Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2012 Publisher: Roche Products Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Rocephin is contraindicated in patients with known hypersensitivity to beta-lactam antibiotics.
In patients hypersensitive to penicillin, the possibility of allergic cross-reactions should be borne in mind.
Hyperbilirubinaemic newborns and preterm newborns should not be treated with ceftriaxone. In vitro studies have shown that ceftriaxone can displace bilirubin from its binding to serum albumin and bilirubin encephalopathy can possibly develop in these patients.
Premature newborns up to a corrected age of 41 weeks (weeks of gestation + weeks of life).
Full-term newborns (up to 28 days of age):
Contraindications of lidocaine must be excluded before intramuscular injection of ceftriaxone when lidocaine is used as a solvent.
As with other cephalosporins, anaphylactic reactions with fatal outcome were also reported, even if a patient is not known to be allergic or previously exposed.
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 (see Section 4.3). 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.
Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and kidneys in premature and full-term newborns aged less than 1 month have been described. At least one of them had received ceftriaxone and calcium at different times and through different intravenous lines. In the available scientific data, there are no reports of confirmed intravascular precipitations in patients, other than newborns, treated with ceftriaxone and calcium-containing solutions or any other calcium-containing products. In vitro studies demonstrated that newborns have an increased risk of precipitation of ceftriaxone-calcium compared to other age groups.
In patients of any age ceftriaxone must not be mixed or administered simultaneously with any calcium-containing IV solutions, even via different infusion lines or at different infusion sites. However, in patients older than 28 days of age ceftriaxone and calcium-containing solutions may be administered sequentially one after another if infusion lines at different sites are used, or if the infusion lines are replaced or thoroughly flushed between infusions with physiological salt-solution to avoid precipitation. In patients requiring continuous infusion with calcium-containing TPN solutions, healthcare professionals may wish to consider the use of alternative antibacterial treatments which do not carry a similar risk of precipitation. If use of ceftriaxone is considered necessary in patients requiring continuous nutrition, TPN solutions and ceftriaxone can be administered simultaneously, albeit via different infusion lines at different sites. Alternatively, infusion of TPN solution could be stopped for the period of ceftriaxone infusion, considering the advice to flush infusion lines between solutions. (see sections 4.3, 4.8, 5.2 and 6.2).
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including Rocephin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Superinfections with non-susceptible micro-organisms may occur as with other antibacterial agents.
An immune mediated haemolytic anaemia has been observed in patients receiving cephalosporin class antibacterials including Rocephin. Severe cases of haemolytic anaemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anaemia while on ceftriaxone, the diagnosis of a cephalosporin associated anaemia should be considered and ceftriaxone discontinued until the aetiology is determined.
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.
In severe renal and hepatic insufficiency, dosage should be reduced according to given recommendations (see section 4.2).
Rocephin may precipitate in the gallbladder and then be detectable as shadows on ultrasound (see section 4.8). 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 Rocephin on a body weight basis. In children, doses greater than 80mg/kg body weight should be avoided 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 Rocephin. As the condition appears to be transient and reversible upon discontinuation, therapeutic procedures are not normally indicated.
Shadows, which have been mistaken for gallstones are however, precipitates of calcium ceftriaxone which disappear on completion or discontinuation of Rocephin therapy. Rarely have these findings been associated with symptoms. In symptomatic cases, conservative nonsurgical management is recommended.
Discontinuation of Rocephin treatment in symptomatic cases should be at the discretion of the physician.
Cephalosporins as a class 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 Rocephin. Most patients presented with risk factors for biliary stasis and biliary sludge, e.g. preceding major therapy, severe illness and total parenteral nutrition. A trigger or cofactor role of Rocephin-related biliary precipitation can not be ruled out.
Safety and effectiveness of Rocephin in neonates, infants and children have been established for the dosages described under Dosage and administration. Studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin.
During prolonged treatment a complete blood count should be performed at regular intervals.
In case lidocaine is used as a solvent Ceftriaxone solutions should only be used for intramuscular injection.
The stated dosage should not be exceeded.
Each gram of Rocephin contains approximately 3.6mmol sodium. To be taken into consideration by patients on a controlled sodium diet.
No impairment of renal function has so far been observed after concurrent administration of large doses of Rocephin and potent diuretics (e.g. furosemide).
No interference with the action or increase in nephrotoxicity of aminoglycosides has been observed during simultaneous administration with Rocephin.
No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent to the administration of Rocephin. Ceftriaxone does not contain an N-methylthiotetrazole moiety associated with possible ethanol intolerance and bleeding problems of certain other cephalosporins. The elimination of Rocephin is not altered by probenecid.
In an in-vitro study antagonistic effects have been observed with the combination of chloramphenicol and ceftriaxone. The clinical relevance of this finding is unknown, but caution is advised if concurrent administration of ceftriaxone with chloramphenicol is proposed.
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to reconstitute Rocephin vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Precipitation of ceftriaxone-calcium can also occur when Rocephin is mixed with calcium-containing solutions in the same IV administration line. Rocephin must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates, Rocephin and calcium-containing solutions may be administered sequentially, of one another, if the infusion lines are thoroughly flushed between infusions with a compatible fluid. In vitro studies using adult and neonatal plasma from umbilical cord blood demonstrated that neonates have an increased risk of precipitation of ceftriaxone-calcium.
Based on literature reports ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.
In patients treated with Rocephin, the Coombs' test may rarely become false-positive. Rocephin, like other antibiotics, may result in false-positive tests for galactosaemia. Likewise, non-enzymatic methods for glucose determination in urine may give false-positive results. For this reason, urine-glucose determination during therapy with Rocephin should be done enzymatically.
Ceftriaxone may adversely affect the efficacy of oral hormonal contraceptives. Consequently, it is advisable to use supplementary (non-hormonal) contraceptive measures during treatment and in the month following treatment.
For ceftriaxone, limited clinical data on exposed pregnancies are available. Ceftriaxone crosses the placental barrier. Reproductive studies in animals have shown no evidence of embryotoxicity, foetotoxicity, teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal development. In primates, no embryotoxicity or teratogenicity has been observed. Since safety in human pregnancy is not established ceftriaxone should not be used unless absolutely indicated.
Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when ceftriaxone is administered to a nursing woman.
Since Rocephin sometimes induces dizziness the ability to drive and use machines can be impaired.
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.
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).
Rare (≥ 0.01% - < 0.1%): Mycosis of the genital tract.
Superinfections of various sites with yeasts, fungi or other resistant organisms are possible.
Rare (≥ 0.01% - < 0.1%): Neutropenia, leucopenia, eosinophilia, thrombocytopenia, anaemia (including haemolytic anaemia), slight prolongation of prothrombin time.
Very rare (< 0.01 %) 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.
Rare (≥ 0.01% - < 0.1%): Anaphylactic (e.g. bronchospasm) and anaphylactoid reactions (see section 4.4)
Rare (≥ 0.01% - < 0.1%): Headache, dizziness.
Common (≥ 1% - < 10%): Loose stools or diarrhoea, nausea, vomiting.
Rare (≥ 0.01% - < 0.1%): Stomatitis, glossitis. These side effects are usually mild and commonly disappear during treatment or after discontinuation of treatment.
Very rare (< 0.01%) including isolated reports: Pseudomembranous colitis (mostly caused by Clostridium difficile), pancreatitis (possibly caused by obstruction of bile ducts). Therefore, the possibility of the disease should be considered in patients who present with diarrhoea following antibacterial agent use.
Rare (≥ 0.01% - < 0.1%): Increase in serum liver enzymes (AST, ALT, alkaline phosphatase).
Precipitation of ceftriaxone calcium salt in the gallbladder has been observed (see section 4.4), 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.
Uncommon (≥ 0.1% - < 1%): Allergic skin reactions such as maculopapular rash or exanthema, urticaria, dermatitis, pruritus, oedema.
Very rare (< 0.01%) including isolated reports: Erythema multiforme, Stevens Johnson Syndrome, Lyell’s Syndrome/toxic epidermal necrolysis.
Rare (≥ 0.01% - < 0.1%): Increase in serum creatinine, oliguria, glycosuria, haematuria.
Very rare (< 0.01%) 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.
Rare (≥ 0.01% - < 0.1%): 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 solution is painful.
Solutions containing ceftriaxone should not be mixed with or added to solutions containing other agents. In particular, diluents containing calcium, (e.g. Ringer’s solution, Hartmann’s solution) should not be used to reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a precipitate can form. Ceftriaxone must not be mixed or administered simultaneously with calcium-containing solutions (see section 4.2, 4.3, 4.4 and 4.8). Based on literature reports, ceftriaxone is not compatible with amsacrine, vancomycin, fluconazole, aminoglycosides and labetalol.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
