CLOXAPEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLOXAPEN (CLOXAPEN).
Cloxapen inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), specifically PBPs involved in the transpeptidation step of peptidoglycan cross-linking. It is resistant to staphylococcal beta-lactamases.
| Metabolism | Hepatic metabolism via hydrolysis to penicilloic acid and other metabolites; undergoes enterohepatic circulation. |
| Excretion | Renal 70-80% as unchanged drug and active metabolite; biliary 5-10%; fecal <5% |
| Half-life | Terminal elimination half-life 1.5-2 hours; prolonged to 2.5-4 hours in severe renal impairment; clinical context: requires frequent dosing in normal renal function |
| Protein binding | 90-95% bound primarily to albumin; also binds to alpha-1-acid glycoprotein |
| Volume of Distribution | 1-2 L/kg; high distribution indicates extensive tissue binding, especially vascular smooth muscle |
| Bioavailability | Oral: 90-95% (extensive first-pass metabolism minimal); IV: 100% |
| Onset of Action | Oral: 15-30 minutes (therapeutic effect); IV: 2-5 minutes (antihypertensive effect) |
| Duration of Action | Oral: 4-6 hours; IV: 2-4 hours; clinical notes: duration shorter in hypertensive patients, longer in heart failure |
Oral: 250-500 mg every 6 hours. IV: 1-2 g every 4-6 hours.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: extend interval to every 8-12 hours. GFR <10 mL/min: extend interval to every 12-24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce dose by 25%. Class C: reduce dose by 50%. |
| Pediatric use | Children <40 kg: 25-50 mg/kg/day in divided doses every 6 hours; maximum 100 mg/kg/day. Children >40 kg: adult dose. |
| Geriatric use | Start at lower end of dosing range; monitor renal function; adjust dose based on creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CLOXAPEN (CLOXAPEN).
| Breastfeeding | Cloxacillin is excreted into breast milk in small amounts. The milk-to-plasma (M/P) ratio is approximately 0.02-0.1. At typical maternal doses, levels in milk are low and unlikely to cause adverse effects in the nursing infant. However, potential for disruption of infant gastrointestinal flora (diarrhea, candidiasis) exists. Consider benefits of breastfeeding vs risks. No contraindication. |
| Teratogenic Risk | Cloxapen (cloxacillin) is a penicillinase-resistant penicillin. Human data on teratogenicity are limited. In animal studies, no evidence of fetal harm was observed. However, as with all penicillins, use during pregnancy should be cautious. There are no adequate and well-controlled studies in pregnant women. The drug should be used during pregnancy only if clearly needed. No specific trimester risks are well-documented. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to penicillins or cephalosporins","History of cholestatic jaundice or hepatic dysfunction associated with cloxacillin or other penicillins","Neonates (risk of hyperbilirubinemia)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Clostridium difficile-associated diarrhea","Superinfection with resistant organisms","Hematologic toxicity (neutropenia, agranulocytosis) with prolonged therapy"] |
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| Fetal Monitoring | Monitor for maternal allergic reactions (rash, anaphylaxis). In prolonged therapy, monitor renal, hepatic, and hematologic function. Fetal monitoring: standard prenatal care; no specific fetal monitoring required. |
| Fertility Effects | No known adverse effects on fertility in animal studies. Human data not available. |