Synopsis
Recognise drug-induced liver injury, manage paracetamol exposure through the current toxicology pathway, and prevent delayed antidote, rechallenge and acute liver failure.
- Drug-induced liver injury is a diagnosis of careful exclusion based on exposure, latency, biochemical pattern, dechallenge and competing causes; there is no single confirmatory blood test.
- Record prescription, non-prescription, herbal, bodybuilding, weight-loss, recreational and recently stopped products, with start dates, dose changes and last doses.
- Use the R ratio at first recognition to describe hepatocellular, cholestatic or mixed injury, but interpret laboratory upper limits and clinical context rather than relying on the label alone.
- Stop the suspected non-essential agent promptly in significant injury and avoid deliberate rechallenge when the prior reaction was serious.
- A single acute paracetamol ingestion with reliable timing can use the UK treatment nomogram from four hours; staggered, repeated or uncertain ingestions must not be plotted as one event.
- If more than eight hours have elapsed after a potentially toxic ingestion, start acetylcysteine while obtaining the concentration and advice because delay reduces protection.
- A low or undetectable late paracetamol concentration does not exclude established toxicity, and the nomogram does not determine treatment in a symptomatic late presenter.
- Report suspected serious or unusual adverse drug reactions through the MHRA Yellow Card scheme and give the patient a precise written avoidance plan.
Key red flags
ALT predominates relative to alkaline phosphatase and symptoms may include malaise, nausea, right upper-quadrant discomfort and jaundice. Severe cases can progress rapidly to coagulopathy and encephalopathy.
Fever, rash, facial oedema, eosinophilia, lymphadenopathy or other organ involvement suggests a hypersensitivity syndrome such as DRESS and needs urgent multispecialty assessment.
Nausea, vomiting or no symptoms can occur in the first day, so clinical wellness cannot replace timed concentration and toxicology assessment. Right upper-quadrant pain and rising ALT develop later.
Marked aminotransferases, INR prolongation, metabolic acidosis, lactataemia, hypoglycaemia, kidney injury and encephalopathy indicate severe toxicity even if the drug concentration is now low.
Multiple doses over more than an hour, therapeutic duplication or chronic excess creates unreliable timing and cannot be assessed with the single-ingestion nomogram; follow TOXBASE laboratory and treatment criteria.
Investigation priorities
Guide treatment after a single acute ingestion with reliable timing.
Management branches
One ingestion event with a reliable time and presentation before established hepatotoxicity.
- Establish exact time, amount, formulation, co-ingestants and body weight; assess self-harm risk and obtain a plasma concentration at or after four hours with baseline liver, renal and coagulation tests.
- If presentation is beyond eight hours after a potentially toxic dose, start acetylcysteine immediately while results are pending; otherwise use the current UK nomogram and TOXBASE treatment line.
- Prescribe the locally authorised acetylcysteine regimen using checked weight-based tables and independent calculation safeguards, monitoring closely for infusion reactions and fluid volume.
- At the defined endpoint, repeat required tests and continue acetylcysteine if the current stopping criteria are not met; seek NPIS or hepatology advice for any ambiguity.