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General Points

  1. The US believes a high proportion of paracetamol associated hepatoxicity cases is caused by unintentional overdoses. That view differs to the UK understanding where direct research, particularly by Professor Hawton's group at Oxford, shows that almost all paracetamol overdoses are intentional.

    The US view appears to be based on patient reports and may not stand up to robust investigation.

    The FDA working group recommendations are based largely on reducing such accidental overdoses - these are very infrequent in the UK and the FDA approach would not be suitable for the UK situation.

    The causes of the apparent accidental overdoses in the US are unknown and the proposals have therefore adopted a scatter gun approach to cover all possibilities, without any hard data on the causes or circumstances of the reported overdoses.

  2. The FDA states that toxicity of paracetamol when misused is not a reason to discourage its proper use.

  3. The FDA does not want paracetamol use to be replaced by NSAID use because of the potential toxicity of NSAIDs.

  4. The FDA does not want to adopt the UK approach (the 1998 legislation on pack sizes) because they cannot separate the effect of pack size legislation from the effect of restriction on numbers of tablets per sale. This is puzzling as they are advocating a multifactorial approach themselves.

Sales restriction is not legally an option in the USA, although it has been judged successful in the UK.

Specific Recommendations Suggested by the FDA WGR

  1. Improve labelling: The FDA suggestions for health warning and package labelling are simply catching up with that already implemented in the UK. (Except that they include an alcohol warning, considered inappropriate in the UK.) In the US, consumers are often not aware of the active component in their medicine as paracetamol is referred to by a number of different names. That does not apply in the UK where all medicines containing paracetamol are clearly labelled as such.

  2. Limit Maximum Adult Daily Dose, and Limit Tablet Strength and Single Adult Dose: The FDA recommendation for reducing the adult maximum daily dose from 4g to 3.25g is based on reports of liver injury where the dose ingested was close to the recommended dosage. Such cases have largely been discredited in the UK and measured blood levels preferred as evidence to patient histories which can be unreliable, and which are the main source of low dose toxicity reports.

    The WGR recommended lower tablet strength and single dosage may well be less effective at pain relief and could lead to increased cases of patients deliberately taking more than the recommended dosage in a bid to increase therapeutic benefit. This would therefore be counterproductive.

  3. Limit Options in Liquid Paediatric Formulation: The limitation on paediatric liquid formulation would appear to have no basis in toxicity reports. Paracetamol overdosage in patients below the age of 12 is very rare.

    Although in the UK the fear of accidental overdosing in children leads to a high number of questions to help lines and A & E centres by parents, it is rare that any child requires treatment. The National Poisons Information Service states that paracetamol poisoning with children's liquid preparations is rarely serious.

  4. Eliminate Combination Products: The elimination of all combination products is a very blunt approach. In the UK the combination product implicated in serious overdosage (coproxamol) was identified and withdrawn individually leaving other useful combination products available to the public. The FDA WGR acknowledges that they have very little data on whether combination products may have been implicated in their liver failure reports, and have no data on which combinations, if any, may have caused toxicity. Many patients and consumers value the use of combination products and to withdraw them without any evidence appears to be an unnecessary hardship.

In general the FDA WGR have taken a very broad, catch all approach that in their own admission is not based on good data, but appears to be a 'try everything and hope some of it works' approach.