cloxacillin sodium

Available forms
Available by prescription only
Capsules: 250 mg, 500 mg
Oral solution: 125 mg/5 ml (after reconstitution)

Indications and dosages
 Systemic infections by penicillinase-producing staphylococci organisms.
Adults: 250 to 500 mg P.O. q 6 hours.
Children: 50 to 100 mg/kg P.O. daily, divided into doses given q 6 hours.

Pharmacodynamics
Antibiotic action: Cloxacillin is bactericidal; it adheres to bacterial penicillin-binding proteins, thereby inhibiting bacterial cell wall synthesis. Cloxacillin resists the effects of penicillinases-enzymes that inactivate penicillin-and therefore is active against many strains of penicillinase-producing bacteria; this activity is most pronounced against penicillinase-producing staphylococci; some strains may remain resistant. Cloxacillin is also active against gram-positive aerobic and anaerobic bacilli but has no significant effect on gram-negative bacilli.

Pharmacokinetics
Absorption: Absorbed rapidly but incompletely (37% to 60%) from the GI tract; it’s relatively acid stable. Food may decrease both rate and extent of absorption.
Distribution: Distributed widely. CSF penetration is poor but enhanced in meningeal inflammation. Cloxacillin crosses the placental barrier and is 90% to 96% protein-bound.
Metabolism: Only partially metabolized.
Excretion: Excreted in urine by renal tubular secretion and glomerular filtration; also appears in breast milk. Elimination half-life in adults is 1/2 to 1 hour, extended to 2 1/2 hours in patients with renal impairment.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other penicillins.

Interactions
Drug-drug. Aminoglycosides: Produces synergistic bactericidal effects against Staphylococcus aureus. However, the drugs are physically and chemically incompatible and are inactivated when mixed or given together. Avoid use together.
Probenecid: Increases serum cloxacillin level. Probenecid may be used for this purpose.
Drug-food. Any food: Decreases drug absorption. Advise taking drug on an empty stomach.
Carbonated beverages, fruit juices: May inactivate drug. Discourage use together.

Adverse reactions
CNS: lethargy, hallucinations, seizures, anxiety, confusion, agitation, depression, dizziness, fatigue.
GI: nausea, vomiting, epigastric distress, diarrhea, enterocolitis, pseudomembranous colitis, black "hairy" tongue, abdominal pain.
GU: interstitial nephritis, nephropathy.
Hematologic: eosinophilia, anemia, thrombocytopenia, leukopenia, hemolytic anemia, agranulocytosis.
Hepatic: intrahepatic cholestasis.
Other: hypersensitivity reactions (rash, urticaria, chills, fever, sneezing, wheezing, anaphylaxis), overgrowth of nonsusceptible organisms.

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, and LDH levels.
• May increase eosinophil count. May decrease hemoglobin, hematocrit, and platelet, WBC, RBC, and granulocyte counts.

Overdose and treatment
Overdose may cause neuromuscular irritability or seizures. No specific recommendation is available.
 Treatment is symptomatic. After recent ingestion (within 4 hours), empty the stomach by induced emesis or gastric lavage; follow with activated charcoal to reduce absorption. Cloxacillin isn’t appreciably removed by hemodialysis or peritoneal dialysis.

Special considerations
• Give dose on empty stomach with water.
• Refrigerate oral suspension and discard unused medication after 14 days. Unrefrigerated suspension is stable for 3 days.
• Cloxacillin alters test results for urine and serum proteins; it produces false-positive or elevated results in turbidimetric urine and serum protein tests using sulfosalicylic acid or trichloroacetic acid; it also may produce false results on the Bradshaw screening test for Bence Jones protein.
• Cloxacillin may falsely decrease serum aminoglycoside levels.
• Periodically assess renal, hepatic, and hematopoietic function in patients receiving long-term therapy.
Breast-feeding patients
• Drug appears in breast milk; use cautiously in breast-feeding women.
Pediatric patients
• Elimination of cloxacillin is reduced in neonates; safety of drug in neonates hasn’t been established.

Patient education
• Inform patient of potential adverse reactions (such as fever, chills, or rash); advise him to report adverse reactions promptly.
• Instruct patient to take drug on an empty stomach and take with water only.
• Tell patient to refrigerate oral suspension and to discard unused suspension after the course of treatment.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use