Ximvex

Each vial contains: Cefotaxime (as sodium) 1 g.
Cefotaxime sodium is a white or slightly yellow powder, hygroscopic, freely soluble in water and sparingly soluble in methanol.

Pharmacology: Pharmacokinetics: Cefotaxime is given by injection as the sodium salt. It is rapidly absorbed after intramuscular injection and mean peak plasma concentrations of about 12 and 20 micrograms/mL have been reported 30 minutes after doses of 500 mg and 1 g of cefotaxime, respectively. Immediately after intravenous injection of 500 mg, 1 g, or 2 g of cefotaxime, mean peak plasma concentrations of 38, 102, and 215 micrograms/mL, respectively, have been achieved with concentrations ranging from about 1 to 3 micrograms/mL after 4 hours. The plasma half-life of cefotaxime is about 1 hour and that of the active metabolite desacetylcefotaxime about 1.5 hours; half-lives are increased in neonates and in patients with severe renal impairment, especially those of the metabolite, and a reduction in dosage may be necessary. The effects of liver disease on clearance of cefotaxime and its metabolite have been variable, but in general, dosage adjustment has not been considered necessary. About 40% of cefotaxime is reported to be bound to plasma proteins.
Cefotaxime and desacetylcefotaxime are widely distributed in body tissues and fluids; therapeutic concentrations are achieved in the Cerebro Spinal Fluid particularly when the meninges are inflamed. Cefotaxime crosses the placenta and low concentrations have been detected in breast milk.
Following partial metabolism in the liver to desacetylcefotaxime and inactive metabolites, elimination is mainly by the kidneys and about 40 to 60% of a dose has been recovered unchanged in the urine within 24 hours; a further 20% is excreted as the desacetyl metabolite. Relatively high concentrations of cefotaxime and desacetylcefotaxime are achieved in the bile and about 20% of the dose has been recovered in the faeces.
Probenecid competes for renal tubular secretion with cefotaxime resulting in higher and prolonged plasma concentrations of cefotaxime and its desacetyl metabolite. Cefotaxime and its metabolites are removed by hemodialysis.
When microbiological assays have been used, reported pharmacokinetic values may relate to cefotaxime plus its active metabolite, desacetylcefotaxime.
Microbiology: Antimicrobial Action: Cefotaxime is a third-generation cephalosporin. It has a bactericidal action similar to cefamandole, but a broader spectrum of activity. It is highly stable to hydrolysis by most beta-lactamases and has greater activity than first- or second-generation cephalosporins against Gram-negative bacteria. Although cefotaxime is generally considered to have slightly less activity than first-generation cephalosporins against Gram-positive bacteria, many streptococci are very sensitive to it.
Desacetylcefotaxime is an active metabolite of cefotaxime and there may be additive or synergistic effects against some species.
Spectrum of activity: Among Gram-negative bacteria, cefotaxime is active in vitro against many Enterobacteriaceae including Citrobacter and Enterobacter spp., Escherichia coli, Klebsiella spp., both indole-positive and indole-negative Proteus, Providencia, Salmonella, Serratia, Shigella, and Yersinia spp. Other susceptible Gram-negative bacteria, including penicillin-resistant strains, are Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis), Neisseria gonorrhoeae, and N. meningitides. Brucella melitensis is also reported to be moderately sensitive. Some strains of Pseudomonas spp. are moderately susceptible to cefotaxime, but most are resistant. Desacetylcefotaxime is active against many of these Gram-negative bacteria, but not against Pseudomonas spp.
Among Gram-positive bacteria, cefotaxime is active against staphylococci and streptococci. Staphylococcus aureus, including penicillinase-producing strains but not methicillin-resistant Staph. aureus, is sensitive. Staph. epidermidis is also sensitive but penicillinase-producing strains are resistant. Streptococcus agalactiae (group B streptococci), Str. pneumoniae, and Str. pyogenes (group A streptococci) are all very sensitive although truly penicillin-resistant pneumococci are apparently not sensitive. Enterococci and Listeria monocytogenes are resistant.
Cefotaxime is active against some anaerobic bacteria. Bacteroides fragilis may be moderately sensitive, but many strains are resistant; synergy has been demonstrated with desacetylcefotaxime in vitro. Clostridium perfringens is sensitive, but most Cl. difficile are resistant.
Other organisms sensitive to cefotaxime include the spirochaete Borrelia burgdorferi and Haemophilus ducreyi.
Activity with other antimicrobials: In addition to possible synergy or additive effects with desacetylcefotaxime, the activity of cefotaxime may be enhanced by aminoglycosides such as gentamicin; synergy has been demonstrated in vitro against Gram-negative bacteria including Pseudomonas aeruginosa. There have also been reports of enhanced activity in vitro with other antibacterials including fosfomycin and ciprofloxacin and variable results with penicillins.
Resistance may develop during treatment with cefotaxime due to derepression of chromosomally mediated beta-lactamases, and has been reported particularly in Enterobacter spp., with multiresistant strains emerging during treatment. This type of resistance has also developed in other bacteria including Citrobacter, Serratia, and Pseudomonas spp. Another mechanism of cefotaxime resistance is the development of plasma-mediated, extended-spectrum beta-lactamases, and this has occurred in Klebsiella spp. and also other Enterobacteriaceae. Resistance in Str. pneumoniae is due to the production of altered penicillin-binding proteins.

Cefotaxime is used for the treatment of lower respiratory tract infections including pneumonia; Genitourinary infections including uncomplicated gonorrhea; Gynecologic infections including pelvic inflammatory disease, endometritis and pelvic cellulitis; Bacteremia/septicemia; Skin and skin structure infections. Intra-abdominal infections including peritonitis; Bone and/or joint infections; Central Nervous System infections e.g. meningitis and ventriculitis.

Cefotaxime is given as the sodium salt by deep intramuscular (IM) injection or intravenously (IV) by slow injection over 3 to 5 minutes or by infusion over 20 to 60 minutes. Doses are expressed in terms of the equivalent amount of cefotaxime. 1.05 g of cefotaxime sodium is approximately equivalent to 1 g of cefotaxime. It is usually given in doses of 2 to 6 g daily in 2 to 4 divided doses to adults. In severe infections up to 12 g may be given daily by the intravenous route in up to 6 divided doses; pseudomonal infections usually require more than 6 g daily, but a cephalosporin with greater antipseudomonal activity, such as ceftazidime, is preferable. Children may be given 100 to 150 mg/kg (50 mg/kg for neonates) daily in 2 to 4 divided doses, increased in severe infections to 200 mg/kg (150 to 200 mg/kg for neonates) daily if necessary.
Neonates, Infants and Children: Neonates (birth to 1 month): 0-1 week of age - 50 mg/kg per dose every 12 hours IV.
1-4 weeks of age - 50 mg/kg per dose every 8 hours IV.
It is not necessary to differentiate between premature and normal-gestational age infants.
Infants and Children (1 month to 12 years): Body weight (BW) <50 kg, recommended daily dose is 50 to 180 mg/kg IM or IV, BW divided into four to six equal doses. The higher dosages should be used for more severe or serious infections; including meningitis.
BW ≥ 50 kg - usual adult dosage; not exceeding 12 g.
In the treatment of gonorrhoea, a single dose of 500 mg or 1 g of cefotaxime is given.
For Gonococcal urethritis/Cervicitis in males and females and Rectal gonorrhea in females: 500 mg IM once daily.
Rectal gonorrhea in Males: 1 g IM once daily.
Uncomplicated infections: 1 g IM or IV twice daily.
Moderate to severe infections: 1-2 g every 8 hours IM or IV.
Infections commonly needing antibiotics in higher dosage (e.g. septicemia): 2 g every 6-8 hours IV.
Life-threatening infections: 2 g every 4 hours IV.
If C. trachomatis is a suspected pathogen appropriate anti-chlamydial coverage should be added, because cefotaxime sodium has no activity against this organism.
For surgical infection prophylaxis: 1 g is given 30 to 90 minutes before surgery. At caesarean section, 1 g is given intravenously to the mother as soon as the umbilical cord is clamped and two further doses intramuscularly or intravenously 6 and 12 hours later.
Cefotaxime may be used with an aminoglycoside as synergy may occur against some Gram-negative organisms, but the drugs should be administered separately. It has sometimes been used with another beta lactam to broaden the spectrum of activity. Cefotaxime has also been used with metronidazole in the treatment of mixed aerobic-anaerobic infections.
Dosage in renal impairment: Doses of cefotaxime should be reduced in severe renal impairment; after an initial loading dose of 1 g for adults, halving the dose while maintaining the usual frequency of dosing has been suggested.

Sterile Cefotaxime Sodium is contraindicated to patients with known hypersensitivity to cephalosporins.

Use in Lactation: Although cefotaxime is excreted in breast milk in small amounts, no adverse effects have been observed in breast-fed infants whose mothers were receiving cefotaxime, and the American Academy of Pediatrics considers that it is therefore usually compatible with breastfeeding.

Use in Lactation: Although cefotaxime is excreted in breast milk in small amounts, no adverse effects have been observed in breast-fed infants whose mothers were receiving cefotaxime, and the American Academy of Pediatrics considers that it is therefore usually compatible with breastfeeding.

The most common are hypersensitivity reactions, including skin rashes, urticaria, eosinophilia, fever, reactions resembling serum sickness, and anaphylaxis. Arrhythmias have been associated with rapid bolus administration through a central venous catheter in a few cases.

As for many cephalosporins, probenecid reduces the renal clearance of cefotaxime, resulting in higher and prolonged plasma concentrations of cefotaxime and its desacetyl metabolite.
The total body clearance of cefotaxime has been reduced in patients with normal and reduced renal function by the ureidopenicillins azlocillin or mezlocillin. Doses of cefotaxime may need to be reduced if either of these penicillins is being given. Encephalopathy with focal motor status and generalised convulsions have been reported in a patient with renal failure given cefotaxime and high doses of azlocillin.

Incompatibility: Cefotaxime sodium has been reported to be incompatible with alkaline solutions such as sodium bicarbonate. The manufacturers recommend that it should be administered separately from aminoglycosides.

Store at temperatures not exceeding 30°C. Protect from light.

Cephalosporins

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

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