Help me understand the link between drug side effects and delivery mechanisms.

November 22, 2011 2:23 PM

Is a transdermal patch or topical version of a given prescription drug any less likely to cause side effects that result from taking the oral form?

About a year ago I was prescribed the oral pill form of oxybutynin for overactive bladder. It worked quite well, but after a few weeks I had fairly noticeable hair loss. I checked with my doctor, who said this was a rare but known side effect of oxybutynin. I stopped using the drug, and my hair grew back.

I've tried samples of several other drugs in this class (anticholinergics), but none worked nearly as well as this one.

I've since found that there is a topical gel form of the same drug, marketed as Gelnique. However, after my last experience I'm afraid to try it. My doctor said he doesn't know if the gel form would produce the same side effects or not.

I don't understand pharmacology and biology well enough to know much about this, but is there any reason to believe that using a topical or patch form of a drug might result in fewer side effects vs. an oral form of that drug? Does anyone really understand why certain drugs cause hair loss in the first place?

posted by anonymous to health & fitness (4 answers total)

The third page of this article says, "Transdermal oxybutynin is as effective as the current ‘gold standard’ treatment, oxybutynin IR, and as efficacious at treating symptoms of OAB as tolterodine XL. This is achieved with a comparatively low systemic dose of oxybutynin, with the additional benefit of avoiding high concentrations of N-DEO, which have been associated with antimuscarinic adverse effects." If nobody else has anything I'd search for antimuscarinic and hair loss.

To answer the question in your first sentence, a drug I'm on, an MAOI called Emsam, has a far lower risk of potentially fatal complications in transdermal form. Normally patients on MAOIs have to avoid foods high in tyramine, like old cheese and tap beer, lest they risk hypertensive crisis. But on the lowest dose of the patch, you can eat anything. It's a matter of inhibiting MAO-A and MAO-B vs. A-only. The drug interactions are still in place, though.

An article in Psychiatry Weekly says, "[The Emsam patch] was well tolerated in clinical depression studies, with the principal side effects noted being local dermal reactions and insomnia, both of which were dose-related. Other side effects commonly encountered with MAOIs, such as postural hypotension, sexual dysfunction, excessive weight gain, and peripheral edema were either infrequent or not evident." I don't know how the oral version of this drug compares to other MAOIs, though. That's annoying. I can say that I'm not having those side effects on the patch, though, aside from skin redness. So there's one anecdote.
posted by Adventurer at 4:46 PM on November 22, 2011

I recommend calling your pharmacist. Pharmacists are experts at dealing with real life drug problems. They can tell you if it will likely cause the same side effects in a different formulation.

(Note: I am a medical librarian and did not find hair loss listed as a side effect of any formulation of oxybutynin (using 2 different professional pharmacy databases) nor could I locate any scholarly articles that discussed this drug and hair loss in Medline, so if he/she asks you to call back later after they can do some research, that might be why-- this is not an easily-found nor frequently-discussed side effect of this drug in professional sources. I know you can google it and find some reports from the FDA, but those are simply reports-- I could contact the FDA and file a report that drug X made me do thing Y, but it's not verified by any authority when I add the report; the FDA investigates some reports and if they are warranted, creates further warnings for drug labels. The most recent new warnings for this drug do not include hair loss/alopecia. So I would take those reports with a grain of salt.)
posted by holyrood at 4:49 PM on November 22, 2011

I'm a pharmacist, and I think it might work. It seems like a bit of a long shot, but it would be nice to be able to get the benefit of the drug without the side effect.

Some side effects come when you have a relatively high level of the drug in your bloodstream, higher than necessary for the drug to work. If this is the case, you can hit a sweet spot (high enough levels for the drug to work, but low enough to avoid the side effect) using smaller, more frequent doses. For example, two Benadryl every 6 hours might control your allergies, but make you sleepy, but one Benadryl every 4 hours might control your allergies without the drowsiness, with the added benefit that you only take 6 pills per day instead of 8.

A patch is the ultimate low-and-slow delivery system because it maintains a constant lower level of the drug in your body as opposed to intermittent big doses. A gel might give you that benefit too.

Personally, if it were me, I'd try it and see if it works. You already know that the hair loss reversed after you stopped last time, so you could always stop again if it looked like it was happening again.
posted by selfmedicating at 5:31 PM on November 22, 2011 [1 favorite]

One potential is that the side effects would only happen at a high amount of active pharmaceutical ingredient (API) present in your blood stream. All APIs have clearance rates and you can imagine your body like a cup with a hole in it. Taking a pill is like putting water in the cup and then it leaks out over the course of a day. When you take another pill it adds more water to the cup and depending on the size of the hole and the amount of water (API) you are adding the cup can overflow. The cup needs to be more than 25% full (just an example) to have the desired effect, but the overflow causes the side effects.

Now with a transdermal patch instead of pouring a bunch of water in all at once you have a slow drip of water into the cup continuously. If the drip of incoming water is the same as the drip of the outgoing water then you will reach an equilibrium and the cup would never overflow.

All APIs will have off target effects that will turn up at different concentrations. Things are considered selective when they have 1000x more affinity to something than everything else, but due to migration and lifetimes you can possibly get 1000x more concentrated API given a once daily dosing regime.

Again I am not your pharmacist, I am though a medicinal chemist who makes drugs in a lab and tests them for pharmacokinetics.
posted by koolkat at 2:01 AM on November 23, 2011