Ceftriaxone Sodium Powder Injection Medicine 1.0g Antibiotic Drugs
Each vial contains:
Ceftriaxone sodium (Sterile)
equivalent to ceftriaxone 1 g
A 20.1.1. Broad and medium spectrum antibiotics
Ceftriaxone is a broad-spectrum cephalosporin with a long plasma
elimination half-life of approximately 8 hours in normal adults.
(In vitro sensitivity does not necessarily imply in vivo efficacy).
The in vitro spectrum of activity of ceftriaxone encompasses:
(a) Gram-positive organisms:
Streptococcus pneumoniae, Streptococcus Group A (including Streptococcus pyogenes), Streptococcus Group B (including Streptococcus agalactiae), Streptococcus viridans, Streptococcus bovis (Group D), Staphylococcus aureus (methicillin sensitive). Peptostreptococcus sp., and Clostridium sp.
Note: Methicillin-resistant Staphylococcus spp. are resistant to ceftriaxone. Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are resistant.
(b) Gram-negative organisms:
Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Neisseria meningitidis, Neisseria
gonorrhoeae (including penicillin-resistant strains),Escherichia coli, Klebsiella sp**, Enterobacter sp*, Serratia marcescens, Citrobacter sp., Proteus mirabilis, Indole-positive Proteus (including Morganella morganii),Salmonella sp., Shigella sp., Yersinia pestis and Treponema pallidum (in animal experiments).
*Some isolates of these species are resistant to ceftriaxone, due
to the production of the chromosomally encoded beta-lactamases.
**Some isolates of these species are resistant due to production of
extended spectrum plasmid mediated beta-lactamase.
(c) Organisms which are only partially sensitive to ceftriaxone in vitro. Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter sp. and Bacteroides sp. Ceftriaxone is stable in relation to the majority of
The following organisms are resistant:
Ureaplasma urealyticum, Mycoplasma sp., Mycobacterium sp., Fungi.
It is essential to note that recommended media (free from
inhibitory substances especially thymidine and thymine) and methods
must be used for satisfactory sensitivity testing.
The maximum plasma concentration after a single IM dose of 1.0 g is
about 81 mg/L and is reached in 2-3 hours after the dose. The area
under the plasma concentration-time curve after IM administration
is equivalent to that after IV administration of an equivalent
dose, indicating 100% bioavailability of intramuscularly
On intravenous administration, ceftriaxone diffuses into the tissue
fluid, where-if it is given in the recommended dosage
range-bactericidal concentrations lasting 24 hours may be
maintained. Ceftriaxone is reversibly bound to albumin, and the
binding decreases with the increase in concentration e.g. from 95%
binding at plasma concentrations of <100 mg/L to 85% binding at
300 mg/L. Owing to the lower albumin content, the proportion of
free ceftriaxone in interstitial fluid is correspondingly higher
than in plasma.
The volume of distribution of ceftriaxone is 7-12 L. After a dose
of 1-2 g, concentrations above the minimal inhibitory
concentrations of most pathogens responsible for infection are
detected for more than 24 hours in the following tissues or body
fluids: lung, heart, biliary tract/liver, tonsil, middle ear and
nasal mucosa, bone; and cerebral, pleural, prostatic and synovial
In healthy, young adult volunteers the total plasma clearance is
10-22 mL/min. The renal clearance is 5-12 mL/min. 50-60% of
ceftriaxone is excreted unchanged in the urine, while 40-50% is
excreted unchanged in the bile. The elimination half life in adults
is about eight hours.
The substance is largely inactivated in the faeces due to
metabolism by intestinal flora.
The mean plasma elimination half life is 8 hours in healthy, young
adult volunteers. In neonates, urinary recovery accounts for about
70% of the dose. In infants aged less than eight days and in
elderly persons aged over 75 years, the average elimination half
life is usually 2-3 times that in the young adult group.
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.
In meningitis patients, administration of 50 mg per kg bodymass
leads within 2-24 hours to cerebro spinal fluid concentrations
several times as high as the minimum in vitro inhibitory concentrations required for the most common causative
organisms of meningitis.
Infections caused by pathogens sensitive to ceftriaxone such as
|-||meningitis in neonates and infants|
|-||perioperative prophylaxis of infections|
|-||renal and urinary tract infections|
|-||respiratory tract infections, particularly pneumonia, and ear, nose
and throat infections.|
|-||infections of the bones, joints, soft tissue, skin and of wounds.|
|-||abdominal infections (peritonitis, infections of the biliary
Allergy to cephalosporins. In patients hypersensitive to
penicillin, the possibility of allergic cross reactions should be
borne in mind. (see warnings)
Pregnancy and Lactation
Safety in human pregnancy has not been established. As ceftriaxone
is excreted in the breast milk at low concentrations, caution is
advised in nursing mothers.
Before therapy with Ceftriaxone is instituted, careful inquiry
should be made to determine whether the patient has had previous
hypersensitivity reactions to cephalosporins, penicillins or other
medicines. About 10% of penicillin-sensitive patients may also be
allergic to cephalosporins although the true incidence is
uncertain. Great care should be taken if Ceftriaxone is to be given
to such patients.
DOSAGE AND DIRECTIONS FOR USE:
Adults and children over twelve: 1-2g ceftriaxone once daily (every
In severe infections and in cases in which the pathogens are only
moderately sensitive to ceftriaxone, the daily dosage may be
increased to 4 g administered daily.
Infants and young children may receive from 20-80 mg per kg
body-mass daily; depending on the severity of the infection,
usually 12-24 hourly.
In cases of premature babies, the daily dosage should not exceed 50
mg per kg body mass on account of the immaturity of the infant’s
Elderly patients: The dosages recommended for adults require no modification in the
case of geriatric patients.
Duration of therapy: The duration of therapy varies according to the course of the
disease. 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.
Special dosage instructions: Meningitis: In bacterial meningitis in neonates and children,
treatment begins with doses of 100 mg per kg (not to exceed 4 g)
once daily. As soon as the causative organism has been identified
and its sensitivity determined, the dosage can be reduced
Gonorrhoea: For the treatment of gonorrhoea
(penicillinase-producing and non-penicillinase- producing strains),
a single IM dose of 250 mg ceftriaxone is recommended.
Perioperative prophylaxis: A single dose of 1-2 g ceftriaxoneadministered 30-90 minutes prior
to surgery. In colorectal surgery, concurrent (but separate)
administration of ceftriaxone with a 5-nitroimidazole, eg.
ornidazole, has proven effective.
Impaired renal and hepatic function: In patients with impaired renal function, there is no need to
reduce the dosage ofceftriaxoneprovided that the hepatic function
In case of severe renal failure (creatinine clearance <10
mL/min) the ceftriaxone dosage should not exceed 2 g daily. In
patients with liver damage, there is no need for the dosage to be
reduced provided renal function is intact.
In cases of concomitant severe renal and hepatic dysfunction, the
plasma concentrations of ceftriaxone should be determined at
regular intervals. 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.
For IM injection, Ceftriaxone 250 should be dissolved in 2 mL and
Ceftriaxone 1 g in 3.5 mL of water for injection. Ceftriaxone
dissolved in a 1% lidocaine solution can reduce pain at the site of
injection. Ceftriaxone must be injected well within the body of a
relatively large muscle. It is recommended that not more than 1 g
be injected on either side. Reconstitution with 1% lidocaine
(without adrenaline) has no effect on the absorption or the
elimination of Ceftriaxone. The lidocaine solution must never be
For IV injection, Ceftriaxone 250 is dissolved in 5 mL water for
injection and Ceftriaxone 1 g dissolved in 10 mL water for
injection. The intravenous administration should be given over two
to four minutes.
The infusion should be given over a period of at least 30 minutes.
For IV infusion, 2 g of Ceftriaxone is dissolved in approximately
40 mL of sterile water for injection.
Ceftriaxone solutions should not be mixed with or piggybacked into
solutions containing other antimicrobial drugs or into diluent
solutions other than those listed above, owing to possible
Incompatibilities: Ceftriaxone should not be added to solutions containing calcium
such as Hartmann’s solution and Ringers solution. Ceftriaxone is
incompatible with amsacrine, vancomycin and fluconazole and
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Gastro-intestinal complaints: Loose stools/diarrhoea, nausea, vomiting, stomatitis, glossitis.
Haematological changes: Eosinophilia, haematoma or bleeding, thrombocytopenia,
neutropenia, leukopenia, granulocytopenia and haemolytic anaemia.
Isolated cases of agranulocytosis (<500/mm³) have been reported,
most of them following total doses of 20 g or more.
Exanthema, allergic dermatitis, pruritus, urticaria, oedema,
erythema multiforme may occur.
Other side effects include headaches and dizziness, increase in
liver enzymes, oliguria, increase in serum creatinine, mycosis of
the genital tract, fever, shivering and anaphylactic or
Nephrotoxicity has been reported. Acute interstitial nephritis is
also a possibility as a manifestation of hypersensitivity.
Anaphylactic shock may occur: Anaphylactic shock requires immediate
Acute renal tubular necrosis has followed excessive dosage and has
also been associated with the use of Ceftriaxone in older patients
or those with pre-existing renal impairment, or with the
concomitant administration of nephrotoxic agents such as
Hepatitis and cholestatic jaundice have occurred less frequently.
Prolonged use may result in overgrowth of non-susceptible
Pseudomembranous colitis has been reported with Ceftriaxone.
Therefore, it is important to consider this diagnosis in patients
who present with diarrhoea subsequent to the administration of
Ceftriaxone. Superinfections with non-susceptible micro-organisms
Inflammatory reactions in the vein wall may occur after IV
administration. These may be minimised by slow (2-4 minutes)
injection of Ceftriaxone.
Intramuscular injection without lidocaine solution is painful.
Shadows which have been mistaken for gall stones have been detected
by sonograms of the gallbladder, usually following higher than the
standard recommended dose.
These shadows are, however, precipitates of calcium ceftriaxone
which disappear on completion or discontinuation of ceftriaxone
In less frequent cases, these findings have been associated with
symptoms. In symptomatic cases, conservative non-surgical
management is recommended. Discontinuation of Ceftriaxone treatment
in symptomatic cases should be at the discretion of the clinician.
Studies have shown that Ceftriaxone, can displace bilirubin from
serum albumin. Caution should be exercised when considering
Ceftriaxone treatment in hyperbilirubinemic neonates. Ceftriaxone
should not be used in neonates (especially prematures) at risk of
developing bilirubin encephalopathy.
During prolonged treatment the blood profile should be checked at
Renal and haemotological status should be monitored especially
during prolonged and high dose therapy.
No impairment of renal function has been observed after concurrent
administration of large doses of Ceftriaxone and potent diuretics
(eg. furosemide). There is no evidence that Ceftriaxone increases
renal toxicity of aminoglycosides. No effects similar to that of
disulfiram has been demonstrated after administration of alcohol
Ceftriaxone does not contain an N-methyl-thiotetrazole moiety
associated with possible ethanol intolerance and bleeding problems.
The elimination of Ceftriaxone is not altered by probenecid.
In an in vitro study antagonistic effects have been observed with the combination
of chloramphenicol and Ceftriaxone.
There may be antagonism between Ceftriaxone and bacteriostatic
antibacterial agents. Ceftriaxone may interfere with the Jaffe
method of measuring creatinine concentrations and may produce
falsely high values; this should be borne in mind when measuring
In patients treated with ceftriaxone the Coombs’test may become
false positive. Ceftriaxone may result in false positive tests for
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
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In the case of overdosage, plasma concentration would not be
reduced by haemodialysis or peritoneal dialysis. Treatment is
supportive and symptomatic.
White to yellowish orange, crystalline powder in 15 ml clear glass
USP type I, moulded vials with blue flip-off seals.
On constitution a pale yellow to reddish orange clear solution is
Ceftriaxone 1g: Cartons containing 1 clear glass USP Type I vial.
Store below 25°C, protected from light and moisture. Do not freeze.
Reconstituted solution to be stored in original vials.
KEEP OUT OF REACH OF CHILDREN.