CEPHALOTHIN SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEPHALOTHIN SODIUM (CEPHALOTHIN SODIUM).
Cephalothin is a first-generation cephalosporin with bactericidal activity by inhibiting bacterial cell wall synthesis via binding to penicillin-binding proteins (PBPs).
| Metabolism | Partially metabolized via deacetylation; primarily hepatic. |
| Excretion | Primarily renal (60-90% unchanged via glomerular filtration and tubular secretion). Minor biliary excretion (1-5%). Fecal elimination negligible. |
| Half-life | Terminal elimination half-life: 0.5-1.0 hour in adults with normal renal function. In anuria, prolonged to 2.5-8 hours. Dose adjustment required for CrCl <50 mL/min. |
| Protein binding | 65-80% bound to serum albumin (primarily). Binding decreases in uremia. |
| Volume of Distribution | Vd: 0.1-0.2 L/kg. Low distribution (primarily extracellular fluid). Does not penetrate CSF unless inflamed. Distributes into pleural and synovial fluids. |
| Bioavailability | IM: ~70-80% absorbed. Not orally bioavailable (<1% due to acid lability). Only parenteral routes (IV/IM) used. |
| Onset of Action | IM: 1-2 hours to peak serum concentration; IV: immediate therapeutic levels. Time to clinical effect: typically within 1-2 hours post-dose for susceptible organisms. |
| Duration of Action | Duration of antimicrobial effect: 4-6 hours based on dosing interval (every 4-6 hours). Dose-dependent; continuous infusion may provide sustained levels. |
1-2 g IV every 4-6 hours; maximum 12 g/day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 50-90 mL/min: 1 g every 6 hours; CrCl 10-49 mL/min: 1 g every 8 hours; CrCl <10 mL/min: Loading dose 1-2 g, then 1 g every 12 hours. |
| Liver impairment | No specific adjustment for Child-Pugh class; monitor for toxicity in severe hepatic impairment. |
| Pediatric use | Infants and children: 75-125 mg/kg/day IV divided every 4-6 hours; maximum 6 g/day. |
| Geriatric use | No defined specific dosing; use lower end of dosing interval based on renal function; monitor for renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEPHALOTHIN SODIUM (CEPHALOTHIN SODIUM).
| Breastfeeding | Cephalothin is excreted into breast milk in low concentrations (<0.1% of maternal dose). M/P ratio is approximately 0.12. Considered compatible with breastfeeding due to poor oral bioavailability, but monitor infant for diarrhea or allergic reactions. |
| Teratogenic Risk | No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. First trimester: risk cannot be excluded but appears low. Second/third trimesters: no known fetal harm. However, use only if clearly needed. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["History of severe hypersensitivity to cephalosporins or penicillins","Use in patients with anuria or severe renal impairment without appropriate dose adjustment (relative)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis (cross-sensitivity with penicillins and other beta-lactams)","Clostridioides difficile-associated diarrhea","Renal impairment: dose adjustment required","Coagulation abnormalities (e.g., hypoprothrombinemia, bleeding) with prolonged use","Drug-induced neutropenia or thrombocytopenia"] |
| Food/Dietary | No specific food-drug interactions. However, alcohol should be avoided during therapy and for 48 hours after cessation due to potential disulfiram-like reaction (nausea, vomiting, flushing, headache). |
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| Fetal Monitoring |
| Monitor for signs of hypersensitivity, superinfection, and bleeding (due to interference with prothrombin activity). Renal function should be assessed periodically. Fetal monitoring not required unless maternal infection complicates pregnancy. |
| Fertility Effects | No documented effects on human fertility. Animal studies show no impairment of fertility. |
| Clinical Pearls | Cephalothin is a first-generation cephalosporin with activity against Gram-positive cocci including Staphylococcus aureus (non-MRSA) and Streptococcus pyogenes. Due to poor oral bioavailability, it is administered intravenously or intramuscularly. It has a short half-life (~0.5-1 hour) and is renally eliminated; dose adjustment required in renal impairment (CrCl <30 mL/min). Cross-allergenicity with penicillins occurs in ~5-10% of patients; caution in penicillin allergy. It causes a false-positive direct Coombs test and may interfere with urine glucose testing (Clinitest). Not effective against MRSA, Enterococcus, or most Gram-negative bacilli (except some E. coli and Klebsiella). Use in surgical prophylaxis for clean-contaminated procedures. Avoid in patients with cephalosporin allergy. Monitor renal function and complete blood count during prolonged therapy. |
| Patient Advice | Take this medication exactly as prescribed; it is given by injection or infusion in a healthcare setting. · Inform your healthcare provider if you have any allergies, especially to penicillins or cephalosporins. · Report any signs of allergic reaction such as rash, itching, swelling, or difficulty breathing immediately. · This medication may cause diarrhea; contact your doctor if you experience watery or bloody stools. · If you have kidney problems, your dose may need adjustment; follow your doctor's instructions. · This medicine may interfere with certain lab tests; let your doctor know you are taking cephalothin. · Avoid alcohol while on this medication and for 48 hours after stopping due to possible disulfiram-like reaction. · Notify your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |