CLOXACILLIN SODIUM
Clinical safety rating: safe
Human studies have proved safety
Cloxacillin is a beta-lactam antibiotic that binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, inhibiting transpeptidases and thus preventing the cross-linking of peptidoglycan chains. This leads to cell lysis and death, primarily mediated by autolytic enzymes. It is resistant to penicillinase (beta-lactamase) produced by staphylococci.
| Metabolism | Primarily hepatic, with about 30% excreted unchanged in urine. Metabolism involves hepatic enzymes, though specific CYP pathways are not well defined. |
| Excretion | Renal (70-80% unchanged via glomerular filtration and tubular secretion); biliary/fecal (small amount, <10%) |
| Half-life | 0.5-1.1 hours in adults with normal renal function; prolonged in neonates, elderly, and renal impairment (up to 2-4 hours in anuria) |
| Protein binding | 90-94% bound to serum albumin |
| Volume of Distribution | 0.1-0.25 L/kg; low, reflecting limited extravascular distribution |
| Bioavailability | Oral: 37-50% (reduced by food); IM: ~70-80% |
| Onset of Action | Oral: 30-60 minutes; IM: 15-30 minutes; IV: immediate (within minutes) |
| Duration of Action | 4-6 hours for bacterial growth suppression; dose adjustment may be needed for severe infections or renal impairment |
| Molecular Weight | 457.9 |
250-500 mg orally every 6 hours on an empty stomach; 250 mg - 2 g IV/IM every 4-6 hours depending on severity; maximum 12 g/day for serious infections.
| Dosage form | FOR SOLUTION |
| Renal impairment | CrCl > 50 mL/min: no adjustment; CrCl 10-50 mL/min: no adjustment; CrCl < 10 mL/min: dose no adjustment needed but avoid in anuria; not significantly removed by hemodialysis. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A/B): no adjustment needed; severe hepatic impairment (Child-Pugh C): use with caution, consider 50% dose reduction. |
| Pediatric use | Oral: 12.5-25 mg/kg/day divided every 6 hours; IV/IM: 25-50 mg/kg/day divided every 6 hours; severe infections: up to 100 mg/kg/day. Maximum 4 g/day. |
| Geriatric use | No specific dose adjustment required; monitor renal function due to age-related decline; start at lower end of dosing range; careful administration to avoid dehydration. |
| 1st trimester | Generally considered safe; no evidence of teratogenicity in animal studies, but use only if clearly needed. |
| 2nd trimester | Generally considered safe; monitor for maternal allergic reactions. |
| 3rd trimester | Generally considered safe; potential for altered fetal gut flora if administered near term. |
Clinical note
Probenecid may decrease excretion Serious and occasionally fatal hypersensitivity reactions have been reported.
| Placental transfer | Crosses the placenta; achieves therapeutic levels in fetal tissues. Low protein binding (50-60%) contributes to transfer. |
| Breastfeeding | Minimal excretion into breast milk; amounts are not expected to cause adverse effects in the infant. May alter infant gut flora if high maternal doses are used. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to penicillinsHistory of severe anaphylactic reaction to beta-lactam antibiotics
| Precautions | Severe and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported., Prolonged use may result in superinfection due to overgrowth of non-susceptible organisms, including Clostridioides difficile., Use with caution in patients with renal impairment, as dose adjustment may be necessary., Leukopenia, neutropenia, and thrombocytopenia have been associated with high doses or prolonged therapy. |
| Food/Dietary | Avoid taking with food, particularly dairy products and acidic beverages (e.g., fruit juices, colas), as they significantly reduce absorption. Take on an empty stomach. Small amounts of water are acceptable. No other specific food interactions noted. |
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| Lactation Rating |
| L1 (Safest) - Usually compatible with breastfeeding. |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, and no adequate human studies exist. Risk cannot be ruled out but appears low across all trimesters. |
| Fetal Monitoring | Routine maternal monitoring of renal function, hepatic function, and complete blood count due to potential hematologic adverse effects. Fetal monitoring as per standard obstetric care; no specific fetal monitoring required. |
| Fertility Effects | No known adverse effects on fertility in animal studies. No human data available. |
| Clinical Pearls | Cloxacillin is a penicillinase-resistant penicillin used for infections caused by penicillinase-producing staphylococci, including methicillin-sensitive Staphylococcus aureus (MSSA). It is not active against methicillin-resistant Staphylococcus aureus (MRSA). Administer on an empty stomach (1 hour before or 2 hours after meals) for optimal absorption. Monitor renal function in patients with pre-existing impairment and adjust dose accordingly. Use with caution in patients with a history of cephalosporin allergy due to potential cross-sensitivity. Therapeutic drug monitoring is not routinely required but may be considered in severe infections or renal impairment. |
| Patient Advice | Take this medication on an empty stomach, at least 1 hour before or 2 hours after meals, with a full glass of water. · Complete the full course of therapy even if you feel better to prevent resistance and recurrence. · Do not take with acidic fruit juices (e.g., orange juice, grapefruit juice) as they may reduce absorption. · Report any signs of allergic reaction (rash, itching, swelling, difficulty breathing) immediately. · Common side effects include nausea, vomiting, diarrhea, and taste disturbances; notify your doctor if severe or persistent. · This medication may alter the effectiveness of oral contraceptives; consider using an additional non-hormonal contraceptive method. · Store at room temperature away from moisture and heat; do not freeze. |