re: Ann: Productive Meeting With FDA Regardin... Not sure that...

re: Ann: Productive Meeting With FDA Regardin... Not sure that the FDA (and its clinical advisors in pain management) are all that keen on combination preparations combining two relatively short acting opioids. The question of respiratory depression becomes a real issue when you realize that in pain management patients will be commonly taking many other medications as well.

For example for chronic pain, patients are likely to be using a long acting preparation (Morphine SR, Oxycodone CR, Buprenorphine patches or Fentanyl patches)for baseline pain relief. Short acting opioids like oxycodone or morphine are in nthe main used individually as top ups for breakthrough pain.

For short term pain relief in severe acute situations you are usually only going to use a single opioid short term in combination with a non opioid analgesic (paracetamol and/or an NSAID plus maybe some diazepam as a muscle relaxant or for sedation and/or anxiety).

In addition Oxycodone metabolism is via cytochrome P450 enzymes(CYP450) which can be inhibited by a lot of other common medications a patient may be taking. I wonder down the review time line will the FDA want any interaction studies with patients taking inhibitors of CYP450 or other medications which also can cause respiratory depression. This seems to be the main issue they are focussing on.

The other consideration that has to be taken into account by the FDA is in overdose situations. We all know how dangerous and difficult to treat this can be when there are multiple drugs involved. Respiratory depression is what kills people! At higher doses do we see different pharmacokinetic properties and clearance of potentially dangerous metabolites?

What about development of tolerance. Will patients need increaded doses to get the same pain relief but be at increased risk of side effects.

I suspect pain management clinicians will also take convincing that MoxDuo has enough positives with regard to safety and efficacy to change away from current pain management principles and therapeutic guidelines that do not usually include concurrent use of two immediate release opioid drugs together.

The other issue of concern is even if it is approved, that to command a substantial pricing premium in the market place over morhine or oxycodone given individually or combined as single dosage forms the FDA approved labelling will have to support solid promotional claims of significantly better and safer pain relief (not just "same as"). Morphine and Oxycodone are two of the cheapest oral opioids on the market so to get substantial higher pricing to make marketing a new product worthwhile it will need unequivocal evidence.

Combination of highly potent drugs with narrow therapeutic margins of safety is questionable! Sorry just my opinion.