The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases.

OBJECTIVE: The use of the standard procedure for managing overdoses with immediate release (IR) paracetamol is questionable when applied to overdoses with modified release (MR) formulations. This study describes the pharmacokinetics of paracetamol and the clinical outcomes following overdoses with a MR formulation. METHODS: Medical records including laboratory analyses concerning overdoses of MR paracetamol from 2009 to 2015 were collected retrospectively. Inclusion criteria were ingestion of a toxic dose, known time of intake and documented measurements of serum paracetamol and liver function tests. Graphical analysis, descriptive statistics and population pharmacokinetic modelling were used to describe data. RESULTS: Fifty-three cases were identified. Median age was 26 years (range 13-68), median dose was 20 g (range 10-166) and 74% were females. The pharmacokinetic analysis showed a complex, dose dependent serum versus time profile with prolonged absorption and delayed serum peak concentrations with increasing dose. Ten patients had persistently high serum levels for 24 h or more, six of them had a second peak 8-19 h after ingestion. Seven of 34 patients receiving N-acetylcysteine (NAC) within 8 h had alanine aminotransferase (ALT) above reference range. Three of them developed hepatotoxicity (ALT >1000 IU/l). DISCUSSION AND CONCLUSIONS: The pharmacokinetic and clinical analysis showed that the standard treatment protocol, including risk assessment and NAC regimen, used for IR paracetamol poisoning not appear suitable for MR formulation. Individual and tailored treatment may be valuable but further studies are warranted to determine optimal regimen of overdoses with MR formulation.

Increased availability of paracetamol in Sweden and incidence of paracetamol poisoning: using laboratory data to increase validity of a population-based registry study.

PURPOSE: To estimate the incidence trend and outcome of paracetamol poisoning, in relation to increased availability of paracetamol from non-pharmacy outlets in 2009. METHOD: Patients' serum paracetamol results over 14 years (2000-2013) from 20 (out of 21) regions in Sweden were linked to national registers of hospital care, cause of death, and prescriptions. Paracetamol poisonings were defined by serum paracetamol levels, hospital diagnoses, or cause of death. The change in incidence of poisonings following increased availability of paracetamol was analysed by using segmental regression of time series. RESULTS: Of the 12 068 paracetamol poisonings, 85% were classified as intentional self-harm. Following increased availability from non-pharmacy outlets, there was a 40.5% increase in the incidence of paracetamol poisoning, from 11.5/100 000 in 2009 to 16.2/100 000 in 2013. Regression analyses indicated a change in the trend (p < 0.0001) but not an immediate jump in the incidence (p = 0.5991) following the increased availability. Adjusting for trends in hospital episodes for self-harm, suicides, and the sales volume of paracetamol did not influence the result. All-cause mortality at 30 days (3.2%) did not change over time. CONCLUSIONS: The incidence of paracetamol poisoning in Sweden has increased since 2009, contrasting the decreased incidence in the period of 2007-2009. The change in trend was temporally associated with the introduction of availability of paracetamol from non-pharmacy outlets but did not appear to be related to sales volume of paracetamol or general trends in self-harm or suicides. © 2017 Commonwealth of Australia. Pharmacoepidemiology and Drug Safety © 2017 John Wiley & Sons, Ltd.

[Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre]. / Överdosering av paracetamol med modifierad frisättning ökar - Etablerad behandlingsregim med N-acetylcystein otillräcklig ­ Giftinformationscentralen ger ut nya behandlingsråd.

Overdose of modified-release paracetamol calls for changed treatment routines. New guidelines from the Swedish Poisons Information Centre  The sales of modified-release paracetamol tablets are steadily increasing in Sweden as are the number of overdose cases with this formulation. The Swedish Poisons Information Centre has noted that the standard treatment protocol with N-acetylcysteine (NAC), which is based on overdoses with immediate-release paracetamol formulations, is often inadequate in this setting. In this paper, an adult who overdosed on 66.5 grams of modified-release paracetamol tablets and developed severe liver impairment (max ALT 6,660 U/l) despite timely and rigorous NAC treatment is presented. The patient's peak S-paracetamol of 2,800 µmol/l was delayed to 19 hours post-ingestion. Moreover, a pharmacokinetic and clinical study of similar cases showed that seven (21%) of the 34 patients who received NAC treatment within 8 hours after ingestion developed liver impairment. Finally, new Swedish guidelines for management of these cases are presented. The guidelines are also available on www.giftinfo.se.

Gender differences in secondary prevention of coronary heart disease: reasons to worry or not?

OBJECTIVE: To analyse potential gender differences in cardiovascular risk factors and treatment patterns, reflecting clinical practice in secondary prevention. DESIGN: Observational national study during 3 years of patients eligible for secondary prevention of coronary heart disease (CHD). SETTING: Fifty-two healthcare districts in Sweden, involving primary health care and hospitals in collaboration, participating in a national quality assurance programme for the prevention of CHD. SUBJECTS: A national sample of male and female patients surviving acute myocardial infarction, or following CABG/PTCA interventions for CHD, controlled at 3-6 months (n = 9135) and 12 months (n = 4802) of follow-up. The proportion of female patients (25%) did not differ between visits. MAIN OUTCOME MEASURES: Self-reported data on lifestyle, drug treatment and cardiovascular risk factor levels after consultation in general practice or at hospital policlinics. RESULTS: No major gender differences were recorded in risk factor levels or in cardiovascular drug treatment patterns at 12 months of follow-up. Female patients participated in educational programmes to improve lifestyle to a higher degree than males (52.0 vs 45.1%), but after 1 year were more often (p < 0.001) self-reported smokers (11.7 vs 8.4%). Female patients showed higher levels of blood pressure, total cholesterol and HDL cholesterol, but not LDL cholesterol compared to male patients. CONCLUSIONS: In general, a gender-equal level of lipid control and access to medical drug treatment has been established for patients in secondary prevention from a national sample in Sweden, followed for 1 year after CHD manifestations and related interventions.