Usage
Ceftriaxone is a third-generation cephalosporin antibiotic prescribed for a wide range of bacterial infections. Its pharmacological classification is antibacterial/antibiotic. It exerts its bactericidal effect by inhibiting bacterial cell wall synthesis, ultimately leading to cell death.
Alternate Names
Ceftriaxone is also known internationally by the same name. Brand names include Rocephin, Ceftriax, Biotraxon, Cefaxone, and many others depending on the region and manufacturer.
How It Works
Pharmacodynamics: Ceftriaxone disrupts the synthesis of the bacterial cell wall peptidoglycan by binding to penicillin-binding proteins (PBPs). This binding inhibits the cross-linking of peptidoglycan chains, weakening the cell wall and causing bacterial lysis.
Pharmacokinetics:
- Absorption: Ceftriaxone is well-absorbed after intramuscular administration, reaching peak plasma concentrations in 2-3 hours. Intravenous administration results in immediate peak concentrations.
- Distribution: Widely distributed throughout the body, including cerebrospinal fluid, achieving therapeutic levels in meningitis. Highly protein-bound (85-95%).
- Metabolism: Minimal metabolism.
- Elimination: Primarily excreted unchanged through renal (50-60%) and hepatic (40-50%, biliary excretion) pathways. The elimination half-life is approximately 8 hours in adults with normal renal function and may be prolonged in patients with renal impairment. No significant removal by hemodialysis.
Dosage
Standard Dosage
Adults:
1-2 g IV or IM once daily. For severe infections, up to 4 g daily in single or divided doses. IV doses greater than 2g should be administered by infusion over at least 30 minutes.
Children:
- Neonates (up to 14 days): 20-50 mg/kg once daily (maximum 50 mg/kg/day). IV administration should be infused over 60 minutes.
- Infants and children (15 days to 12 years, <50 kg): 20-80 mg/kg/day once daily (maximum 4g daily, administered over at least 30 minutes).
- Children ≥12 years or ≥ 50kg: Same as adult dose.
Special Cases:
- Elderly Patients: Dose adjustment generally not required unless significant renal or hepatic impairment exists. Caution with doses exceeding 2g daily if impaired renal and liver function.
- Patients with Renal Impairment: Dosage adjustment may be necessary in severe renal impairment (creatinine clearance < 10 mL/min). Maximum dose 2 g daily. No supplemental dose needed after dialysis, but plasma level monitoring is recommended.
- Patients with Hepatic Dysfunction: Dose adjustments usually unnecessary if renal function is normal.
- Patients with Comorbid Conditions: Evaluate individually, considering drug interactions and disease states.
Clinical Use Cases:
Dosages provided are general guidelines and may need to be adjusted based on the specific pathogen, severity of infection, and patient characteristics. Always consider local treatment guidelines.
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: 1-2 g IV/IM as a single preoperative dose 30-90 minutes before the procedure, or depending on the surgical procedure and the perceived risk of infection.
- Meningitis: 2 g IV every 12 hours for 7-14 days (adults). In pediatric cases, initiate with 100 mg/kg (up to 4 g) once daily, adjusting after pathogen identification and susceptibility testing.
- Emergency Situations (Sepsis): 2-4g daily IV/IM in single or divided doses, according to the severity of the infection.
Dosage Adjustments:
Consider renal and hepatic function and other comorbid conditions. Therapeutic drug monitoring can be useful in severe infections and impaired organ function.
Side Effects
Common Side Effects:
Pain, tenderness, or induration at the injection site, diarrhea, rash, eosinophilia, elevated liver enzymes.
Rare but Serious Side Effects:
Severe allergic reactions (anaphylaxis, angioedema), Clostridium difficile colitis (pseudomembranous colitis), seizures, encephalopathy (especially in patients with renal impairment or CNS disorders), hemolytic anemia, Stevens-Johnson syndrome.
Long-Term Effects:
With prolonged use, potential for superinfection, vitamin K deficiency, and biliary pseudolithiasis.
Adverse Drug Reactions (ADR):
Severe hypersensitivity reactions, severe diarrhea, signs of acute renal failure, hematological abnormalities, evidence of gallbladder disease, neurological changes.
Contraindications
Hypersensitivity to cephalosporins or penicillin. Neonates (≤ 28 days) requiring treatment with calcium-containing IV solutions. Premature neonates up to 41 weeks postmenstrual age (gestational age + chronological age) especially with hyperbilirubinemia. Concomitant use of IV ceftriaxone and calcium solutions in neonates, due to the risk of precipitation.
Drug Interactions
Ceftriaxone can interact with:
- Anticoagulants (e.g., warfarin): May potentiate anticoagulant effect.
- Calcium-containing solutions: Risk of precipitation in neonates.
- Probenecid: Reduced renal clearance of ceftriaxone.
- Other antibiotics (e.g., aminoglycosides, chloramphenicol): May enhance or reduce efficacy, monitor for adverse effects.
Pregnancy and Breastfeeding
- Pregnancy: FDA Pregnancy Category B. Generally considered safe, but weigh benefits versus potential risks.
- Breastfeeding: Low levels are excreted in breast milk. Generally considered safe, but monitor infant for diarrhea, thrush, or other signs of gastrointestinal upset.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis.
- Side Effects: Injection site reactions, diarrhea, rash; rarely, allergic reactions, colitis, seizures.
- Contraindications: Cephalosporin/penicillin hypersensitivity, neonates receiving calcium-containing IV solutions.
- Drug Interactions: Anticoagulants, calcium-containing solutions, probenecid.
- Pregnancy & Breastfeeding: Generally safe, but consider individual circumstances.
- Dosage: Adults: 1-2 g daily; children: weight-based. Adjust for renal impairment.
- Monitoring Parameters: Renal and liver function, complete blood count during prolonged therapy, signs of superinfection.
Popular Combinations
Ceftriaxone is often used in combination with other antibiotics, such as metronidazole, for synergistic effects in treating intra-abdominal infections, pelvic inflammatory disease, and other mixed infections.
Precautions
Caution in patients with a history of gastrointestinal disorders, renal/hepatic impairment, bleeding disorders, or allergies to other beta-lactams. Monitor for superinfection and adverse reactions. Evaluate renal and hepatic function, especially during prolonged treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ceftriaxone?
A: Adults: 1-2 g IV/IM daily; children: weight-based dosing; neonates: specific dosing guidelines apply. Adjust for renal impairment.
Q2: What infections is Ceftriaxone used to treat?
A: Ceftriaxone is indicated for various bacterial infections, including meningitis, pneumonia, sepsis, urinary tract infections, gonorrhea, and surgical prophylaxis.
Q3: What are the common side effects of Ceftriaxone?
A: Common side effects include pain at the injection site, diarrhea, and skin rash.
Q4: What are the serious side effects of Ceftriaxone?
A: Serious side effects include severe allergic reactions, C. difficile colitis, seizures, and encephalopathy.
Q5: Can Ceftriaxone be used during pregnancy and breastfeeding?
A: Generally considered safe but should be used cautiously and under the supervision of a physician.
Q6: What are the contraindications for Ceftriaxone use?
A: Contraindications include known hypersensitivity to cephalosporins or penicillin, and concomitant administration with calcium-containing intravenous solutions in neonates.
Q7: What drugs interact with Ceftriaxone?
A: Ceftriaxone can interact with anticoagulants (e.g., warfarin), calcium-containing solutions, probenecid, and certain other antibiotics.
Q8: How is Ceftriaxone administered?
A: Ceftriaxone can be administered intravenously (IV) or intramuscularly (IM). IV doses greater than 2g should be administered by infusion.
Q9: Does Ceftriaxone require dose adjustment in elderly patients?
A: Dose adjustments may be required for elderly patients with renal and hepatic impairment. Avoid doses over 2 g daily for patients with both issues.
Q10: What monitoring is required for patients on Ceftriaxone?
A: Renal and hepatic function tests, complete blood counts during prolonged therapy, and monitoring for signs and symptoms of superinfection or other adverse reactions.
