What is the reaction of Ceftriaxone (Rocephin) in patients with a Penicillin (PCN) allergy?

From the Guidelines

Patients with a penicillin (PCN) allergy have a low cross-reactivity risk with Rocephin (ceftriaxone), and the risk is generally estimated to be around 1-2% for mild to moderate PCN allergies and 4-10% for severe PCN allergies. For patients with mild to moderate PCN allergies, such as a rash, the cross-reactivity with cephalosporins like Rocephin is approximately 1-2% 1. However, patients with severe PCN allergies, such as anaphylaxis, angioedema, or Stevens-Johnson syndrome, have a higher risk, around 4-10%, and should avoid Rocephin if possible 1.

Key Considerations

• The cross-reactivity occurs because both PCN and cephalosporins share a beta-lactam ring structure, though third-generation cephalosporins like Rocephin have modified side chains that reduce this risk compared to earlier generations 1.
• Always document the specific nature of the PCN allergy (type of reaction, timing, severity) to make better-informed decisions about using Rocephin in these patients.
• If Rocephin is clinically necessary for a patient with severe PCN allergy, consider consultation with an allergist for skin testing or graded challenge, or use desensitization protocols in a monitored setting 1.

Skin Testing and Desensitization

• Skin testing may be useful for patients with anaphylactic or convincing histories of IgE-mediated reactions, and patients with a history of penicillin hypersensitivity 1.
• A positive cephalosporin skin test suggests drug-specific IgE antibodies, and the patient should receive a skin test–negative alternative cephalosporin or alternate antibiotic, or the patient should undergo desensitization 1.
• A negative cephalosporin skin test should be followed by a drug challenge to confirm tolerance 1.

Clinical Decision-Making

• The reaction rate among patients with a confirmed penicillin allergy was recently determined to be just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic 1.
• In a meta-analysis of 77 studies, a cefazolin allergy was identified in 3.0% of patients with confirmed penicillin allergy (95% CrI: 0.01%-17.0%) 1.
• Ceftibuten, a third-generation oral cephalosporin, also has unique side chains from any penicillin and all currently available cephalosporins that may also make cross-reaction rates exceedingly rare 1.

From the FDA Drug Label

WARNINGS Hypersensitivity Reactions Before therapy with ceftriaxone for injection is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins and other beta-lactam agents or other drugs. This product should be given cautiously to penicillin and other beta-lactam agent-sensitive patients 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

Key Considerations:

• Patients with a history of hypersensitivity reactions to penicillins and other beta-lactam agents may be at greater risk of hypersensitivity to ceftriaxone.
• Ceftriaxone should be given cautiously to patients with a history of hypersensitivity to penicillin and other beta-lactam agents.
• The decision to administer ceftriaxone to a patient with a PCN allergy should be made with caution, considering the potential risk of a hypersensitivity reaction 2 2. Clinical Decision: Given the potential risk of a hypersensitivity reaction, it is recommended to exercise caution when administering ceftriaxone to a patient with a PCN allergy. A thorough assessment of the patient's medical history and a careful evaluation of the potential benefits and risks of ceftriaxone therapy should be conducted before making a decision.

From the Research

Rocephin Reaction with PCN Allergy

• Rocephin, also known as ceftriaxone, is a third-generation cephalosporin antibiotic 3
• The risk of cross-reactivity between penicillin and cephalosporins, including Rocephin, is generally considered to be low, around 1-2% 4, 5
• Studies have shown that the risk of allergic reaction to cephalosporins, including Rocephin, is higher in patients with a history of penicillin allergy, but this risk is still considered to be relatively low 6, 7
• The R1 side chain of cephalosporins is thought to be responsible for cross-reactivity with penicillin, and Rocephin has a different R1 side chain than penicillin 4
• Patients with a history of penicillin allergy can be evaluated for their risk of allergic reaction to Rocephin using penicillin skin testing and/or amoxicillin challenge 5
• Clinicians should consider the individual patient's medical history and risk factors when deciding whether to prescribe Rocephin to a patient with a reported penicillin allergy 6, 7

Key Findings

• The overall cross-reactivity rate between penicillin and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 4
• Third- or fourth-generation cephalosporins, such as Rocephin, carry a negligible risk of cross-allergy in patients with penicillin allergy 4, 3
• Patients with a history of anaphylaxis or positive penicillin skin testing are considered to be at high risk for allergic reaction to cephalosporins, including Rocephin 5