In a report to federal regulators, the manufacturer of buprenorphine has provided the starkest evidence to date that misuse of the drug is growing in parts of the country where it is most widely prescribed as an addiction treatment.
Reckitt Benckiser Pharmaceuticals Inc. outlines problems such as a rise in the number of children sickened by accidentally ingesting the pills; an increase, in some areas, of people taking the drug to get high; and commonplace street sales in some cities for as little as $2 per tablet.
The U.S. Food and Drug Administration received the report Jan. 8. A spokesman for the agency said it is under review but declined to comment further. If federal officials conclude that abuse of the drug has become a problem, they can seek further controls over its distribution.
The report linked misuse and illicit sales to the federally sanctioned practice of allowing doctors to prescribe large quantities of the drug for patients to take at home. "It was the patients in treatment for opioid abuse - no doubt selling or trading their own supply of buprenorphine - who were seen as major contributors to the street supply," the report stated.
Federal officials didn't anticipate such abuses when they spent $26 million to develop the drug and help Reckitt Benckiser bring it to market. Congress considered buprenorphine, sold mainly in the U.S. as Suboxone, the centerpiece of its plan to broaden access to addiction treatment.
The latest report closely parallels the findings of a series published in December in The Sun, which revealed that while buprenorphine has been shown to be highly effective as an addiction treatment, its misuse is increasing. The newspaper also identified patterns of illegal sales as well as several deaths caused by taking the drug in combination with other substances.
Many specialists in addiction medicine believe that in the five years the drug has been on the market, its benefits have outweighed any problems. That's also the view of Baltimore's health commissioner, Dr. Joshua M. Sharfstein, who has asked the General Assembly for $5 million to expand buprenorphine treatment for heroin addicts.
Reckitt Benckiser submits the reports as part of a "post marketing surveillance" system as a condition of the FDA's 2002 approval of the drug. The surveillance, conducted by a consultant hired by the company, is intended to alert U.S. regulators to any abuse. A copy of the document was obtained by The Sun.
The report, covering the period from July through September 2007, is based largely on questionnaires to patients seeking drug treatment and to doctors and workers at drug clinics, including three in Baltimore. The consultant also conducts "street-level" interviews, analyzes poisoning and injury data, and reviews postings on Internet sites frequented by drug abusers.
The surveillance revealed:
• There was a substantial increase in the numbers of patients entering drug treatment who were aware of abuse and illegal sales of buprenorphine - on par with methadone for the first time. They described street sales in a number of places, including Chicago's West Side, where the drug was "easy to purchase" for $2 to $5 per tablet. Most addicts reported using it on the street to avoid withdrawal sickness.
• At poison control centers across the nation, more than a quarter of 1,876 buprenorphine exposures involved children under 6 years of age from Jan. 1, 2006, to Sept. 30, 2007, the company said. The rate of buprenorphine exposures in children was higher than the rates for methadone and oxycodone, which are far more commonly prescribed, the report said. The children who ingested buprenorphine, whose names and locations were not stated, all recovered.
The levels have been mirrored in Maryland, according to the Maryland Poison Center at the University of Maryland School of Pharmacy. Over the past three years, 35 children were exposed to buprenorphine, amounting to 28 percent of the total of 121 exposures. By comparison, 27 children were exposed to methadone, or 9 percent of the 293 cases for that medication, and 75 were exposed to oxycodone, or 14 percent of the 501 exposures to that medication.
• A major source of illegal Suboxone, according to 17 percent of doctors surveyed, was "lax or inappropriate" prescribing of the drug by their peers. More than half the doctors questioned in New England, where Suboxone is most widely available as an addiction treatment, said they believed it was just as easy to buy illegally as methadone and other widely abused narcotics. Drug abusers who were interviewed generally agreed.
• Interviews with drug treatment clients in Lynn, Mass., suggested that growing numbers of drug abusers might be turning to Suboxone to get high. In past reports, company officials have said 90 percent of people abusing Suboxone buy it on the street to ward off symptoms of narcotics withdrawal. But a third of the drug abusers questioned in Massachusetts said they used the drug to get high.
In Vermont, a researcher reported that 14 percent of prescription opioid abusers reported that buprenorphine was their "primary opioid of abuse."
"There is evidence that there is experimental use and illegal diversion of buprenorphine, especially the most frequently prescribed product - Suboxone," the report said.
Harriet Ullman, a spokeswoman for Richmond, Va.-based Reckitt Benckiser, said that no one at the company was available to comment and referred questions to the company's consultant, Dr. Charles R. Schuster, managing member of CRS Associates LLC. Schuster said in an interview that "a small percentage" of drug abusers have been experimenting with the drug. He said the company is working to help train doctors how to reduce abuse of the drug.
Dr. Sidney H. Schnoll, a Connecticut physician and a member of an eight-member advisory group established to review the quarterly surveillance reports, conceded that the company faces "issues" with abuse of the drug.
But he said that all drugs have risks. "You have to balance the benefits with the risks," Schnoll said. "Right now [the balance is] in favor of this drug."
Suboxone, which is dissolved under the tongue, relieves addicts' cravings for narcotics and the sickness that comes on when they stop using them abruptly. Some patients say the pills free them from the need to obtain street drugs, allowing them to focus on seeking jobs or taking other steps to turn their lives around.
Unlike methadone, which is distributed by clinics that often require patients to show up every day to receive their doses, Suboxone is designed to be taken unsupervised. Take-home policies in the United States, where doctors are permitted to prescribe a month's supply with up to five refills, are more lenient than those in many other countries.
Baltimore health officials said they hope to avoid some of the illegal diversion by starting addicts in clinic settings and stabilizing them before referring them to private doctors. These clinics are also providing extensive counseling services, which many private doctors are unable or unwilling to provide across the country.
Sharfstein and state health officials recently told Maryland lawmakers they were taking steps to minimize misuse as they expand treatment with the drug.
City officials conceded that "bupe" can be purchased illegally on Baltimore streets, just like heroin and other narcotics. Schuster said that the company has plans to step up surveillance in Baltimore by conducting more "street" interviews but that details were still being worked out.