CLOXACILLIN SODIUM, CLOXACILLIN BENZATHINE

For general information on the penicillins, including adverse effects, contraindications, overdosage, drug interactions and monitoring parameters, refer to the monograph: Penicillins, General Information.
Chemistry - An isoxazolyl-penicillin, cloxacillin sodium is a semisynthetic penicillinase-resistantpenicillin. It is available commercially as the monohydrate sodium salt which occurs as an odorless, bitter-tasting, white, crystalline powder. It is freely soluble in water and soluble in alcohol and has apKa of 2.7. One mg of cloxacillin sodium contains not less than 825 micrograms of cloxacillin.
Cloxacillin sodium may also be known as sodium cloxacillin, chlorphenylmethyl isoxazolylpenicillin sodium or methylchlorophenyl isoxazolyl penicillin sodium.
Cloxacillin benzathine occurs as white or almost white powder that is slightly soluble in water andalcohol. A 1% (10 mg/ml) suspension has a pH from 3-6.5.

Storage, Stability, Compatibility

Cloxacillin sodium capsules and powder for oral solutionshould be stored at temperatures less than 40°C and preferably at room temperature (15-30°C).
After reconstituting, refrigerate any remaining oral solution and discard after 14 days. If stored atroom temperature, the oral solution is stable for 3 days.
Unless otherwise instructed by the manufacturer, cloxacillin benzathine mastitis syringes shouldbe stored at temperatures less than 25°C in tight containers.

Pharmacology/Uses, Indications

Cloxacillin, dicloxacillin and oxacillin have nearly identicalspectrums of activity and can be considered therapeutically equivalent when comparing in vitroactivity. These penicillinase-resistant penicillins have a more narrow spectrum of activity than thenatural penicillins. Their antimicrobial efficacy is aimed directly against penicillinase-producingstrains of gram positive cocci, particularly Staphylococcal species. They are sometimes called antistaphylococcal penicillins. There are documented strains of Staphylococcus that are resistant to these drugs (so-called methicillin-resistant Staph), but these strains have not as yet been a major problem in veterinary species. While this class of penicillins do have activity against some other gram positive and gram negative aerobes and anaerobes, other antibiotics (penicillins and otherwise) are usually better choices. The penicillinase-resistant penicillins are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma and viruses.
The veterinary use of these agents has been primarily in the treatment of bone, skin, and other softtissue infections in small animals when penicillinase-producing Staphylococcus species have beenisolated, or in the treatment of mastitis with cloxacillin in dairy cattle.
Pharmacokinetics (specific) - Cloxacillin is only available in oral and intramammary dosageforms. Cloxacillin sodium is resistant to acid inactivation in the gut, but is only partially absorbed.
The bioavailability after oral administration in humans has been reported to range from 37-60%, and if given with food, both the rate and extent of absorption is decreased.
The drug is distributed to the liver, kidneys, bone, bile, pleural fluid, synovial fluid and ascitic fluid.
Only minimal amounts are distributed into the CSF, as with the other penicillins. In humans, approximately 90-95% of the drug is bound to plasma proteins.
Cloxacillin is partially metabolized to both active and inactive metabolites. These metabolites andthe parent compound are rapidly excreted in the urine via both glomerular filtration and tubularsecretion mechanisms. A small amount of the drug is also excreted in the feces via biliaryelimination. The serum half-life in humans with normal renal function ranges from about 24-48minutes. In dogs, 30 minutes has been reported as the elimination half-life.