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 |
| Molecular Weight | 435.88 |
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 | Cloxapen (cloxacillin) is generally considered safe during first trimester; no increased risk of major birth defects reported in animal studies. Use only if clearly needed. |
| 2nd trimester | Safe for use during second trimester; penicillin-class antibiotics are widely used with no documented teratogenic effects. |
| 3rd trimester | Safe during third trimester; no known adverse fetal effects near term. |
Clinical note
Comprehensive clinical and safety monograph for CLOXAPEN (CLOXAPEN).
| Placental transfer | Crosses placenta; fetal levels are lower than maternal levels but bactericidal concentrations can be achieved in fetal tissues. |
| Breastfeeding | Excreted into breast milk in small amounts; unlikely to be harmful to infant. Theoretical risk of alteration of infant gut flora or allergic sensitization, but typically considered compatible with breastfeeding. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to cloxacillin or any penicillinHistory of anaphylactic reaction to beta-lactams
| Precautions | Hypersensitivity reactions including anaphylaxis, Clostridium difficile-associated diarrhea, Superinfection with resistant organisms, Hematologic toxicity (neutropenia, agranulocytosis) with prolonged therapy |
| Food/Dietary | Food decreases absorption; take on empty stomach. Avoid acidic beverages (e.g., fruit juices) that may reduce stability. |
| Clinical Pearls |
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| Lactation Rating | L1: Safe |
| 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. |
| 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. |
| Cloxapen (cloxacillin) is a penicillinase-resistant penicillin primarily used for methicillin-susceptible Staphylococcus aureus infections. Ensure adequate dosing in renal impairment: CrCl <10 mL/min requires dose reduction. Monitor for hypersensitivity reactions, especially in patients with penicillin allergy. Use with caution in hepatic impairment. Administer on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. |
| Patient Advice | Take this medication on an empty stomach, at least 1 hour before or 2 hours after food. · Complete the full course of therapy even if you feel better, to prevent resistance. · Inform your doctor if you have a history of penicillin allergy or liver disease. · Report any skin rash, itching, difficulty breathing, or severe diarrhea immediately. · Do not use this medication for viral infections (e.g., colds, flu). |