New Marketed Combinations With Novel Therapies

Benjamin W. Friedman, MD, MS: I want to talk about some of the specific medication combinations that are marketed because the marketed combinations make it a little easier for patients to take the combination rather than getting 2 separate vials of medication. Among the different available combination therapies, the common ones are oxycodone combined with either aspirin or acetaminophen, hydrocodone with the same, or a new combination with tramadol and celecoxib [Celebrex]. Does anybody prefer any of these specific combinations? Are there any pros or cons that we should discuss? Jeff, is it OK if I turn to you for this?

Jeff Gudin, MD: Sure, Ben. I’ll jump in. There was a period where many of my colleagues said, “If I want to use an opioid, I’m going to use a straight opioid, not a combination. If I want to use acetaminophen or ibuprofen, I’m going to use that separately.” I can buy into that philosophy, especially in the chronic pain world, where we might go higher on our doses of opioids and there aren’t higher fixed-dose combinations available. But in the acute pain space, I still appreciate the combination agents, hydrocodone-acetaminophen or oxycodone-acetaminophen. I like that patients don’t have to think about taking 2 different drugs or when to take one vs the other. There’s some synergy in the combinations.

You mentioned a new formulation of tramadol and Celebrex, which is quite a bit different. Many clinicians still don’t understand tramadol’s mechanism of action. It’s in the opioid-like class because it binds very weakly to the mu opioid receptor, but it also works a little like antidepressants. And we know that modulating serotonin and norepinephrine has a benefit on certain pain conditions.

I’ve used tramadol in my practice for 20 or 25 years, both the immediate release and the extended release. But now there’s a formulation available combined with an NSAID [nonsteroidal anti-inflammatory drug] in celecoxib. And apparently there’s something about this formulation called co-crystal technology, meaning you can put more than 1 class of drug into the crystal—drugs with complementary mechanisms of action, such as tramadol and Celebrex. That hits our multimodal analgesic approach, as we talked about before, using different classes of drugs. With tramadol, you get a little of the mu opioid receptor. You get an SSRI [selective serotonin reuptake inhibitor]–like effect. And with celecoxib, you get the COX-2 NSAID effect. That intrinsic chemistry seems to work well together.

Francesca Beaudoin, MD, MS, PhD: I’m eager for new options to treat both acute and chronic pain in people along that spectrum, and new technologies, such as this co-crystal technology. I’m also looking toward the pipeline of therapeutics, what’s out there and what’s coming. We’re all still waiting for additional tools to treat acute pain, specifically when we’re talking about pharmacologic therapies.

Paul Arnstein, RN, PhD, FAAN: And when we look at these combinations that have been legacy combinations that we’ve had, a lot of them have been combined with acetaminophen, which doesn’t have the anti-inflammatory effect that we’d want to limit some of the transduction of pain. Some of the combinations with ibuprofen have created some GI [gastrointestinal] adverse effects or intolerance related to that, but they’ve tended to work better than combinations with acetaminophen. I’m excited to see some of the pipeline medications coming down, such as tramadol and celecoxib, because that checks the boxes of transduction, transmission, modulation, and perception.

Transcript Edited for Clarity