© 2003-17 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D. Published by
Elephant Care International
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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-resistant penicillin. 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 a pKa 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 isoxazolyl penicillin sodium or methylchlorophenyl isoxazolyl penicillin sodium.
Cloxacillin benzathine occurs as white or almost white powder that is slightly soluble in water and alcohol. A 1% (10 mg/ml) suspension has a pH from 3-6.5.
Storage/Stability/Compatibility – Cloxacillin sodium capsules and powder for oral solution should 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 at room temperature, the oral solution is stable for 3 days.
Unless otherwise instructed by the manufacturer, cloxacillin benzathine mastitis syringes should be stored at temperatures less than 25°C in tight containers.
Pharmacology/Uses/Indications – Cloxacillin, dicloxacillin and oxacillin have nearly identical spectrums of activity and can be considered therapeutically equivalent when comparing in vitro activity. These penicillinase-resistant penicillins have a more narrow spectrum of activity than the natural penicillins. Their antimicrobial efficacy is aimed directly against penicillinase-producing strains of gram positive cocci, particularly Staphylococcal species. They are sometimes called anti-staphylococcal 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 soft tissue infections in small animals when penicillinase-producing Staphylococcus species have been isolated, or in the treatment of mastitis with cloxacillin in dairy cattle.
Pharmacokinetics (specific) – Cloxacillin is only available in oral and intramammary dosage forms. 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 and the parent compound are rapidly excreted in the urine via both glomerular filtration and tubular secretion mechanisms. A small amount of the drug is also excreted in the feces via biliary elimination. The serum half-life in humans with normal renal function ranges from about 24-48 minutes. In dogs, 30 minutes has been reported as the elimination half-life.
Doses – Author’s (Plumb) note: Injectable form is not available in the U.S.A.
For mastitis (treatment or prophylaxis) caused by susceptible organisms:
a) Lactating cow (using lactating cow formula; Dari-Clox®): After milking out and disinfecting teat, instill contents of syringe; massage. Repeat q12h for 3 total doses.
Dry (non-lactating) cows (using dry cow formula; benzathine): After last milking (or early in the dry period), instill contents of syringe and massage into each quarter. (Package inserts; Dari-Clox®, Orbenin-DC®—Beecham; Dri-Clox®—Fort Dodge)
Client Information – Unless otherwise instructed by the veterinarian, this drug should be given orally on an empty stomach, at least 1 hour before feeding or 2 hours after. Keep oral solution in the refrigerator and discard any unused suspension after 14 days.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times –
Cloxacillin Benzathine 500 mg (of cloxacillin) in a peanut-oil gel; 10 ml syringe for intramammary infusion
Orbenin-DC® (Pfizer), Dry-Clox® (Fort Dodge); (Rx) Approved for use in dairy cows during the dry period (immediately after last milking or early in the dry period). Do not use within 30 days prior to calving (28 days for Orbenin-DC®). Slaughter withdrawal = 30 days (28 days for Orbenin-DC®). A tolerance of 0.01 ppm has been established for negligible residues in uncooked edible meat and milk from cattle.
Cloxacillin Sodium 200 mg (of cloxacillin) in vegetable oils; 10 ml syringe for intramammary infusion
Dari-Clox® (Pfizer); (Rx) Approved for use in lactating dairy cows. Milk withdrawal = 48 hours; Slaughter withdrawal = 10 days.
Cloxacillin Sodium Capsules 250 mg, 500 mg; Tegopen® (Apothecon) (Rx),Cloxapen® (SK-Beecham) (Rx), generic; (Rx)
Cloxacillin Sodium Powder for Oral Solution 125 mg/5 ml in 100 & 200 ml bottles; Tegopen® (Apothecon) (Rx), generic; (Rx)