Low rates of hepatotoxicity among Asian patients with paracetamol overdose: a review of 1024 cases.

BACKGROUND: The metabolism of paracetamol in Asians is thought to differ from Westerners. Detailed clinical features of paracetamol -induced hepatotoxicity among Asians remains largely unreported. METHODS: A retrospective review of adult cases with paracetamol overdose over a five-year duration was performed in two of the largest public institutions in this country. Prevalence and predictive factors for hepatotoxicity were determined. RESULTS: Data on 1024 patients (median age 23 years, 82.0% female, ethnic groups: Malays 40.8%, Chinese 20.9% , Indian 33.2%) were obtained from January 2005 to December 2009. The median amount of paracetamol ingestion was 10.0 (IQR 5.0 - 15.0) g and the median serum paracetamol level was 274.80 (IQR 70.0 - 640.0) µmol/L at presentation. 75 (7.3%) patients developed hepatotoxicity. 23/ 55 (41.8%) patients who had ingested > 10 g of paracetamol and had a delayed (> 24 hour) administration of N-acetyl cystine (NAC) developed hepatotoxicity. No patients developed acute liver failure nor suffered any mortality (0%). Independent predictors for hepatotoxicity were identified as Malay (OR 2.22, 95% CI = 1.13-4.37) and Chinese (OR 3.26, 95% CI = 1.55-6.84) ethnicity, paracetamol dose > 10 g (OR 2.61, 95% CI = 1.53-4.46), prolonged duration of time from paracetamol ingestion to hospital presentation (> 24 hours OR 10.71, 95% CI = 3.46-33.15) and prolonged duration of time from paracetamol ingestion to NAC administration (> 24 hours OR 9.02, 95% CI = 2.97-27.45). CONCLUSIONS: Paracetamol-induced hepatotoxicity rates in a multi-ethnic Asian population was low at 7.3%. Mortality and morbidity were non-existent despite high doses of paracetamol ingestion and delayed presentations to hospital.

Effectiveness of open-label losartan/hydrochlorothiazide combination therapy in Asian patients with hypertension not controlled with ACE inhibitor or ARB monotherapy.

Antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been adequately studied in Asians. In this open-label, 12-week study in seven Asian areas, patients on monotherapy with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) but not at blood pressure (BP) goal (sitting diastolic BP (SiDBP) <90 mm Hg in non-diabetics and <80 mm Hg in diabetics) were switched to losartan 50 mg/HCTZ 12.5 mg. At 4 and 8 weeks, the therapy for patients not at goal BP was titrated to losartan 100 mg/HCTZ 12.5 mg and to losartan 100 mg/HCTZ 25 mg, respectively. Data analysis included 430 patients with mean (s.d.) age 53.0 (10.1) years and 51.9% of the female gender. After 8 weeks (primary end point; titration up to losartan 100 mg/HCTZ 12.5 mg), 73.5% (95% confidence interval (CI): 69.0-77.6) of patients reached BP goal; 63.4 and 78.1% of patients reached BP goal at 4 weeks (titration up to losartan 50 mg/HCTZ 12.5 mg) and at 12 weeks (titration up to losartan 100 mg/HCTZ 25 mg). The mean changes from baseline (95% CI) in sitting systolic BP and SiDBP at 8 weeks were -16.7 (-18.0 to -15.4) mm Hg and -12.1 (-12.9 to -11.4) mm Hg, respectively. Clinical and laboratory adverse experiences (AEs) were reported in 27.5 and 21.0% of patients, respectively. Nine patients were discontinued because of drug-related clinical AEs. Switching Asian patients currently not at BP goal with ARB or ACEI monotherapy to a losartan/HCTZ combination achieved BP goal in the majority of patients. Losartan/HCTZ combinations were generally well tolerated.