Yes, a patient with a Motrin (ibuprofen) allergy can safely receive Keflex (cephalexin).
Ibuprofen and cephalexin are completely unrelated drug classes with no cross-reactivity, so a Motrin allergy does not contraindicate Keflex use.
Why This Is Safe
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) from the propionic acid class, while cephalexin is a beta-lactam antibiotic (first-generation cephalosporin). These medications have:
- Completely different chemical structures
- Entirely different mechanisms of action
- No shared allergenic epitopes
- No documented cross-reactivity
The FDA label for Keflex 1 warns about cross-reactivity with penicillins and other beta-lactam antibiotics only—not NSAIDs like ibuprofen. The warning states: "CAUTION SHOULD BE EXERCISED BECAUSE CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED."
What You Need to Verify
Before prescribing Keflex, confirm the patient does not have:
- Penicillin or other beta-lactam allergy (this is the relevant concern, not ibuprofen)
- Previous cephalosporin allergy
- History of severe delayed immunologic reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced liver injury, acute interstitial nephritis)
Clinical Context
The evidence about ibuprofen hypersensitivity 2 discusses cross-reactivity with aspirin and other NSAIDs—not antibiotics. This is a completely separate allergic pathway involving cyclooxygenase inhibition and arachidonic acid metabolism, which has nothing to do with beta-lactam antibiotic allergies.
Bottom line: Prescribe Keflex without hesitation in patients allergic to Motrin, as long as they have no beta-lactam antibiotic allergies.