|The undesirable effects usually are mild and short-term.Rarely, severe, and in some cases fatal, adverse reactions have been reported in preterm and full term newborns (aged <28 days) who had been treated with intravenous ceftriaxone and calcium. Precipitations of ceftriaxone-calcium salt have been observed in lung and kidneys post-mortem. The high risk of precipitation in newborns is due to their low blood volume and the longer half life of ceftriaxone compared with adults (see sections 4.3, 4.4 and 5.2).Ceftriaxone must not be mixed or administered simultaneously with calcium-containing solutions or products, even via different infusion lines.|
Gastrointestinal Common (≥ 1% - <10%): Loose stools or diarrhoea (diarrhoea may sometimes be a symptom of pseudomembranous colitis, see 4.4 Special warnings and precautions for use), nausea, vomiting, stomatitis and glossitis. Rare (≥ 0.01% - < 0.1%): Abdominal pain.
InfectionsSuperinfection caused by microorganisms non-susceptible to ceftriaxone such as yeasts, fungi (mycosis of the genital tract) or other resistant microorganisms may develop. Pseudomembranous colitis is a rare undesirable effect caused by infection with Clostridium difficile during treatment with ceftriaxone. Therefore, the possibility of the disease should be considered in patients who present with diarrhoea following antibacterial agent use.
Hypersensitivity Uncommon (≥ 0.1% - < 1%): Maculopapular rash or exanthema, pruritus, urticaria, oedema, shivering and anaphylactic or anaphylactoid reactions (e.g. bronchospasm) and allergic dermatitis have occurred. Rare (≥ 0.01% - < 0.1%): Drug fever, shivering. Anaphylactic-type reactions such as bronchospasm are rare.Very rare (< 0.01%): Isolated cases of severe cutaneous adverse reactions (erythema multiforme, Stevens Johnson Syndrome and Lyell's Syndrome/toxic epidermal necrolysis) have been reported.
Blood and lymphatic system disorders Common (≥1% - ≤10%):Haematological reactions have included anaemia (all grades), haemolytic anaemia, granulocytopenia, leucopenia, neutropenia, thrombocytopenia and eosinophilia. Coagulation disorders have been reported as very rare side effects.Unknown frequency of agranulocytosis (<500/mm3) has been reported, mostly after 10 days of treatment and following total doses of 20g or more. There have been rare reports of fatal haemolysis in association with ceftriaxone. Ceftriaxone has rarely been associated with prolongation of prothrombin time, however, bleeding and bruising due to hypoprothrombinaemia may be more prevalent in patients with renal or hepatic impairment, malnourished patients or those with low vitamin K levels and patients receiving prolonged ceftriaxone therapy.
Central Nervous systemRare (≥ 0.01% - < 0.1%): Headache, vertigo and dizziness. Administration of high doses of cephalosporins, particularly in patients with renal insufficiency, may result in convulsions.
Renal and UrinaryRare (≥ 0.01% - < 0.1%): Glycosuria, oliguria, haematuria, increase in serum creatinine. Very rare (< 0.01%): Cases of renal precipitation have been reported, mostly in children older than 3 years and who have been treated with either high daily doses (e.g.≥ 80mg/kg/day) or total doses exceeding 10 grams and presenting other risk factors (e.g. fluid restrictions, confinement to bed, etc.). The risk of precipitate formation is increased in immobilized or dehydrated patients. This event may be symptomatic or asymptomatic, may lead to renal insufficiency and anuria, and is reversible upon discontinuation of ceftriaxone.Acute renal tubular necrosis may occur rarely with ceftriaxone.
Hepatobiliary systemRare (≥ 0.01% - < 0.1%): Hepatitis and/or cholestatic jaundice, increase in liver enzymes.Transient elevations in liver function tests have been reported in a few cases.Shadows which have been mistaken for gallstones, but which are precipitates of calcium ceftriaxone, have been detected by sonograms. These abnormalities are commonly observed after an adult daily dose of two grams per day or more, or its equivalent in children; these abnormalities were particularly observed in children with an incidence of above 30% in isolated reports. At doses of two grams a day or above these biliary precipitates may occasionally cause symptoms. Should patients develop symptoms, non-surgical management is recommended and discontinuation of ceftriaxone should be considered. The evidence suggests biliary precipitates usually disappear once ceftriaxone has been stopped. The risk of biliary precipitates may be increased by treatment duration greater than 14 days, renal failure, dehydration or total parenteral nutrition.
Pancreas Very rare (< 0.01%): There have been isolated reports of pancreatitis although a causal relationship to ceftriaxone has not been established.
Local effects Rare (≥ 0.01% - < 0.1%): Pain or discomfort may be experienced at the site of intramuscular injection immediately after administration but is usually well tolerated and transient. Intramuscular injection without lidocaine solution is painful. Local phlebitis has occurred rarely following intravenous administration but can be minimised by slow injection over at least 2-4 minutes.
Influence on diagnostic testsIn patients treated with ceftriaxone the Coombs' test rarely may become false-positive. Ceftriaxone, like other antibiotics, may result in false-positive tests for galactosemia.Likewise, nonenzymatic methods for the glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with ceftriaxone should be done enzymatically.