Dangerous Opioid Drug Interactions

Patient Expert

When it comes to discussions about opioid drugs in the media, they almost always focus on the potential for abuse and addiction.   In the chronic pain community, the discussion often centers around how difficult it is to find a doctor who will prescribe the pain medications we need and the stigma placed on anyone taking opioids, regardless the reason.   What we rarely, if ever, hear is an educated discussion of the possible dangerous interactions that may occur when we take other medications in addition to the opioids.

It is estimated that 70 percent of patients taking an opioid pain reliever also take at least one nonprescription drug or substance and a majority also take one or more prescription medications.   It is so important to be aware of possible interactions whenever any drug is mixed with one or more other drugs or supplements.

Complexities of Opioid Interactions

A drug interaction occurs when two or more substances (drugs, supplements, or even some foods) affect each other in such a way that the metabolism, elimination, effectiveness, and/or toxicity of one or more of the drugs is changed.   Simply put, a drug interaction causes one or more of the medications you're taking not to work as they should.   This can have dangerous, even deadly, results.

One of the more complex problems when it comes to drug interactions in general and opioid-drug interactions in particular involves the enzymes our bodies use to metabolize the medications.   According to Dr. Stewart B. Leavitt, Executive Director of Pain Treatment Topics, "A special concern is with drugs metabolized and cleared via the cytochrome P450 (CYP450) enzyme system, primarily in the liver. While this is a complex subject, and there are dozens of different CYP450 genes in humans, relatively few of the gene-encoded enzymes play a role in drug metabolism; most prominently involved are the CYP1, CYP2, CYP3 families and the CYP3A4 and CYP2D6 isoforms."

Sound like Greek?   I agree.   Basically what happens is that when two or more medications that are metabolized by the same enzyme(s) are taken, they complete with each other for use of the enzyme(s).   The drug that attracts more of the enzyme(s) is the winner.   If the opioid "wins" it may be metabolized more quickly than it should be and the pain relief won't last as long as it should.   If the opioid loses the race, it can be metabolized more slowly than it should be.   That not only means you'll get less pain relief than you should, but it could result in toxic accumulations of the opioid in your system, which could cause an accidental overdose.

When it comes to opioid pain relievers, a few like morphine, hydromorphone, and oxymorphone are basically unaffected by CPY450 metabolism.   Most other opioids, including, codeine, hydrocodone, oxycodone, tramadol, fentanyl, and methadone, are metabolized via CYP3A4 and CYP2D6.   Methadone also uses CYP1B6.   If you are taking other medications that rely on the same enzymes for metabolism, you could be facing an opioid-drug interaction problem.

Help My Drug Test Was Wrong

Sometimes I get questions from people who insist they were taking their opioid medication exactly as prescribed by their doctor, yet their urine drug test showed there was little or none of the drug in their system.   Often their doctor dismisses them because he thinks they've been selling their medication.   Other times people tell me their drug test showed too much of the opioid in their system and their doctor accused them of abusing their medication.   Many times they, too, are dismissed for misusing their drugs.

Of course, I can't say what caused the errors in their drug tests, but a possible interaction with another medication that uses the same enzymes for metabolism should be considered before a patient is dismissed.   Unfortunately, too many doctors overlook the possibility of two drugs competing for use of the same enzymes.

Preventing Opioid-Drug Interactions

In ideal circumstances, patients will tell their doctor and their pharmacist about all medications - both prescribed and over-the-counter - they are taking as well as any vitamins or herbal supplements.   And both physicians and pharmicists will carefully check for possible interactions before prescribing or dispensing a new medication.

But let's face it - we're all human and as hard as we may try, we sometimes make mistakes.   Patients may forget to tell their doctor about a medication prescribed by another doctor or one they picked up at their local drugstore.   Or they may purposely not reveal something they are taking for fear the doctor won't approve.   A normally conscientious physician may be rushed and forget to double check for interactions before writing a prescription.   There may be a computer glitch at your pharmacy, or your pharmacist may be having a bad day and miss an alert about about a possible interaction when filling your prescription.

For these reasons, I always encourage patients to do their own double checking, just to be on the safe side.   After all, it is your health and life that could be in jeopardy.   Drugs.com offers a very good Drug Interaction Checker.   Just enter all of the medications you are taking, or thinking of taking, and it will give you the potential interactions between them.   (Don't forget the over-the counter meds and supplements.)   It will also tell you about any foods that may interact with your medications.

If you find there are possible interactions between medications you are taking, talk with your doctor about them.   Sometimes all that is necessary is to monitor you for possible adverse reactions.   Your doctor may recommend that you have certain blood tests done on a regular basis to make sure a particular problem is not developing.   Other times your doctor might want you to try a different medication.   Regardless, to quote the old English idiom, "Better safe than sorry."

If you would like to read a more detailed description of the opioid-drug interaction problem written for physicians, which includes a list of helpful resources, see:   Avoid Trouble: Consider Opioid-Drug Interactions

Leavitt SB. Avoid Trouble: Consider Opioid-Drug Interactions. Pain Treatment Topics. October 23, 2010.
Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed 4/29/11.

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