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Old Doc New Drug: Tapentadol

The second instalment of the series of newfangled pharmacological favourites for your edification.

This post is all about tapentadol… and its friends.  If you are like me you probably started noticing a trickle, then a flood of patients being discharged from big city hospitals on this new drug.  Now I am a simple rural doctor.  When I saw the name “TAPENTADOL” I immediately assumed that it was a new version of TRAMADOL, but with more letters to confuse the chaps over at the patent office… and I was sort of correct.

These drugs are very similar, so for the uninitiated here is a quick rundown on tramadol and how it works (or doesn’t) Tramadol is possibly the most maligned medication in the FOAMed world. It is unpredictable, with a lot of side effects and often just doesn’t really provide much relief.   So here are a few molecular diagrams to aid the discussion:

TRamadol is a pro-drug. On its own, tramadol doesn’t do much of anything.   It gets metabolised in the liver by the cytochrome p450 enzymes into a few active chemicals… and here is the problem… the actual amounts of each of the active metabolites is a bit of a genetic lottery.  Depending on the makeup of your cytochromes you may get:

  • a bunch of destramadol (aka M1) – which has a strong mu-opioid receptor affinity and acts like morphine
  • some venlafaxine – which is a serotonin/noradrenaline reuptake inhibitor
  • some mixture of both
  • plus a whole bunch of other receptors eg. n & M Acetylcholine, direct serotonin agonist…  there’s a list..

So, to some extent, you can ask the patient what effects they felt if they had a dose of tramadol previously.  In my experience you get pretty clear ‘likes’ and aversion to tramadol.  Thought he most common reply is: “oh, the drug that made me spew!”

And then there is the serotonin syndrome and seizure risk.  This may come about for a few reasons eg:

  • older patients or folk with renal / liver disease don’t clear metabolites and they build up;
  • the combination with other serotonin / norad active drugs eg. antidepressants, leads to a double whammy
  • patients with little metabolism to M1 take more and more doses to achieve analgesia… and end up with a bunch of the SNRI metabolites in their systems.

So, now enters TAPENTADOL.  Which is the all new and improved (not hard to do!) version of tramadol.  So how is the new kid on the block different to its somewhat nasty cousins?

  • Tapentadol is not a prodrug – it does not rely on metabolism to get it working. So it is what it says on the box.
  • It has a strong mu-opioid receptor agonist effect – similar to oxycodone
  • It also has noradrenaline reuptake inhibitory effects, but…. not much serotonin reuptake effects, so a little cleaner.
  • There are no known active metabolites … yet. So that sounds cleaner too

That all sounds nice and neat.  A cleaner, direct acting opioid with fewer side effects!  But there must be a catch eh? There always is!

The biggest issue is that there just is not yet enough data about either the safety or efficacy of tapentadol.  IN the trials used to get it registered it was only just better than placebo for chronic pain.  We need to see some real-world safety data and harder clinical outcome studies to say exactly how much of what this drug does.

As with any potent opioid, it is to be used with caution in patients with respiratory failure, other sedatives or noradrenergic agents.  It needs to be avoided for at least 2 weeks after ceasing any MAOIs eg. moclobemide ( though this is rarely used in Australia).

Side effects are predictable: constipation, nausea and vomiting with some dizziness in up to a third of patients.

The risk of developing tolerance and potential for abuse or diversion is likely to be similar to other opiates once the word on the street gets out!  So it is definitely one to watch carefully when prescribing.  There are a few interesting observational trials looking at chat forums for recreational opiate-users… it does not seem to have caught on yet, or maybe it is just not as fun as other opiates?

Opiate dose equivalences (oral)

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