INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo REFTAX 500 (Injection)
REFTAX 1g (Injection)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

REFTAX 500 (Injection)
REFTAX 1g (Injection)

COMPOSITION:
Reftax 500
Each vial contains:
Cefotaxime sodium (Sterile)
equivalent to
cefotaxime         500 mg

Reftax 1g
Each vial contains:
Cefotaxime sodium (Sterile)
equivalent to
cefotaxime         1g

PHARMACOLOGICAL CLASSIFICATION:
A20.1.1 Broad and medium spectrum antibiotics

PHARMACOLOGICAL ACTION
Mechanism of action
Cefotaxime is a third-generation cephalosporin antibiotic. The bactericidal action of cefotaxime results from inhibition of cell wall synthesis of the bacterial cell wall.
Antibacterial spectrum
Cefotaxime has in vitro activity against a wide range of gram-positive and gram-negative organisms. Cefotaxime has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Cefotaxime is active against the following microorganisms in vitro (In vitro sensitivity does not necessarily imply in vivo efficacy):
Gram-positive aerobes:
Staphylococcus aureus, including certain penicillinase and non-penicillinase producing strains, Staphylococcus epidermidis, Streptococcus pyogenes (Group A beta-hemolytic streptococci), Streptococcus agalactiae (Group B streptococci) (Note: most strains of enterococci e.g. S. faecalis are resistant), Streptococcus pneumoniae.
Gram-negative aerobes:
Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae (including ampicillin-resistant H. influenzae),Klebsiella spp. (including K. pneumoniae), Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Proteus morganella, Proteus rettgeri, Providencia spp., Serratia spp., Salmonella spp.(including S .typhi), Shigella spp.
Anaerobes:
Bacteroides spp., Clostridium spp., (Note: most strains of C. difficile are resistant), Peptococcus spp., Peptostreptococcus spp.
Resistant strains:
Most Pseudomonas species, most anaerobic bacteria, some Klebsiella and Serratia species and Candida.
Most Enterococci, Listeria monocytogenes, most Clostridium difficile strains, penicillinase producing Staphylococcus epidermidis strains and methicillin resistant Staphylococcus aureus.
Chlamydia
S. faecalis.
Pharmacokinetics
IM injection
Following IM injection of doses of 0,25g, 0,5g and 1g, peak plasma levels are reached at 30 minutes. The level increases according to the dose administered and is approximately 24 mcg/mL after the 1g injection. Urinary excretion in the 24 hours after injection is 50-60% of the dose administered. It is 44-55% in the first 6 hours after IM injection. The plasma protein binding of the medicine is approximately 38%.
IV injection
The initial phase half-lives for whole blood and plasma are 4,5 and 8 minutes respectively. Terminal phase half-lives for whole blood and plasma are 1,3 and 2,2 hours respectively. Of the administered dose 85 to 90% is excreted in the urine and 7-9,5% in the faeces. Most of the dose is excreted within 4 hours of administration. Approximately 20-36% of an IV administered dose of cefotaxime is excreted by the kidney as the unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. Desacetylcefotaxime has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3) account for 20-25%. They lack bactericidal activity. After a single IV injection of cefotaxime 1g, serum protein binding of the drug is approximately 44%.
IV infusion
Loading dose of 0,5 g, 1g and 2g administered over 15 minutes followed by sustaining infusions of 0,5g, 1g and 2g per hour produces mean peak serum levels of 41, 93 and 160 mcg/mL respectively. The mean terminal half-life is 75+7 minutes. 63+9% of the dose is excreted within 24 hours by the kidneys. Plasma protein binding is approximately 35%.

INDICATIONS:
Cefotaximeis indicated for use primarily in the treatment of infections of the genito-urinary, gastro-intestinal and respiratory tracts, and in the skin and soft tissues and meningitis in children caused by susceptible strains of the following organisms.
Staphylococcal infections (including infections caused by both penicillinase producing and non-penicillinase producing strains): abscess, furunculosis, bronchitis and impetigo.
Streptococcal infections: (both -hemolytic and group D streptococci), cellulitis, pneumonia, follicular tonsillitis, otitis media, pharyngitis, sinusitis, scarlet fever, septic sore throat, urinary tract infections (Enterococci) and meningitis in children.
Pneumococcal infections: Lobar pneumonia, bronchitis, cellulitis and otitis media.
Haemophilus influenzae infections: Otitis media, laryngotracheobronchitis and meningitis in children.
E. coli infections: Lobar pneumonia, urinary tract infections and meningitis in children.
Shigella infections: Bacillary dysentery.
Salmonella infections: Enteritis.
Sensitive strains of Pseudomonas aeruginosa: Sepsis.
Gonococcus: Gonorrhoea.
Neisseria meningitidis: Meningitis in children.
Bacteriological studies to determine the causative organisms and their sensitivity to cefotaxime should be performed.
Prophylactic Uses: The administration of cefotaxime pre-operatively may reduce the incidence of certain post-operative infections in patients undergoing surgical procedures that are classified as potentially contaminated. The minimum effective dose has been found to be 1g cefotaxime 30-90 minutes prior to surgery.

CONTRA-INDICATIONS
Cefotaxime is contra-indicated in patients who are allergic to the cephalosporin group of antibiotics.
Pregnancy: There are no well controlled studies pertaining to the use of cefotaxime in pregnant women, although animal studies have not shown any teratogenic effect.
Lactation: Cefotaxime is excreted in human milk in low concentrations. Caution should be exercised when cefotaxime is administered to a nursing woman.

WARNINGS
Before therapy with cefotaxime is instituted, careful inquiry should be made to determine whether the patient had previous hypersensitivity reactions to cefotaxime sodium, cephalosporins or penicillins. If an allergic reaction to cefotaximeoccurs, discontinue treatment with the drug. Strict medical supervision is required throughout treatment.
Pseudomembranous colitis has been reported with the use of cephalosporins (and other broad-spectrum antibiotics); therefore, it is important to consider its diagnosis in patients who develop diarrhoea in association with antibiotic use.

DOSAGE AND DIRECTIONS FOR USE:
Cefotaxime is given as deep intramuscular injection or by slow intravenous injection over 3-5 minutes or by infusion over 20-60 minutes.
Adults
Dosage and route of administration should be determined by susceptible organisms, severity of the infection, and the condition of the patient. The maximum daily dose should not exceed 12 grams.
The usual dose is 2g daily in 2 x 1g injections. Severe cases may be given 3-4g daily in 2 to 4 administrations
In the treatment of gonorrhoea a single 1g dose of cefotaxime is given.
To prevent postoperative infection, the recommended dose is a single dose of 1 gram IM or IV administered 30 to 90 minutes before surgery.
In the treatment of beta-hemolytic streptococcal infections, a therapeutic dose must be administered for at least 10 days.
Neonates, Infants and Children
Children and infants
50-100 mg/kg/day in 2-4 divided doses. A maximum dose of 200 mg/kg/day in 2-4 divided doses may be given in exceptional cases.
Neonates
The following dosage schedule is recommended.
Up to 1 week of age 50 mg (base)/kg IV every 12 hourly
1-4 weeks of age 50 mg (base)/kg IV every 8 hourly
It is not necessary to differentiate between premature and normal-gestational age infants.
Renal Failure
It is suggested that the dosage of cefotaxime be halved in patients with creatinine clearance less than 20 mL/min. The dosage interval should not be modified.

Method of Preparation
Reconstitute the contents with sterile water for injection. Shake well until dissolved and then withdraw the entire contents of the vial into the syringe and use immediately. The dilution table is given below:
Vial Size         Volume of Water for Injection to be added 
                        IM         IV*
500 mg         2 mL         10 mL
1 g         4 mL         10 mL
* For direct intravenous use, the resulting solution should be administered over a 3 to 5 minute period.
Intravenous Infusion: Cefotaxime may be administered by intravenous infusion. 1 to 2g are dissolved in 40 to 100 mL of water for injection or in the infusion fluids (See “Stability”). The prepared infusion solution should be administered over 20 to 60 minutes.
Warning: Do not mix cefotaxime with another antibiotic in the same syringe or infusion.
Stability: The stability of cefotaxime in a concentration of 1Sg per 250 mL in the following infusions is satisfactory for 24 hours in a refrigerator or 12 hours at a temperature not exceeding 25°C: 0,9% sodium chloride, 5% dextrose, Ringer’s sterile solutions.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side Effects
The most common adverse effects are hypersensitivity reactions including skin rashes, skin eruptions, urticaria, eosinophilia, fever, reactions resembling serum sickness, and anaphylaxis. Acute interstitial nephritis is also a possibility as a manifestation of hypersensitivity.
There may be a positive response to Coombs’test although hemolytic anemia rarely occurs. Neutropenia and thrombocytopenia have occasionally been reported with cefotaxime. Agranulocytosis has been associated rarely with some cephalosporins including cefotaxime. As in the case of some other cephalosporins, bleeding complications related to hypoprothrombinemia and/or platelet dysfunction may occur.
Transient increases in liver enzyme values including transaminases and alkaline phosphatases have been reported.
Gastrointestinal adverse effects such as nausea, vomiting and diarrhoea have been reported rarely.
Prolonged use may result in overgrowth of non-susceptible organisms and, as with other broad-spectrum antibiotics, pseudomembranous colitis may develop.
Deep phlebitis after IV injection has been reported occasionally.
Precautions
General
The broad-spectrum third-generation cephalosporins have the potential for colonisation and super-infection with resistant organisms such as Pseudomonas aeroginosa, Enterobacter spp., Candida, and enterococci, at various sites in the body, although the incidence has generally been low with cefotaxime.
As high and prolonged serum antibiotic concentrations can occur from usual doses in patients with transient or persistent reduction of urinary output because of renal insufficiency, the total daily dosage should be reduced when cefotaxime is administered to such patients.
About 10% of penicillin-sensitive patients may also be allergic to cephalosporins although the true incidence is uncertain. Great care should be taken if cefotaxime is to be given to such patients. Care is also necessary in patients with known histories of allergies.
Geriatrics
Elderly patients are more likely to have an age-related decrease in renal function necessitating dosage adjustment.
Interactions:
Increased nephrotoxicity has been reported following concomitant administration of cephalosporins and aminoglycoside antibiotics. There is also some evidence for enhanced nephrotoxicity with a loop diuretic like furosemide.
Concomitant administration of probenecid with cephalosporins decreases tubular secretion of cephalosporins resulting in their increased and prolonged serum concentration.
There may be antagonism between cefotaxime and bacteriostatic antibacterial agents. Cefotaxime may interfere with the Jaffe‘ method of measuring creatinine concentrations and may produce falsely high values; this should be borne in mind when measuring renal function.
Laboratory Value Alterations
A positive Coombs’reaction frequently appears in patients who receive large doses of cephalosporin.
A false positive reaction may occur on testing for glucose in the urine with reducing substances, but this can be avoided with the use of methods that are specific to gluco-oxidase.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See side effects. Treatment is symptomatic and supportive

IDENTIFICATION:
Reftax 500
White or slightly yellow powder, hygroscopic, filled in 15 mL USP Type I clear, colourless glass vial fitted with grey rubber plug and coloured flip-off seal.
Reftax 1g
White or slightly yellow powder, hygroscopic, filled in 15 mL USP Type I clear, colourless glass vial fitted with grey rubber plug and coloured flip-off seal.
On constitution a pale yellow to yellow clear solution is formed

PRESENTATION:
Reftax 500:Carton containing vial of 500 mg in clear, colourless glass USP Type I vial.
Reftax 1 g: Carton containing vial of 1g in clear, colourless glass USP Type I vial.

STORAGE INSTRUCTIONS:
Store below 25°C, protected from light. Store in the outer carton until required for use.
Reconstituted solution to be used within 24 hours if stored at 2-8°C in a refrigerator or within 12 hours if stored below 25°C. Do not freeze the reconstituted solution.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS :
Reftax 500:        34/20.1.1/0255.
Reftax 1 g:         34/20.1.1/0256.

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
RANBAXY (SA) (PTY) LTD
3rd Floor
Outspan House
1006 Lenchen Avenue North
Centurion

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
October 2001

New addition to this site: March 2002

SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2006