Intramuscular, Intravenous Staphylococcal infections resistant to benzylpenicillin
Adult: 1,000-2,000 mg 6 hourly; may be increased to 2,000 mg 4 hourly in more severe infections. Doses are given via IV inj, IV infusion, or IM inj. Dose and duration of treatment may vary based on the infecting organism, infection severity, and patient response. Refer to specific product or local treatment guidelines. Child: Neonates ≤7 days of age <2 kg: 25 mg/kg 12 hourly via IV inj or infusion; ≥2 kg: 25 mg/kg 8 hourly via IV inj or infusion. 7-28 days <2 kg: 25 mg/kg 8 hourly via IV inj or infusion; ≥2 kg: 25 mg/kg 6 hourly via IV inj or infusion. For treatment of meningitis, doses may be doubled and given via IV inj or infusion. ≥1 month <20 kg: 50-100 mg/kg daily (Max: 4,000 mg) divided 6 hourly via IV inj, IV infusion, or IM inj; may be increased for severe infections up to 200 mg/kg daily (Max: 12,000 mg) in divided doses via IV inj or infusion; ≥20 kg: Same as adult dose. Dosage or treatment recommendations may vary among countries and individual products. Refer to specific product or local treatment guidelines.
Oral Staphylococcal infections resistant to benzylpenicillin
Adult: 250-500 mg 6 hourly; may be increased for severe infections. Max: 6,000 mg daily. Dose and duration of treatment may vary based on the infecting organism, infection severity, and patient response. Refer to specific product or local treatment guidelines. Child: ≤20 kg: 25-50 mg/kg daily in divided doses 6 hourly; >20 kg: Same as adult dose. Dose and duration of treatment may vary based on the infecting organism, infection severity, and patient response. Treatment recommendations may vary among countries and individual products. Refer to specific product or local treatment guidelines.
Administration
Should be taken on an empty stomach.
Reconstitution
Powder/granules for oral solution: Reconstitute powder or granules by adding the appropriate volume of water as specified on the bottle, to make a final concentration of 125 mg/5 mL. IV inj: Reconstitute vial with the appropriate volume of sterile water for inj to yield a final concentration of 50 mg/mL or 100 mg/mL; further dilution in a compatible solution may be needed for IV infusion. IM inj: Reconstitute vial with the appropriate volume of sterile water for inj to yield a final concentration of 125 mg/mL or 250 mg/mL. Refer to specific product guidelines for further instructions on reconstitutions.
Incompatibility
Incompatible with aminoglycosides, tetracyclines, erythromycin, polymyxin B, chloramphenicol, and sulfonamides.
Contraindications
Hypersensitivity to cloxacillin, other penicillins, or cephalosporins.
Special Precautions
Patient with history of allergy (particularly to drugs or multiple allergens), history of seizure disorder, asthma, syphilis. Renal impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Haematologic disorders (e.g. neutropenia, agranulocytosis, thrombocytopenia), bacterial or fungal superinfection (including pseudomembranous colitis, Clostridium difficile-associated diarrhoea). Gastrointestinal disorders: Diarrhoea, nausea, vomiting, epigastric discomfort, flatulence. General disorders and administration site conditions: Fever. Hepatobiliary disorders: Intrahepatic cholestasis. Immune system disorders: Angioedema. Investigations: Increased AST, ALT, lactate dehydrogenase, and alkaline phosphatase. Musculoskeletal and connective tissue disorders: Joint pains. Nervous system disorders: Seizures, headache. Renal and urinary disorders: Acute interstitial nephritis, azotaemia. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: Hypersensitivity reactions including anaphylactoid and severe cutaneous adverse reactions.
Monitoring Parameters
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor renal function, LFTs, and haematological status during prolonged and high-dose therapy. Assess for signs and symptoms of anaphylaxis during the initial dose.
Drug Interactions
Bacteriostatic drugs (e.g. chloramphenicol, erythromycin, sulfonamides, tetracyclines) may interfere with the bactericidal effect of cloxacillin. May reduce the efficacy of oral contraceptives (e.g. estrogen), resulting in menstrual irregularities, intermenstrual bleeding, and unplanned pregnancy. May decrease the clearance of methotrexate. Decreased renal tubular secretion with probenecid. May occasionally potentiate the risk of bleeding with oral anticoagulants (e.g. dicumarol, anisindione). Therapeutic effects of BCG, typhoid, and cholera vaccines, and Na picosulfate may be diminished. May reduce the serum concentrations of mycophenolic acid.
Food Interaction
Food reduces the absorption of cloxacillin.
Lab Interference
May cause false-positive results with cupric sulfate tests (Benedict's, Clinitest®); false-positive urine and serum proteins, uric acid and urinary steroids.
Action
Description: Mechanism of Action: Cloxacillin, an isoxazolyl penicillin, is a bactericidal antibiotic that binds to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thereby inhibiting cell wall synthesis. Bacterial lysis eventually occurs due to the ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Pharmacokinetics: Absorption: Incompletely absorbed from the gastrointestinal tract. Reduced absorption with food. Time to peak plasma concentration: 1-2 hours (oral); approx 0.5-1 hour (IM). Distribution: Widely distributed to tissues and body fluids, including blister fluid, peritoneal fluid, pleural fluid, middle ear fluid, urine, intestinal mucosa, gallbladder, lung, bone, female reproductive tissues, and bile. Minimal diffusion into the CSF except when meninges are inflamed. Crosses the placenta and enters breast milk. Plasma protein binding: Approx 94%, mainly to albumin. Metabolism: Metabolised in the liver. Excretion: Via urine (approx 35%, as unchanged drug and metabolites); bile (up to 10%). Elimination half-life: 0.5-1.5 hours.
Chemical Structure
Cloxacillin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6098, Cloxacillin. https://pubchem.ncbi.nlm.nih.gov/compound/Cloxacillin. Accessed Sept. 28, 2022.
J01CF02 - cloxacillin ; Belongs to the class of beta-lactamase resistant penicillins. Used in the systemic treatment of infections.
References
Anon. Cloxacillin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/09/2022.Buckingham R (ed). Cloxacillin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/09/2022.Cloxabiotic Injection 250 mg, 500 mg (Averroes Pharmaceuticals Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/09/2022.Cloxacilla Powder for Syrup 125 mg/5 mL (Idaman Pharma Manufacturing Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/09/2022.Cloxin 500 mg Capsule; 125 mg/5 mL Powder for Solution (Medhaus Pharma, Inc.). MIMS Philippines. http://www.mims.com/philippines. Accessed 01/09/2022.Meiclox Capsules (Thai Meiji Pharmaceutical Co., Ltd.). MIMS Thailand. http://www.mims.com/thailand. Accessed 01/09/2022.Monoclox 250 mg Hard Gelatin Capsules (Komedic Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/09/2022.Monoclox 250 mg, 500 mg Powder for Solution for Injection or Infusion (Komedic Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/09/2022.Oxacil Capsule; Granules 125 mg/5 mL (Duopharma [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/09/2022.
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