From John Ray's shorter notes

Bex and the demonization of APCs

April, 2010

Grouch and grumble: Bring back Bex

I am a terrible skeptic. I don't believe in Jesus Christ, Mohammed, Karl Marx, Barack Obama, global warming, the benefits of a low-fat diet or the evils of obesity. And I put plenty of salt on my fries. So I guess it should be no surprise that I don't believe in the evils of Bex either -- though I know that that is going to raise a few eyebrows.

Let's start from the present: If you have got aches and pains these days, your doctor will always recommend paracetamol (acetaminophen) -- because it is "safer" than apririn. That paracetamol can destroy your liver while aspirin only causes microscopic stomach bleeding seems not to be considered.

Australia used to have an over-the-counter pharmaceutical called Bex, which was hugely popular in Australia, particularly among Australian women. It contained aspirin, phenacetin and caffeine. Everybody knows about two of those ingredients but guess what phenacetin was? It was a analgesic known since the 19th century which broke down in your body to -- wait for it -- paracetamol.

But the do-gooders condemned Bex because it was so popular. It was so popular that some people would go through a whole box (12 powders) in a couple of days. There were labels on the packet telling you not to do that -- saying that long-term heavy usage was harmful but what the heck!

The particular harm that Bex did was thought to come from the phenacetin: A tiny percentage of users -- very heavy users -- got kidney failure and Australia had the world's highest incidence of kidney failure. So the Becker company was told to convert their powders to aspirin only.

The customers however thought that the new Bex was "not the same" so stopped buying it and it is no longer produced. So what's the problem with that?

One problem is that many Bex users went onto Valium instead -- with its attendant risk of making you drowsy when you're driving. So did the ban on Bex kill people in road accidents? Probably.

But the main problem is that something was taken away from people which they found very beneficial -- all because a tiny minority misused it. You can misuse anything by taking it in excess -- even water can kill you if drink too much of it. Google "hyponatremia" if you doubt it. So should we ban water? They would if they could, I suspect.

So why did Australian housewives like Bex so much? Because it gave them a small lift while taking their aches and pains away. They would come home from their shopping, make themselves a cup of tea, take a Bex then have "a good lie down". And after their nap they would wake up refreshed ready to deal with the rest of the day.

That was however only one use of Bex. You basically took Bex for ANY aches and pains. It kept a lot of people away from the doctor when they had colds and flu, for instance.

And a VERY important use of Bex was as an early treatment for what is still a dreaded and all too common ailment: migraines. Migraine sufferers generally get some warning when a migraine is due to strike, an aura, jaw stiffening etc. And as soon as anybody prone to migraines felt the slightest suspicion that one was about to strike, they would grab their nearby packet of Bex and slam one into themselves quick smart. And it did help. If you got the Bex into yourself straight away, the migraine would either not develop or would be less severe than a full-blown attack.

I know an old lady now in her 90s who was prone to migraines in her youth (migraines in women tend to stop after menopause) and she took a LOT of Bex. AND THERE IS NOTHING WRONG WITH HER KIDNEYS. She would hardly be around at age 92 if there were. So let me note again that it was only a tiny minority of Bex users who got problems from it.

It is true that soluble aspirin can also help with migraines if you take it quickly enough but I suspect that Bex did a better job. I am of the Bex generation. I took it on rare occasions when I had a headache (which I rarely do). And I certainly remember fewer complaints about migraines back then than I hear now. That's pure anecdote of course and Bex probably didn't help all migraine sufferers, but why not test it out properly? Nobody seems to have done so. The simple-minded do-gooders who always know better than ourselves what is good for us just banned it.

Now here's the final kicker: Something that is often prescribed for aches and pains these days is NSAIDS (Ibuprofen etc.). And guess what is a major side effects of NSAIDS? Kidney damage. NSAIDS are hundreds of times more toxic to the kidneys than Bex ever was. So let's ban NSAIDS!

Sometimes the wisdom of the past WAS better than the wisdom of the present

UPDATE: I suspected that APC preparations such as Bex and Vincent's were not unique to Australia but could find no mention of it. The following comment from a reader does however confirm my speculation:
"Bex... It contained aspirin, phenacetin and caffeine"

Ah yes, the APC pill. I first encountered them when I enlisted in the US Army, 1965. Wonderful, knocked out a headache in fifteen minutes vs the sixty-to-ninety of plain aspirin.

While a prescription drug outside the Armed Services, they were handed out by orderlies more readily than a stick of chewing gum. Now entirely illegal to manufacture in combination.

The great Phenacetin folly

Phenacetin was once a widely used pain-relieving drug that was particularly good at relieving rheumatoid arthritis (joint pain caused by an autoimmune reaction). It was once widely used as one of the drugs in APCs (compounds of aspirin, phenacetin and caffeine) but it is now banned from most applications -- for very dubious reasons.

There is NO double-blind evidence that I can find showing that phenacetin is harmful in humans -- but there is certainly strong epidemiological evidence that heavy use over very long periods does do some harm to a small minority of people -- causing kidney failure in extreme cases. So it has been banned from most pharmaceutical use and is no longer available in "over the counter" (OTC) medications such as APCs.

It is however an excellent analgesic (pain reliever) and antpyretic (it reduces temperatures when you have a fever). It is also now in some parts of the world widely used as an illegal drug as part of street cocaine!

The definitive study of the evils of phenacetin appears to be this one. It is a 20 year follow-up of 1244 women, half of whom were regular phenacetin users and half of whom were not. Keep that "20 year" figure in mind. At the end of the period 12% of the phenacetin users had died, versus 4% of the control group. The logic then is that phenacetin killed 8% of its regular users over a 20 year period

It is however flawed logic. The study was epidemiological, not experimental. So why were the women regularly taking phenacetin in the first place? Obviously because they had a lot of aches and pains. So is it at all surprising that, over a 20 year period, women with lots of aches and pains were 8% more likely to die than women who did not have lots of aches and pains?

Among the 74 phenacetin users who died, however, there was an exceptionally high incidence of kidney disease so the reasonable assumption was made that phenacetin did that. But wait a minute there too: The comparative incidence of kidney disease among users was much higher than the incidence of death! What does that mean? It would seem to mean that, although phenacetin was bad for the kidneys in a small minority of women, it also had some health-protective effects elsewhere. It was very bad for the kidneys of some women but good for preventing other causes of death.

With such evidence in mind, the normal, logical course of action would be to allow continued use of phenacetin but periodically monitor its effect on the kidneys of those using it. Its damaging effect on the kidneys is obviously so slight in normal usage that it develops only over long periods so annual (say) testing should provide a sufficient warning to the minority whom it might be harming. Instead of such a rational approach, however, phenacetin has been banned outright in most countries.

Let us compare that logic with the logic governing the use of another class of painkillers -- NSAIDS such as Naproxen -- sold over the counter in the USA as Aleve and in the UK as Feminax. I won't bore you with the very long list of names under which NSAIDS are sold, but, whatever you are using, you should look it up -- as we shall see: NSAIDS can give you acute kidney failure within 30 days of taking it. Forget 20 years, think 30 days! So which would you rather be taking? Phenacetin or NSAIDS?

I will leave that question hanging in the air as mute testimony to the insanity of modern medical regulations. Bring back phenacetin!

But wait! There's more (as the steak knife salesmen used to say)! As I pointed out, the evidence mentioned above is epidemiological and, as such, is heavily reliant on inferences and assumptions ("guesswork", to be blunt). What about direct experimental evidence? Remember the role of phenacetin in APCs as I leave you with this little gem from 1967:
"Dr. Laurence F. Prescott, who was doing clinical investigation at Johns Hopkins University, tested four ingredients in widely used analgesics, alone and in combination. He reported in The Lancet that healthy volunteers who took ten aspirin tablets a day began to excrete damaged kidney cells, reflecting at least temporary kidney injury. Surprisingly, this effect was less marked with APCs. It was also less conspicuous when he tested phenacetin alone, and still less so with medicinal caffeine. Dr. Prescott's conclusion: phenacetin alone is not the primary villain in analgesic kidney damage."

The deeper I get into the evidence on this, the worse it looks.

I would attempt to draw all this to the attention of the FDA but I know better than to waste my time banging my head on the defensive brick wall of a vast bureaucracy -- all the more so now that President Obama has appointed two highly politicized people to run the agency.

More (indirect) vindication of APCs

I documented above how in the old days users of the now banned and demonized APCs, which contained a lot of aspirin, used to get relief from migraines by getting APCs into themselves promptly. So some recent wisdom (below) is interesting

People who suffer migraines should take more than the standard recommended dose of aspirin to combat a debilitating headache, a review of medical studies suggests today. Taking up to three tablets — up to 1,000mg — in one go could leave one in four (25 per cent) sufferers pain-free within two hours, researchers from the University of Oxford said.

A standard tablet contains about 300-350mg of aspirin, and adults are commonly advised not to take more than two in one go. But for more than half (52 per cent) of patients who took a higher dose of 900-1,000mg, symptoms went from “moderate to severe” to mild over the same time.

Migraine affects about 18 per cent of women and 8 per cent of men in Britain, with most sufferers aged between 30 and 50.

The latest review, published by the respected Cochrane Collaboration, analysed 13 previous studies involving 4,222 people in total. It found that aspirin also helped to prevent nausea, vomiting and sensitivity to light commonly caused by migraines — but sachet formulations combining another anti-sickness drug, metoclopramide, worked best at this.

David Kernick, a spokesman on headache for the Royal College of GPs, said that most people could manage their migraines with over-the-counter medication — two paracetamol for pain, 600mg of aspirin for inflammation and another drug, 10mg of domperidone, for sickness.

But many experts recommended a higher dose of aspirin, such as that recommended by the Cochrane researchers, despite exceeding the licensed use of the drug.

He said that medication worked best if taken as soon as possible after the onset of symptoms, because stomach cramps can slow the absorption of drugs. He added: “There is a risk of internal bleeding with aspirin, but you are unlikely to get it with a single dose. The longer you leave it, the less likely it is to work.

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