Evidence into Practice: Paracetamol toxicity' a focus on the process

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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

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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

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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

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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

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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 gt3 standard drinks per
  day (gt30g/day)
• Concurrent use of drugs that induce CYP450 eg
  isoniazid, carbamazepine
• Small body mass
• Sepsis

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Lubel JS, Angus PW, Gow PJ. Accidental
paracetamol poisoning. Med J Aust 2007 186(7)
371-2

• Normal healthy patient
• Most conjugated excreted
• Small amount metabolised by CYP450 to NAPQI
  (liver toxin)
• Conjugated excreted
• Prolonged starvation
• Co-substrates for conjugation depleted
• Glutathione stores depleted
• NAPQI accumulates
• Alcohol other CYP450 inducers
• Increase production of NAPQI
• Chronic alcohol depletes glutathione

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What dont 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?

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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, n389)
• Paracetamol dose ordered administered
• Risk factors
• Liver function tests
• Data currently being analysed

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Initial data on risk factors (n389)
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What dont 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

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Not the whole answer!

• Experience dictates leakage from system due to
  borrowing
• Wont stop inappropriate oral dosing
• Important role for education by ward pharmacists
• Medication safety requires approaches from a
  number of angles

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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