CEPHALOTHIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEPHALOTHIN (CEPHALOTHIN).
Cephalothin is a first-generation cephalosporin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), thereby blocking peptidoglycan cross-linking. It has activity against gram-positive cocci (e.g., Staphylococcus aureus, Streptococcus pyogenes) and some gram-negative bacilli (e.g., Escherichia coli, Klebsiella pneumoniae).
| Metabolism | Cephalothin is rapidly metabolized via deacetylation in the liver to desacetylcephalothin, which has 10-20% of the antimicrobial activity of the parent compound. Both the parent drug and metabolite undergo renal excretion. |
| Excretion | Primarily renal (60-90% unchanged) via tubular secretion and glomerular filtration; minor biliary excretion (less than 5%); hepatic metabolism to desacetylcephalothin (active but less potent) accounts for about 20-30% of dose; fecal elimination negligible. |
| Half-life | 0.5-1 hour in patients with normal renal function; prolonged to 2-8 hours in moderate renal impairment (CrCl 30-50 mL/min); up to 20-30 hours in end-stage renal disease; due to rapid elimination, frequent dosing (q4-6h) is required for continuous bactericidal levels. |
| Protein binding | 65-80% bound, primarily to serum albumin. |
| Volume of Distribution | 0.2-0.3 L/kg, consistent with distribution primarily into extracellular fluid; low Vd indicates limited tissue penetration except in inflamed tissues (e.g., synovial, pleural, pericardial fluids); does not cross blood-brain barrier well in uninflamed meninges. |
| Bioavailability | Intravenous: 100%; intramuscular: approximately 80-90% relative to IV due to first-pass metabolism; oral: not available (poor oral absorption, degraded by gastric acid). |
| Onset of Action | Intravenous: immediate (minutes); intramuscular: 15-30 minutes to peak serum concentrations (after 0.5-1 hour); clinical effect within hours for susceptible infections. |
| Duration of Action | Approximately 4-6 hours in normal renal function; bactericidal activity persists as long as serum concentrations exceed MIC; short half-life necessitates frequent dosing; no long-acting formulation available. |
1-2 g IV every 4-6 hours; maximum 12 g/day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 50-89 mL/min: 1-2 g every 6-8 hours; CrCl 10-49 mL/min: 1-2 g every 8-12 hours; CrCl <10 mL/min: 0.5-1 g every 12 hours. |
| Liver impairment | No specific adjustment recommended for Child-Pugh A or B; use with caution in severe hepatic impairment (Child-Pugh C) due to potential coagulopathy or encephalopathy. |
| Pediatric use | Neonates (≤1 week): 20-40 mg/kg IV every 12 hours; Infants/children: 20-40 mg/kg IV every 4-6 hours; maximum dose 12 g/day. |
| Geriatric use | Adjust dose based on renal function; reduced clearance may require increased dosing interval (e.g., every 8-12 hours). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEPHALOTHIN (CEPHALOTHIN).
| Breastfeeding | Cephalothin is excreted into human breast milk in low concentrations (M/P ratio approximately 0.02-0.05). It is generally compatible with breastfeeding due to poor oral bioavailability in the infant. However, caution should be exercised, and the infant should be monitored for potential gastrointestinal disturbances (e.g., diarrhea, candidiasis). |
| Teratogenic Risk | Cephalothin is a first-generation cephalosporin classified as FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, and there are no adequate well-controlled studies in pregnant women. Use during pregnancy is considered safe when clinically indicated. No specific teratogenic effects have been reported in any trimester. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to cephalothin or any cephalosporin antibiotic","History of severe immediate hypersensitivity (e.g., anaphylaxis) to penicillins or other beta-lactams"]
| Precautions | ["Serious hypersensitivity reactions (anaphylaxis, angioedema) can occur, especially in patients with penicillin allergy (cross-sensitivity up to 10%).","Clostridioides difficile-associated diarrhea (CDAD) may occur with use.","Use with caution in patients with renal impairment; reduce dose accordingly.","Prolonged therapy may cause overgrowth of non-susceptible organisms (e.g., Candida, Enterococcus).","False-positive urine glucose test (Clinitest) may occur; use glucose oxidase methods.","Avoid rapid intravenous bolus to prevent phlebitis or injection site reaction."] |
| Food/Dietary | No significant food interactions. However, alcohol should be avoided as it may increase the risk of adverse effects (e.g., disulfiram-like reaction). No specific dietary restrictions. |
Loading safety data…
| Fetal Monitoring | No specific maternal-fetal monitoring is required beyond routine clinical observation. Prolonged use may necessitate monitoring for superinfection or Clostridioides difficile diarrhea. In pregnant women with renal impairment, monitor renal function and adjust dose accordingly. |
| Fertility Effects | No adverse effects on fertility have been reported in animal studies or clinical experience. Cephalothin is not known to impair male or female reproductive function. |
| Clinical Pearls | Cephalothin is a first-generation cephalosporin with activity against gram-positive cocci (except MRSA and enterococci) and some gram-negative bacilli. It is not active against Pseudomonas aeruginosa. It is commonly used for surgical prophylaxis. Note that cephalothin has a short half-life (~0.5-1 hour) and requires frequent dosing (every 4-6 hours). It can cause a false-positive urine glucose test (Clinitest) but not with glucose oxidase methods. Cross-allergenicity with penicillins exists in about 5-10% of patients. Monitor renal function in patients with pre-existing renal impairment. |
| Patient Advice | Take this medication exactly as prescribed, usually every 4-6 hours. · Complete the full course even if you feel better. · Report any signs of allergic reaction: rash, itching, swelling, difficulty breathing. · Inform your doctor if you have a history of penicillin allergy. · May cause diarrhea; contact your doctor if severe or bloody. · Avoid alcohol while on this medication. · If you have diabetes, note that this drug may interfere with urine glucose tests (Clinitest); use glucose oxidase tests instead. |