For two decades, the U.S. Food and Drug Administration approved dangerous dosing information about methadone for pain patients, but ordered safe doses for addiction patients.

People take the prescription drug methadone for two purposes: to relieve pain or to stop cravings for heroin, OxyContin and other narcotics.

Starting in the 1980s, the FDA ordered a much lower starting dose of methadone for addiction patients than for pain patients, even though pain patients could be at greater risk of an accidental overdose.

The FDA said a methadone clinic could give no more than 40 milligrams of methadone a day to a new addiction patient. The patient could be given more only if a doctor gave special permission.

But for pain patients, until last month, the FDA approved a �usual adult dose� up to twice that amount, 80 milligrams a day.

Patients could die if they took that much. Studies have found that doses of 50 milligrams or less of methadone have killed people who are �opioid naive� � not used to narcotics.

People addicted to heroin and OxyContin are not opioid-naive. Just the opposite � their bodies often have built up a tremendous tolerance to drugs.

So, why the difference?

�That�s a very good question,� said Mark Parrino, president of the American Association for the Treatment of Opioid Dependence, a New York-based nonprofit that supports methadone for addiction treatment.

�If methadone is being so carefully prescribed in the methadone maintenance programs, why weren�t the labeling guidelines made equally clear and conservative for pain physicians?�

On Monday, six months after a Sunday Gazette-Mail series revealed the potentially deadly dosing information for pain patients, the FDA announced it is changing that information. The new prescribing information for doctors says they should give no more than 30 milligrams a day to new pain patients.

The FDA also released a public health advisory titled �Methadone Use for Pain Control May Result in Death.� It warned of methadone�s unique properties � how it slows breathing, how it can stay in the body for days, how taking an extra pill can kill a patient.

It was �about six months ago� that the FDA became aware that many people dying from methadone overdoses were legitimate patients with a prescription, said Dr. Bob Rappaport, director of the FDA�s Division of Analgesics, Anesthetics and Rheumatology Products.

Rappaport requested that the FDA�s Office of Surveillance and Epidemiology do its own study. Two months ago, he received that report.

�It became apparent that the problem was at least partially, if not significantly related to improper prescribing practices,� Rappaport said. �Once this became clear where the problem was headed, we took some rapid action.�

The makers of methadone also bear responsibility for the information on the package insert, since the FDA is required to collaborate with the drug companies on any label changes.

Neither of the two methadone manufacturers, Tyco/Mallinckrodt and Roxane Laboratories, responded to requests for comment for this article.

The FDA knew by 2004

The FDA became aware of the potentially deadly dosing information patients were getting with their methadone pain pills �about two or three years ago,� Rappaport said.

The FDA definitely knew by 2004, when it increased the warnings on one type of methadone � the type given intravenously to hospital patients, said Dr. Celia Winchell, medical team leader for addiction drug products at the FDA.

And in 2003, Rappaport, Winchell and other FDA officials participated in a conference devoted to the rise in methadone overdose deaths. News reports were blaming the deaths on methadone being abused or illegally sold by drug treatment patients.

When Rappaport and Winchell walked out of the conference, they believed that most of the people overdosing on methadone were taking it illegally, they said.

For two decades, the U.S. Food and Drug Administration approved dangerous dosing information about methadone for pain patients, but ordered safe doses for addiction patients.

People take the prescription drug methadone for two purposes: to relieve pain or to stop cravings for heroin, OxyContin and other narcotics.

Starting in the 1980s, the FDA ordered a much lower starting dose of methadone for addiction patients than for pain patients, even though pain patients could be at greater risk of an accidental overdose.

The FDA said a methadone clinic could give no more than 40 milligrams of methadone a day to a new addiction patient. The patient could be given more only if a doctor gave special permission.

But for pain patients, until last month, the FDA approved a �usual adult dose� up to twice that amount, 80 milligrams a day.

Patients could die if they took that much. Studies have found that doses of 50 milligrams or less of methadone have killed people who are �opioid naive� � not used to narcotics.

People addicted to heroin and OxyContin are not opioid-naive. Just the opposite � their bodies often have built up a tremendous tolerance to drugs.

So, why the difference?

�That�s a very good question,� said Mark Parrino, president of the American Association for the Treatment of Opioid Dependence, a New York-based nonprofit that supports methadone for addiction treatment.

�If methadone is being so carefully prescribed in the methadone maintenance programs, why weren�t the labeling guidelines made equally clear and conservative for pain physicians?�

On Monday, six months after a Sunday Gazette-Mail series revealed the potentially deadly dosing information for pain patients, the FDA announced it is changing that information. The new prescribing information for doctors says they should give no more than 30 milligrams a day to new pain patients.

The FDA also released a public health advisory titled �Methadone Use for Pain Control May Result in Death.� It warned of methadone�s unique properties � how it slows breathing, how it can stay in the body for days, how taking an extra pill can kill a patient.

It was �about six months ago� that the FDA became aware that many people dying from methadone overdoses were legitimate patients with a prescription, said Dr. Bob Rappaport, director of the FDA�s Division of Analgesics, Anesthetics and Rheumatology Products.

Rappaport requested that the FDA�s Office of Surveillance and Epidemiology do its own study. Two months ago, he received that report.

�It became apparent that the problem was at least partially, if not significantly related to improper prescribing practices,� Rappaport said. �Once this became clear where the problem was headed, we took some rapid action.�

The makers of methadone also bear responsibility for the information on the package insert, since the FDA is required to collaborate with the drug companies on any label changes.

Neither of the two methadone manufacturers, Tyco/Mallinckrodt and Roxane Laboratories, responded to requests for comment for this article.

The FDA knew by 2004

The FDA became aware of the potentially deadly dosing information patients were getting with their methadone pain pills �about two or three years ago,� Rappaport said.

The FDA definitely knew by 2004, when it increased the warnings on one type of methadone � the type given intravenously to hospital patients, said Dr. Celia Winchell, medical team leader for addiction drug products at the FDA.

And in 2003, Rappaport, Winchell and other FDA officials participated in a conference devoted to the rise in methadone overdose deaths. News reports were blaming the deaths on methadone being abused or illegally sold by drug treatment patients.

When Rappaport and Winchell walked out of the conference, they believed that most of the people overdosing on methadone were taking it illegally, they said.

But conference participants concluded that liquid methadone from drug-treatment clinics was not the culprit � pain pills were.

Therefore, changing the label or sending out a warning to the public would do little good, they said.

�At the time, it didn�t seem like physicians and patients were the problem,� Winchell said. �It seemed like it was people who got ahold of the drug who weren�t patients.�

The conference report did say that doctors and legitimate patients were part of the problem. One of three likely scenarios for a methadone overdose death was �in the context of legitimate patient care, methadone accumulates to harmful serum levels during the first few days of treatment for addiction or pain.�

�Radical� dose change

In June, the Sunday Gazette-Mail investigation revealed for the first time that the increasingly popular painkiller methadone is a factor in the deaths of more people nationwide than any other prescription narcotic � 2,992 people in 2003.

The investigation also found that some people took their methadone exactly as prescribed and died anyway. It found that the �usual adult dosage� on the package insert patients got with their bottles of methadone pills could kill. It found that despite knowing about methadone�s dangers, federal officials had not strengthened warnings on the pain pills.

The findings alarmed Dr. Robert Newman, director of the International Center for Advancement of Addiction Treatment, Baron Edmond de Rothschild Chemical Dependency Institute of Beth Israel Medical Center in New York.

He had assumed pain patients got the same low, safer starting methadone doses that addiction patients get.

�The first public reference [to the dosing discrepancy] I have seen came from your article in the Gazette,� said Newman, who has spent his career advocating access to methadone treatment for addiction. �If I had known, I would have been on the warpath ....

�There is nobody in this field, going back 25 years, that would say there was any question: If you exceed 30 to 40 milligrams on day one for a methadone maintenance patient, you are risking an overdose situation.�

The Compliance Office, the branch of the FDA that knew about the difference, dealt with methadone clinics in the 1980s. It is not the same branch that deals with painkiller safety, said Winchell of the FDA.

Newman worries doctors and pharmacists won�t notice that the FDA has cut its maximum dosing recommendation for pain methadone in half.

The new �usual dose� is mentioned once, on page 15 of a 17-page �prescribing information� document.

�I think the real story is the usual dosage has changed radically,� Newman said. �It�s not even mentioned in the [public health] advisory. It�s not even mentioned in the patient information sheet.

�How is a physician, reading the press or reading the advisory, going to be tipped off that there has been a radical change? How is the pharmacist going to know?�

The FDA believes any doctor who reads the public health advisory will check the dosing recommendations, Rappaport said.

Newman said he would like to see the FDA send every Drug Enforcement Agency-registered physician � all of them can prescribe methadone � �a separate, strongly worded advisory saying, �This is the change in dosage.��

Otherwise, he said, doctors might not realize they could be part of the overdose problem.

�Reading the advisory, the only conclusion a reasonable person can make is, �Gee, I guess patients have just been taking this stuff the wrong way.��

To contact staff writers Scott Finn or Tara Tuckwiller, use e-mail or call 357-4323 or 348-5189.