(Ceftriaxone Sodium)

COMPOSITION

Each vial contains 1g Ceftriaxone in the form of Ceftriaxone Sodium. Each diluent ampoule contains 10ml water for injection.

DESCRIPTION

This product is white or off-white colour crystal powder. Main ingredient of this product is Ceftiraxone Sodium. Ceftriaxone Sodium is chemically designated as (6R ; 7R)-7-[2-(2-Amino- 4 -thiazoly) glyoxylamido]-8-oxo-3 {[(1,2,5,6-tetrahydro-2-methyl-5, 6-dioxo-as-triazin-3-yl)-thio] methyl}-5 -thia-1-azabicyclo [4.2.0] oct-2-ene-2- carboxylic acid, 7²(Z)-(0-methyloxime), disodium salt, sesquaterhydrate.

The chemical formula is C₁₈H₁₆N₈Na₂O₇S₃3.¹/₂H₂O.Ceftriaxone Sodium has molecular weight of 661.59.

CHEMICAL STRUCTURE:

PHARMACOLOGY

Mode of Action:       

Ceftriaxone is a third generation bactericidal cephalosporin that inhibit bacterial cell wall synthesis. It acylates membrane bound transpeptidase enzymes thus preventing the cross linking of pepetidoglycan necessary for bacterial cell wall strength and rigidity. Ceftriaxone has a high degree of stability in the presence of beta-laactamases, produced by Gram-negative and Gram-positive bacteria.

Susceptible Organisms:

Staphylococcus aureus (including penicillinase-producing strains), Staphylococcus epidermidis, Pneumococcus, group A streptococcus, group B streptococcus (streptococcus aqalactiae), Streptococcus viridans, Streptococcus bovis, Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp.(some strains are resistant), Esherichia coli, Haemophilus ducreyi, Haemophilus influenzae (including ampicillin resistant strains), Haemophilus parainfluenzae, Klebsiella spp.(klebsiella pneumoniae), Moraxella, Proteus morganii, Proteus  mirabilis, Proteus vulgaris, Providencia, Neisseria gonorrhoeae (including penicillinase producing strains),Neisseria meninigitidis, Plesimonas shigelloides,Pseudomonas aeruginosa (some strains are resistant).Salmonella spp.(including samonella typhi), Serratia spp.(including S. marcescens), Shigella spp.,Yersinia spp.(including Y.enterocolitical), Treponema pallidum, Bacteroides spp. (including some strains of Bacteroides fragilis), Clostridium spp. (except clostridium difficile), Fusobacterium spp.(except F. Mortiferum,F. Varium),Peptococcus spp.,Peptostreptocccus spp.

Pharmacokinetics:

Peak serum concentrations are attained in about 2 hours. Following intramuscular administration of ceftriaxone 0.5g and 1g, the peak concentrations attained are 43mg/L and 80mg/L respectively. The plasma concentrations after 0.5mg IM after 24 hours are 6.0mg/L. The elimination half-life (t_1/2b) of ceftriaxone is 7.1 hours. The prompt maximum plasma concentrations (C_max) following a single 1-minute intravenous (IV) infusion of 0.5 is 150.9mg/L, average plasma concentration is 9.3mg/L during 24hours. The average values of CSF concentration at 6hours and 12hours after 15-20mg/kg intramuscular doses per day in patients suffering from suppurative meningitis are 5.16mg/L and 2.3mg/L respectively. After a 1g IV dose, the concentrations in gallbladder bile are 1600mg/L and 13.5mg/L respectively at 5hours and 14hours post dosing. The protein-binding rate is 95%. Ceftriaxone is not metabolizable in human dody, and 40% of a dose is excreted through biliary tract and intestinal tract as unchanged drug, while the remaining 60% is excreted in the urine. Probenecid can not increase the plasma concentration or prolong the half-life period of the drug.

INDICATIONS:

Duselfin-D^® is indicated for the treatment of the lower respiratory infections, urinary tract infections, biliary tract infections, abdominal cavity infections, pelvic cavity infections, skin and soft tissue infections, bone and joint infections, septicaemia, meningitis and so on when caused by susceptible organisms and the prophylaxis against infections in operations. Single dose of the drug can be used to treat simple gonorrhea.

Dosage & Administration:

Duselfin-D^® can be administered intravenously or intramuscularly.

Adults and children over 12 years of age: The usual adult daily dose is 1.2g (potency) given once daily, intravenously or intramuscularly. The total daily dose may increase up to 4g (potency) depending on the and severity of infection.

Neonates: In neonates (within 14days of age),the usual daily dose is 20-50mg (potency) per kg body weight once daily. The total daily dose should not exceed 50mg (potency) per kg body weight. The dosage in neonates does not have to differentiate between premature and mature babies.

Neonates and Children (15 days to 12 years of age): The usual daily dose is 20-80mg (potency) per kg body weight once daily. Children weighing 50kg or more should receive the usual adult dosage of ceftriaxone. In the intravenous administration of over 50mg per kg body weight, should be administered at least for 30 minutes by i.v. Infusion.

Elderly: The elderly should receive the usual adult dosage of ceftriaxone.

Meningitis: For the treatment of bacterial meningitis, the initial dosage of neonates and children is 100mg per kg body weight once daily. (The total dose should not exceed 4g.)

Dosages may be decreased immediately when pathogen and sensitivity of infection or organism are clarified.

The following duration of therapy has been known effective for the treatment of:

Nisseria meningitidis                         : 4 days

Haemophilus influenzae                    : 6 days

Streptococcus pneumococcus            : 7 days

Gonorrhea: For the treatment of gonorrhea caused by penicillin susceptible and resistant organisms, the dose is 250 mg (potency) once intramuscularly.

Prophylaxis of peri-operative infections: A single dose of 1-2g (potency) administered 30-90 minutes before surgery is recommended in order to prevent postoperative infections in surgical operations which was contaminated or have potential to contaminate. In colorectum operation, the administration of the drug with 5 nitro-imidazole (ex.ornidazole) respectively separatively,simultaneously is effective.

Renal or Hepatic Disorder: No dosage adjustment is necessary for patients with both renal and hepatic dysfunctions; the daily dose should not exceed 2g.

-Duration of Therapy:

The duration of therapy depends on the type and severity of infection, and generally therapy should be continued for at least 48-72 hours after the patient becomes asymptomatic or evidence of the infection has been obtained.

Preparation of the Solution:

1. Intramuscular Adminstration:

Add 3.6ml sterile water for injection, sodium chloride, 5% glucose or Lidoject –1 to the bottle containing 1g of the drug, to prepare the solution with 250mg ceftriaxone per milliliter.

2. Intravenous Administration:

Inject the dilute mentioned before (except lidocaine) into 1g bottle, to reconstitute the solution with 100mg ceftriaxone per milliliter, which should be diluted with 100 – 250ml 5% glucose or sodium chloride injection for intravenous drip infusion.

CONTRAINDICATIONS:

Duselfin – D® is contraindicated in patients with known allergy to the celphalosporin class of antibiotics.

Patients with hypersensitivity to anilide local anaesthetic such as lidocaine.

WARNINGS AND PRECAUTIONS

1. Cross anaphylaxis: Those who are allergic to one kind of cephalosporins or the cephamycins may be also allergic to other kinds. Anaphylaxis to cephalosporins or cephamycins may occur in the patients who are allergic to penicillins and their derivants or penicillamine. Among the patients allergic to penicillin, 5- 10% may also allergic to cephalosporins; and 20% may allergic in immunological reactions examinations.
2. The administration of the drug on the patients allergic to penicillins should be determined after thorough consideration on their conditions. Those who have experienced allergic shocks to penicillin or immediate reactions shouldn’t be administered cephalosporins.
3. Cautions should be exercised when the drug is administered to the cases with disease history in gastrointestinal tract, especially ulcerative colitis’s deseases or antibiotic relative colonitis (pseudomembranous colitis selom occurs to cephalosporins).
4. With low toxicity in cephalosporins, the dosage of this drug needn’t be adjusted when administered to chronic hepatopathes. But it needs adjusting if the patients are suffering from severe impairment to liver and kidney or hepatic cirrhosis.
5. For the patients of renal inadequacy with CCR>5ml/min, if the drug is administered less than 2g per day, the dosage adjustment is not necessary. The drug can be merely cleaned up in hematodialysis, so no supplement is need after dialysis.
6. Interference to diagnosis: false positive reaction may occur in urine glucose examination with copper sulfate methods, except for the examination with glucose enzymic method; temporary elevation may occur to blood urea nitrogen and serum creatine; serum bilirub, AKP, ALT and AST may be hightened.

KEEP OUT OF THE REACH OF CHILDREN.

ADVERSE REACTIONS

            The adverse reactions are related to the therapeutic dose and course of treatment.

            Local reactions    – phlebitis (1.86%)

            Hypersensitivity  – rash, pruritus, fever, bronchospasm and serum disease (2.77%)

            Headache and dizzy (0.27%)

Gastrointestinal – diarrhea, nausea, vomitus, abdominal pain, colonitis, jaundice, gaseous distention, dysgeusis and dyspepsia (3.45%).

Abnormity in laboratory examination (19%) – hematological abnormity (14%), including eosinophilia, thrombocytosis or thrombocytopenia and hypoleukia.

Hepatic or renal disfunction (5% and 1.4% respectively)

USE IN PREGNANCY

Since safety use in pregnancy has not been established, therefore, Duselfin-D^® should be used during pregnancy only when the expected benefits clearly outweigh the potential risks.

USE IN LACTATION

Small amount of the drug has been distributed in human milk. Therefore, the administration to nursing mothers should be cautioned.

USE IN NEONATES AND PREMATURES

Safety use in neonates and prematures has not been established.

In vitro studies have shown that ceftriaxone, like some other cephalosporins, can displace bilirubin from serum albumin. Duselfin-D^® should not be administered to hyperbilirubinemic neonates, especially prematures.

CLINICAL TESTS

Pseudopositive reflex may develop in urinary glucose determinations using Benedict’s solution, Fehling’s solution, Clinitest except Test-Tape reaction, should therefore be cautioned.

Coomb’s test positive may occur, should therefore be cautioned

Pseudopositive response may develop in the galactosemia test, as other antibiotic dose.

DRUG INTERACTIONS

1.Turbidness may occur if erythromycin, cyclomycin, amphotericin B, vasoactive drugs(metaraminol,norepinephrine andso on),phenytoin,chloropromazine,isopropanol, vitaminB, vitaminC and so on are added to intravenous transfusion of cephalosporins.

2.Some individuals may appear disulfiram-like reaction when drinking wine or taking medicine containing alcohol, so alcohol and these medicines should be avoided during and in several days after the administration.

3.In test tube test, concomitant admimnistration with chloramphenicol has been observed antagonism.

STORAGE

The drug should be stored in cool and dry place, protected from light and closed tightly.

PRESENTATION

1.og x 1 vial 1 box (include 1 vial contains 10ml sterile water for injection)