be mixed with alkaline solutions such as sodium bicarbonate injection or solutions containing aminophylline.

Cefotaxime should not be admixed with aminoglycosides. If they are used concurrently they should be administered in separate sites.

Cefotaxime should not be mixed with other medicinal products except those listed in section 5.6.