CEFTRIAXONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEFTRIAXONE (CEFTRIAXONE).
Ceftriaxone is a third-generation cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to cell lysis and death. It has broad-spectrum activity against gram-positive and gram-negative bacteria.
| Metabolism | Ceftriaxone is not metabolized significantly; it is excreted unchanged in the urine (33-67%) and bile (rest). It undergoes hepatic metabolism to inactive metabolites? (minor pathway, but primary elimination is renal-biliary). |
| Excretion | Renal (33-67% unchanged) and biliary (up to 40%) with fecal elimination. In neonates, renal excretion is lower (~20%). |
| Half-life | Terminal half-life: 5.8-8.7 hours in adults; prolonged to 12-24 hours in neonates and 30-90 hours in severe renal impairment. |
| Protein binding | 85-95% bound to albumin (primarily), saturable at high concentrations. |
| Volume of Distribution | 0.12-0.14 L/kg (increased in neonates: 0.3-0.5 L/kg); reflects extracellular fluid distribution. |
| Bioavailability | IM: 100% (complete absorption). |
| Onset of Action | IV: immediate (peak plasma level at end of infusion); IM: 1-2 hours for peak serum concentration. |
| Duration of Action | 24 hours due to prolonged half-life; bactericidal concentrations maintained for 12-24 hours in most tissues. |
| Molecular Weight | 554.58 |
1-2 g IV/IM every 24 hours; maximum 4 g/day.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <10 mL/min: maximum 2 g/day; no adjustment for CrCl >10 mL/min. |
| Liver impairment | No adjustment required; caution in severe hepatic impairment with concurrent renal failure. |
| Pediatric use | 50-75 mg/kg IV/IM every 24 hours; maximum 2 g/day. For meningitis: 100 mg/kg IV/IM every 24 hours; maximum 4 g/day. |
| Geriatric use | No dose adjustment based solely on age; monitor renal function and adjust per CrCl. |
| 1st trimester | Generally considered safe; crosses placenta; no evidence of teratogenicity in humans. |
| 2nd trimester | Considered safe; use when clearly needed. |
| 3rd trimester | Safe; avoid if risk of neonatal hyperbilirubinemia (displaces bilirubin from albumin). |
Clinical note
Comprehensive clinical and safety monograph for CEFTRIAXONE (CEFTRIAXONE).
| Placental transfer | Crosses placenta readily; achieves therapeutic concentrations in fetal tissues and amniotic fluid. |
| Breastfeeding | Excreted into breast milk in low concentrations (approximately 4% of maternal dose); compatible with breastfeeding. May alter infant gut flora or cause diarrhea; monitor for rash or candidiasis. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to cephalosporins or any componentPrevious immediate-type hypersensitivity reaction (e.g., anaphylaxis) to penicillins or other beta-lactams (cross-sensitivity risk)
| Precautions | Hypersensitivity reactions including anaphylaxis, Clostridioides difficile-associated diarrhea, Hemolytic anemia (immune-mediated), Biliary pseudolithiasis (sludge, especially in pediatric patients), Renal impairment: adjust dose in severe renal failure (CrCl < 10 mL/min), Concomitant use with calcium-containing IV solutions may cause precipitation; avoid within 48 hours of each other, Pancreatitis (rare), Encephalopathy (especially in renal impairment) |
| Food/Dietary | No significant food interactions. Avoid alcohol (disulfiram-like reaction possible). May interfere with urine glucose tests (Clinitest). |
Loading safety data…
| L1 (Compatible) |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human studies. Avoid in first trimester unless benefit outweighs risk. Possible association with neonatal hyperbilirubinemia if used near term due to albumin displacement. |
| Fetal Monitoring | Monitor maternal renal/hepatic function. In third trimester, observe neonate for hyperbilirubinemia. No fetal monitoring required. |
| Fertility Effects | No adverse effects on human fertility reported; animal studies show no impairment. |
| Clinical Pearls | Ceftriaxone is a third-generation cephalosporin with excellent CNS penetration; use for meningitis. Avoid in neonates with hyperbilirubinemia due to bilirubin displacement from albumin. Administer IV over 30 minutes; IM injections can cause pain at site. Do not mix with calcium-containing solutions (risk of precipitation, especially in neonates). |
| Patient Advice | Complete the full course even if you feel better. · Report any signs of severe diarrhea, rash, or jaundice. · May cause dizziness; avoid driving until you know how it affects you. · For IM injection, notify if severe pain or swelling at injection site. · Avoid alcohol during treatment and for 72 hours after to prevent disulfiram-like reaction. |