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MELBOURNE HEALTH Evidence into Practice: Paracetamol toxicity. (a focus on the process) Kirstie Galbraith Clinical Senior Lecturer, Victorian College of Pharmacy, Monash University Senior Pharmacist, Research & Education, RMH What do we know? • Paracetamol perceived to be a “safe” drug in normal therapeutic doses • Known to be dangerous in overdose – Fulminant hepatic failure • Many forms of oral paracetamol available – Potential for accidental overdose 2 What do we know? • Intravenous paracetamol relatively new on market – Approved for restricted use at MH in Nov 2004 – Maybe exposing a new populations of patients who are “nil orally” & potentially at risk of toxicity – Significantly more expensive than oral/rectal • Quantities of IV paracetamol being dispensed indicates significant usage without approval from Pain Service 3 What do we know? • 2004: 2 deaths at RMH due to liver toxicity associated with therapeutic doses of paracetamol – Both malnourished & underweight – Prescribed paracetamol up to 4g/d but no accurate record of doses administered (not at MH) • Presented at Medications Safety Week Dec 2005, Grand Round 2006, InphaRMHation Jan 2007 • Presentation at SHPA by Paul Gow (Austin) – Publication of paper in MJA 2007 4 What do we know? • Suggested risk factors for paracetamol toxicity (where reduced dosing should be considered): – Prolonged fasting or “nil oral” patients – Malnourished patients – Prolonged duration with risk of accumulation – Elderly patients with renal & cardiopulmonary insufficiency – Acute hepatitis of any cause – Chronic liver disease including cirrhosis – Regular alcohol intake of >3 standard drinks per day (>30g/day) – Concurrent use of drugs that induce CYP450 eg isoniazid, carbamazepine – Small body mass – Sepsis 5 Lubel JS, Angus PW, Gow PJ. Accidental paracetamol poisoning. Med J Aust 2007; 186(7): 371-2 A. Normal healthy patient • Most conjugated & excreted • Small amount metabolised by CYP450 to NAPQI (liver toxin) • Conjugated & excreted B. Prolonged starvation • • Co-substrates for conjugation depleted • Glutathione stores depleted • NAPQI accumulates Alcohol & other CYP450 inducers • Increase production of NAPQI • Chronic alcohol depletes glutathione 6 What don’t we know? (Our knowledge gaps) • In patients admitted to The Royal Melbourne Hospital, is paracetamol being prescribed appropriately taking into account potential risk factors for hepatotoxicity? • Are doctors at The Royal Melbourne Hospital seeking appropriate approval to prescribe intravenous paracetamol according to DTC restrictions? 7 Filling our knowledge gaps • In patients admitted to The Royal Melbourne Hospital, is paracetamol being prescribed appropriately taking into account potential risk factors for hepatotoxicity? – Audit undertaken recently (1 day, n=389) > Paracetamol dose ordered & administered > Risk factors > Liver function tests > Data currently being analysed 8 Initial data on risk factors (n=389) Risk Factor Number at risk Number ordered at least 4g/d Number administered at least 4g/d Weight <50kg 19 18 2 Malnourished 9 9 1 Acute hepatitis 5 5 2 Nil orally > 3 days 8 7 4 >3 drinks per day 11 9 5 9 What don’t we know? (Our knowledge gaps) • Are doctors at The Royal Melbourne Hospital seeking appropriate approval to prescribe intravenous paracetamol according to DTC restrictions? – Anecdotally NO! – Being included in iApprove to streamline use according to approved indications & durations 10 11 12 13 14 Not the whole answer! • Experience dictates leakage from system due to borrowing • Won’t stop inappropriate oral dosing – Important role for education by ward pharmacists • Medication safety requires approaches from a number of angles 15 MELBOURNE HEALTH Evidence into Practice: Paracetamol toxicity. (a focus on the process) Kirstie Galbraith Clinical Senior Lecturer, Victorian College of Pharmacy, Monash University Senior Pharmacist, Research & Education, RMH