CEFTRIAXONE SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEFTRIAXONE SODIUM (CEFTRIAXONE SODIUM).
Ceftriaxone inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidase activity, and disrupting peptidoglycan cross-linking.
| Metabolism | Ceftriaxone is not extensively metabolized; it undergoes negligible hepatic metabolism. Approximately 33-67% is excreted unchanged in urine, and the remainder is excreted in feces via bile. |
| Excretion | Ceftriaxone is eliminated 33-67% unchanged in urine via glomerular filtration and tubular secretion, and the remainder is excreted in feces (primarily as microbiologically inactive metabolites) via biliary secretion. Biliary excretion accounts for approximately 35-45% of total clearance. |
| Half-life | Terminal elimination half-life is 5.8-8.7 hours in adults with normal renal and hepatic function. In neonates, half-life is prolonged (up to 16 hours). In patients with renal impairment, half-life increases to 12-18 hours; in hepatic impairment, it may be 15-20 hours. Dose adjustment is not typically required unless both renal and hepatic impairment are present. |
| Protein binding | Ceftriaxone is 85-95% bound to plasma proteins, primarily albumin. Binding is saturable and concentration-dependent; free fraction increases at higher concentrations. |
| Volume of Distribution | Volume of distribution is 0.5-0.7 L/kg in adults, indicating extensive distribution into extracellular fluid and tissues. Vd is higher (0.8-1.0 L/kg) in neonates and decreased in elderly patients. |
| Bioavailability | IM: 100% bioavailable. Oral: not applicable (administered parenterally). |
| Onset of Action | IV: Immediate (within 5 minutes for therapeutic serum concentrations). IM: Peak plasma concentrations occur 1.5-2 hours after administration; clinical effect begins within 1-2 hours. |
| Duration of Action | Therapeutic concentrations persist for 24 hours in most tissues, allowing once-daily dosing. Bactericidal activity continues for at least 12-24 hours after a single dose due to the long half-life and post-antibiotic effect. |
1-2 g IV/IM every 12-24 hours; maximum 4 g/day.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl <10 mL/min: 2 g every 24 hours. No adjustment for CrCl >=10 mL/min. |
| Liver impairment | No adjustment required for Child-Pugh Class A or B. For Class C, use with caution; no specific dose adjustment defined. |
| Pediatric use | 50-75 mg/kg/day IV/IM divided every 12-24 hours; maximum 2 g/day. |
| Geriatric use | No specific adjustment; monitor renal function and adjust based on CrCl as per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEFTRIAXONE SODIUM (CEFTRIAXONE SODIUM).
| Breastfeeding | Ceftriaxone is excreted into breast milk in low amounts, with a milk-to-plasma (M/P) ratio of approximately 0.03. It is considered compatible with breastfeeding, but monitor the infant for potential gastrointestinal disturbances or allergic reactions. |
| Teratogenic Risk | In animal studies, ceftriaxone sodium did not demonstrate teratogenicity. Human data are limited but do not indicate a significant risk of major birth defects. Use during the first trimester is generally considered safe, but caution is advised due to the bilirubin displacement potential in the third trimester, which may increase the risk of kernicterus in neonates. |
■ FDA Black Box Warning
Do not use in neonates (≤28 days) if they are premature or have hyperbilirubinemia due to risk of bilirubin encephalopathy. Ceftriaxone displaces bilirubin from albumin, increasing risk of kernicterus. Calcium-containing solutions should not be administered within 48 hours of ceftriaxone use in neonates due to risk of fatal precipitation in lungs and kidneys.
| Serious Effects |
["Hypersensitivity to ceftriaxone or any component","Hypersensitivity to cephalosporins","Premature neonates (≤41 weeks postmenstrual age)","Neonates (≤28 days) with hyperbilirubinemia","Neonates requiring calcium-containing IV solutions within 48 hours of ceftriaxone"]
| Precautions | ["Hypersensitivity reactions (anaphylaxis)","Clostridioides difficile-associated diarrhea","Risk of bilirubin encephalopathy in neonates with hyperbilirubinemia","Immune-mediated hemolytic anemia","Pancreatitis","Biliary sludge and pseudolithiasis","Seizures with high doses or renal impairment","Superinfection","Prolonged PT/INR (monitor in patients at risk)","Renal impairment: dose adjustment may be needed"] |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal renal function and bilirubin levels in the third trimester. In pregnant women, assess fetal growth and amniotic fluid volume if prolonged treatment is required. |
| Fertility Effects | No significant adverse effects on human fertility have been reported. Animal studies have not shown impaired fertility. |
| No significant food interactions. However, avoid alcohol (including in food/drink) during therapy and for 48 hours after last dose due to risk of disulfiram-like reaction (flushing, headache, nausea, vomiting). |
| Clinical Pearls | Do not co-administer with calcium-containing IV solutions (including Ringer's lactate) due to risk of precipitation; avoid in neonates (<28 days) if requiring IV calcium. Administer IM deep intragluteal, not more than 1g per site. Crosses inflamed meninges; CSF levels 5-40% of serum. Highly protein-bound; displace bilirubin and may cause kernicterus in neonates. Monitor for biliary pseudolithiasis in prolonged use. |
| Patient Advice | Complete the full course even if you feel better. Do not skip doses. · Report any signs of allergy (rash, itching, swelling, difficulty breathing) immediately. · May cause loose stools or diarrhea; notify your doctor if severe or persistent. · Avoid alcohol during treatment and for 48 hours after last dose to prevent disulfiram-like reaction. · If receiving this medication intravenously, inform staff if you are on calcium supplements or calcium-containing IV solutions. |