BACKGROUND: Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear. METHODS: The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients. RESULTS: Adverse effects were minimal in 101 (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%), chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101 mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L), p = 0.002. Family history of allergy and female gender were independent risk factors for adverse effects. Severity of adverse effects was associated with histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60 to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p = 0.01). There was no increase in tryptase and no differences between groups for NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX, X, vWF, tPA, IL6, and CRP). CONCLUSION: Severity of adverse effects correlates with the extent of histamine release. Histamine release appears independent of tryptase suggesting a non-mast cell source. Acetaminophen is protective against adverse effects of NAC, and mechanisms by which acetaminophen might lessen histamine release require further attention.
BACKGROUND: Adverse effects to N-acetylcysteine (NAC) are well recognized, but their etiology and incidence are unclear. METHODS: The nature and severity of adverse effects were prospectively studied in 169 patients and potential reaction mediators studied in 22 patients. RESULTS: Adverse effects were minimal in 101 (59.8%), moderate in 51 (30.2%), and severe in 17 (10.1%). Features were nausea (70.4%), vomiting (60.4%), flushing (24.9%), pruritus (20.1%), dyspnea (13.6%), chest pain (7.1%), dizziness (7.7%), fever (4.7%), wheeze and bronchospasm (7.1%), and rash and urticaria (3.6%). Serum acetaminophen concentration was lower in patients with severe adverse effects: median (IQR) 46 mg/L (0 to 101 mg/L), moderate 108 mg/L (54 to 178 mg/L), and minimal 119 mg/L (77 to 174 mg/L), p = 0.002. Family history of allergy and female gender were independent risk factors for adverse effects. Severity of adverse effects was associated with histamine release: AUC for change from baseline histamine was -6 ng/mL min (-60 to 11 ng/mL min) in the minimal group, 26 ng/mL min (3-129 ng/mL min) in the moderate group, and 49 ng/mL min (21-68 ng/mL min) in the severe group (p = 0.01). There was no increase in tryptase and no differences between groups for NAC concentrations or hemostatic and inflammatory variables (factors II, VII, IX, X, vWF, tPA, IL6, and CRP). CONCLUSION: Severity of adverse effects correlates with the extent of histamine release. Histamine release appears independent of tryptase suggesting a non-mast cell source. Acetaminophen is protective against adverse effects of NAC, and mechanisms by which acetaminophen might lessen histamine release require further attention.
Authors: Kerry Layne; Louise Hope; Edmund Rab; John Archer; David M Wood; Paul I Dargan Journal: Br J Clin Pharmacol Date: 2018-11-08 Impact factor: 4.335
Authors: George P Bailey; Javad Najafi; Muhammad E M O Elamin; W Stephen Waring; Simon H L Thomas; John R H Archer; David M Wood; Paul I Dargan Journal: Br J Clin Pharmacol Date: 2016-08-10 Impact factor: 4.335
Authors: Mark Yarema; Puja Chopra; Marco L A Sivilotti; David Johnson; Alberto Nettel-Aguirre; Benoit Bailey; Charlemaigne Victorino; Sophie Gosselin; Roy Purssell; Margaret Thompson; Daniel Spyker; Barry Rumack Journal: J Med Toxicol Date: 2018-02-08
Authors: George P Bailey; David M Wood; John R H Archer; Edmund Rab; Robert J Flanagan; Paul I Dargan Journal: Br J Clin Pharmacol Date: 2016-09-29 Impact factor: 4.335