Oxidil Leaflet (Front)

19-04-2011

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Gram-negative bacilli (Anaerobes)

Oxidil
Ceftriaxone
Injection
Bacteroides spp.
Bacteroides fragilis (Some strains are resistant)
Fusobacterium spp. (Except Fusobacterium mortiferum & Fusobacterium varium)
Prevotella spp.
Prevotella melaninogenicus
Sodium Note: Methicillin-resistant Staphylococcus spp. and most strains of Enterococci (e.g. Streptococcus faecalis) are
resistant to cephalosporins, including ceftriaxone sodium. Many strains producing B-lactamase (e.g. Bacteriodes fragilis) are
3rd GENERATION CEPHALOSPORIN: resistant to ceftriaxone sodium
Ceftriaxone sodium is a semi-synthetic, 3rd-generation cephalosporin antibiotic, with the high degree of stability to B-lactamases, ADMINISTRATION:
broad-spectrum activity, and the effectiveness and convenience of long action
Ceftriaxone sodium can only be administered parenterally by IM or IV route
COMPOSITION:
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Oxidil vial contains sterile powder of Ceftriaxone Sodium USP PHARMACOKINETICS:
equivalent to Ceftriaxone .........................250mg/500mg/1g
Absorption
MICROBIOLOGY: Mean peak plasma concentrations of ceftriaxone sodium of 82.0, 150.7, 256.9 mg/L were obtained after 30
Ceftriaxone sodium binds to penicillin-binding proteins (PBP) located on walls of susceptible organisms and minutes infusions of 500mg, 1g, and 2g respectively. The bioavailability of an IM dose of ceftriaxone sodium is
exerts strongly bactericidal action by inhibiting the synthesis of dipeptidoglycan, a substance necessary for bacterial similar to the following IV administration although mean plasma concentrations are lower. Peak plasma concentrations
cell wall strength and rigidity, thus killing the bacterium. Ceftriaxone sodium is active against a wide variety occur from 1-3 hours following IM administration
of gram-positive and gram-negative bacteria and has potent activity against all the Enterobacteriaceae. Ceftriaxone
sodium is also active against some organisms resistant to first generation, second generation cephalosporins, Distribution in the body
currently available aminoglycoside and penicillins, e.g., Haemophilus influenzae, Neisseria meningitidis, Neisseria
gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens Extravascular penetration after single dose. Ceftriaxone sodium penetrates well into the extravascular spaces,
tissue fluids and the synovial fluid of inflamed joints were, similar to serum, its half-life is longer than that of other
Ceftriaxone sodium also has some activity against Treponema pallidum. Clinical investigations indicate that cephalosporins. The concentrations in most extracellular foci reach or exceed several times the MIC of most
primary and secondary syphillis respond well to ceftriaxone sodium. Ceftriaxone sodium is highly resistant to hydrolysis by both pathogens for at least 24 hours after a single administration. Ceftriaxone sodium reaches adequate levels in
R-plasmid and chromosomally mediated B-lactamase (Penicillinases & cephalosporinases) of both gram-positive and gram-negative umbilical cord blood, amniotic fluid and placenta. Concentration achieved in tissues in sufficient for a therapeutic
bacteria effect. Ceftriaxone sodium enters in breast milk
SPECTRUMS: Penetration in meninges
Ceftriaxone sodium is active against the following micro-organisms in vitro and in clinical infection Ceftriaxone sodium has a good CNS penetration, especially with inflamed meninges. Ceftriaxone sodium has the
Gram-positive cocci (Aerobes) long CSF half-life and duration of bactericidal activity. Ceftriaxone sodium reaches therapeutically effective
Catalase-positive concentrations in patients with bacterial meningitis which are at least ten-fold the MICs of common pathogens
Staphylococcus aureus (Including B-lactamase producing strains) such as Enterobacteriaceae, H. influenzae, Meningococci, Pneumococci and Group B Streptococci
Staphylococcus epidermidis
Other coagulase-negative Staphylococcus Protein binding
Catalase-negative Ceftriaxone sodium is reversibly bound to human serum protein to 95% protein binding decreases with the increase
Streptococcus pneumoniae in the concentration. e.g. from 95% binding at plasma concentration of <25mg/L to 85% binding at 300mg/L owing
Streptococcus pyogenes (Streptococcus group A) to the lower albumin content, the proportion of free ceftriaxone sodium in interstitial fluid is correspondingly higher
Streptococcus agalactiae (Streptococcus group B) than in plasma. Protein bound drug may serve as a circulating drug reservoir, which releases more drug as the
Streptococcus viridans drug is distributed or excreted
Streptococcus bovis
Gram-negative cocci (Aerobes) Half-Life
Moraxella catarrhalis The elimination half-life of ceftriaxone sodium is 8 hours. This 8 hours half-life maintains bactericidal concentration
Neisseria gonorrhea
Neisseria meningitidis against the relevant pathogens for 24 hours when given in once daily dosing providing a prolong antibiotic effect
Gram-negative rods (Aerobes) Metabolism
Enterobacteriaceae Ceftriaxone sodium is not metabolized in the body and is eliminated unchanged via two pathways, urine and bile
Citrobacter spp.
Enterobacter Spp. Elimination
Escherichia coli
Klebsiella morganii Ceftriaxone sodium has a unique feature of unusually long elimination half-life of about 8 hours in healthy adults,
Proteus spp. which permits once daily dosing
Providencia spp. Urine - In healthy adults 40-50% of a parenterally administrated dose is excreted unchanged in urine with in 48
Salmonella spp. hours as active drug. Thus high concentrations are excreted in urine. Ceftriaxone sodium renal elimination rate
Salmonella typhi is very slow elimination may be caused by the high protein binding (95%) of the drug. Renal elimination is about
Serratia spp. 7% of glomerular filtration rate and tubular secretion does not occur. Ceftriaxone is not reabsorbed by renal tubules.
Serratia marcescens In neonates, renal elimination accounts for about 70% of the dose, and in infants aged less than 8 days and in
Shigella spp. persons over 75 years of age, the average elimination half life is twice as long
Yersinia spp.
Yersinia entercolitica Bile - Whatever is not excreted through kidney is excreted through bile. The remainder of a dose (40-50%) appear
Fermentive non-Enterobacteriaceae to be excreted unchanged in bile. Biliary excretion varies with individuals. After biliary excretion, the intestinal flora:
Aeromonas spp. transforms ceftriaxone sodium into inactive metabolities. After IV administration of radioactive-labelled ceftriaxone
Pasteurella multocida sodium to human volunteers, 44% of the dose was recovered as microbiologically inactive material in the feces
Vibrio spp.
Vibrio cholerae IMPAIRED RENAL AND HEPATIC FUNCTION:
Non-fermentive non-Enterobacteriaceae Pharmacokinetics of ceftriaxone sodium are only slightly alter and the elimination half-life is negligibly
Acinetobactor spp. increased in patients with mild to moderate renal impairment in patients with various degrees of liver insufficiency
Alcaligenes spp. there was a little alteration in the pharmacokinetic properties. If kidney function alone is impaired, biliary elimination
Pseudomonas spp. of ceftriaxone sodium is increased; if liver function alone is impaired, renal elimination is increased
Pseudomonas aeruginosa (Some strains are resistant)
Gram-negative coccobacilli (Aerobes) INDICATIONS:
Haemophilus spp.
Haemophilus influenzae Infections caused by susceptible organisms in
Haemophilus parainfluenzae Septicemia, sepsis,
Haemophilus duceryi Bacterial meningitis,
Surgical prophylaxis,
Gram-positive bacilli (Anaerobes) Nosocomial infections,
Non-spore-forming Intra-abdominal infections,
Actinomyces spp. Post operative and wound infections,
Endospore-forming
Clostridium spp. (Except Clostridium difficile) Pneumonia and other lower respiratory tract infections,
Infections of the skin and skin structures,
Gram-positive cocci (Anaerobes) Infections in patients with impaired defense mechanism,
Peptococcus spp. Pelvic inflammatory diseases,
Peptostreptococcus spp. Sexually transmitted disease (Gonorrheae, chancroid, syphilis),
Urinary tract infections (Complicated by underlying urological abnormalities)
 Oxidil Leaflet (Back)
19-04-2011

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DOSAGE: COMPATIBILITY AND STABILITY OF Oxidil (IN VARIOUS DILUENTS):
In mild to moderate infections Ceftriaxone sodium sterile powder should be stored at room temperature or below and protected from light
For adults and children over 12 years IV/IM 1-2g once a day After reconstitution, protection from normal light is not necessary. The color of solution ranges from light yellow to
For infants and young children IV/IM 20-50mg/kg once a day amber, depending on the length of storage, concentration and dilution used. Ceftriaxone sodium IV is also
stable at room temperature for 24 hours at concentration between 10mg/ml and 40mg/ml in; sodium lactate, 5%
In moderate to severe infections sodium bicarbonate, 5% mannitol and 10% mannitol. After the indicating stability time periods, unused portions
For adults and children over 12 years IV/IM 1-2g once a day (Max. 4g/d) should be discarded. Frozen solutions should be thawed at room temperature before use. After thawing unused
For infants and young children IV/IM 20-50mg/kg once a day (Max. 2g/d) portions should be discarded. Do not refreeze. Ceftriaxone sodium solution should not be physically mixed
with or into solutions containing other anti-microbial drugs. Reconstituted solutions retain their physical and chemical
In meningitis stability for six hours at room temperature (Or 24 hours at 5 degree centigrade). As a general rule, however the
For adults and children over 12 years IV/IM 4g once a day solution be used immediately after preparation
For infants and young children IV/IM 100mg/kg once a day
CAN THE IV SOLUTION BE USED FOR IM ADMINISTRATION?
In surgical prophylaxis Since ceftriaxone sodium is a highly acidic drug, it causes pain at the site of injection when administered
For adults and children over 12 years IV/IM 1-2g 30-90minutes before surgery intramuscularly. However up to dose of ceftriaxone sodium 250mg, dissolved in 2.5ml sterile water for
injection can be used for intramuscular use. When given in doses exceeding 250mg or to patients with little muscle,
In gonorrhea ceftriaxone sodium for intramuscular injection should be dissolved in a 1% lignocaine solution and administered
For adults and children over 12 years IM 250mg as single dose by deep intragluteal injection to minimize pain

In renal and hepatic impairment CONTRA-INDICATIONS:

Normal dose guidelines may be followed in-patients with impaired function provided liver functions is intact. Only in
cases of end stage renal failure (Creatinine clearance <10ml/min) dosage should not exceed 2gm daily. similarly
inpatients with liver damage no adjustment is required if renal function is intact. But in cases of concomitant severe
renal and hepatic dysfunction, the plasma concentrations of ceftriaxone sodium should be determined at
regular intervals
In neonates (Up to 2weeks)
A daily dose of 20-50mg/kg bodyweight, not to exceed 50mg/kg on account of the immaturity of infants enzyme
systems. It is not necessary to differentiate between premature and infant born at term
Elderly patients
The dosage recommended for adults require no modification in the geriatric patients
DURATION OF THERAPY:
Bacterial infections
The duration of therapy varies in accordance with the different infections. Generally antibiotics should continue for a
minimum of 48-72 hours after patient is afebrile or after evidence of bacterial eradication has been obtained
Surgical prophylaxis
Discontinue prophylactic use within 24 hours after the surgical procedure. In surgery where infection may be particularly
devastating prophylactic use may continue for 3-5 days following surgery completion. If there are signs of infection,
obtain culture to perform sensitivity tests
COMBINATION THERAPY:
In severe, life-threatening infections, the combination of ceftriaxone sodium with aminoglycosides is indicated
without awaiting the results of sensitivity tests. Because of physical incompatibility the two drugs must be administrated
separately, not mixed in one syringe. Infections with Pseudomonas aeruginosa may require concomitant treatment
SIDE EFFECTS:
Ceftriaxone sodium is found to be very well tolerated. The majority of side effects with this drug are transient
and seldom require withdrawal of therapy. Following side effects may be observed rarely, but mostly disappear after
withdrawal of the drug
Hypersensitivity reactions
Allergic rashes occur but are uncommon. Transient eosinophilia and / or a positive Coombs test without hemolysis
may occasionally occur with ceftriaxone sodium as with other cephalosporins
Nephrotoxicity
Nephrotoxic potential of ceftriaxone sodium is found to be very low than other cephalosporins and ceftriaxone
sodium has been used with furosemide or aminoglycosides without encountering renal toxicity
Ceftriaxone sodium is contraindicated in patients with known hypersensitivity to the cephalosporins class
of antibiotics. In patients hypersensitivity to penicillin, the possibility of allergic cross-reactions should be born in
mind. Although the relevant preclinical investigations revealed neither mutagenic nor teratogenic effects. Ceftriaxone
sodium should not be used in pregnancy (Particularly in first trimester) unless absolutely indicated
Use of ceftriaxone sodium is contraindicated in hyperbilirubinemic neonates, especially those who are premature
ceftriaxone sodium can displace bilirubin from binding to serum albumin, potentially leading to bilirubin
encephalopathy. Ceftriaxone sodium should not be mixed with calcium-containing solution/products or
reconstituted with calcium-containing diluents such as Ringers or Hartmanns solution because of the risk for particulate
precipitation
WARNING:
Concomitant administration of ceftriaxone sodium with calcium-containing solutions or products is contraindicated, even
via different infusion lines; 48 hours should elapse between the last dose of ceftriaxone sodium and their use
PRECAUTIONS:
In-patients hypersensitive to penicillin, a cross sensitivity may occur, therefore, use with caution. Alteration in
prothorombin times have occurred rarely in patients treated with ceftriaxone sodium. Patients with impaired
vit K synthesis or low vit K stores e.g. chronic hepatic disease and malnutrition may require monitoring of prothrombin
time during ceftriaxone sodium treatment. Vit K administration (10mg Weekly) may be necessary if the
prothombin time is prolonged before or during therapy. Ceftriaxone sodium should be prescribed with caution
in individuals with the history of gastro-intestinal disease, especially colitis. There have been reports of sonographic
abnormalities in the gall bladder of patients treated with ceftriaxone sodium. Some of these patients also
had symptoms of gall bladder disease. This condition appears to be transient and reversible upon discontinutation
of ceftriaxone sodium and institution of conservative management. Therefore, ceftriaxone sodium
should be discontinued in patients who develop sign and symptoms suggestive of gall bladder disease
Anaphylactic shock requires immediate counter measures such as intravenous epinephrine followed by a glucocorticoid.
In-vitro studies have shown that ceftriaxone sodium, like some other cephalosporins, can displace bilirubin
from serum albumin. Caution should be exercised when considering ceftriaxone sodium for hyperbilirubinemic
neonates, especially premature. During prolonged treatment the blood picture should be checked at regular intervals
DRUG INTERACTIONS:
Probenecid decreases renal elimination ceftriaxone sodium. No impairment of renal function has so far
been observed after concurrent administration large doses of ceftriaxone sodium and potent diuretic (e.g.
Furosemide). There is no evidence that ceftriaxone sodium increases renal toxicity of aminoglycoside. No
effect similar to that of disulfiram has been demonstrated after ingestion subsequent to the administration of
aminoglycoside. No effect similar to that of disulfiram has been demonstrated after ingestion of alcohol subsequent
to the administration of ceftriaxone sodium. Ceftriaxone sodium dose not contain an N-methylthiotetrazole moiety associated
with possible ethanol intolerance and bleeding problems of certain other cephalosporins. The elimination of ceftriaxone sodium
is not altered by probenecid
STABILITY:
See expiry on the pack

Gastrointestinal side effects PRESENTATION:

Nausea, vomiting, diarrhoea has been observed occasionally and pseudomembranous enterocolitis has been reported R
Oxidil 250mg IV injection: Contains a vial with dry substance equivalent to 250mg ceftriaxone sodium and 1 ampoule
in a small number of patients with this drug. Transient elevation of SGOT, not necessitating cessation of treatment, of 5ml sterile water for injection
has also been noted in few patients R
Oxidil 250mg IM injection: Contains a vial with dry substance equivalent to 250mg ceftriaxone sodium and 1 ampoule
of 2ml 1% lignocaine solution
Local side effects R

In rare cases phlebitis reactions occurred after IV administration. These may be prevented slow (Two to four minutes) Oxidil 500mg IM injection: Contains a vial with dry substance equivalent to 500mg ceftriaxone sodium and 1 ampoule
injection of the substances. Intramuscular injection without lignocaine solution is painful of 2ml 1% lignocaine solution
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Oxidil 500mg IV injection: Contains a vial with dry substance equivalent to 500mg ceftriaxone sodium and 1 ampoule
DIRECTION FOR RECONSTITUTION: of 5ml sterile water for injection
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Oxidil IV - To be reconstituted in sterile water for injection Oxidil 1g IV injection: Contains a vial with dry substance equivalent to 1g ceftriaxone sodium and 1 ampoule
For IV injection: Ceftriaxone sodium 250mg is dissolved in 5ml, ceftriaxone sodium 500mg is dissolved of 10ml sterile water for injection
in 5ml and ceftriaxone sodium 1g in 10ml, of sterile water for injection and then administrated by IV injection
lasting two to four minutes INSTRUCTIONS:
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Keep out of reach of children
Oxidil Intravenous Infusion Avoid exposure to heat, light and humidity
For IV infusion: Ceftriaxone sodium is dissolved in 40ml of one of the following calcium-free infusion solutions; Store at 25C or below
sodium chloride 0.9% sodium chloride 0.45% + dextrose 2.5%, dextrose 5%, levulose 5%, dextran 6% in dextrose, Improper storage may deteriorate the medicine
sterile water for injections, ceftriaxone sodium solution should not be mixed with piggy backed into solutions
containing other anti-microbial drug or into diluent solution other than those listed above owing to possible incompatibility
should last at least 30 minutes SAMI PHARMACEUTICALS (PVT) LTD.
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Oxidil IM - To be reconstituted in lignocaine IV solution www.samipharmapk.com
For IM injection: Ceftriaxone sodium 250mg or 500mg is dissolved in 2ml of 1% lignocaine solution and
ceftriaxone sodium 1gm is dissolved in 3.5ml of 1% lignocaine solution and administered by deep intragluteal
injection. It is recommended that more than 1gm be injected on either side. The lignocaine solution must never be
administered intravenously