From the Guidelines
Management of Taxol (paclitaxel) induced late hypersensitivity reactions requires prompt recognition and appropriate intervention, with a focus on preventing morbidity, mortality, and improving quality of life. For mild to moderate reactions (grade 1-2), temporarily stop the infusion and administer diphenhydramine 25-50 mg IV, hydrocortisone 100 mg IV, and ranitidine 50 mg IV (or famotidine 20 mg IV) as recommended by the ESMO clinical practice guidelines 1. Once symptoms resolve, restart the infusion at a slower rate with close monitoring. For severe reactions (grade 3-4), immediately discontinue the infusion, administer the same medications plus epinephrine 0.3-0.5 mg IM (1:1000 solution), provide supplemental oxygen, and consider IV fluids for hypotension. Future paclitaxel administration typically requires a more intensive premedication regimen: dexamethasone 20 mg IV or PO 12 and 6 hours before treatment, diphenhydramine 50 mg IV 30-60 minutes before, and ranitidine 50 mg IV 30-60 minutes before infusion, as suggested by the guidelines 1. Desensitization protocols may be necessary for patients with severe reactions, involving administration of gradually increasing concentrations of paclitaxel under close supervision by allergists/oncologists, with a focus on minimizing the risk of recurrent reactions and ensuring the patient's safety 1. Key considerations in managing these reactions include:
- Prompt recognition and intervention to prevent severe outcomes
- Use of premedication regimens to reduce the risk of reactions
- Close monitoring of patients during and after infusion
- Consideration of desensitization protocols for patients with severe reactions
- Focus on minimizing morbidity, mortality, and improving quality of life.
From the FDA Drug Label
Hypersensitivity Reactions: Patients with a history of severe hypersensitivity reactions to products containing Polyoxyl 35 Castor Oil, NF (e.g., cyclosporin for injection concentrate and teniposide for injection concentrate) should not be treated with paclitaxel. In order to avoid the occurrence of severe hypersensitiv reactions, all patients treated with paclitaxel shouldbe premedicated with corticosteroids (such as dexamethasone), diphenhydramine and H2 antagonists (such as cimetidine or ranitidine) Minor symptoms such as flushing, skin reactions, dyspnea, hypotension, or tachycardia do not require interruption of therapy. However, severe reactions, such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria require immediate discontinuation of paclitaxel and aggressive symptomatic therapy Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel.
Management of Taxol induced late hypersensitivity reactions:
- Premedication with corticosteroids, diphenhydramine, and H2 antagonists is recommended to prevent severe hypersensitivity reactions.
- Minor symptoms do not require interruption of therapy, but severe reactions require immediate discontinuation of paclitaxel and aggressive symptomatic therapy.
- Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel. 2
From the Research
Management of Taxol Induced Late Hypersensitivity Reactions
- Taxol (paclitaxel) is associated with hypersensitivity reactions (HSRs) in up to 9% of patients despite premedication 3.
- The cause of these reactions is unknown, but the vehicle for paclitaxel, Cremophor EL, is suspected to be a direct histamine releaser 4, 5.
- Symptoms of HSRs to taxanes include dyspnea, hypotension, bronchospasm, urticaria, and erythematous rashes 4, 5.
- Premedication regimens and longer infusion times can lower the incidence of reactivity 4, 5.
- Rapid desensitization protocols can provide a safe and effective strategy for the re-administration of paclitaxel or docetaxel even after severe HSRs 3, 6, 7.
- A standardized desensitization protocol can be used to successfully complete planned cycles of desensitization to paclitaxel or docetaxel 3.
- Retreatment with the original Taxol solution is safe and cost effective in most patients with hypersensitivity reactions, and should be completed within 24 h 6.
- Almost all patients that experience HSRs to taxanes can be safely re-exposed to taxanes either through desensitization or challenge 7.
Treatment Options
- Rapid desensitization protocol: a 6- to 7-h standard desensitization protocol can be used to re-administer paclitaxel or docetaxel 3.
- Retreatment with the original Taxol solution: starting at a slower rate and completing the infusion within 24 h 6.
- Desensitization or challenge: can be used to safely re-expose patients to taxanes 7.