Clinical Communications IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron John Leung, MD, Autumn Guyer, MD, and Aleena Banerji, MD Clinical Implication
Palonosetron may be safe to use in selected patients with ondansetron hypersensitivity.
TO THE EDITOR: Selective 5-HT3 receptor antagonists (5-HT3-RAs) are the cornerstone for the prevention and treatment of chemotherapyinduced nausea and vomiting.1 Therapeutic options are limited in patients with 5-HT3-RA hypersensitivity because there is a concern for cross-reactivity between different 5-HT3-RAs.2 Palonosetron is the newest 5-HT3-RA, and its chemical structure is different from the other 5-HT3-RAs (tropisetron, ondansetron, granisetron, and ondansetron).3 We describe a patient with ondansetron hypersensitivity who tolerated palonosetron. A 38-year-old woman was undergoing chemotherapy for advanced lung cancer. Seven days after she received her second cycle of Alimta/cisplatin, she noted periorbital and hand swelling, as well as urticaria on her upper and lower extremities, 20
minutes after she took her scheduled dose of ondansetron 8 mg orally. She did not have wheezing, shortness of breath, or lightheadedness. She started taking ondansetron 8 mg orally twice daily 1 week before and had never taken ondansetron or any other 5-HT3-RAs previously. Her symptoms resolved within 24 hours with oral antihistamines. She was evaluated in our clinic, and we performed skin testing. Her skin prick test with ondansetron was positive at 2 mg/mL. Prick skin test to saline was negative and histamine was positive. On the basis of published reports4,5 and our own experience with seven healthy controls and eight patients with suspected ondansetron allergy, ondansetron at 2 mg/mL is not an irritating concentration. Given her positive skin test and convincing clinical history, we concluded that she had hypersensitivity to ondansetron. Alimta/ cisplatin are unlikely causes for her hypersensitivity symptoms because her reaction occurred 7 days after the infusion, and she tolerated subsequent doses without any adverse events. We performed palonosetron prick, intradermal test (IDT), and intravenous provocative test 3 weeks after her initial reaction. Prick tests to palonosetron at 0.05 mg/mL (undiluted concentration) and IDTs at 0.0005 mg/mL and 0.005 mg/mL were all negative. Appropriate responses of prick test and IDTs to both the negative saline control and positive histamine control were seen. We performed skin prick test with palonosetron at 0.05 mg/mL and IDTs at 0.05 mg/mL, 0.005 mg/mL, and 0.0005 mg/mL on six healthy controls with no known palonosetron allergy. All six control subjects had positive IDT at
TABLE I. Suggested 5-HT3-RA concentrations for skin testing 5-HT3-RA
Prick
Intradermal
Irritating concentration
Reference
Ondansetron (2 mg/mL)
1:1
1:100
1:1 0 intradermal
Granisetron (1 mg/mL)
1:1
—
Dolasetron (20 mg/mL)
1:1
Palonosetron (0.05 mg/mL)
1:1
1:1000 1:100 1:100 1:10 1:1 1:100 1:10
Bousquet et al, 20055 Fernando and Broadfoot, 20094 Demir et al, 20106 Kanny et al, 20019
—
Bousquet et al, 20055
1:1 intradermal
Our own experience
TABLE II. Reported cases of giving alternative 5HT3-RA to patients with documented 5-HT3-RA allergy and their outcomes
Cases
Case series of 2 patients undergoing chemotherapy Man, 42 years old, with pancreatic cancer undergoing chemotherapy Girl, 1 year old, with brain cancer undergoing chemotherapy Woman, 38 years old, with breast cancer undergoing chemotherapy Woman, 38 years old, with lung cancer undergoing chemotherapy
526
Clinical history of hypersensitivity to 5-HT3-RA
Alternative 5-HT3-RA patient was challenged with
Tropisetron Ondansetron
Outcome
Reference
Ondansetron Tropisetron
Anaphylaxis Throat pruritus and asthma attack
Kataja and de Bruijn, 19962
Ondansetron
Granisetron
Tolerated
Bousquet et al, 20055
Ondansetron
Granisetron
Tolerated
Demir et al, 20106
Granisetron
Ondansetron
Tolerated
Kanny et al, 20019
Ondansetron
Palonosetron
Tolerated
Our own experience
J ALLERGY CLIN IMMUNOL: IN PRACTICE VOLUME 1, NUMBER 5
0.05 mg/mL, suggesting that it is an irritating skin testing concentration. She then underwent provocative test with 0.25 mg of palonosetron intravenously (10% of the target dose). She tolerated this, and a subsequent 2.25 mg of palonosetron was given intravenously without any adverse events. The patient completed two additional cycles of Alimta/cisplatin with palonosetron without any hypersensitivity reactions. Hypersensitivity to ondansetron is rare but can be fatal.4,6-8 Allergy to 5-HT3-RAs has been considered as a class effect, until two recent reports showed the safe use of granisetron in patients with ondansetron.5,6 It has been speculated that the indole ring shared by ondansetron and tropisetron (but not granisetron) act as the drug epitope and is responsible for their cross-reactivity.2 Palonosetron does not have the indole ring and, instead, has a fused tricyclic ring attached to a quinuclidine moiety.3 In conclusion, skin testing can be performed with nonirritating skin testing concentrations in patients with suspected hypersensitivity to 5-HT3-RAs (Table I).4-6,9 There are safe alternative 5-HT3-RAs (ie, granisetron and palonosetron) for patients with ondansetron hypersensitivity and positive skin testing (Table II). This is particularly relevant when newer 5-HT3-RA palonosetron has been shown to be more effective than ondansetron in preventing acute and delayed chemotherapy-induced nausea and vomiting.10,11 Department of Rheumatology, Immunology and Allergy, Harvard Medical School/ Massachusetts General Hospital, Boston, Mass No funding was received for this work. Conflicts of interest: A. Guyer has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication April 4, 2013; revised May 3, 2013; accepted for publication May 6, 2013. Available online June 27, 2013.
CLINICAL COMMUNICATIONS
527
Cite this article as: Leung J, Guyer A, Banerji A. IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron. J Allergy Clin Immunol: In Practice 2013;1:526-7. http://dx.doi.org/10.1016/j.jaip.2013.05.004. Corresponding author: Aleena Banerji, MD, 55 Fruit Street, Cox-2, Allergy Associates, Boston, MA 02114. E-mail: [email protected]. 2213-2198/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2013.05.004 REFERENCES 1. Billio A, Morello E, Clarke MJ. Serotonin receptor antagonists for highly emetogenic chemotherapy in adults. Cochrane Database Syst Rev 2010:CD006272. 2. Kataja V, de Bruijn KM. Hypersensitivity reactions associated with 5hydroxytryptamine(3)-receptor antagonists: a class effect? Lancet 1996;347:584-5. 3. Rojas C, Stathis M, Thomas AG, Massuda EB, Alt J, Zhang J, et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 2008;107:469-78. 4. Fernando SL, Broadfoot AJ. Ondansetron anaphylaxis: a case report and protocol for skin testing. Br J Anaesth 2009;102:285-6. 5. Bousquet PJ, Co-Minh H-B, Demoly P. Isolated urticaria to ondansetron and successful treatment with granisetron. Allergy 2005;60:543-4. 6. Demir HA, Batu ED, Yalçõn B, Civelek E, Saçkesen C, Büyükpamukçu M. Anaphylactic reaction owing to ondansetron administration in a child with neuroblastoma and safe use of granisetron: a case report. J Pediatr Hematol Oncol 2010;32:e341-2. 7. Ross AK, Ferrero-Conover D. Anaphylactoid reaction due to the administration of ondansetron in a pediatric neurosurgical patient. Anesth Analg 1998;87:779-80. 8. Weiss KS. Anaphylactic reaction to ondansetron. Arch Intern Med 2001;161:2263. 9. Kanny G, Beaudouin E, Moneret-Vautrin DA. IgE-mediated allergy to granisetron and safe use of ondansetron. J Allergy Clin Immunol 2001;108:1059-60. 10. Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003;98:2473-82. 11. Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a doubleblind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003;14:1570-7.
Palonosetron may be safe to use in selected patients with ondansetron hypersensitivity.
TO THE EDITOR: Selective 5-HT3 receptor antagonists (5-HT3-RAs) are the cornerstone for the prevention and treatment of chemotherapyinduced nausea and vomiting.1 Therapeutic options are limited in patients with 5-HT3-RA hypersensitivity because there is a concern for cross-reactivity between different 5-HT3-RAs.2 Palonosetron is the newest 5-HT3-RA, and its chemical structure is different from the other 5-HT3-RAs (tropisetron, ondansetron, granisetron, and ondansetron).3 We describe a patient with ondansetron hypersensitivity who tolerated palonosetron. A 38-year-old woman was undergoing chemotherapy for advanced lung cancer. Seven days after she received her second cycle of Alimta/cisplatin, she noted periorbital and hand swelling, as well as urticaria on her upper and lower extremities, 20
minutes after she took her scheduled dose of ondansetron 8 mg orally. She did not have wheezing, shortness of breath, or lightheadedness. She started taking ondansetron 8 mg orally twice daily 1 week before and had never taken ondansetron or any other 5-HT3-RAs previously. Her symptoms resolved within 24 hours with oral antihistamines. She was evaluated in our clinic, and we performed skin testing. Her skin prick test with ondansetron was positive at 2 mg/mL. Prick skin test to saline was negative and histamine was positive. On the basis of published reports4,5 and our own experience with seven healthy controls and eight patients with suspected ondansetron allergy, ondansetron at 2 mg/mL is not an irritating concentration. Given her positive skin test and convincing clinical history, we concluded that she had hypersensitivity to ondansetron. Alimta/ cisplatin are unlikely causes for her hypersensitivity symptoms because her reaction occurred 7 days after the infusion, and she tolerated subsequent doses without any adverse events. We performed palonosetron prick, intradermal test (IDT), and intravenous provocative test 3 weeks after her initial reaction. Prick tests to palonosetron at 0.05 mg/mL (undiluted concentration) and IDTs at 0.0005 mg/mL and 0.005 mg/mL were all negative. Appropriate responses of prick test and IDTs to both the negative saline control and positive histamine control were seen. We performed skin prick test with palonosetron at 0.05 mg/mL and IDTs at 0.05 mg/mL, 0.005 mg/mL, and 0.0005 mg/mL on six healthy controls with no known palonosetron allergy. All six control subjects had positive IDT at
TABLE I. Suggested 5-HT3-RA concentrations for skin testing 5-HT3-RA
Prick
Intradermal
Irritating concentration
Reference
Ondansetron (2 mg/mL)
1:1
1:100
1:1 0 intradermal
Granisetron (1 mg/mL)
1:1
—
Dolasetron (20 mg/mL)
1:1
Palonosetron (0.05 mg/mL)
1:1
1:1000 1:100 1:100 1:10 1:1 1:100 1:10
Bousquet et al, 20055 Fernando and Broadfoot, 20094 Demir et al, 20106 Kanny et al, 20019
—
Bousquet et al, 20055
1:1 intradermal
Our own experience
TABLE II. Reported cases of giving alternative 5HT3-RA to patients with documented 5-HT3-RA allergy and their outcomes
Cases
Case series of 2 patients undergoing chemotherapy Man, 42 years old, with pancreatic cancer undergoing chemotherapy Girl, 1 year old, with brain cancer undergoing chemotherapy Woman, 38 years old, with breast cancer undergoing chemotherapy Woman, 38 years old, with lung cancer undergoing chemotherapy
526
Clinical history of hypersensitivity to 5-HT3-RA
Alternative 5-HT3-RA patient was challenged with
Tropisetron Ondansetron
Outcome
Reference
Ondansetron Tropisetron
Anaphylaxis Throat pruritus and asthma attack
Kataja and de Bruijn, 19962
Ondansetron
Granisetron
Tolerated
Bousquet et al, 20055
Ondansetron
Granisetron
Tolerated
Demir et al, 20106
Granisetron
Ondansetron
Tolerated
Kanny et al, 20019
Ondansetron
Palonosetron
Tolerated
Our own experience
J ALLERGY CLIN IMMUNOL: IN PRACTICE VOLUME 1, NUMBER 5
0.05 mg/mL, suggesting that it is an irritating skin testing concentration. She then underwent provocative test with 0.25 mg of palonosetron intravenously (10% of the target dose). She tolerated this, and a subsequent 2.25 mg of palonosetron was given intravenously without any adverse events. The patient completed two additional cycles of Alimta/cisplatin with palonosetron without any hypersensitivity reactions. Hypersensitivity to ondansetron is rare but can be fatal.4,6-8 Allergy to 5-HT3-RAs has been considered as a class effect, until two recent reports showed the safe use of granisetron in patients with ondansetron.5,6 It has been speculated that the indole ring shared by ondansetron and tropisetron (but not granisetron) act as the drug epitope and is responsible for their cross-reactivity.2 Palonosetron does not have the indole ring and, instead, has a fused tricyclic ring attached to a quinuclidine moiety.3 In conclusion, skin testing can be performed with nonirritating skin testing concentrations in patients with suspected hypersensitivity to 5-HT3-RAs (Table I).4-6,9 There are safe alternative 5-HT3-RAs (ie, granisetron and palonosetron) for patients with ondansetron hypersensitivity and positive skin testing (Table II). This is particularly relevant when newer 5-HT3-RA palonosetron has been shown to be more effective than ondansetron in preventing acute and delayed chemotherapy-induced nausea and vomiting.10,11 Department of Rheumatology, Immunology and Allergy, Harvard Medical School/ Massachusetts General Hospital, Boston, Mass No funding was received for this work. Conflicts of interest: A. Guyer has received royalties from UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. Received for publication April 4, 2013; revised May 3, 2013; accepted for publication May 6, 2013. Available online June 27, 2013.
CLINICAL COMMUNICATIONS
527
Cite this article as: Leung J, Guyer A, Banerji A. IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron. J Allergy Clin Immunol: In Practice 2013;1:526-7. http://dx.doi.org/10.1016/j.jaip.2013.05.004. Corresponding author: Aleena Banerji, MD, 55 Fruit Street, Cox-2, Allergy Associates, Boston, MA 02114. E-mail: [email protected]. 2213-2198/$36.00 Ó 2013 American Academy of Allergy, Asthma & Immunology http://dx.doi.org/10.1016/j.jaip.2013.05.004 REFERENCES 1. Billio A, Morello E, Clarke MJ. Serotonin receptor antagonists for highly emetogenic chemotherapy in adults. Cochrane Database Syst Rev 2010:CD006272. 2. Kataja V, de Bruijn KM. Hypersensitivity reactions associated with 5hydroxytryptamine(3)-receptor antagonists: a class effect? Lancet 1996;347:584-5. 3. Rojas C, Stathis M, Thomas AG, Massuda EB, Alt J, Zhang J, et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 2008;107:469-78. 4. Fernando SL, Broadfoot AJ. Ondansetron anaphylaxis: a case report and protocol for skin testing. Br J Anaesth 2009;102:285-6. 5. Bousquet PJ, Co-Minh H-B, Demoly P. Isolated urticaria to ondansetron and successful treatment with granisetron. Allergy 2005;60:543-4. 6. Demir HA, Batu ED, Yalçõn B, Civelek E, Saçkesen C, Büyükpamukçu M. Anaphylactic reaction owing to ondansetron administration in a child with neuroblastoma and safe use of granisetron: a case report. J Pediatr Hematol Oncol 2010;32:e341-2. 7. Ross AK, Ferrero-Conover D. Anaphylactoid reaction due to the administration of ondansetron in a pediatric neurosurgical patient. Anesth Analg 1998;87:779-80. 8. Weiss KS. Anaphylactic reaction to ondansetron. Arch Intern Med 2001;161:2263. 9. Kanny G, Beaudouin E, Moneret-Vautrin DA. IgE-mediated allergy to granisetron and safe use of ondansetron. J Allergy Clin Immunol 2001;108:1059-60. 10. Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, et al. Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 2003;98:2473-82. 11. Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a doubleblind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 2003;14:1570-7.
