Drugs 5: Drug Interactions

Drug Interactions is one of the first things I look at when I look at a patient's profile in the Infectious Diseases clinic.   While I have looked at my own before, it was well after I started on all these medications.  However, this is because my regimen is very standard and no serious interactions were expected.  Additionally, it is because there are other pharmacists who are looking into it for me, both in the cancer center, and also I figured Sarah would be on top of it as well.    

Prior to cancer, I only used two medications:  Zyrtec and Flonase for allergies.  Once in a while I'll use atrovent nasal for a runny nose while working out.   As you can see, my list has grown quite a bit.   No real secret about what I take, so, here they are.

Josh Medications:
Adriamycin, Bleomycin, Vinblastine, Dacarbazine - these are the actual chemotherapy agents
Aprepitant (Emend), Ondansetron (Zofran), Dexamethasone - these are the anti-nausea medications
Lorazepam (Ativan) - this is an anti-anxiety / anti-nausea medication for anticipatory nausea.  I take it before chemo.
Zolpidem (Ambien) - this is a hypnotic for sleep I was given.  I do not use it often.
Omeprazole (Prilosec) - Suddenly, with cancer, I now have occasionally very bad GERD.  (?)
Cetirizine (Zyrtec) - This is an antihistamine for allergies
Fluticasone (Flonase) - This is a nasal steroid for allergies
Acetaminophen & Ibuprofen - Occasionally for aches and pains

So, what does my interaction profile look like?   Courtesy of being able to dial in to several databases remotely, here it is in raw format from Lexi-Comp:

You can click on this to enlarge it, but don't bother.  As you can see, tons of things "flag."   So much so that I didn't even grab the entire screen.   As you can see, drug-drug interactions are "graded" as A, B, C, D, or X.  In clinical practice, A, B, and C can be fairly unimportant.  This can be for a variety of different reasons.  It may be that the documentation around the interaction isn't all that good.  Likewise, it may be that the interaction itself is theoretical and hasn't been proven clinically, or, hasn't been proven to be important clinically.   As such, I usually screen out interactions that are not at least a D or an X rating.   D interactions are potentially serious, and X interactions are usually contraindications.

Why do you get all this info if you just bypass it?  It is nice to have if you are wondering about a theoretical interaction, or hear of one, or have concerns with certain medications to know what might happen.  So, the A's, B's, and C's are good to have, but not always clinically relevant.

So, here is that same profile with the A's, B's, and C's screened out:

As you can see, there is only one drug-drug interaction that screens as a "D" and no "X's."  What is it? 

Aprepitant may increase the serum concentration of Corticosteroids (Systemic).

So, the Emend I take on "Chemo Mondays" as well as the two days after chemo doses can boost the concentrations of the dexamethasone I also take on Chemo Mondays, which is given IV.  This seems to be due to a cytochrome P450 3A4 inhibition by the aprepitant.  This may well have been a grade "C" interaction, but the manufacturer does recommend a dose change for the dexamethasone, from what may have been recommended for dexamethasone doses in regimens before aprepitant was widely used.  No big deal.   In fact, many drug-drug interactions are like this:  You must evaluate what could happen, how likely it is to happen, and how wide the therapeutic window of the agents involved actually is.  What would be the result of extra dexamethasone once every other week?  Possibly more hunger on those days.  Slightly more immune-system suppression?  Well, I already have that.  Maybe more "jittery-ness." 

So, that's what Lexi-Comp thinks of my regimen.  What about Micromedex?  

They seem to think even less.  This is why I like to use both programs:  they don't always agree completely.  Micromedex has completely screened out most of the unimportant interactions Lexi gave us.   Micromedex notes that aprepitant can boost vinblastine.   They call the interaction "major" with "fair" documentation.   This is why Lexi's screen is nice.  I can go back and see that, yes, Lexi did note this, and they called it a "C" interaction.    So, Micromedex gave this interaction more importance than Lexi did.  I'm unsure if ABVD regimens were changed after aprepitant became mainstream a few years ago or not.  I suspect not, however, because I do not see it in the medication's literature, and more so because I see no actual recommendations for dosing changes.   Which brings us to an important question:  What would you do even if you wanted to?   There isn't enough literature to suggest an empiric dose change.   P450 interactions are highly individualized, and therefore, what may be the perfect adjustment for patient "X" may not work for patient "Y."  So, we manage this interaction rather than avoid it.

Curiously, as you can see, Micromedex placed the previously noted aprepitant / dexamethasone interaction as less important than Lexi did.  They just don't agree and it is worthwhile to look at both.

The last interaction Micromedex noted was lorazepam and zolpidem.  As noted, zolpidem is a hypnotic for sleep, and lorazepam is a benzodiazepine.  Put them together and it is no surprise that you will be more sedated than with either one alone.  So, be careful if you intend to operate heavy machinery and all that.  (Lexi also called this interaction a "C.")

So, drug-drug interactions, in my opinion, are extremely interesting but very often misinterpreted.  My personal experience is that some patients tend to worry far too much about them and others tend to not worry enough.  Drug-drug interactions can be chemical interactions, but rarely result in the colorful explosions you may see in a chemistry experiment gone bad.   However, this is not to say that they cannot be deadly, given the right combination and timing.  Of course, as you can see from above the vast majority are not concerning enough to make changes.   Hopefully this was moderately interesting to you, the reader.