July 20, 2005

Duragesic under the microscope

Filed under: Medicine

Duragesic is a patch to deliver fentanyl, a class II controlled substance, through the skin over a period of 72 hours. The patches are only used for those with chronic pain (much like OxyContin), and they work pretty well. They’re especially popular among cancer patients who may not be able to tolerate oral opioids for various reasons.

Now Duragesic is under investigation for causing drug overdoses in some patients. The FDA recently issued a public health advisory because “some patients and doctors might not be fully aware of its dangers.”

The advisory notes that people wearing the patches may suffer overdoses or other serious side effects if they drink alcohol, have an increase in body temperature or are exposed to heat from sources like heating pads, electric blankets, heat lamps, saunas, hot tubs or heated water beds. Certain medicines, including antifungals and some drugs used to treat H.I.V., can also lead to fentanyl overdoses in people wearing the patches.

Most of this is fairly common knowledge, particularly about the contraindications with other medicines, especially antifungals and anti-retrovirals (ARVs). Using Duragesic with a medication like ketoconazole or Lamisil can lead to toxic fentanyl levels. The same is true with many ARVs.

As with other opioids, symptoms of overdose are depressed breath and heart rates, extreme fatigue and weakness, etc. Opioid overdose is fairly straightforward to deal with: naloxone (Suboxone) can reverse the depressed breathing and restore a patient by essentially kicking off fentanyl because naloxone has a much greater affinity for the mu and kappa receptors than does fentanyl (or any other narcotic analgesic).

One of the issues with delivering a drug transdermally is the skin itself. Skin is the first line of defense against pathogens — or anything else for that matter. Only small, lipid-soluble drug molecules are able to penetrate the skin, and keeping the rate of drug delivery constant is always a challenge. When formulating a drug patch, one typically must have very high concentrations of the drug on the patch to get even a little bit of it into the body. Naturally, a concentration gradient must be present, and things like changing the body temperature (either too hot or cold) can affect the rate of drug absorption through the skin: heat causes the body to soak the drug up through the patch more readily, mainly because the sweat pores are open, and the patch becomes wet. (Duragesic patches are waterproof, except of course, when the moisture comes from the skin itself.) This is an over-simplified look at the way transdermal patches deliver medications; the reality is that formulating the materials in a patch themselves to effectively deliver the drug over a long period of time is almost far more complicated than making a “simple” tablet or capsule.

Using a transdermal patch is more convenient for patients but it also requires greater caution:

In June, Janssen sent a warning letter to doctors stating that deaths and other serious medical problems had occurred in people who were accidentally exposed to Duragesic by sitting on a patch or touching it while putting it on someone else. In addition, a patch accidentally stuck to a child who was hugged by an adult who had been wearing it; the company did not say whether the child survived.

Most drugs when in pill form do not affect you if you touch them, unless you’re allergic. In the case of transdermal patches, this is not the case, and people need to be more careful with their medications. Perhaps building in a temperature barrier could help keep these adverse effects to a minimum: the patch must reach body temperature before the drug is released. That, at least, would give a short lead time before the drug is released.

Fentanyl lollipops, anyone?

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