What is the risk of cross-sensitivity between aspirin (acetylsalicylic acid) and Toradol (ketorolac) in patients with a known allergy to aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Cross-Sensitivity Between Aspirin and Toradol (Ketorolac)

Patients with aspirin allergy should avoid ketorolac (Toradol) due to significant cross-sensitivity risk, as both medications belong to different chemical classes of NSAIDs but share similar mechanisms of action through COX-1 inhibition. 1

Understanding the Cross-Sensitivity Mechanism

Cross-sensitivity between aspirin and ketorolac occurs primarily through their shared pharmacological mechanism:

• Both drugs inhibit cyclooxygenase-1 (COX-1) enzyme, altering arachidonic acid metabolism 1, 2
• This is not a true IgE-mediated allergy but rather a pharmacological effect 2
• Chemical classification: Aspirin belongs to salicylates while ketorolac is an acetic acid derivative NSAID 1

Types of Hypersensitivity Reactions

1. NSAID-Exacerbated Respiratory Disease (AERD):

   • Most common in patients with asthma and nasal polyps
   • Prevalence up to 21% in adults with asthma 1
   • Symptoms include bronchospasm and rhinitis
   • High cross-reactivity between aspirin and other NSAIDs including ketorolac 3

2. NSAID-Exacerbated Cutaneous Disease:

   • Worsening of pre-existing urticaria or angioedema
   • Cross-reactivity with other COX-1 inhibitors including ketorolac 2

3. Single NSAID-Induced Reactions:

   • Specific to one NSAID chemical class
   • Less common than cross-reactive patterns 1

Clinical Implications and Management

For patients with known aspirin allergy:

• Avoid ketorolac: The FDA label explicitly states ketorolac "should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs" 4
• Severe reactions possible: Anaphylactic-like and bronchospastic life-threatening reactions have been reported with ketorolac use in aspirin-sensitive patients 3
• All administration routes affected: Even topical ketorolac has been reported to cause severe asthma exacerbations in aspirin-sensitive patients 5

Alternative Options

For patients requiring anti-inflammatory or analgesic therapy:

1. Acetaminophen (Paracetamol):

   • Generally safe in low to moderate doses (<1000mg)
   • May cause reactions in a small percentage of highly sensitive patients 6, 7

2. Selective COX-2 Inhibitors:

   • Well tolerated by almost all aspirin-sensitive patients 7
   • Examples include celecoxib
   • Safer alternative for patients with aspirin hypersensitivity

3. Aspirin Desensitization:

   • Option for patients requiring aspirin for cardiovascular protection
   • Should only be performed by specialists in controlled settings 2
   • Requires continued daily therapy to maintain tolerance

Key Precautions

• Always obtain a complete history of aspirin/NSAID reactions, asthma, rhinitis, and nasal polyps before administering ketorolac 3
• The combination of asthma and nasal polyps should raise suspicion for potential aspirin/NSAID sensitivity 1
• Cross-reactivity is highest with strong COX-1 inhibitors like ketorolac 7
• Patients with aspirin-sensitive asthma are at particularly high risk for severe reactions to ketorolac 3, 5

The evidence clearly demonstrates that ketorolac should be avoided in patients with known aspirin allergy due to the significant risk of cross-sensitivity reactions that can be severe and potentially life-threatening.