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August 28, 2009

Oxycodone: Be Careful What You Take With It

Recent studies show that certain drugs taken together with oxycodone (PERCODAN, TYLOX, OXYCONTIN) can dramatically affect the response to the widely used painkiller, resulting in problems such as excessive sedation, slowed breathing or, potentially, decreased painkilling effects of oxycodone.

How do these drugs interact, exactly? The use of other drugs with oxycodone can cause the levels of oxycodone in the blood to either increase or decrease.

This happens because oxycodone, an opioid drug, is metabolized mainly in the liver by the enzyme CYP3A4. This enzyme is commonly inhibited by other drugs, and when drugs that inhibit CYP3A4 are taken with oxycodone, the blood levels of oxycodone may increase substantially.

A recent report from Finland found that one CYP3A4 inhibitor, voriconazole (VFEND), produced almost a four-fold increase in the blood levels of oxycodone. (For a more complete list of drugs that inhibit CYP3A4 and thus are likely to increase the risk of oxycodone toxicity, see Table 1. Because the extent of CYP3A4 inhibition by the various drugs in the list in Table 1 varies, the magnitude of the interactions with oxycodone may vary depending on which drug is used as well as the dose and duration of the drug.)


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On the other hand, some drugs can increase the activity of CYP3A4, which would markedly reduce blood levels of oxycodone. Such lowering the blood levels of oxycodone lowers the painkilling effects of the drug.

Another recent study from Finland found a dramatic reduction in oxycodone blood levels when people were given the "enyzyme inducer" TB drug rifampin (RIFADIN, RIMACTANE) concurrently. Rifampin is one of the most potent medications for increasing CYP3A4 activity.

Other enzyme inducers are also likely to reduce oxycodone blood levels by speeding up its elimination, but the effect of these medications on oxycodone may be less than with rifampin. (For a more complete list of drugs that increase CYP3A4 activity and thus are likely to decrease oxycodone levels, see Table 2.)

What You Can Do

If you are taking oxycodone with one or more of the drugs listed in tables 1 and/or 2, keep in mind that drug interactions may increase oxycodone toxicity or reduce oxycodone’s anagesic effects. Talk to your doctor to find alternate solutions by using drugs that are less likely to interact.


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Other opioid analgesics

Oxycodone is in a drug family called opioid analgesics; these drugs suppress feelings of pain and are used for moderate to more severe pain management. As drugs in the same family can sometimes have similar effects and reactions, we will discuss the potential for this interaction with other opioid analgesics.

Other opioids metabolized by CYP3A4.

Alfentanil (ALFENTA), fentanyl (SUBLIMAZE) and sufentanil (SUFENTA) are metabolized by CYP3A4 and these drugs are likely to interact with the CYP3A4 inhibitors and inducers in much the same way as oxycodone. Methadone is partially metabolized by CYP3A4 and may also interact with CYP3A4 inhibitors and inducers.


Morphine is not metabolized by CYP3A4 or other CYP450 enzymes, so it is unlikely to interact with CYP3A4 inhibitors, leading to higher blood levels. Nonetheless, its effect can reduced by the "enzyme inducers" listed above, because they increase morphine metabolism, leading to lower blood levels.


As we discussed in the June 2008 issue of Worst Pills, Best Pills News, in order to work, codeine must be metabolized to morphine by the enzyme CYP2D6. Inhibitors of CYP2D6 reduce codeine’s effect, but inhibitors of CYP3A4 would not be expected to affect codeine. Because codeine acts by being converted to morphine, however, it can be affected by "enzyme inducers" as described for morphine. "Codeine-like" opioids such as hydrocodone (VICODIN) and dihydrocodeine (SYNALGOS-DC) probably are like codeine in that they are inhibited by CYP2D6 inhibitors but not affected by CYP3A4 inhibitors.

Table 1. Drugs That May Increase Blood Levels and Effect


amiodarone (CORDARONE, PACERONE)***

amprenavir (AGENERASE)

aprepitant (EMEND)

atazanavir (REYATAZ)

clarithromycin (BIAXIN)**

cyclosporine (NEORAL, SANDIMMUNE)

darunavir (PREZISTA)

delavirdine (RESCRIPTOR)


erythromycin (E-MYCIN, EES, ERYTHROCIN)

fluconazole (DIFLUCAN)

fluvoxamine (LUVOX)**

imatinib (GLEEVEC)

indinavir (CRIXIVAN)

itraconazole (SPORANOX)*

ketoconazole (NIZORAL)

posaconazole (NOXAFIL)

quinupristin (SYNERCID)

ritonavir (KALETRA, NORVIR)


tamoxifen (NOLVADEX)**

telithromycin (KETEK)*


voriconazole (VFEND)

Table 2. Drugs That May Decrease Blood Levels and Effect


carbamazepine (CARBATROL, TEGRETOL)

efavirenz (SUSTIVA)

nafcillin (NALLPEN, UNIPEN)

nevirapine (VIRAMUNE)

oxcarbazepine (TRILEPTAL)

phenobarbital (LUMINAL, SOLOFTEN)**

phenytoin (DILANTIN)

primidone (MYSOLINE)

rifabutin (MYCOBUTIN)

rifapentine (PRIFTIN)

St. John’s wort

* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills
*** Last Choice in Worst Pills, Best Pills