How do you deprescribe a penicillin allergy?

Penicillin Allergy Delabeling

Most patients with reported penicillin allergy can be safely delabeled through direct oral drug challenge or clinical history alone, as less than 5% of labeled patients have confirmed true allergy. 1

Risk Stratification by Clinical History

Start by categorizing patients based on their reported reaction type:

• Low-risk patients (suitable for direct delabeling): Those reporting clearly non-immunologic reactions such as nausea, headache, or fatigue can be delabeled by clinical history alone without any testing 1

• Low-risk patients (suitable for oral challenge): Those with vague childhood rashes occurring over 10 years ago, or mild delayed reactions (>72 hours after exposure) can proceed directly to supervised oral challenge 2

• Higher-risk patients requiring formal evaluation: Those reporting immediate reactions (<1 hour) including urticaria, angioedema, or anaphylaxis; accelerated reactions (1-72 hours); or severe delayed reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis 1

Delabeling Approaches

Direct Oral Drug Challenge (Preferred Method)

For low-risk patients, proceed directly to a two-step oral challenge without skin testing, as this approach is faster, simpler, and equally safe. 3

Protocol specifics:

• Administer 1/10 of the target therapeutic dose 3
• Observe for 30 minutes 3
• Give full therapeutic dose 3
• Observe for 60 minutes post-administration 3
• Total procedure time: 60-120 minutes 3

Safety data strongly supports this approach: A meta-analysis of five studies comparing direct oral challenge versus skin testing showed immediate allergic reactions occurred in only 2.3% of direct challenge patients versus 11.5% in the skin testing group (RR = 0.25,95% CI 0.15-0.45), with no anaphylaxis or deaths observed in either group 1

Skin Testing Followed by Challenge (Alternative)

For patients with more concerning histories or when institutional protocols require it, perform penicillin skin testing first. 3

Testing sequence:

• Epicutaneous (prick) test: Place duplicate drops on volar forearm, pierce epidermis with 26-gauge needle, read at 15 minutes (positive if wheal ≥4 mm larger than negative control) 3
• If prick test negative, proceed to intradermal test: Inject 0.02 mL using 26-27 gauge needle, read at 15 minutes (positive if wheal >2 mm larger than initial size and >2 mm larger than negative control) 3
• If skin tests negative, proceed to oral challenge as described above 4
• Total duration: approximately 72.7 minutes for skin testing plus 60-120 minutes for challenge 3

Critical Safety Considerations

Antihistamine washout is mandatory before testing to avoid false-negative results:

• Chlorpheniramine or terfenadine: 24 hours 3
• Diphenhydramine or hydroxyzine: 4 days 3
• Astemizole: 3 weeks 3

All testing and challenges must be performed in a supervised healthcare setting equipped to manage anaphylaxis. 1

For high-risk patients (history of anaphylaxis, asthma, or on beta-blockers), begin with 100-fold dilutions before standard testing, adding 15-30 minutes to the procedure 3

Follow-up is essential: Contact patients at 5 days post-challenge to assess for delayed hypersensitivity reactions, which occur in approximately 1.7% of cases 3

Clinical Impact and Outcomes

The safety profile of delabeling is excellent: A Bayesian meta-analysis of 112 studies including 26,595 participants showed severe reactions occurred in only 0.06% (95% CrI 0.01-0.13%), with most being anaphylaxis at 0.03% frequency, and no fatal reactions reported 1

Successful delabeling dramatically reduces inappropriate antibiotic use: Implementation of systematic delabeling protocols decreased vancomycin use from 68.3% to 37.2%, aztreonam from 11.5% to 0.5%, aminoglycosides from 6.0% to 1.1%, and fluoroquinolones from 15.3% to 3.3% 5

Common Pitfalls to Avoid

Do not assume family history indicates true allergy: Approximately 90% of patients labeled with penicillin allergy are not truly allergic when properly tested, meaning most "inherited" labels represent inherited misinformation rather than genetic predisposition 6

Do not automatically avoid penicillins based on label alone: The American Academy of Allergy, Asthma, and Immunology advises against assuming inherited penicillin allergy without confirmation, as consequences of incorrect labels include increased mortality, higher rates of resistant infections, longer hospital stays, and increased costs 6

Do not perform routine pharmacogenomic testing: No actionable single-allele markers exist for penicillin allergy, making genetic testing clinically unhelpful 6

Recognize that penicillin allergies are not lifelong: Approximately 50% of confirmed penicillin allergies are lost over five years, making historical labels increasingly unreliable over time 2