New Research Increases Safety of Methadone Use

Methadone has been used for addiction treatment in America for decades, and in the last decade or so, analgesic use of the opiate medication has skyrocketed.

Unfortunately, increases in methadone prescriptions for pain relief have led to substantial increases in the numbers of people who are killed each year from methadone overdoses. Annual deaths from methadone overdose increased by 400 percent between 1999 and 2004, rising from 786 deaths to 3,849 over that five-year period.

Researchers with Washington University School of Medicine and the University of Washington say that their latest findings should help make the medication a little bit safer for patients. They say that erroneous beliefs about the way the body processes and eliminates the medication may be responsible for some unintentional underdosing or overdosing, which can result in side effects, insufficient pain relief, and death.

HIV Drugs and Methadone

According to a March 8 article on the ScienceDaily medical new website, the Washington researchers investigated how certain HIV medications, protease inhibitors, interacted with methadone.

  • Protease inhibitors suppress the activity of the enzyme P4503A in the liver, and in doing so increase immune functioning.
  • Enzyme P4503A was thought to be an essential enzyme for the processing and elimination of methadone.
  • The researchers thought it was important to know how the two medications interacted, as AIDS patients are often given methadone for pain relief, and many HIV positive patients may also use methadone for addiction treatment.
  • To test the interaction, the researchers gave protease inhibitors and small doses of methadone to healthy study subjects. The protease inhibitors reduced the activity of P4503A, which should have reduced the clearance of methadone from the body – but this didn't occur. The methadone was cleared normally.

Further testing with various protease inhibitors under a variety of protocols confirmed the initial finding that P4503A does not affect the body's clearing of methadone.

Doctors Received Incorrect Information

The methadone package insert warns physicians to be careful of prescribing methadone with drugs that affect P4503A.

Evan D. Kharasch, M.D. Ph.D., who led the Washington research, said that since guidelines for prescribing methadone seem to be incorrect in some cases, the methadone package insert "needs to be reevaluated, as do guidelines that explain methadone dosing and potential drug interactions."

Kharasch explained that doctors who are concerned about the influence of methadone and medications that affect P4503A might prescribe either too little of the medication (which could lead to incomplete pain relief) or too much (which could result in overdose, especially during the risky first two weeks of a patient's methadone treatment).

There are about a dozen liver enzymes related to P4503A, and Kharasch believes that one of these enzymes may be involved in methadone clearance. His team is currently testing P4503B, and he believes that this enzyme may actually be involved, although he says more testing is needed to confirm his suspicions.

Kharasch said that he and his team believe that a fuller understanding of the enzymes at work in the metabolism of methadone will save lives by decreasing adverse drug events. "If we can provide clinicians with better dosing guidelines, then I believe we will be able to better treat pain and limit deaths," he said.

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