Detailed Product Description

DESCRIPTION:

A white or almost white, hygroscopic, crystalline powder

INDICATION:

Cloxacilline is an isoxazolyl penicillin used primarily for the treatment of infections due to staphylococci resistant to benzylpenicillin. These include bone and joint infections, endocarditis, pneumonia, skin infections (including soft-tissue infections), and toxic shock syndrome. For discussions of these infections and their treatment, see under Choice of Antibacterial.

PHARMACODYNAMIC AND TOXICOLOGICAL PROPERTIES:

Cloxacilline is incompletely absorbed from the gastrointestinal tract, and absorption is reduced by the presence of food in the stomach. After an oral dose of 500 mg, a peak plasma concentration of 7 to 15 micrograms/mL is attained in fasting subjects in 1 to 2 hours. Absorption is more complete when given by intramuscular injection and peak plasma concentrations of about 15 micrograms/mL have been observed 30 minutes after a dose of 500 mg. Doubling the dose can double the plasma concentration. About 94% of cloxacilline in the circulation is bound to plasma proteins. Cloxacilline has been reported to have a plasma half-life of 0.5 to 1 hour. The half-life is prolonged in neonates.

Cloxacilline crosses the placenta and is distributed into breast milk. There is little diffusion into the CSF except when the meninges are inflamed. Therapeutic concentrations can be achieved in pleural and synovial fluids and in bone.

Cloxacilline is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. About 35% of an oral dose is excreted in the urine and up to 10% in the bile. Cloxacilline is not removed by haemodialysis.

DOSAGE AND ADMINISTRATION:

Cloxacilline is given by mouth as the sodium salt and doses are expressed in terms of the equivalent amount of cloxacillin; 1.09 g of cloxacillin sodium is equivalent to about 1 g of cloxacilline. It should be given at least 30 minutes before meals as the presence of food in the stomach reduces absorption.

Usual oral doses are 250 to 500 mg four times daily. Children may be given 50 to 100 mg/kg daily in divided doses every 6 hours.

Cloxacilline sodium has also been given by intramuscular or slow intravenous injection or infusion. Other routes have included intra-articular or intrapleural injection, and inhalation.

Cloxacilline may be used with other antibacterials, including ampicillin, to produce a wider spectrum of activity.

SIDE-EFFECTS:

The most common adverse effects of benzylpenicillin are hypersensitivity reactions, especially skin rashes; anaphylaxis occasionally occurs and has sometimes been fatal.

Gastrointestinal effects such as diarrhoea and nausea are the most common adverse effects following oral use of benzylpenicillin; a sore mouth or tongue or a black hairy tongue have occasionally been reported. Pseudomembranous colitis has been associated with the use of most antibiotics and, of the penicillins, ampicilline or amoxicilline have been implicated most frequently.

CONTRAINDICATION:

A history of to any of the penicillins is a contraindication.

WARNING AND PRECAUTION:

Hepatitis and cholestatic jaundice have been reported occasionally with cloxacillin and may be delayed in onset for up to 2 months after treatment has been stopped; older patients and those receiving cloxacillin for more than 2 weeks are at greater risk. Fatalities have occurred, usually in patients with serious underlying hepatic disease. There have been rare reports of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis associated with cloxacillin. Agranulocytosis and neutropenia have been associated rarely with isoxazolyl penicillins such as cloxacillin. Phlebitis has followed intravenous infusion.

INTERACTION:

Probenecid prolongs the half-life of benzylpenicillin by competing with it for renal tubular secretion and may be used therapeutically for this purpose. Benzylpenicillin may also interact with bacteriostatic antibacterials such as chloramphenicol and tetracyclines, and may be incompatible in vitro with other drugs, including some other antibacterials.

STORAGE:

Store this medication in tight containers at room temperature and protect from light.

Keep this medicine out of the reach of children and away from pets.