FDA Advisory Warns Of Fatal Cardiac, Respiratory Risks Associated With Methadone

Public health advisory notes that use of the Boehringer Ingelheim drug may cause death or life-threatening injury during initiation or conversion of pain patients to methadone from other opioid agonists.

A Nov. 27 FDA public health advisory is cautioning that use of methadone may be associated with higher incidences of cardiac and respiratory deaths.

"FDA has received reports of death and life-threatening side effects in patients taking methadone," the agency says. "These deaths and life-threatening side effects have occurred in patients newly starting methadone for pain control and in patients who have switched to methadone after being treated for pain with other strong narcotic pain relievers."

The advisory notes that "methadone should only be prescribed for patients with moderate to severe pain when their pain is not improved with other non-narcotic pain relievers."

"Pain relief from a dose of methadone lasts about four to eight hours. However, methadone stays in the body much longer - from eight to 59 hours after it is taken. As a result, patients may feel the need for more pain relief before methadone is gone from the body. Methadone may build up in the body to a toxic level if it is taken too often, if the amount taken is too high, or if it is taken with certain other medicines or supplements."

In addition to issuing the alert, FDA asked methadone marketer and Boehringer Ingelheim subsidiary Roxane Labs to update labeling for its 5 mg and 10 mg Dolophine tablets. The labeling revision, which also applies to Dolophine generics, occurred Nov. 17.

"The information in the new prescribing information is based on a review of the scientific literature completed by FDA," and includes new information on pharmacology, drug interactions and converting patients, the agency says, adding it will also issue a Medication Guide for patients.

A "black box" warning in the Dolophine label notes that "deaths, cardiac and respiratory, have been reported during initiation and conversion of pain patients to methadone treatment from treatment with other opioid analgesics."

Respiratory depression is the main hazard related to methadone use, the warning states, adding the drug's "peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly during treatment initiation and dose titration."

"In addition, cases of QT interval prolongation and serious arrhythmia have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used in maintenance treatment of opioid addiction."

-Brooke McManus ([email protected])