What are the recommendations for using Keflex (cephalexin) in patients with a known cephalosporin allergy?

From the Guidelines

Keflex (cephalexin) should generally be avoided in patients with a known cephalosporin allergy due to the risk of cross-reactivity, as recommended by the Dutch Working Party on Antibiotic Policy (SWAB) guideline 1. Patients with a documented cephalosporin allergy should not receive Keflex unless the benefits clearly outweigh the risks and only under close medical supervision. For patients with a history of mild non-anaphylactic reactions to cephalosporins, a graded challenge or desensitization protocol may be considered in a controlled setting with emergency medications readily available, as suggested by the guideline 1. If a patient reports a penicillin allergy but no specific cephalosporin allergy, the cross-reactivity risk is approximately 1-10%, and Keflex might be cautiously used after careful assessment of the nature and severity of the penicillin reaction, considering the side-chain similarity between cefalexin and other penicillins 1. Some key points to consider when evaluating the risk of cross-reactivity include:

• The side-chain structure of the cephalosporin, as cross-reactivity is more likely to occur between cephalosporins with similar side chains 1
• The severity and time since the index reaction, as patients with a suspected non-severe, delayed-type allergy to a cephalosporin may be able to receive penicillins with dissimilar side chains or cephalosporins with a dissimilar side chain 1
• The use of alternative antibiotic classes, such as fluoroquinolones, macrolides, or tetracyclines, which may be considered based on the infection being treated 1. Skin testing may help determine the risk of reaction before administration, although the predictive value of negative tests and the pattern of possible cross-reactivity may vary 1. Ultimately, the decision to use Keflex in a patient with a known cephalosporin allergy should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history, and considering the recommendations outlined in the SWAB guideline 1.

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 There is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and the cephalosporins Patients have been reported to have had severe reactions (including anaphylaxis) to both drugs. Any patient who has demonstrated some form of allergy, particularly to drugs, should receive antibiotics cautiously. No exception should be made with regard to cephalexin

Patients with a known cephalosporin allergy should exercise caution when taking Keflex (cephalexin), as there is evidence of partial cross-allergenicity between penicillins and cephalosporins.

• Severe reactions, including anaphylaxis, have been reported in patients with allergies to both drugs.
• A careful medical history is necessary to determine the risk of an allergic reaction.
• Cautious use of antibiotics is recommended for patients with a history of allergy, particularly to drugs 2.

From the Research

Cephalosporin Allergy and Keflex (Cephalexin) Use

• Patients with a known cephalosporin allergy may be able to take Keflex (cephalexin) depending on the specific circumstances of their allergy 3, 4, 5, 6, 7.
• The risk of cross-reactivity between cephalosporins and other beta-lactams, such as penicillins, is relatively low, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 4.
• Cephalosporins can be prescribed safely for penicillin-allergic patients, with some exceptions, such as cefprozil, cefuroxime, cefpodoxime, ceftazidime, and ceftriaxone, which do not increase the risk of an allergic reaction 6.
• The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy 4.
• Keflex (cephalexin) is a first-generation cephalosporin, and its use in patients with a known cephalosporin allergy should be approached with caution, taking into account the specific circumstances of the allergy and the potential for cross-reactivity 3, 4, 5, 6, 7.

Factors Influencing Cross-Reactivity

• The R1 side chain of cephalosporins is responsible for cross-reactivity with other beta-lactams, such as penicillins 4, 5.
• The chemical structure of cephalosporins and the exact allergenic determinants are not yet fully understood, making standardized diagnostic skin testing not available for cephalosporins 5.
• Skin testing to the cephalosporin in question, using a nonirritating concentration, can provide additional information to guide the work-up of a patient suspected of having an allergy to that drug 5.

Recommendations for Use

• Clinicians should consider the low likelihood of true cephalosporin allergy when clinically indicated 3.
• The use of cephalosporins, including Keflex (cephalexin), in patients with a known cephalosporin allergy should be individualized, taking into account the specific circumstances of the allergy and the potential for cross-reactivity 3, 4, 5, 6, 7.