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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEFTRIAXONE (CEFTRIAXONE).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Amount subtherapeutic; considered compatible with breastfeeding. Monitor infant for diarrhea, rash, or changes in gut flora. |
| 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 |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to ceftriaxone or any cephalosporin","Previous severe hypersensitivity to penicillins (cross-sensitivity)","Premature neonates (up to 41 weeks postmenstrual age) due to calcium binding risk","Hyperbilirubinemic neonates (risk of bilirubin encephalopathy)","Concomitant IV calcium administration in neonates (within 48 hours of ceftriaxone)"]
| 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). |
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| 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. |