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No cure for pain: study links excess paracetamol use to fatal liver damage

Life-threatening liver damage can occur without the intention of self harm in desperate patients trying to get some relief for pain. Melissa Baldwin

Medicines need not only to be effective but also safe. Now a Scottish study has shown that paracetamol, perhaps the most commonly consumed painkiller in the country, could lead to death if taken in large doses over a period of time.

In the last couple of days, we’ve also heard other adverse information about widely used painkillers, which raises concerns about the dwindling pool of available medicines for pain. And now it seems patients being led to apparently safer alternatives may be risking their lives.

Although the number of individual pain relieving medications on the market is very large, they all come from only a very small number of drug classes. We have the familiar paracetamol and aspirin, another group called the non-steroidal anti-inflammatory drugs (NSAIDS), opioids and adjuvant drugs, which include antidepressants and anti-epileptics.

Earlier this week, the Australian drug regulator, the Therapeutic Goods Administration (TGA), announced it would be removing four products containing dextropropoxyphene – Capadex, Di-Gesic, Doloxene and Paradex – from the market by March 1.

The withdrawal follows adverse assessments from US and European regulators because of concerns about causing ECG changes, which could lead to cardiac arrest.

However, some years ago, when the availability of such drugs was severely restricted in the United Kingdom, patients flooded back to their doctors because they weren’t able to get comparable relief from other products.

Painkiller safety issues

There’s increasing concern over the long-term safety of the opioids. The adverse effects of NSAIDS on the gastrointestinal and cardiovascular systems has been widely reported in the mainstream press. These effects have been the reason for high profile withdrawals, such as that of Merck’s Vioxx.

Aspirin is not used for pain very much given its well-recognised potential to cause ulcers and bleeding the gastrointestinal tract. So doctors like myself frequently advise patients to return to the ubiquitous and everyday paracetamol. At recommended doses paracetamol is remarkably safe although it’s known that even moderate excess can cause fatal hepatotoxicity or overdose death.

Dennis Wegner

As many of these overdoses have traditionally been impulsive, major reductions in mortality in the United Kingdom were brought about by the simple step of reducing pack size.

So doctors are familiar with advising patients not to exceed the recommended dose of 8 tablets a day. But an article published yesterday in the British Journal of Clinical Pharmacology has shown that inadvertent “overdoses” from consuming large quantities over a period of time in an attempt to control pain cause also cause life-threatening liver damage.

Paracetamol study

The authors of the paper looked at data from a large university-linked referral unit where patients showing probable or suspected paracetamol hepatotoxicity were treated. They compared patients with a typical “single overdose”, with patients who’d taken large doses of paracetamol over a period of a few days and suffered a “staggered overdose”.

The major reason for the single overdose was attempted suicide. But this was only the motive in one-third of the patients who had a staggered overdose. The majority of these people had simply been seeking pain relief.

Somewhat surprisingly, the average total dose in the staggered group (24 grams) was less than that in the single overdose (27 grams). And of greatest concern is that the minimum dose in the staggered group was 10 grams, which is only 20 tablets.

Clearly, the key message here is that life-threatening liver damage can occur without the intention of self harm in desperate patients trying to get some relief for pain.

Taking care

Although people recognise that the number of pills they can take at any given time may not be safely increased, they may take the drug at more frequent intervals than recommended, losing track of cumulative dose and unintentionally putting themselves at risk.

Unfortunately, it seems therapeutic options are being reduced by safety concerns – perhaps appropriately – but even the drugs thought to be relatively safe may unintentionally be posing a risk.

The key to preventing the problem of staggered paracetamol overdose is education and we are fortunate in Australia to have an organisation such as National Prescribing Service (NPS), which is best placed to do this.

We also need education about how medicines may not produce adequate analgesia and that other approaches are needed. Ideally, a mixed approach will enable doctors to help patients manage their pain in the face of the shrinking number of safe therapeutic options.

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