Sa’ed H Zyoud1, Rahmat Awang1, Syed Azhar Syed Sulaiman2.

1 WHO Collaborating Centre for Drug Information, Clinical Toxicology Program, National Poison Centre, Universiti Sains Malaysia (USM), 11800 Penang, Malaysia. 2 Clinical Pharmacy Program, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), 11800 Penang, Malaysia.

Objectives: Intravenous N-acetylcysteine (IV-NAC) is widely recognized as the antidote of choice for acetaminophen overdose. However, its use is not without adverse drug reactions (ADR) which might affect therapeutic outcome or lead to treatment delay. The aims of this study were to investigate the type and incidence of ADR induced by IV-NAC in patients treated for acetaminophen overdose and to assess the causality of individual ADR to IV-NAC using Naranjo\\\'s algorithm. Methods: This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (January 1, 2004 to December 31, 2008). The primary outcome of interest in this study was the occurrence of ADR during NAC administration. The probability of an ADR was assessed using the Naranjo algorithm, which consists of ten questions, and has been used to determine the likelihood that an ADR was related to a specific medication. The Naranjo score takes into account other possible influences such as drugs or disease. The association scores were: ≥9 = “definite”, 5 to 8 = “probable”, 1 to 4 = “possible”, and 0 = “doubtful”. Results: During the study period, 305 patients with a diagnosis of overdose of paracetamol-containing compounds were admitted to the hospital for monitoring and treatment. Different types of ADR occurred in 137 patients (137/305; 44.9 %). Of those patients who had an ADR, 98 (98/137; 71.5 %) had been treated with IV-NAC and 39 (39/137; 28.5 %) had not (p < 0.001). Comparison of different ADR in all patients showed that the following ADR were significantly associated with IV-NAC administration: nausea (p = 0.004), vomiting (p < 0.001), flushing (p < 0.001), rash (p < 0.001), pruritus (p < 0.001), chest pain (p = 0.001), bronchospasm (p = 0.015), coughing (p = 0.017), headache (p < 0.001), dizziness (p < 0.001), convulsion (p = 0.035), and hypotension (p = 0.001). Based on Naranjo’s algorithm, 226 events were judged to be NAC related—31.1 % probably and 67.9 % possibly drug related. None of the events were definitely drug related.