CEFOTAXIME

Cefotaxime sodium may be administered intravenously, by bolus injection or infusion, or intramuscularly. The dosage, route and frequency of administration should be determined by the severity of infection, the sensitivity of causative organisms and condition of the patient.

Therapy may be initiated before the results of sensitivity tests are known. The clinician should consult published protocols for information on dosage regimens in specific conditions such as gonorrhoea, Pseudomonas infections and CNS infections.

Dosage and type of administration depend on the severity of the infection, the sensitivity of the bacterium and the condition of the patient. The duration of the treatment depends on the course of the disease. As a general rule Cefotaxime is administered for a further 3 to 4 days after improvement/regression of the symptoms.

Adults and children over 12 years in general receive 1 g Cefotaxime every 12 hours. In severe cases, the daily dose can be increased up to 12 g. Daily doses up to 6 g can be divided into at least two individual administrations at 12 hourly intervals.

Higher daily doses must be divided into at least 3 to 4 individual administrations at 8 or 6 hour intervals respectively.

The following table may serve as a guide to dosages:

Type of Infection Single Dose Cefotaxime Dose Interval Daily Dose Cefotaxime Typical infections, in which sensitivity is demonstrated and bacterium is proven or suspected 1 g 12 h 2 g Infections, in which various bacteria with high to medium sensitivity are demonstrated or suspected 2 g 12 h 4 g Unclear bacterial illness which cannot be localised and where the patient is critically ill 2 – 3 g 8 h up to 6 h up to 6 h 6 g up to 8 g up to 12 g For the treatment of gonorrhoea in adults, 1 vial of Cefotaxime 500mg powder for solution for injection or infusion administered as a single administration.

e. 1 g Cefotaxime. Examination for syphilis needs to be carried out before commencing therapy. Perioperative Prophylaxis For peri-operative infection prophylaxis the administration of a single dose of 1 to 2 g Cefotaxime 30 to 60 minutes prior to the operation is recommended.

Another antibiotic to cover anaerobic organisms is necessary. A repeat dose is required if the duration of the operation exceeds 90 minutes.

Special Dose Recommendations Lyme borrelisosis:

A daily dose of 6 g Cefotaxime (14 to 21 days duration). The daily dose was generally administered divided into 3 parts (2 g Cefotaxime 3 times daily). Infants and children up to 12 years receive 50 to 100 mg Cefotaxime according to the severity of the infection (up to 150 mg) per kilogram of body weight per day, divided into equal doses, administered at 12 (up to 6) hour intervals.

In individual cases – particularly in life threatening situations – it may be necessary to increase the daily dose to 200 mg Cefotaxime per kilogram of body weight. In neonates and infants doses of 50 mg Cefotaxime per kilogram of body weight per day should not be exceeded in view of not fully matured kidney clearance.

In case of life-threatening situations it may be necessary to increase the daily dose. In those situations the following table is recommended. Age Daily Dose of Cefotaxime 0 – 7 days 50 mg/kg every 12 hours IV 7 days – 1 month 50 mg/kg every 8 hours IV > 1 month 75 mg/kg every 8 hours IV It is not necessary to differentiate between premature and normal-gestational age infants.

Dosage in the Case of Impaired Renal Function With patients with a creatinine clearance of 20ml/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. 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.

Elderly Patients No dosage adjustments are needed in patients with normal function.

Other Advice Electrolyte content of the injections solutions:

Since Cefotaxime is available as the sodium salt, the sodium content per dose should be taken into account within the framework of the overall therapy and with special balance checks. 1 mmol sodium. Posology and Method of Administration Intravenous Injection For IV, Cefotaxime 500mg powder for solution for injection or infusion is dissolved in at least 2 ml water for injections, Cefotaxime 1 g powder for solution for injection or infusion in at least 4 ml and subsequently injected directly into the vein over 3 to 5 minutes or after clamping of the infusion tube into the distal end of the tube.

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. Infusion For brief infusion 2g of Cefotaxime powder for solution for injection or infusion is dissolved in 100 ml of isotonic sodium chloride or glucose solution and subsequently IV infused over 50 to 60 minutes.

Another compatible infusion solution can also be used for the solution. Intramuscular Injection For intramuscular injection. Cefotaxime 500mg powder for solution for injection or infusion is dissolved in 2 ml and Cefotaxime 1 g powder for solution for injection or infusion in 4 ml water for injections respectively.

Afterwards the injection should take place deep into the gluteal muscle. Pain with the IM injection can be avoided by dissolving Cefotaxime 500mg powder for solution for injection or infusion in 2ml or Cefotaxime 1 g powder for solution for […]

Adverse reactions to cefotaxime sodium have occurred relatively infrequently and have generally been mild and transient. g. 4) Renal and urinary disorders Decrease in renal function/increas e of creatinine (particularly when co- prescribed with aminoglycoside s) Interstitial nephritis General disorders and administratio n site conditions Pain at the injectio n site Fever Inflammatory reactions at the injection site including phlebitis, thrombophlebiti s 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. Reporting of suspected adverse reactions 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. uk/yellowcard

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.

Anaphylactic reactions 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.

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. Severe skin reaction 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.

g. pseudomembranous colitis) 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. Haematological reactions 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.

8). Patients with renal insufficiency The dosage should be modified according to the creatinine clearance calculated. 5). Renal function must be monitored in these patients, the elderly and those with pre-existing renal impairment. g. 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.

2). 3 for contraindications for formulations 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-oxidase specific method is used. 2 mg/g) should be taken into account when prescribing to patients requiring sodium restriction.

Known or suspected hypersensitivity to Cefotaxime or other cephalosporins. 4). Cefotaxime constituted with Lidocaine Injection BP must never be used: - by the intravenous route - in infants under 30 months of age - in subjects with a previous history of hypersensitivity to Lidocaine or other local anaesthetics of the amide type - in patients who have a non-paced heart block - in patients with severe heart failure.