How to manage an allergic reaction to paclitaxel (Taxol)?

Management of Paclitaxel Allergic Reactions

For mild to moderate reactions (Grade 1-2), immediately stop or slow the infusion rate and administer symptomatic treatment with antihistamines and corticosteroids; for severe reactions (Grade 3-4), permanently stop the infusion, administer intramuscular epinephrine, and consider desensitization protocols if paclitaxel remains the preferred therapy. 1

Immediate Recognition and Acute Management

Grade 1-2 Reactions (Mild to Moderate)

• Stop or significantly slow the infusion rate when symptoms appear, including flushing, rash, chills, or mild chest discomfort 1
• Administer symptomatic treatment with diphenhydramine 50 mg IV, H2 receptor antagonist (ranitidine 50 mg or cimetidine 300 mg IV), and corticosteroids 1
• Monitor vital signs continuously and assess for progression of symptoms 2
• The infusion can be restarted at a much slower rate (typically 50% of original rate) if symptoms resolve and the patient, physician, and nursing staff are all comfortable proceeding 1
• Emergency equipment must be immediately available in the treatment area 1

Grade 3-4 Reactions (Severe/Life-Threatening)

• Immediately stop the infusion completely 1, 2
• Administer epinephrine 0.3-0.5 mg intramuscularly into the lateral thigh for anaphylaxis, repeating every 5-15 minutes as needed 2
• Provide aggressive symptomatic therapy including oxygen, nebulized bronchodilators, IV corticosteroids, and IV antihistamines (both H1 and H2 blockers) 1, 2
• Monitor for cardiac problems, bronchospasm, and blood pressure changes that require immediate treatment 1
• Do not rechallenge with paclitaxel until evaluated by an allergist or specialist with desensitization expertise 1

Prevention: Mandatory Premedication Protocol

All patients must receive premedication before paclitaxel administration to reduce severe reactions from 30% to 2-4% 1

• Dexamethasone: One dose IV (20 mg for solid tumors; 10 mg for AIDS-related Kaposi's sarcoma) administered 30 minutes before paclitaxel 1, 3
• Diphenhydramine: 50 mg IV given 30 minutes before infusion 1
• H2 receptor antagonist: Ranitidine 50 mg or cimetidine 300 mg IV administered 30 minutes before paclitaxel 1
• IV dexamethasone is associated with fewer side effects than oral dexamethasone without difference in hypersensitivity reaction rates 1

Timing and Risk Factors

• Paclitaxel reactions occur within the first 10 minutes of infusion, typically during the first or second dose 1
• Reactions occur in up to 30% of patients without premedication, but only 2-4% with proper premedication 1
• The reactions are believed to be anaphylactoid (non-IgE mediated), likely due to direct mast cell mediator release from paclitaxel or its diluent kolliphor EL (formerly cremophor EL) 1
• Symptoms typically improve quickly once the infusion is stopped, distinguishing paclitaxel reactions from platinum-based drug allergies 1

Desensitization Protocols for Recurrent Use

After a severe hypersensitivity reaction, desensitization is the only safe method to continue paclitaxel if it remains the preferred therapy 1

When to Consider Desensitization

• Patient has had a Grade 3-4 reaction but paclitaxel remains first-line therapy 1
• Despite adequate premedication, approximately 1-2% of patients will experience severe reactions requiring desensitization 1
• Patients who have had very severe life-threatening anaphylactic reactions should not receive paclitaxel again unless under specialized allergist care 1

Desensitization Protocol Details

• Use a standardized 6-7 hour desensitization protocol with serial 10-fold dilutions (up to 1:100,000) of the actual paclitaxel solution 4, 5
• Administer escalating doses in successive volumes of 1,2,4, and 8 mL at 15-minute intervals for each dilution 5
• After the last diluted dose, give 1 mL of undiluted solution; if no reaction occurs, deliver the remaining dose at a 3-hour infusion rate 5
• Desensitization must be performed with each subsequent infusion, as it does not provide lasting tolerance 1
• Success rate is high: 77 planned cycles completed in 17 patients, with only 4 developing mild reactions during desensitization that were much less severe than original reactions 4

Alternative Taxane Considerations

• Cross-reactivity between paclitaxel and docetaxel ranges from 50-90% in the literature, though unpublished clinical experience suggests lower rates 1
• Nab-paclitaxel (albumin-bound paclitaxel) is well tolerated in patients with paclitaxel and docetaxel allergy because it lacks the kolliphor EL diluent 1
• Skin testing can help assess cross-reactivity risk before attempting an alternative taxane 1

Critical Pitfalls to Avoid

• Never delay epinephrine administration in suspected anaphylaxis; it is the first-line treatment and should be given intramuscularly immediately 2
• Premedication with corticosteroids and antihistamines does not prevent recurrent severe reactions in sensitized patients; desensitization is required 1
• Do not confuse paclitaxel infusion reactions (which occur early and resolve quickly) with platinum-based allergic reactions (which occur after multiple cycles and persist after stopping infusion) 1
• Ensure proper mixing of paclitaxel with kolliphor EL before administration, as incomplete mixing can lead to complement activation and increased reaction risk 1
• Standing orders for emergency intervention must be written before each infusion, and emergency equipment must be immediately available 1
• Patients and families must be counseled about reaction signs/symptoms and instructed to report them immediately, even after leaving the clinic 1