CEFOTAXIME

Cefotaxime may be administered by intravenous bolus injection, by intravenous infusion, or by intramuscular injection, after reconstitution of the solution according to the directions given below. Dosage, route and frequency of administration should be based on the severity of the infection, susceptibility of the causative organism and the patient's condition.

Therapy may be started before the results of sensitivity tests are known. Cefotaxime and aminoglycosides should not be mixed in the same syringe or perfusion fluid.

Dose recommendations:

Adults and adolescents (12 to 16-18 years) The usual dose is 1 g cefotaxime every 12 hours. However, dosage may be varied according to the severity of the infection, sensitivity of causative organisms and condition of the patient. 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 hour 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 a sensitive 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 Severe infections 2-3g 8 h 6 h 6-9 g 8-12 g Infants, toddlers (28 days to 23 months) and children (2 to 11 years) The usual dose is 50 to 150 mg cefotaxime according to the severity of the infection per kilogram of body weight per day in 2 to 4 divided doses (every 12 - 6 hours).

In very severe infections up to 200 mg/kg/day divided into 2-4 doses may be required. For children >50 kg the adult dosage should be used, without exceeding the maximum daily dosage of 12 g. Neonates (0-27 days) The recommended dosage is 50 mg cefotaxime per kilogram of body weight per day in 2 to 4 divided doses (every 12-6 hours).

In case of life-threatening situations it may be necessary to increase the daily dose. For severe infections 150-200 mg/kg/day, in divided doses have been given. v. v.

Elderly:

No dosage adjustment is required, provided that the renal and hepatic functions are normal. 5 g – 1 g is administered (intramuscularly or intravenously). For complicated infections consideration should be given to available official guidelines.

Syphilis should be excluded before initiating the treatment. 1).

Bacterial meningitis:

Adults and adolescents over 12 years: In adults daily doses of 6 to 12 g divided into equal doses every 6 to 8 hours are recommended. Infants and children (from 1 month up to 12 years of age): 150 to 200 mg/kg divided into equal doses every 6 to 8 hours.

Neonates:

In neonates 0-7 days old 50 mg/kg cefotaxime may be administered every 12 hours and in infants 8 -28 days old every 8 hours.

Duration of therapy:

The duration of therapy with Cefotaxime depends on the clinical condition of the patient and varies according to the cause of the disease. Administration of Cefotaxime should be continued until symptoms have subsided or evidence of bacterial eradication has been obtained.

Treatment over at least 10 days is necessary in infections caused by Streptococcus pyogenes (parenteral therapy may be switched to an adequate oral therapy before the end of the 10 day period).

Impaired renal function:

In adult patients with a creatinine clearance of ≤ 5 ml/min, the initial dose is equal to the recommended usual dose but the maintenance dose should be reduced by half without change in the frequency of dosing. v. 5-2 g, administered at the end of each dialysis session and repeated every 24 hours, is sufficient to treat most infections effectively.

4). 6 In order to avoid any risk of infection, the reconstitution of the infusion should be done in close aseptic conditions. Do not postpone the infusion after the reconstitution of the solution.

Intravenous infusion:

For short intravenous infusion: Following reconstitution the solution should be administered as a 20 minute intravenous infusion.

For long lasting intravenous infusion:

Following reconstitution, the solution should be administered as a 50-60 minutes intravenous infusion. V. injections, the solution must be injected over a period of 3 to 5 minutes.

Intramuscular injection:

The solution should be administered by deep intramuscular injection. The following table shows the volume of dissolution for each vial size. 6.

g. 4) Renal and Urinary disorders Decrease in renal function/increase of creatinine (particularly when co-prescribed with aminoglycosides) Interstitial nephritis General disorders and administration site conditions For IM formulations: Pain at the injection site Fever Inflammatory reactions at the injection site, including phlebitis/ thrombophlebitis For IM formulations (sincethe solvent containslidocaine): Systematic reactions to lidocaine * Postmarketing experience Information about selected adverse reactions: Jarisch-Herxheimer reaction For the treatment of borreliosis (Lyme’s Disease), a Jarisch- Herxheimer reaction may develop during the first days of treatment.

The occurrence of oneor more of the following symptoms has been reported after several weeks’ treatment of borreliosis: skin rash, itching, fever, leucopenia, increase in liver enzymes, difficulty 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 andelicit 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 balanceof the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

8). If a hypersensitivity reactions 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. In patients with previously documented history of hypersensitivity to penicillins or other β-lactam antibiotics, special care is required.

Cross- sensitivity may occur with cephalosporin antibiotics, including cefotaxime. In this situation the possibility of anaphylactic reactions, which may be serious, or even fatal, should be borne in mind. Cefotaxime should be used with caution in patients with allergic diathesis and asthma.

8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur. 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 pseudo- membranous colitis. As with all cephalosporins, pseudomembranous colitis may rarely occur during or after treatment with cefotaxime. In patients developing fever, diarrhoea and abdominal cramps, the possibility of this diagnosis must be seriously considered.

If this occurs, the drug should be stopped immediately and investigation by sigmoidoscopy and stool culture conducted, followed by appropriate therapy as necessary. Clostridium difficile associated disease can be favoured by faecal stasis.

Medicinal products that inhibit peristalsis should not be given. • Haematological reactions Leukopenia, 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 cases of eosinophilia and thrombocytopenia, rapidly reversible on stopping treatment, have been reported.

8). 2; Posology and Method of Administration). 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). In case of severe infections, intramuscular injection is not recommended. It is recommended that no more than 4 ml is injected unilaterally. v. route is recommended. • 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. • Cefotaxime constituted with lidocaine should never be used: − by the intravenous route − in infants under 30 months − in subjects with a previous history of hypersensitivity to this product − in patients who have unpaced heart block − in patients with severe heart failure • The product information of the chosen lidocaine-containing medicinal product must be regarded.

09mmol) per gram, approximately 48mg per vial) should be taken into account if intended for use in patients on sodium-restricted diets (see section 2).

Hypersensitivity to cefotaxime or other cephalosporins. History of an acute and/or severe hypersensitivity to penicillin or any other type of beta-lactam antibiotic.