Is cephalexin (Cephalexin) safe to use in patients with a mild penicillin (PCN) allergy?

From the Guidelines

Cephalexin can generally be used with caution in patients with mild penicillin allergies, with a cross-reactivity risk of approximately 1-5%. For patients who have experienced only mild reactions to penicillin (such as a minor rash without hives, itching, or systemic symptoms), cephalexin is typically considered safe 1. However, cephalexin should be avoided in patients with severe penicillin allergies, including those who have experienced anaphylaxis, angioedema, respiratory distress, or severe skin reactions like Stevens-Johnson syndrome.

Key Considerations

• Before prescribing cephalexin to a patient with a penicillin allergy, it's essential to thoroughly assess the nature and severity of their previous allergic reaction.
• If cephalexin is deemed appropriate, the typical adult dosage is 250-500 mg orally every 6 hours, or 500-1000 mg every 12 hours, depending on the infection being treated.
• The first dose should ideally be administered in a monitored setting if there are any concerns about potential cross-reactivity.
• Cross-reactivity occurs because cephalosporins and penicillins share a similar beta-lactam ring structure, though first-generation cephalosporins like cephalexin have lower cross-reactivity rates than earlier thought 1.

Recent Guidelines

• The Dutch Working Party on Antibiotic Policy (SWAB) guideline recommends that patients with a suspected immediate-type allergy to cephalosporins can receive penicillins with dissimilar side chains, irrespective of severity and time since the index reaction 1.
• The guideline also suggests that cephalosporins with a dissimilar side chain can be used in patients with a suspected immediate-type allergy to a cephalosporin, irrespective of severity and time since the index reaction.

Patient Safety

• It's crucial to prioritize patient safety and take a cautious approach when prescribing cephalexin to patients with a penicillin allergy.
• A thorough assessment of the patient's medical history and allergy status is necessary to minimize the risk of adverse reactions.
• In cases where cephalexin is contraindicated, alternative antibiotics should be considered, and the patient's treatment plan should be adjusted accordingly.

From the FDA Drug Label

WARNINGS BEFORE THERAPY WITH CEPHALEXIN IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALEXIN, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS IF THIS PRODUCT IS TO BE GIVEN TO PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.

The use of cephalexin in patients with a mild PCN allergy should be approached with caution due to the potential for cross-hypersensitivity among beta-lactam antibiotics, which may occur in up to 10% of patients with a history of penicillin allergy 2.

• Key considerations:
  • Careful medical history is necessary to determine previous hypersensitivity reactions
  • Caution should be exercised when administering cephalexin to penicillin-sensitive patients
  • Severe reactions, including anaphylaxis, have been reported in patients with a history of penicillin allergy
• Clinical decision: Use cephalexin with caution in patients with a mild PCN allergy, and closely monitor for signs of an allergic reaction.

From the Research

Use of Cephalexin with Mild PCN Allergy

• Cephalexin is a cephalosporin antibiotic that can be used in patients with a mild penicillin (PCN) allergy, as the cross-reactivity between penicillin and cephalosporins is low 3, 4, 5.
• The overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 5.
• A study found that cephalexin can be prescribed safely for penicillin-allergic patients, with a low risk of allergic reaction 4.
• Another study found that patients with a self-reported nonsevere, nontype I allergic reaction to penicillin who received cephalexin had a 0% incidence of allergic reactions 6.

Patient Evaluation

• Patients with a low-risk allergy history, such as isolated nonallergic symptoms or a family history of penicillin allergy, can be evaluated with a direct amoxicillin challenge or penicillin skin testing 3.
• Patients with a moderate-risk history, such as urticaria or other pruritic rashes, can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% 3.
• Patients with a high-risk history, such as anaphylaxis or positive penicillin skin testing, should avoid cephalosporins or undergo desensitization 3.

Antibiotic Stewardship

• The use of broad-spectrum antibiotics in patients with a reported penicillin allergy can increase the risk of antimicrobial resistance and adverse events 3, 7.
• Evaluating penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship 3, 7.