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Joint symptoms in patients on bupropion therapy
Joint Bone Spine 71 (2004) 583–585 http://france.elsevier.com/direct/BONSOI/
Case report
Joint symptoms in patients on bupropion therapy Paul Ornetti a, Anne Disson-Dautriche b, Géraldine Muller c, Anne Cherasse a, Christian Tavernier a, Jean-François Besancenot c, Catherine Sgro b, Jean-Francis Maillefert a,* a
Rheumatology Department, General Hospital, Dijon Teaching Hospitals, 3, rue du Faubourg Raines, 21000 Dijon, France b Drug Surveillance Center, General Hospital, Dijon Teaching Hospitals, Dijon, France c Internal Medicine and Systemic Diseases Department, General Hospital, Dijon Teaching Hospitals, Dijon, France Received 13 June 2003; accepted 2 October 2003 Available online 19 November 2003
Abstract Objective. – To describe joint symptoms related to bupropion therapy. Methods. – We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. Results. – Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. Conclusion. – Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case. © 2003 Elsevier SAS. All rights reserved. Keywords: Bupropion; Adverse reactions; Arthralgia; Serum sickness-like reactions; Arthritis
1. Introduction Bupropion is a selective inhibitor of neuronal reuptake of catecholamines (noradrenalin and dopamine) that was first developed as an antidepressant. The international nonproprietary name, amfebutamone, is a reminder that bupropion shares structural similarities with amphetamine derivatives such as amfepramone and diethylpropion [1]. In 2001, bupropion became the second medication available in France as an aid to smoking cessation. Its mechanism of action in reducing nicotine dependency is not understood [2]. A review of the international literature found fewer than 10 reports of bupropion-related arthralgia, usually due to semidelayed hypersensitivity reactions similar to serum sickness [3–7]. The objective of this study was to describe bupropionrelated joint symptoms reported to the drug surveillance center in Bourgogne, a region of France. * Corresponding author. E-mail address: [email protected] (J.-F. Maillefert). © 2003 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2003.10.004
2. Methods We retrospectively reviewed all adverse events in patients on bupropion reported to the Bourgogne Drug Surveillance Center between September 2001 and December 2002. We identified and analyzed the cases of joint symptoms in which the results of the causality assessment pointed to a relation with bupropion.
3. Results Of the adverse events reported during the study period, 896 were ascribed to a medication. In 16 cases, the medication was bupropion, and four of these 16 events were joint symptoms. We analyzed these four events in detail. They occurred in two men and two women aged 23–45 years. The symptoms began 5 days–2 weeks after bupropion initiation.
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P. Ornetti et al. / Joint Bone Spine 71 (2004) 583–585
3.1. Case 1 This 34-year-old man with a history of hypertension was admitted for arthralgia, myalgia, and urticaria that started 5 days after the initiation of combination therapy with bupropion, prazosin, magnesium, and tiapride. At admission, he described inflammatory joint pain in the right wrist and left knee. No joint effusions were found. The muscle pain predominated in the proximal thighs. He had no edema of the oral cavity or pharynx. Auscultation was normal, and there was no fever. Oral glucocorticoid and antihistamine therapy was added to the previous regimen. The symptoms resolved completely within a week. The causality assessment by the French method [8] classified the event as C2S2B3 (C for chronology and S for semiology: intrinsic evidence for causality; B for bibliography: extrinsic evidence for causality). A role for the other medications was not ruled out, but the causality scores were lower (C2S1B0, C2S1B3, and C2S1B0 for prazosin, magnesium, and tiapride, respectively). 3.2. Case 2 A 23-year-old woman with a history of periodic atopic dermatitis was admitted for diffuse itchy skin lesions and arthralgia that had started 24 h earlier. She was on oral contraception with an estrogen–progestagen combination. Two weeks earlier, she had started a smoking cessation program that included bupropion therapy. The pruriginous eruption of erythematous and papular lesions had started at the legs and nape of the neck, spreading rapidly to the rest of the body. Diffuse inflammatory joint pain occurred concomitantly. Physical findings included urticaria, a fever of 38.1 °C, and pain upon movement of the large joints. There was no evidence of synovitis. Laboratory tests showed leukocytosis (11°200/mm3) with a predominance of neutrophils, lymphopenia (890/mm3), and inflammation (Creactive protein, 133 mg/l, and fibrinogen, 4.9 g/l). Liver and kidney function tests were normal. At admission, proteinuria of 230 mg/24 h was found. Findings were normal or negative from tests for infection (urinary sediment and urine cultures; blood cultures; and serological tests for hepatitis B and C, cytomegalovirus, parvovirus B19, chlamydia, and mycoplasma) and immune dysfunction (antinuclear antibodies, CH50, circulating immune complexes, antineutrophil cytoplasmic antibody (ANCA), anticardiolipin antibody, electrophoresis, and immunofixation on blood and urine). An antihistamine was given per os and the bupropion was stopped. The symptoms resolved within 72 h. The causality assessment by the French method classified the event as C2S2B3. 3.3. Case 3 A 35-year-old man with insulin-dependent diabetes mellitus came to the emergency room with a 24-hour history of diffuse arthralgia, fever, and rash. He had started bupropion therapy 6 days earlier as part of a smoking cessation pro-
gram. The only other concomitant medication was insulin used subcutaneously. Physical findings consisted of a highgrade fever (39 °C), diffuse asymmetric arthralgia with no joint effusion, and diffuse urticaria. There was no evidence of shock or angioedema, and auscultation of the heart and lungs was normal. The bupropion was discontinued and intravenous glucocorticoid therapy with step 1 analgesics and oral antihistamine agents was given. The arthralgia, fever, and urticaria resolved within 48 h. The causality assessment by the French method classified the event as C2S2B3. 3.4. Case 4 This 45-year-old woman had an unremarkable medical history and was in good general health when she was referred on an emergency basis to a rheumatology outpatient clinic for inflammatory incapacitating pain in her left wrist. The pain had started 7 days after bupropion therapy initiation for smoking cessation. Monoarthritis of the left wrist was the only musculoskeletal abnormality. Edema of the eyelids was noted. Other physical findings were unremarkable; in particular, she had no fever, skin lesions, or oropharyngeal edema. The only concomitant medication was oral magnesium, which she had been taking for a few months. There was no recent history of immunization. Laboratory test results were as follows: C-reactive protein, 6 mg/l (normal, <5 mg/l), erythrocyte sedimentation rate, 13 mm/h (normal, <10 mm/h), liver and kidney function tests, normal; serum uric acid, normal, and leukocyte count, 7100/mm3. Tests were negative for antinuclear antibodies and rheumatoid factors. Radiographs of the wrist were normal. A nonsteroidal antiinflammatory drug and analgesics were given, and the bupropion was stopped. The symptoms resolved promptly, and there were no recurrences during the 1-year follow-up. Causality was C2S2B3 according to the French method (the B3 score was assigned because of the eyelid edema).
4. Discussion We report four cases of adverse musculoskeletal events ascribed to bupropion. Our objective was not to provide information on the incidence rate of these events, as data collection by the Drug Surveillance Center is passive and no information is available on the amount of bupropion used in the Bourgogne region during the study period. Our objective was to supply clinicians with information on the type of joint symptoms that can be caused by bupropion. We are not aware of publications reporting similar manifestations after use of medications belonging to the same class, such as diethylpropion. Adverse events reported by more than 1% of patients on bupropion include asthenia, headache, gastrointestinal symptoms, neuropsychiatric symptoms (tremor, insomnia, depression, irritability, and seizures), and a variety of erup-
P. Ornetti et al. / Joint Bone Spine 71 (2004) 583–585
tions [2]. Hypersensitivity reactions seem to be a fairly common pattern of eruption [9]; more specifically, semi-delayed (type III) reactions have been reported. These acute serum sickness-like reactions are ascribable to the presence of circulating immune complexes, in which the active ingredient of the medication is the hapten [10]. Soluble circulating immune complexes can deposit on the vessel walls, where they trigger a local inflammatory response, which is usually (but not only) mediated by complement activation (C3a, C5a). Mastocyte degranulation with histamine release and an influx of polymorphonuclear cells occur, producing the clinical manifestations: fever, urticaria, edema, arthralgia, lymph node enlargement, vasculitis and, in some cases, glomerulonephritis. Of the four cases reported here, three were serum sickness-like reactions. The symptoms were severe enough to require hospital admission in all four patients. The time from bupropion initiation to symptom onset ranged from 5 to 15 days. The symptoms started abruptly and included urticaria and joint pain with no effusions. Two of the three patients had a fever. Angioedema did not occur. The only patient with possible evidence of deep organ involvement was case 2, who had proteinuria, although there were no other abnormalities suggesting glomerulonephritis. Furthermore, of these three patients admitted for delayed hypersensitivity reactions, only one (case 2) had a history of allergic disease. Laboratory test abnormalities were variable and nonspecific, although leukocytosis and moderate-to-severe inflammation were common. The extensive immunological investigations done in case 2 showed no evidence of complement activation or circulating immune complexes, which form the basis for current pathophysiological concepts regarding serum sickness. After bupropion discontinuation and symptomatic treatment (antihistamine agents, with glucocorticoid therapy if needed), the urticaria and joint pain resolved consistently within a few days. The clinical and laboratory test evidence of type III hypersensitivity in these three patients are consistent with the few previous reports [3–7]. Type III hypersensitivity is listed in the French Drug Compendium as a “rare” adverse event (rate of occurrence between 1/1000 and 1/10 000). Case 4 is highly unusual in that it suggests a role for bupropion in the development of acute monoarthritis. Time
585
from bupropion initiation to symptom onset was 1 week. The clinical presentation suggested crystal deposition disease with an allergic component manifesting as eyelid edema. Antiinflammatory treatment ensured prompt resolution of the symptoms. Arguments supporting a role for bupropion were the temporal relationship between bupropion initiation and symptom onset, the eyelid edema, the absence of other causes, and the absence of recurrences. Joint symptoms ascribed to bupropion seem uncommon but fairly severe (particularly when serum sickness occurs). Given the growing popularity of this medication recently introduced in France, prescribing physicians should be alerted to the risk of severe hypersensitivity reactions so that they can inform their patients accordingly. Regarding the possibility that bupropion might induce arthritis, additional cases with longer follow-ups are needed to determine whether the single case reported here was an oddity or preliminary evidence of a clinically meaningful association. A useful step would be to look routinely for a history of bupropion therapy in patients presenting with acute monoarthritis.
References [1]
Masand P, Gupta S. Long-term side effects of newer-generation antidepressants: SSRIS, venlafaxine, nefazodone, bupropion and mirtazapine. Ann Clin Psychiatry 2002;14:175–82. [2] Vervaaeren J. Un nouveau médicament: le Bupropion. J Pharm Belg 2000;55:85–8. [3] Davis JS, Boyle MJ, Hannaford R, Watson A. Bupropion and serum sickness-like reaction. Med J Aust 2001;174:479–80. [4] Mc Collom RA, Elbe DH, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharmacother 2000;34:471–3. [5] Peloso PM, Baillie C. Serum sickness-like reaction with bupropion. JAMA 1999;282:1817. [6] Wooltorton E. Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. CMAJ 2002;166:8. [7] Yolles JC, Armenta WA, Alao AO. Serum sickness induced by bupropion. Ann Pharmacother 1999;33:931–3. [8] Begaud B, Evreux JC, Jouglard J, Lagier G. Imputabilité des effets inattendus ou toxiques des médicaments. Thérapie 1985;40:111–8. [9] Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust 2001;174:650–1. [10] Tripathi A, Greenberger PA. Bupropion hydrochloride induced serum sickness-like reaction. Ann Allergy Asthma Immunol 1999;83:165–6.
Case report
Joint symptoms in patients on bupropion therapy Paul Ornetti a, Anne Disson-Dautriche b, Géraldine Muller c, Anne Cherasse a, Christian Tavernier a, Jean-François Besancenot c, Catherine Sgro b, Jean-Francis Maillefert a,* a
Rheumatology Department, General Hospital, Dijon Teaching Hospitals, 3, rue du Faubourg Raines, 21000 Dijon, France b Drug Surveillance Center, General Hospital, Dijon Teaching Hospitals, Dijon, France c Internal Medicine and Systemic Diseases Department, General Hospital, Dijon Teaching Hospitals, Dijon, France Received 13 June 2003; accepted 2 October 2003 Available online 19 November 2003
Abstract Objective. – To describe joint symptoms related to bupropion therapy. Methods. – We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. Results. – Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. Conclusion. – Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case. © 2003 Elsevier SAS. All rights reserved. Keywords: Bupropion; Adverse reactions; Arthralgia; Serum sickness-like reactions; Arthritis
1. Introduction Bupropion is a selective inhibitor of neuronal reuptake of catecholamines (noradrenalin and dopamine) that was first developed as an antidepressant. The international nonproprietary name, amfebutamone, is a reminder that bupropion shares structural similarities with amphetamine derivatives such as amfepramone and diethylpropion [1]. In 2001, bupropion became the second medication available in France as an aid to smoking cessation. Its mechanism of action in reducing nicotine dependency is not understood [2]. A review of the international literature found fewer than 10 reports of bupropion-related arthralgia, usually due to semidelayed hypersensitivity reactions similar to serum sickness [3–7]. The objective of this study was to describe bupropionrelated joint symptoms reported to the drug surveillance center in Bourgogne, a region of France. * Corresponding author. E-mail address: [email protected] (J.-F. Maillefert). © 2003 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2003.10.004
2. Methods We retrospectively reviewed all adverse events in patients on bupropion reported to the Bourgogne Drug Surveillance Center between September 2001 and December 2002. We identified and analyzed the cases of joint symptoms in which the results of the causality assessment pointed to a relation with bupropion.
3. Results Of the adverse events reported during the study period, 896 were ascribed to a medication. In 16 cases, the medication was bupropion, and four of these 16 events were joint symptoms. We analyzed these four events in detail. They occurred in two men and two women aged 23–45 years. The symptoms began 5 days–2 weeks after bupropion initiation.
584
P. Ornetti et al. / Joint Bone Spine 71 (2004) 583–585
3.1. Case 1 This 34-year-old man with a history of hypertension was admitted for arthralgia, myalgia, and urticaria that started 5 days after the initiation of combination therapy with bupropion, prazosin, magnesium, and tiapride. At admission, he described inflammatory joint pain in the right wrist and left knee. No joint effusions were found. The muscle pain predominated in the proximal thighs. He had no edema of the oral cavity or pharynx. Auscultation was normal, and there was no fever. Oral glucocorticoid and antihistamine therapy was added to the previous regimen. The symptoms resolved completely within a week. The causality assessment by the French method [8] classified the event as C2S2B3 (C for chronology and S for semiology: intrinsic evidence for causality; B for bibliography: extrinsic evidence for causality). A role for the other medications was not ruled out, but the causality scores were lower (C2S1B0, C2S1B3, and C2S1B0 for prazosin, magnesium, and tiapride, respectively). 3.2. Case 2 A 23-year-old woman with a history of periodic atopic dermatitis was admitted for diffuse itchy skin lesions and arthralgia that had started 24 h earlier. She was on oral contraception with an estrogen–progestagen combination. Two weeks earlier, she had started a smoking cessation program that included bupropion therapy. The pruriginous eruption of erythematous and papular lesions had started at the legs and nape of the neck, spreading rapidly to the rest of the body. Diffuse inflammatory joint pain occurred concomitantly. Physical findings included urticaria, a fever of 38.1 °C, and pain upon movement of the large joints. There was no evidence of synovitis. Laboratory tests showed leukocytosis (11°200/mm3) with a predominance of neutrophils, lymphopenia (890/mm3), and inflammation (Creactive protein, 133 mg/l, and fibrinogen, 4.9 g/l). Liver and kidney function tests were normal. At admission, proteinuria of 230 mg/24 h was found. Findings were normal or negative from tests for infection (urinary sediment and urine cultures; blood cultures; and serological tests for hepatitis B and C, cytomegalovirus, parvovirus B19, chlamydia, and mycoplasma) and immune dysfunction (antinuclear antibodies, CH50, circulating immune complexes, antineutrophil cytoplasmic antibody (ANCA), anticardiolipin antibody, electrophoresis, and immunofixation on blood and urine). An antihistamine was given per os and the bupropion was stopped. The symptoms resolved within 72 h. The causality assessment by the French method classified the event as C2S2B3. 3.3. Case 3 A 35-year-old man with insulin-dependent diabetes mellitus came to the emergency room with a 24-hour history of diffuse arthralgia, fever, and rash. He had started bupropion therapy 6 days earlier as part of a smoking cessation pro-
gram. The only other concomitant medication was insulin used subcutaneously. Physical findings consisted of a highgrade fever (39 °C), diffuse asymmetric arthralgia with no joint effusion, and diffuse urticaria. There was no evidence of shock or angioedema, and auscultation of the heart and lungs was normal. The bupropion was discontinued and intravenous glucocorticoid therapy with step 1 analgesics and oral antihistamine agents was given. The arthralgia, fever, and urticaria resolved within 48 h. The causality assessment by the French method classified the event as C2S2B3. 3.4. Case 4 This 45-year-old woman had an unremarkable medical history and was in good general health when she was referred on an emergency basis to a rheumatology outpatient clinic for inflammatory incapacitating pain in her left wrist. The pain had started 7 days after bupropion therapy initiation for smoking cessation. Monoarthritis of the left wrist was the only musculoskeletal abnormality. Edema of the eyelids was noted. Other physical findings were unremarkable; in particular, she had no fever, skin lesions, or oropharyngeal edema. The only concomitant medication was oral magnesium, which she had been taking for a few months. There was no recent history of immunization. Laboratory test results were as follows: C-reactive protein, 6 mg/l (normal, <5 mg/l), erythrocyte sedimentation rate, 13 mm/h (normal, <10 mm/h), liver and kidney function tests, normal; serum uric acid, normal, and leukocyte count, 7100/mm3. Tests were negative for antinuclear antibodies and rheumatoid factors. Radiographs of the wrist were normal. A nonsteroidal antiinflammatory drug and analgesics were given, and the bupropion was stopped. The symptoms resolved promptly, and there were no recurrences during the 1-year follow-up. Causality was C2S2B3 according to the French method (the B3 score was assigned because of the eyelid edema).
4. Discussion We report four cases of adverse musculoskeletal events ascribed to bupropion. Our objective was not to provide information on the incidence rate of these events, as data collection by the Drug Surveillance Center is passive and no information is available on the amount of bupropion used in the Bourgogne region during the study period. Our objective was to supply clinicians with information on the type of joint symptoms that can be caused by bupropion. We are not aware of publications reporting similar manifestations after use of medications belonging to the same class, such as diethylpropion. Adverse events reported by more than 1% of patients on bupropion include asthenia, headache, gastrointestinal symptoms, neuropsychiatric symptoms (tremor, insomnia, depression, irritability, and seizures), and a variety of erup-
P. Ornetti et al. / Joint Bone Spine 71 (2004) 583–585
tions [2]. Hypersensitivity reactions seem to be a fairly common pattern of eruption [9]; more specifically, semi-delayed (type III) reactions have been reported. These acute serum sickness-like reactions are ascribable to the presence of circulating immune complexes, in which the active ingredient of the medication is the hapten [10]. Soluble circulating immune complexes can deposit on the vessel walls, where they trigger a local inflammatory response, which is usually (but not only) mediated by complement activation (C3a, C5a). Mastocyte degranulation with histamine release and an influx of polymorphonuclear cells occur, producing the clinical manifestations: fever, urticaria, edema, arthralgia, lymph node enlargement, vasculitis and, in some cases, glomerulonephritis. Of the four cases reported here, three were serum sickness-like reactions. The symptoms were severe enough to require hospital admission in all four patients. The time from bupropion initiation to symptom onset ranged from 5 to 15 days. The symptoms started abruptly and included urticaria and joint pain with no effusions. Two of the three patients had a fever. Angioedema did not occur. The only patient with possible evidence of deep organ involvement was case 2, who had proteinuria, although there were no other abnormalities suggesting glomerulonephritis. Furthermore, of these three patients admitted for delayed hypersensitivity reactions, only one (case 2) had a history of allergic disease. Laboratory test abnormalities were variable and nonspecific, although leukocytosis and moderate-to-severe inflammation were common. The extensive immunological investigations done in case 2 showed no evidence of complement activation or circulating immune complexes, which form the basis for current pathophysiological concepts regarding serum sickness. After bupropion discontinuation and symptomatic treatment (antihistamine agents, with glucocorticoid therapy if needed), the urticaria and joint pain resolved consistently within a few days. The clinical and laboratory test evidence of type III hypersensitivity in these three patients are consistent with the few previous reports [3–7]. Type III hypersensitivity is listed in the French Drug Compendium as a “rare” adverse event (rate of occurrence between 1/1000 and 1/10 000). Case 4 is highly unusual in that it suggests a role for bupropion in the development of acute monoarthritis. Time
585
from bupropion initiation to symptom onset was 1 week. The clinical presentation suggested crystal deposition disease with an allergic component manifesting as eyelid edema. Antiinflammatory treatment ensured prompt resolution of the symptoms. Arguments supporting a role for bupropion were the temporal relationship between bupropion initiation and symptom onset, the eyelid edema, the absence of other causes, and the absence of recurrences. Joint symptoms ascribed to bupropion seem uncommon but fairly severe (particularly when serum sickness occurs). Given the growing popularity of this medication recently introduced in France, prescribing physicians should be alerted to the risk of severe hypersensitivity reactions so that they can inform their patients accordingly. Regarding the possibility that bupropion might induce arthritis, additional cases with longer follow-ups are needed to determine whether the single case reported here was an oddity or preliminary evidence of a clinically meaningful association. A useful step would be to look routinely for a history of bupropion therapy in patients presenting with acute monoarthritis.
References [1]
Masand P, Gupta S. Long-term side effects of newer-generation antidepressants: SSRIS, venlafaxine, nefazodone, bupropion and mirtazapine. Ann Clin Psychiatry 2002;14:175–82. [2] Vervaaeren J. Un nouveau médicament: le Bupropion. J Pharm Belg 2000;55:85–8. [3] Davis JS, Boyle MJ, Hannaford R, Watson A. Bupropion and serum sickness-like reaction. Med J Aust 2001;174:479–80. [4] Mc Collom RA, Elbe DH, Ritchie AH. Bupropion-induced serum sickness-like reaction. Ann Pharmacother 2000;34:471–3. [5] Peloso PM, Baillie C. Serum sickness-like reaction with bupropion. JAMA 1999;282:1817. [6] Wooltorton E. Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. CMAJ 2002;166:8. [7] Yolles JC, Armenta WA, Alao AO. Serum sickness induced by bupropion. Ann Pharmacother 1999;33:931–3. [8] Begaud B, Evreux JC, Jouglard J, Lagier G. Imputabilité des effets inattendus ou toxiques des médicaments. Thérapie 1985;40:111–8. [9] Benson E. Bupropion-induced hypersensitivity reactions. Med J Aust 2001;174:650–1. [10] Tripathi A, Greenberger PA. Bupropion hydrochloride induced serum sickness-like reaction. Ann Allergy Asthma Immunol 1999;83:165–6.