Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the literature the most frequently reported adverse reactions attributed to intravenous acetylcysteine administration were rash, urticaria and pruritus. The frequency of adverse reactions has been reported to be between 0.2% and 20.8%, and they most commonly occur during the initial loading dose of acetylcysteine.
Loading Dose/Infusion Rate Study
The incidence of drug-related adverse reactions occurring within the first 2 hours following acetylcysteine administration reported in a randomized study in patients with acetaminophen poisoning is presented in Table 5 by preferred term. In this study patients were randomized to a 15-minute or a 60-minute loading dose regimen.
Within the first 2 hours following intravenous acetylcysteine administration, 17% developed an anaphylactoid reaction (18% in the 15-minute treatment group; 14% in the 60-minute treatment group) in this randomized, open-label, multi-center clinical study conducted in Australia to compare the rates of anaphylactoid reactions between two rates of infusion for the intravenous acetylcysteine loading dose [see WARNINGS and Clinical Studies - Loading Dose/Infusion Rate Study (Section 14)].
Table 5: Incidence of Drug-Related Adverse Reactions Occurring Within the First 2 Hours Following Study Drug Administration by Preferred Term: Loading Dose/Infusion Rate Study
|Number of Patients||n=109||n=71|
|Cardiac disorders||5 (5%)||2 (3%)|
|Tachycardia NOS||4 (4%)||1 (1%)||2 (3%)|
|Gastrointestinal disorders||16 (15%)||7 (10%)|
|Nausea||1 (1%)||6 (6%)||1 (1%)||1 (1%)|
|Vomiting NOS||2 (2%)||11 (10%)||2 (3%)||4 (6%)|
|Immune System Disorders||20 (18%)||10 (14%)|
|Anaphylactoid reaction||2 (2%)||6 (6%)||11 (10%)||1 (1%)||4 (6%)||5 (7%)||1 (1%)|
|Respiratory, thoracic and mediastinal disorders||2 (2%)||2 (3%)|
|Throat tightness||1 (1%)|
|Skin & subcutaneous tissue disorders||6 (6%)||5 (7%)|
|Pruritus||1 (1%)||2 (3%)|
|Rash NOS||3 (3%)||2 (2%)||3 (4%)|
|Vascular disorders||2 (2%)||3 (4%)|
|Flushing||1 (1%)||1 (1%)||2 (3%)||1 (1%)|
Postmarketing Safety Study
A large multi-center study was performed in Canada where data were collected from patients who were treated with intravenous acetylcysteine for acetaminophen overdose between 1980 and 2005. This study evaluated 4709 adult cases and 1905 pediatric cases. The incidence of anaphylactoid reactions in adult (overall incidence 7.9%) and pediatric (overall incidence 9.5%) patients is presented in Tables 6 and 7.
Table 6: Distribution of reported reactions in adult patients receiving intravenous acetylcysteine
|Reaction||% of Patients (n=4709)|
Table 7: Distribution of reported reactions in pediatric patients receiving intravenous acetylcysteine
|Reaction||% of Patients (n=1905)|
|*Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm.|