From the FDA Drug Label
CONTRAINDICATIONS Hypersensitivity Ceftriaxone for injection is contraindicated in patients with known hypersensitivity to ceftriaxone, any of its excipients or to any other cephalosporin. Patients with previous hypersensitivity reactions to penicillin and other beta lactam antibacterial agents may be at greater risk of hypersensitivity to ceftriaxone Neonates Premature neonates Ceftriaxone for injection is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age + chronological age). Hyperbilirubinemic neonates Hyperbilirubinemic neonates should not be treated with ceftriaxone for injection Ceftriaxone can displace bilirubin from its binding to serum albumin, leading to a risk of bilirubin encephalopathy in these patients Neonates Requiring Calcium Containing IV Solutions Ceftriaxone for injection is contraindicated in neonates (≤ 28 days) if they require (or are expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition because of the risk of precipitation of ceftriaxone for injection-calcium Lidocaine Intravenous administration of ceftriaxone solutions containing lidocaine is contraindicated
The contraindications for ceftriaxone are:
- Hypersensitivity to ceftriaxone, its excipients, or other cephalosporins
- Premature neonates up to a postmenstrual age of 41 weeks
- Hyperbilirubinemic neonates due to the risk of bilirubin encephalopathy
- Neonates requiring calcium-containing IV solutions due to the risk of precipitation of ceftriaxone-calcium
- Intravenous administration of ceftriaxone solutions containing lidocaine 1
From the Research
Ceftriaxone is contraindicated in patients with known hypersensitivity to ceftriaxone, any component of its formulation, or other cephalosporin antibiotics, as well as in neonates with hyperbilirubinemia and premature infants up to a corrected age of 41 weeks due to the risk of kernicterus and other adverse effects. The contraindications for ceftriaxone can be summarized as follows:
- Known hypersensitivity to ceftriaxone or other cephalosporin antibiotics
- Neonates with hyperbilirubinemia
- Premature infants up to a corrected age of 41 weeks
- Simultaneous administration with calcium-containing intravenous solutions
- Severe hepatic and renal impairment may require dose adjustments rather than complete avoidance
- History of anaphylactic reactions to penicillins should be treated cautiously due to potential cross-reactivity, though this is not an absolute contraindication, as the risk of cross-reactivity is low, especially with third- or fourth-generation cephalosporins, as reported in a study published in 2019 2. The risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients is generally low, with a study published in 2019 finding that the risk of cross-reactivity varied with the degree of similarity between R1 side chains, and was 2.11% for cephalosporins with low similarity scores, and 0.87% for carbapenems 2. It is essential to note that ceftriaxone's high protein binding and calcium-binding properties can lead to dangerous precipitation reactions and displacement of other highly protein-bound substances like bilirubin, as reported in studies published in 2005 and 2015 3, 4. Therefore, clinicians should be aware of these contraindications and take necessary precautions when administering ceftriaxone to patients.