Ceftriaxone sodium is a broad-spectrum bactericidal cephalosporin antibiotic. Ceftriaxone is active in
vitro against a wide range of Gram-positive and Gram-negative organisms, which include β-lactamase
producing strains.
Ceftriaxone is indicated in the treatment of the following infections either before the infecting organism
has been identified or when known to be caused by bacteria of established sensitivity.
Pneumonia
Septicaemia
Meningitis
Skin and soft tissue infections
Infections in neutropenic patients
Gonorrhoea
Peri-operative prophylaxis of infections associated with surgery

Treatment may be started before the results of susceptibility tests are known.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Ceftriaxone may be administered by deep intramuscular injection, or as a slow intravenous injection,
after reconstitution of the solution according to the directions given below. The dosage and mode of
administration should be determined by the severity of the infection, susceptibility of the causative
organism and the patient's condition. Under most circumstances a once-daily dose or, in the specified
indications, one dose will give satisfactory therapeutic results.
Diluents containing calcium, (e.g. Ringer's solution or 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. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed
with calcium-containing solutions in the same IV administration line. Therefore, ceftriaxone and
calcium-containing solutions must not be mixed or administered simultaneously (see sections 4.3, 4.4
and 6.2).
Intramuscular injection: 1g ceftriaxone should be dissolved in 3.5ml of 1% Lidocaine Injection BP. &
500 mg ceftriaxone should be dissolved in 2 ml of 1% Lidocaine injection.The solution should be
administered by deep intramuscular injection. Doses greater than 1g should be divided and injected at
more than one site.

Intravenous injection: 1g ceftriaxone should be dissolved in 10ml of Water for Injections PhEur. & 500
mg ceftriaxone should be dissolved in 5ml of water for injection. The injection should be administered
over at least 2-4 minutes, directly into the vein or via the tubing of an intravenous infusion.
Adults and children 12 years and over:
Standard therapeutic dosage: 1g once daily.
Severe infections: 2-4 g daily, normally as a once daily dose.
The duration of therapy varies 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 evidence of bacterial eradication has been obtained.
Acute, uncomplicated gonorrhoea: One dose of 250mg intramuscularly should be administered.
Simultaneous administration of probenecid is not indicated.

Peri-operative prophylaxis: Usually one dose of 1g given by intramuscular or slow intravenous
injection. In colorectal surgery, 2g should be given intramuscularly (in divided doses at different
injection sites), by slow intravenous injection or by slow intravenous infusion, in conjunction with a
suitable agent against anaerobic bacteria.
Elderly: These dosages do not require modification in elderly patients provided that renal and hepatic
function are satisfactory (see below).
In the neonate, the intravenous dose should be given over 60 minutes to reduce the displacement of
bilirubin from albumin, thereby reducing the potential risk of bilirubin encephalopathy (see Special
warning and precautions for use).

Children under 12 years
Standard therapeutic dosage: 20-50mg/kg body-weight once daily.
Up to 80mg/kg body-weight daily may be given in severe infections, except in premature neonates
where a daily dosage of 50mg/kg should not be exceeded. For children with body weights of 50kg or
more, the usual dosage should be used. 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 because
of the increased risk of biliary precipitates.
Renal and hepatic impairment: In patients with impaired renal function, there is no need to reduce the
dosage of ceftriaxone provided liver function is intact. 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
intact.
In severe renal impairment accompanied by hepatic insufficiency, the plasma concentration of
ceftriaxone should be determined at regular intervals and dosage adjusted.
In patients undergoing dialysis, no additional supplementary dosage is required following the dialysis.
Plasma concentrations should be monitored, however, to determine whether dosage adjustments are
necessary, since the elimination rate in these patients may be reduced.

Ceftriaxone 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. Ceftriaxone is contraindicated in: • 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) with - Jaundice, or who are hypoalbuminaemic or acidotic because these are conditions in which bilirubin binding is likely to be impaired - If they require (or are expected to require) IV calcium treatment, or calcium-containing infusions because of the risk of precipitation of ceftriaxone-calcium (see sections 4.4, 4.8 and 6.2). Contraindications of lidocaine must be excluded before intramuscular injection of ceftriaxone when lidocaine is used as a solvent.

The stated dosage should not be exceeded. If lidocaine is used as a solvent ceftriaxone solutions
should only be used for intramuscular injection.
As with other cephalosporins, anaphylactic shock cannot be ruled out even if a thorough patient
history is taken.
Before therapy with ceftriaxone is instituted, careful inquiry should be made to determine whether the
patient has had any previous hypersensitivity reactions to ceftriaxone, cephalosporins, penicillins, or
other beta-lactam drugs. 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 betalactam
drug (see section 4.3, Contra-indications). 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.
Care is required when administering ceftriaxone to patients who have previously shown
hypersensitivity to penicillins or other non-cephalosporin beta-lactam antibiotics, as occasional
instances of cross allergenicity between cephalosporins and these antibiotics have been recorded.
Anaphylactic shock requires immediate counter measures.
In severe renal impairment accompanied by hepatic insufficiency, dosage reduction is required as
outlined under Posology and method of administration.

Safety and effectiveness of ceftriaxone in neonates, infants and children have been established for the
dosages described under Dosage and administration. 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 neonates
(especially prematures) at risk of developing bilirubin encephalopathy.
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).

Shadows which have been mistaken for gallstones, have been detected on sonograms of the 

gallbladder, usually following doses of higher than the standard recommended dose (see section 4.8).
These shadows are, however, precipitates of calcium ceftriaxone which disappear on completion or
discontinuation of ceftriaxone therapy. Rarely have these findings been associated with symptoms. In
symptomatic cases, conservative nonsurgical management is recommended. Discontinuation of
ceftriaxone treatment in symptomatic cases should be at the discretion of the physician. These
shadows can appear in patients of any age, but are 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 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.

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.
Regular blood counts (haemoglobin, erythrocyte, leucocyte and platelet counts and screening for
prolongation of prothrombin time) should be carried out during treatment.
Cephalosporins may cause bleeding due to hypoprothrombinaemia and should be used with caution in
patients with renal or hepatic impairment, malnourished patients or those with low vitamin K levels
and also in patients receiving prolonged cephalosporin therapy who are at increased risk of developing
hypoprothrombinaemia.
Cases of pancreatitis, possibly of biliary obstruction aetiology, have been rarely reported in patients
treated with ceftriaxone. 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
ceftriaxone-related biliary precipitation cannot be ruled out.
Superinfections with non-susceptible micro-organisms (such as yeasts, fungi) may occur as with other
anti-bacterial agents. A rare side-effect is pseudomembranous colitis which has resulted from infection
with Clostridium difficile during treatment with ceftriaxone.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial
agents, including ceftriaxone, and may range in severity from mild diarrhea 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 diarrhea 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.
Each gram of ceftriaxone sodium contains approximately 3.6mmol sodium.
This should be taken into account for patients on a controlled sodium diet.

Do not use diluents containing calcium, such as Ringer's solution or Hartmann's solution, to
reconstitute ceftriaxone vials or to further dilute a reconstituted vial for IV administration because a
precipitate can form. Precipitation of ceftriaxone-calcium can also occur when ceftriaxone is mixed
with calcium-containing solutions in the same IV administration line. Ceftriaxone must not be
administered simultaneously with calcium-containing IV solutions, including continuous calciumcontaining
infusions such as parenteral nutrition via a Y-site. However, in patients other than neonates,
ceftriaxone 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.
The elimination of ceftriaxone is not altered by probenecid.
Aminoglycoside antibiotics and diuretics: No impairment of renal function has so far been observed
after concurrent administration of large doses of ceftriaxone and potent diuretics (e.g.furosemide).
There is no evidence that ceftriaxone increases renal toxicity of aminoglycosides.
Alcohol: No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol
subsequent to the administration of ceftriaxone. Ceftriaxone does not contain an N-methylthiotetrazole
moiety associated with possible ethanol intolerance and bleeding problems of certain other
cephalosporins.

Antibiotics: In an in vitro study, antagonistic effects have been observed with the combination of
chloramphenicol and ceftriaxone.
Anticoagulants: As ceftriaxone has an N-methylthiotriazine side-chain, it might have the potential to
cause hypoprothrombinaemia (Refer to section 4.8, Undesirable effects) resulting in an increased risk
of bleeding in patients treated with anticoagulants.
Oral Contraceptives: 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.
Based on literature reports ceftriaxone is incompatible with amsacrine, vancomycin, fluconazole and
aminoglycosides.
Interference with Laboratory Tests:
In patients treated with ceftriaxone, the Coombs' test may in rare cases be false-positive.
Ceftriaxone, like other antibiotics, may result in false-positive tests for galactosaemia. Likewise, nonenzymatic
methods such as copper reduction methods (Benedict's, Fehling's or Clinitest) for glucose
determination in urine may give false-positive results. For this reason, urine-glucose determination
during therapy with ceftriaxone should be carried out enzymatically.

Pregnancy:
Ceftriaxone crosses the placental barrier. Safety in human pregnancy has not been established.
Reproductive studies in animals have shown no evidence of embryotoxicity, fetotoxicity,
teratogenicity or adverse effects on male or female fertility, birth or perinatal and postnatal
development. In primates, no embryotoxicity or teratogenicity has been observed. Therefore
ceftriaxone should not be used in pregnancy unless absolutely indicated.
Lactation:
Low concentrations of ceftriaxone are excreted in human milk. Caution should be exercised when
ceftriaxone is administered to a nursing woman

Ceftriaxone has been associated with dizziness, which may affect the ability to drive or operate
machinery.

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.

Infections
Superinfection 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 system
Rare (≥ 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 Urinary
Rare (≥ 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 system
Rare (≥ 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 tests
In 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.

In the case of overdose nausea, vomiting, diarrhoea, can occur. Ceftriaxone concentration cannot be
reduced by haemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is
symptomatic

General Properties
ATC classification: J01DD04

Mode of action
Ceftriaxone has bactericidal activity resulting from the inhibition of bacterial cell wall synthesis
ultimately leading to cell death. Ceftriaxone is stable to a broad range of bacterial β-lactamases.
Mechanism of resistance
Ceftriaxone is stable to a wide range of both Gram-positive and Gram-negative beta-lactamases,
including those which are able to hydrolyse advanced generation penicillin derivatives and other
cephalosporins. Resistance to ceftriaxone is encoded mainly by the production of some beta-lactam
hydrolysing enzymes (including carbapenemases and some ESBLs) especially in Gram-negative
organisms. For Gram-positive organisms such as S. aureus and S. pneumoniae, acquired resistance is
mainly encoded by cell wall target site alterations. Outside of the advanced generation parenteral
cephalosporins, cross-resistance to other drug classes is generally not encountered.

Breakpoints
Current MIC breakpoints used to interpret ceftriaxone susceptibility data are shown below. Values
quoted comprise mg/L (MIC testing).
European Committee on Antimicrobial Susceptibility Testing (EUCAST) Clinical MIC Breakpoints
(V1.1, 31/03/2006)

 

	Susceptible/Resistant
Enterobacteriaceae2	1/2
Pseudomonas	--
Acinetobacter	--
Staphylococcus3	Note3
Enterococcus	--
Streptococcus A, B, C, G	0.5/0.54
Streptococcus pneumoniae	0.5/24
Haemophilus influenzae	0.12/0.124
Moraxella Catarrhalis
Neisseria gonorrhoea	0.12/0.124
Neisseria Meningitidis	0.12/0.124
Gram-negative, anaerobes	--
Non-species related breakpoints1	1/2
S</>R

1. Non-species related breakpoints have been determined mainly on the basis of PK/PD data and are
independent of MIC distributions of specific species. They are for use only for species that have not
been given a species-specific breakpoint and not for those species where susceptibility testing is not
recommended (marked with -- or IE in the table).
2. The cephalosporin breakpoints for Enterobacteriaceae will detect resistance mediated by most
ESBLs and other clinically important beta-lactamases in Enterobacteriaceae. However, some ESBLproducing
strains may appear susceptible or intermediate with these breakpoints. Laboratories may
want to use a test which specifically screens for the presence of ESBL.
3. Susceptibility of staphylococci to cephalosporins is inferred from the methicillin susceptibility
(except ceftazidime which should not be used for staphylococcal infections).
4. Strains with MIC values above the S/I breakpoint are very rare or not yet reported. The identification
and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed
the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for
confirmed isolates with MIC above the current resistant breakpoint (in italics) they should be reported
resistant.

-- = Susceptibility testing not recommended as the species is a poor target for therapy with the drug.
IE = There is insufficient evidence that the species in question is a good target for therapy with the
drug.
RD = rationale document listing data used by EUCAST for determining breakpoints.
Susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species and
local information on resistance is desirable, particularly when treating severe infections. As necessary,
expert advice should be sought when the local prevalence of resistance is such that the utility of the
agent in at least some types of infections is questionable.

 

Ceftriaxone susceptibility among Gram-positive and Gram-negative bacterial species in Europe from
January 1999-December 2001:

Commonly susceptible species (i.e. resistance < 10% in all EU Member States)

Gram-Positive aerobes:
MSa coagulase negative Staphylococcus spp. (including S. epidermis)*
MSbStaphylococcus aureus*
Group B (Streptococcus agalactiae)
Streptococcus bovis
Streptococcus pneumoniae*

Group A Streptococcus (Streptococcus pyogenes)*
Streptococcus viridans*
Gram-Negative aerobes:
Citrobacter spp. (including C.freundii)
Escherichia coli*
Haemophilus influenzae (including beta-lactamase positive isolates)c*
Haemophilus para-influenzae*
Klebsiella spp. (including K. pneumoniae and K. oxytoca)*
Moraxella catarrhalis*
Morganella morganii*
Neisseria gonorrhoea (including penicillin-resistant isolates)*
Neisseria meningitidis*

Proteus spp. (including P. mirabilis and P. vulgaris)*
Salmonella spp. (including S. typhimurium)
Serratia spp. (including Serratia marsescens)*
Shigella spp.
Anaerobes:
Clostridium spp.*

 

Species for which acquired resistance may be a problem (i.e. resistance 10% in at least one EU
Member State)

Gram-Negative aerobes:
Pseudomonas aeruginosa +
Enterobacter spp. (including E. aerogenes and E. cloacae)*+
Acinetobacter spp. (including A. baumanii and A. calcoaceticus)*+
Anaerobes:

Bacteroides spp.*
Peptostreptococcus spp.*

 

Inherently resistant organisms

Gram-Positive aerobes:
MRd coagulase negative Staphylococcus spp. (including S. epidermidis)
MReStaphylococcus aureus
Enterococcus spp.
Gram-Negative aerobes:
Listeria monocytogenes
Mycoplasma spp.
Stenotrophomonas maltophilia
Ureaplasma urealyticum
Others:
Chlamydia spp.

 

aMethicillin-susceptible Coagulase-Negative Staphylococcus
bMethicillin-susceptible Staphylococcus aureus
cNon-susceptible range (no resistant breakpoints defined)
dMethicillin-resistant Coagulase-Negative Staphylococcus
eMethicillin-resistant Staphylococcus aureus
* Species for which the efficacy of ceftriaxone has been demonstrated both in vitro and in vivo
+ Species for which high rates of resistance have been observed in one or more regions within the EU

The pharmacokinetics of ceftriaxone are largely determined by its concentration-dependent binding to
plasma albumin. The plasma free (unbound) fraction of the drug in man is approximately 5% over most
of the therapeutic concentration range, increasing to 15% at concentrations of 300mg/l. Owing to the
lower albumin content, the proportion of free ceftriaxone in interstitial fluid is correspondingly higher
than in plasma.

Plasma concentrations: Mean peak concentrations after bolus intravenous injection are about 120mg/l
following a 500mg dose and about 200mg/l following a 1g dose; mean levels of 250mg/l are achieved
after infusion of 2g over 30 minutes. Intramuscular injection of 500mg ceftriaxone in 1% Lidocaine
Injection BP produces mean peak plasma concentrations of 40-70 mg/l within one hour.
Bioavailability after intramuscular injection is 100%.
Excretion: Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being
excreted in the urine (almost exclusively by glomerular filtration) and the remainder via the biliary and
intestinal tracts. The total plasma clearance is 10-22 ml/min. The renal clearance is 5-12 ml/min. A
notable feature of ceftriaxone is its relatively long plasma elimination half-life of approximately eight
hours which makes single or once daily dosage of the drug appropriate for most patients. The half-life
is not significantly affected by the dose, the route of administration or by repeated administration.
Pharmacokinetics in special clinical situations: In the first week of life, 80% of the dose is excreted in
the urine; over the first month, this falls to levels similar to those in the adult. In infants aged less than
8 days the average elimination half-life is usually two to three times longer than that of young adults.
In elderly persons aged over 75 years, the average elimination half-life is usually two to three times
longer that in the young adult group. As with all cephalosporins, a decrease in renal function in the
elderly may lead to an increase in half-life. Evidence gathered to date with ceftriaxone however,
suggests that no modification of the dosage regimen is needed.
In patients with renal or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally
altered and the elimination half-life is only slightly increased. If kidney function alone is impaired,
biliary elimination of ceftriaxone is increased; if liver function alone is impaired, renal elimination is
increased.
Cerebrospinal fluid: Ceftriaxone crosses non-inflamed and inflamed meninges, attaining
concentrations 4-17% of the simultaneous plasma concentration.

There are no preclinical safety data of relevance to the prescriber that are additional to those included in
other sections

The only ingredient is the active ingredient Ceftriaxone Sodium
Solvent: Sterile water for injection

Solutions containing ceftriaxone should not be mixed with or added to solutions containing other agents
except 1% Lidocaine Injection BP (for intramuscular injection only). 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, pentamidine, clindamycin phosphate and labetalol.

3 years.

Store below 30o C

A carton containing one filled vial, one ampoule of 10 ml sterile water for injection BP ampoule and a
folded leaflet

The reconstituted solution is stable for 6 hours at room temperature (below 30°C)
or for 24 hours in refrigerator (2-8°C).
Ceftriaxone should not be mixed in the same syringe with any drug other than 1 % lidocaine
hydrochloride solution (for intramuscular injection only).
Do not use diluents containing calcium, such as Ringer’s solution or Hartmann’s solution, to
reconstitute ceftriaxone. Particulate formation can result.
Intramuscular injection: Triaxone 0.5g should be dissolved in 2 ml of 1 % lidocaine hydrochloride
solution. Triaxone 1g should be dissolved in 3.5 ml of 1 % lidocaine hydrochloride solution. The
solution should be administered by deep intramuscular injection. Dosages greater than 1 g should be
divided and injected at more than one site. Solutions of lidocaine should not be administered
intravenously.
Intravenous injection: Triaxone 0.5 g is dissolved in 5 ml and Triaxone 1.0 g in 10 ml of water for
injections. The injection should be administered over at least 2 – 4 minutes, directly into the vein or via
the tubing of an intravenous infusion.
Intravenous infusion: Triaxone 1g should be dissolved in 20 to 40 ml of one of the following calciumfree
infusion solutions: Sodium chloride 0.9%, sodium chloride 0.45% and glucose 2.5%, glucose 5 %
or 10%, dextran 6% in glucose 5%, hydroxyethyl starch 6-10% infusions. See also the information
included in section 6.2. The infusion should be administered over at least 30 minutes.

When reconstituted for intramuscular or intravenous injection, the white to yellowish-orange crystalline
powder gives a pale yellow to amber solution.
Reconstituted solutions should be inspected visually. Only clear solutions free of visible particles
should be used. The reconstituted product is for single use only and any unused solution must be
discarded.