Claraxim

2 g: Each vial contains sterile Cefotaxime sodium equivalent to Cefotaxime 2 g.
Each gram of Cefotaxime contains Sodium 50.5 mg (2.2 mmol).

Pharmacology: Pharmacodynamics: Cefotaxime is classified as a third generation cephalosporin. It has a bactericidal effect by inhibiting bacterial cell wall synthesis.
Cefotaxime has a broad spectrum of bactericidal activity and Pseudomonas aeruginosa.
Cefotaxime is active in vitro against the following bacteria: Gram-positive aerobic bacteria: Streptococcus pneumoniae, S. pyogenes (group A beta-hemolytic streptococci), Staphylococcus aureus (penicillinase-producing and nonpenicillinase-producing strains), S. epidermidis and viridans streptococci (some strains).
Gram-negative aerobic bacteria: Escherichia coli, Klebsiella (including K. pneumoniae), Haemophilus influenzae (including ampicillin-resistant strains), H. parainfluenzae, Proteus mirabilis, Serratia marcescens, Citrobacter, Enterobacter, Providencia stuartii, P. rettgeri, Morganella morganii, Neisseria gonorrhoeae, N. meningitidis, Pseudomonas aeruginosa (some strains).
Anaerobic bacteria: Bacteroides (including B. fragilis), Clostridium (including C. perfringens), Fusobacterium (including F. nucleatum), Peptococcus, Peptostreptococcus, Propionibacterium.
Resistance strains of some organisms, especially Enterobacter, Pseudomonas aeruginosa, Serratia, have developed during therapy with Cefotaxime.
Pharmacokinetics: Cefotaxime is not appreciably absorbed from the GI tract which must be given parenterally. Following IM administration, peak serum concentration of the drug are attained within 30 minutes. The antibiotic activity is considered from Cefotaxime and its major metabolite (desacetylcefotaxime). After entering the systemic circulation it is distributed to the body tissues and fluids including aqueous humor, bronchial secretion, sputum, bone, bile, ascitic, pleural and prostatic fluid; penetrates CSF best when meninges are inflamed.
Cefotaxime crosses the placenta and is distributed into milk. It is 13-38% bound to serum proteins and partially metabolized in the liver to desacetylcefotaxime. Cefotaxime is excreted principally in urine as unchanged drug and metabolite. Elimination half-life of Cefotaxime have 2 phases are initial phase and terminal phase; the serum half-life of the drug in the initial phase (t_1/2α) average 0.2-0.4 hours and the serum half-life of the drug in the terminal phase (t_1/2β) average 0.9-1.7 hours. The t_1/2β of desacetylcefotaxime is 1.4-1.9 hours. The t_1/2β of both Cefotaxime and desacetylcefotaxime may be prolonged in patients with impaired hepatic and renal function.
Both Cefotaxime and desacetylcefotaxime are removed by hemodialysis. Only minimal amounts of Cefotaxime are removed by peritoneal dialysis.

For treatment of susceptible bacterial infectious diseases as following: Respiratory tract infections including pneumonia.
Intra-abdominal infections including peritonitis.
Skin and soft tissue infections.
Kidney infections and urinary tract infections.
Gynecologic infections including gonorrhea and pelvic inflammatory disease.
Ear infections.
Bone and joint infections.
Other severe infections: Bacteremia/Septicemia, Endocarditis, Meningitis, For the prophylaxis in patients with reduced resistance and Surgical prophylaxis.

Preparation and administration: For intramuscular injection (IM): The contents of Cefotaxime 1 g are dissolved in 4 ml sterile water for injection or 1% lidocaine HCl injection. Intravenous injection must be prohibited if 1% lidocaine HCl applied. It should be made deeply into gluteal muscles and advisable not to inject more than 4 ml into each side (If an IM dose of 2 g of Cefotaxime is indicated, the dose should be divided and administration at 2 different injection sites or recommend be given IV).
Cefotaxime 2 g should not be given IM.
For intravascular injection (IV bolus injection): The contents of Cefotaxime 500 mg, 1 g and 2 g are dissolved in 2 ml and 4 ml and 10 ml sterile water for injection, respectively. The solution must be inject slowly over a period 3-5 minutes. During post-marketing surveillance, potentially life-threatening arrhythmia has been reported in a very few patients who received rapid intravenous administration of Cefotaxime over less than 1 minute.
For intravascular infusion (IV infusion): Dissolved the contents of Cefotaxime as same as for intravascular injection and then mixed with 40-100 ml of intravascular fluids including 0.9% sodium chloride injection, sodium lactate solution, 5% dextrose injection, lactated Ringer's injection. The concentration of final solution is 20-50 mg/ml.
Intravenous infusion (IV infusion): In the case giving high dose of Cefotaxime.
Intermittent intravenous infusion: dissolve the contents of Cefotaxime 2 g with 40 ml of compatible solvent for IV infusion (see the preparation section). Intermittent IV infusion of Cefotaxime is generally infused over 20 minutes; solutions should preferably be infused via butterfly or scalp vein-type needles.
Continuous intravenous infusion: dissolve the contents of Cefotaxime 2 g with 100 ml of compatible solvent for IV infusion (see the preparation section). Continuous IV infusion of cefotaxime is generally infused over 50-60 minutes; solutions should preferably be infused via butterfly or scalp vein-type needles.
A pale yellowish color of the solution does not indicate impairment of antibiotic activity.
To avoid septic complication on injection care should be taken during reconstitution to ensure aseptic handling. The solution should be used immediately after reconstitution.
Before use the drug should consider precipitate or discoloration of the drug.
Note: Sodium bicarbonate injection is not recommended as a diluent.
Cefotaxime must not be mixed with other antibiotics including aminoglycosides.
Stability: Cefotaxime sterile powder after reconstitution in sterile water for injection is chemically stable: up to 12 hours at room temperature (not exceeding +25 °C/indoor light).
Up to 24 hours under refrigerating condition (+2 °C - +8 °C/protected from light).
Cefotaxime sterile powder after reconstitution in lidocain HCl injection solution 1% is chemically stable: up to 24 hours under refrigerating condition (+2 °C - +8 °C/protected from light).
Cefotaxime sterile powder after reconstitution in infusion fluids including 0.9% sodium chloride injection, sodium lactate solution, 5% dextrose injection is chemically stable: up to 12 hours at room temperature (not exceeding +25 °C/indoor light).
Up to 24 hours under refrigerating condition (+2 °C - +8 °C/protected from light).
Dosage: See table.

Click on icon to see table/diagram/image

The maximum adult dosage recommended is 12 g daily.
Dosage in surgical prophylaxis: the administration of 1-2 g Cefotaxime (IM or IV) 30-60 minutes before the start of surgery is recommended. Doses may be repeated according to the risk of infections.
Dosage in prophylactically in patients undergoing cesarean section: the administration of 1 g given IV as soon as the umbilical cord is clamped, followed by 1 g IM or IV 6 and 12 hours after the first dose.
Dosage in infants and children up to 12 years old (weights less than 50 kg): 50-180 mg/kg/day in equally divided dose every 4-6 hours (IM or IV) and a dosage of 150-200 mg/kg/day for severe infections. The higher dose should be used for more severe or serious infections, including meningitis.
Children weighing 50 kg or more should receive the adult dose, but dose should not exceed 12 g daily. Premature or full-term neonates less than 1 week of age is 50 mg/kg every 12 hours and the usual dose for neonate 1-4 weeks of age is 50 mg/kg every 8 hours.
Dosage in patients with renal and hepatic impairment: Dosage in patients undergoing renal impairment: In patient with creatinine clearance less than 20 ml/min per 1.73 m², dose and/or frequency of administration should be modified in response to the degree of renal impairment. Half of the usual dose is recommended.
Dosage in patients undergoing hemodialysis: 0.5-2 g daily is given after each dialysis period.
Dosage in patients with hepatic impairment: Modification of the usual dosage of Cefotaxime is unnecessary for patient with impaired hepatic function.

Acute overdosage of Cefotaxime in patiens has most frequently resulted in increased serum concentration of BUN and creatinine, but most cases were not associate with overt toxicity. If acute overdosage occurs, the patient should be closely observed and given supportive treatment.

The drug is contraindicated in patients with a history of allergic reactions to the drug.
The drug is contraindicated in patients with a history of allergic reactions to the cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins.

Based on the Ministry of Public Health's Announcement: Do not use in patients who are hypersensitive to Cefotaxime sodium.
Using this drug in patients with hypersensitivity to penicillin can cause severe to fatal allergic reaction.
Stop using this drug and immediately consult the doctor or pharmacist when manifesting any signs and symptoms such as fever, skin rash, blisters, detachment of skin and epithelial lining in oral cavity, throat, nose, genital organ and conjunctivitis after taking the drug.

Prior to initiation of Cefotaxime therapy, careful inquiry should be made concerning previous hypersensitivity reaction to Cefotaxime, cephalosporins, penicillins, or other β-lactam drugs. There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins.
To reduce development of drug-resistance bacteria and maintain effectiveness of Cefotaxime and other antibacterial, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.
Similar to anti-infectives, prolonged use of Cefotaxime may result in over-growth of nonsusceptible organisms, especially Candida and others.
Diarrhea occurring during treatment may be symptomatic of Clostridium difficile-associated diarrhea and colitis which has been reported with almost all anti-infectives, including cefotaxime, and may range in severity from mild diarrhea to fatal colitis. So it should have been monitoring diarrhea, colitis including pseudomembranous colitis closely during treatment with Cefotaxime and after treatment.
Cefotaxime should be used with caution in elderly, patients with renal impairment.
Seizures have been reported with several cephalosporins, particularly in patients with renal impairment in whom dosage of the drug was not reduced. The dosage should be modified according to the creatinine clearance calculated.
Arrhythmias were reported in several patients who received Cefotaxime by rapid (less than 1 minute) bolus injection.

There are no adequate and controlled studies to date using Cefotaxime in pregnant women, and the drug should be used during pregnancy only when clearly needed.
Cefotaxime crosses the placental barrier so should not be used during pregnancy unless strictly indicated. As it is excreted in breast milk breast-feeding or treatment of the nursing women with Cefotaxime should be discontinued.

1% to 10%: Dermatologic: pruritus, rash, pain at injection site, phlebitis.
Gastrointestinal: colitis, diarrhea, nausea, vomiting.
<1%: agranulocytosis, increasing of the liver enzyme e.g. AST, ALT, LDH, GGT, alkaline phosphatase, bilirubin, anaphylaxis, Steven-Johnson syndrome, arrhythmia, pseudomembranous colitis, Coombs test (direct) positive, neutropenia, leukopenia, hemolytic anemia, BUN increased, interstitial nephritis, headache.

Concomitant use of probenecid and Cefotaxime may increase the level of Cefotaxime in blood circulation as probenecid decreases an excretion at glomerular filtration.
Concomitant use of aminoglycosides and Cefotaxime may be additive against some strains of Pseudomonas aeruginosa and Serratia marcescens and may increase the risk of nephrotoxicity. Renal function should be carefully monitored, especially if therapy is prolonged or if high aminoglycoside dosage is used.
Cefotaxime may interfere with laboratory tests e.g. Positive direct antiglobulin test (Coombs' test), urinary glucose determinations using cupric sulfate (Benedict's reagent, Clinitest) and falsely elevated serum or urine creatinine value when the Jaffe reaction used.

Incompatibilities: It is not recommended to use sodium bicarbonate as a dilute.
Cefotaxime must not be mixed with other antibiotics including aminoglycosides.

Store below 25°C protect from light.
The solution should be used immediately after reconstitution.
The stability of diluted solution is as indicated.

Cephalosporins

J01DD01 - cefotaxime ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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