Saturday 27 June 2015

Paracetemol - the hidden dangers

Paracetamol – that seemingly most innocuous of pain killers - is sold under various brand names such as Panadol and in the USA, Tylenol.

Almost everyone has some form of paracetamol in the house and most people take it at some time for all manner of issues – from colds and ‘flu to a hangover. It's the primary ingredient in the popular children's medicine, Calpol.

Paracetemol – along with various forms of non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen – is stocked by supermarkets, the corner dairy and petrol stations.  NZ is the only country in the world, other than the USA, in which pharmaceutical drugs are advertised on television – often by people who are presented as medical experts.

The fine print on a packet of 500 mg Panadol pills sold in New Zealand tells you that it’s safe to take up to 4 grams a day (eight pills) for 4 days at a time but, if symptoms persist, to consult a doctor. The fact that doctors in NZ frequently prescribe the maximum daily dose of paracetamol for 3 months at a time (720 pills) goes a long way to undermining the seriousness of that piece of advice from the manufacturers.

I don’t know the number of prescriptions for paracetamol written by doctors in NZ in a year, or how many paracetamol pills and remedies containing it are bought in over the counter annually but, according to an article in the Guardian, in the UK in 2013 doctors wrote 22.5 million prescriptions for it and around 200 million packets were sold over the counter – two-thirds of all the OTC painkillers sold. 

In the USA around 25 billion doses are sold annually.

It's a fairly safe bet that the majority of elderly people in New Zealand, especially those in rest homes, are on a persistent, maximum daily dose of the drug.

In the UK, a 2007 study found that 84% of babies are given Calpol in their first 6 months of life.

Paracetamol is the most widely prescribed and purchased analgesic in the world because it is very cheap and, compared to the dangers of long term use of the alternatives - steroids, non-steroidal anti-inflammatories (NSAIDs) and opiates, it’s considered to be fairly safe. 

But is it?

The National Institute for Health and Care Excellence (NICE) in the UK issued guidelines in 2013 urging doctors to review the prescription of paracetamol for osteo-arthritic pain but these were withdrawn after agitation from interested parties, notably the Royal College of General Practitioners.

The pharmacentric, symptomatic, pain elimination paradigm that most conventional health professionals are locked into, creates and maintains the patient expectation that, if you are ill or in discomfort, you are prescribed a drug. For doctors confronted with that well established expectation, paracetamol is the reliable old workhorse that they think they can put just about any patient on without fear of them being harmed.

The trouble is that the reliable old workhorse may not be the bullet proof, safe old nag its manufacturers claim and medical professionals believe it is.

Paracetamol causes more deaths world-wide from overdose than any other drug. It is the most common cause of poisoning in children in NZ and it is the single most common cause of acute liver failure in the USA, Australasia and Europe.  Five children a day are admitted to hospital in the UK suffering from paracetamol poisoning.

In overdose - the consumption of more than the recommended maximum adult daily dose  - it can be acutely hepatoxic. A paracetamol overdose that is not treated quickly enough to halt the production of the toxic metabolite NAPQ1, will result in liver damage and may result in acute liver failure and death.

It is also very easy to overdose as paracetamol is an ingredient in most flu and cold remedies, which may be taken at the same time as pills. It is a common cause of overdose in children because the medicines containing it are heavily sweetened and brightly coloured like confectionary.

For people with impaired liver function due to alcohol consumption, or genetic conditions like Gilbert’s Syndrome, or who are on certain barbiturates such as phenobarbitone, or who are malnourished, or have suffered  a recent illness - as little as 5 grams in a day can be acutely hepatoxic.

Even in therapeutic doses, people on long-term maximum doses of the drug suffer impaired liver function although there is no consensus on the clinical significance of this.  But, liver disease is frequently asymptomatic and even quite severe liver damage can be missed by physicians or attributed to factors other than paracetamol use.

IIn NZ the pills sold or prescribed for adult consumption are typically 500mg with no more than 4 grams to be ingested in a given 24 hour period.  In the USA, the recommended oral dose of the drug is 660-1000mg every 4-6 hours not to exceed 3 grams in a 24 hour period. The Food and Drug Agency (FDA) in the USA has also lowered the maximum pill dose to reduce risk of accidental overdoses. Although it is a small reduction given the amounts being prescribed and sold, it is in an indication that some health watchdogs are starting to wake up to the dangers posed by the ubiquity of the drug and the false perception that it is very safe. 

Whilst the toxicity of the drug in overdose is well documented, there’s not as much known about its effects in very long-term use at high doses. Given how many people with chronic pain are prescribed the drug at maximum dose persistently, this absence of data and the apparent lack of concern from health professionals is worrying.

A 2011 UK study concluded that 1 in 5 people who used paracetemol for chronic pain lost blood through internal bleeding, the same proportion of NSAID users in the study. Older people may be more sensitive to GI tract irritation because of a general thinning of tissue, so the fact that most older people in NZ with chronic pain are on long term maximum doses of paracetamol, is very worrying.

Also of concern, are studies that indicate the drug is not very effective at reducing musculo-skeletal pain. If this is the case, the gastro-intestinal, cardio-vascular, hepatic and renal risks make its widespread, long-term, high dose use for chronic musculo-skeletal pain, untenable.

All drugs have to be metabolised and all drugs have effects on the gastro-intestinal tract and the metabolic organs other than the desired effect. The problems associated with chronic high dose paracetamol use may be compounded by the fact that it is often used in conjunction with a range of other drugs. 

The more fragile the person, the more likely it is that there will be side effects and that those side effects may well outweigh any benefits of the drug. 

It’s also logical that, what is reckoned to be a safe dose of any given drug, is not a constant – it varies between individuals and any given person’s tolerance levels may change over time, and may change very quickly.



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