CEFTRIAXONE

6). Following reconstitution, a colourless solution is produced. Dosage and method of administration should be determined by the severity of the infection, susceptibility of the causative organism and the patient's condition. Usually a once daily dose will give satisfactory therapeutic results.

In some indications (see below), a single dose is sufficient. Adults and children over 12 years of age Standard therapeutic dosage: 1g once a day. Severe infections: 2 - 4g daily, normally as a single dose every 24 hours. The duration of therapy should be varied according to the course of the disease.

As with antibiotic therapy in general, administration of ceftriaxone should be continued for a minimum of 48 to 72 hours after the patient has become afebrile or as soon as there is evidence of bacterial eradication.

Acute, uncomplicated gonorrhoea:

A single dose of 250mg intramuscularly should be administered. Simultaneous administration of probenecid is not indicated.

Peri-operative prophylaxis:

Usually 1g as a single intramuscular or slow intravenous dose. In colorectal surgery, 2g should be given intramuscularly or by slow intravenous infusion, in conjunction with a suitable agent against anaerobic bacteria. Elderly As for adult dose, subject to normal hepatic and renal function.

Neonates, infants and children up to 12 years The following dosage schedules are recommended for once daily administration: Neonates A daily dose of 20 - 50mg/kg body weight, not to exceed 50mg/kg. 4). Infants and children of up to 12 years Standard therapeutic dosage: 20 - 50mg/kg body weight once daily.

In severe infections up to 80mg/kg body weight daily may be given. For children with bodyweights of 50kg or more, the usual adult dosage should be given. Doses of 50mg/kg or over should be given by slow intravenous infusion over at least 30 minutes.

Doses greater than 80mg/kg body weight should be avoided except in meningitis (see Special dosage recommendations).

Special dosage recommendations:

Meningitis: Treatment is initiated with 100mg/kg bodyweight once daily – not exceeding 4g daily. After determining the sensitivity of the pathogen, the dose may be reduced accordingly. In new born infants 0-14 days of age the dose should not exceed 50mg/kg/24h Renal and hepatic impairment In patients with impaired renal function, there is no need to reduce the dosage of ceftriaxone provided liver function is normal.

Only in cases of pre-terminal renal failure (creatinine clearance < 10ml per minute) should the daily dosage be limited to 2g or less. In patients with liver damage there is no need for the dosage to be reduced provided renal function is normal.

In severe renal impairment accompanied by hepatic insufficiency, the plasma concentration of ceftriaxone should be determined at regular intervals and dosage adjusted accordingly. In patients undergoing dialysis, no additional supplementary dosing is required following the dialysis.

Serum concentrations should be monitored however, to determine whether dosage adjustments are necessary, since the elimination rate in these patients may be reduced.

Rarely, severe adverse reactions have been reported in preterm and full-term newborns. These reactions have caused death in some cases. These newborns had been treated with intravenous ceftriaxone and calcium. Some of them had received ceftriaxone and calcium at different times and on different intravenous lines.

Precipitations of ceftriaxone-calcium salt have been observed in lungs and kidneys of these dead preterm newborns. The high risk of precipitation was due to the low blood volume of the newborns. Moreover the half life is longer than in adults.

The most frequently reported adverse events for ceftriaxone are diarrhoea, nausea and vomiting. Other reported adverse events include hypersensitivity reactions such as allergic skin reactions and anaphylactic reactions, secondary infections with yeast, fungi or resistant organisms as well as changes in blood cell counts.

1%): Mycosis of the genital tract. Superinfections of various sites with yeasts, fungi or other resistant organisms are possible. 1%): Neutropenia, leucopenia, eosinophilia, thrombocytopenia, anaemia (including haemolytic anaemia), slight prolongation of prothrombin time.

01 %) including isolated reports: Positive Coombs' test, coagulation disorders, agranulocytosis (< 500/m3), mostly after 10 days of treatment and following total doses of 20g ceftriaxone and more. g. 1%): Headache, dizziness. Gastrointestinal disorders Common ( 1% - < 10%): Loose stools or diarrhoea, nausea, vomiting.

1%): Stomatitis, glossitis. These side effects are usually mild and commonly disappear during treatment or after discontinuation of treatment. 01%) including isolated reports: Pseudomembranous colitis (mostly caused by Clostridium difficile), pancreatitis (possibly caused by obstruction of bile ducts).

1%): Increase in serum liver enzymes (AST, ALT, alkaline phosphatase). 4), mostly in patients treated with doses higher than the recommended standard dose. In children, prospective studies have shown a variable incidence of precipitation with intravenous application, in some studies to above 30 %.

The incidence seems to be lower with slow infusion (20-30 minutes). This effect is usually asymptomatic, but in rare cases, the precipitations have been accompanied by clinical symptoms such as pain, nausea and vomiting. Symptomatic treatment is recommended in these cases.

Precipitation is usually reversible upon discontinuation of ceftriaxone. 1% - < 1%): Allergic skin reactions such as maculopapular rash or exanthema, urticaria, dermatitis, pruritis, oedema. 01%) including isolated reports: Erythema multiforme, Stevens Johnson Syndrome, Lyell's Syndrome/toxic epidermal necrolysis.

1%): Increase in serum creatinine, oliguria, glycosuria, haematuria. 01%) including isolated reports: Renal precipitation, mostly in children older than 3 years who have been treated with either high daily doses (80 mg/kg/day and more) or total doses exceeding 10g and with other risk factors such as dehydration or immobilisation.

Renal precipitation is reversible upon discontinuation of ceftriaxone. Anuria and renal impairment have been reported in association. 1%): Phlebitis and injection site pain following intravenous administration. This can be minimised by slow injection over at least 2-4 minutes.

Rigors, pyrexia. An intramuscular injection without lidocaine is painful.

Before therapy with ceftriaxone is instituted, careful inquiry should be made to determine whether the patient has had any previous hypersensitivity reactions to ceftriaxone, any other cephalosporin, or to any penicillin or other beta- lactam drug.

Ceftriaxone 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 beta-lactam drug.

Ceftriaxone should be given with caution to patients who have had any other type of hypersensitivity reaction to a penicillin or any other beta-lactam drug. Ceftriaxone should be given with caution to patients who have other allergic diatheses Antibiotic-associated diarrhoea, colitis and pseudomembranous colitis have all been reported with the use of ceftriaxone.

These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment. Ceftriaxone should be discontinued if severe and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted.

Ceftriaxone should be used with caution in individuals with a previous history of gastro-intestinal disease, particularly colitis. As with other cephalosporins, prolonged use of ceftriaxone may result in the overgrowth of non-susceptible organisms, such as enterococci and Candida spp.

2. In vivo and in vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Clinical data obtained in neonates have confirmed this finding. ceftriaxone should therefore not be used in jaundiced new-borns or in those who are hypoalbuminaemic or acidotic, in whom bilirubin binding is likely to be impaired.

8). This can happen in patients of any age but is more likely in infants and small children who are usually given a larger dose of ceftriaxone on a body weight basis. In children, doses greater than 80mg/kg body weight should be avoided (except in meningitis) because of the increased risk of biliary precipitates.

There is no clear evidence of gallstones or of acute cholecystitis developing in children or infants treated with ceftriaxone. As the condition appears to be transient and reversible upon discontinuation, therapeutic procedures are not normally indicated Cephalosporin antibiotics tend to be absorbed onto the surface of the red cell membranes and react with antibodies directed against the drug to produce a positive Coombs' test and occasionally a rather mild haemolytic anaemia.

In this respect, there may be some cross-reactivity with penicillins. Cases of pancreatitis, possibly of biliary obstruction aetiology, have been rarely reported in patients treated with ceftriaxone. g. preceding major therapy, severe illness and total parenteral nutrition.

A trigger or cofactor role of ceftriaxone-related biliary precipitation cannot be ruled out.

Known hypersensitivity to ceftriaxone or to any of the cephalosporins. Previous immediate and/or severe hypersensitivity reaction to a penicillin or to any other type of beta-lactam In neonates with jaundice or those who are hypoalbuminaemic, acidotic or have other conditions, such as prematurity, in which bilirubin binding is likely to be impaired.

Calcium treatment because of the risk of precipitation of ceftriaxone-calcium salt in term newborn.