Prescribing Trends for Opioids, Benzodiazepines, Amphetamines, and Barbiturates from 1998-2007

1. Prescribing Trends for Opioids, Benzodiazepines, Amphetamines, and Barbiturates from 1998-2007 Sean J. Belouin, Pharm.D. Lieutenant Commander, United States Public Health Service Division of Workplace Programs, Center for Substance Abuse Prevention, Substance Abuse and Mental Health Services Administration Nicholas Reuter, M.P.H. Team Leader, Certification and Waiver Team Division of Pharmacologic Therapies, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration Vicky Borders-Hemphill, Pharm.D. Drug Use Data Analyst Acting Team Leader Division of Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration Hina Mehta, Pharm.D. Drug Use Data Analyst Division of Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration Good morning. Today, I�m presenting on prescribing trends for 15 commonly prescribed controlled drugs that fall within the pharmacologic classes: opioid analgesics; benzodiazepines; stimulants; and barbiturates. All these products are further classified as scheduled controlled substances with a rating of CII through CV. The 15 drugs chosen for this analysis were based on their use relative to all other prescribed controlled drugs, potential for abuse, and potential for diversion from individuals for whom the prescriptions were intended. I would like to thank in advance Nick Reuter from the Division of Pharmacologic Therapies, CSAT, for his assistance in this presentation and a very special thanks to Dr. Hina Mehta and Dr. Vicky Borders-Hemphill, both Pharm.Ds from the Office of Surveillance and Epidemiology, FDA, for completing all the requests for compiling and analyzing the data for this presentation. This presentation could not have been completed without their assistance and the cooperation and partnership that exists between FDA and SAMHSA. Several types of analyses were performed that looked at prescription drug data spanning the last 10 years from 1998 through 2007. The drugs analyzed were oxycodone, hydrocodone, methadone, fentanyl, codeine, propoxyphene, alprazolam, lorazepam, diazepam, clonazepam, temazepam, amphetamine, methamphetamine, butalbital, and phenobarbital. To make the analyses more accurate and complete, we combined brand and generic drug data for each drug to give a more complete picture, e.g., Percocet, Oxycontin, Endocet, Percodan, Tylox, Oxy-IR, and Oxy-Fast, are several brand names containing Oxycodone in addition to firms manufacturing generic Oxycodone.� Some of these brands (and generics) contain not only Oxycodone alone but also contain acetaminophen or aspirin in combination. �Thus, to be complete and accurate, all products containing Oxycodone (brand and generic or combination products, e.g. Oxycodone plus Acetaminophen) have to be combined and accounted for to give a more accurate and complete picture. We created a break down of each drug prescribed by strength. For example, hydrocodone comes as 2.5, 3.5, 4.5, 5, 7, 7.5, and 10mg strengths. We then analyzed the total number of prescriptions dispensed for each drug; for each year; over the last 10 years from 1998 through 2007. We also analyzed the demographics by breaking down each drug into how many prescriptions were filled for men; how many for women; and how many prescriptions were filled for various age ranges using 10 year intervals to get a sense of which age range the drug product was most utilized. Finally, to give a more complete picture, we further analyzed the total number of tablets, capsules, patches, mls, etc., which we refer to as �extended units�, that were dispensed for each drug; for each year, from 1998 through 2007. This would reflect the volume of just how much drug product was being dispensed on a year to year basis. Now, what this presentation does not attempt to do is draw any conclusions or explain the reasons behind the prescribing trends over the last 10 years. I�m deferring to Dr. Wesley Clark, CSATs Center Director, to help shed light on this issue. He will be presenting in the afternoon session at 1:45 pm. The analyses conducted utilized Verispan�s Vector One� National data base, also known as VONA, and IMS Health, IMS National Sales Perspectives: Retail and Non-Retail data base, both of which were utilized to compile and analyze the data. Vector One� database measures retail dispensing of prescriptions or the frequency with which drugs move out of retail pharmacies into the hands of consumers via formal prescriptions. Information on the physician specialty, the patient�s age and gender, and estimates for the numbers of patients that are continuing on or beginning new therapy is available. Vector One� integrates prescription activity from a variety of sources including national retail chains, mass merchandisers, mail order pharmacies, pharmacy benefits managers and their data systems, and provider groups. Vector One� receives over 2.0 billion prescription claims per year, representing over 160 million unique patients. Since 2002, Vector One� has captured information on over 8 billion prescriptions representing 200 million unique patients. Prescriptions are captured from a sample of approximately 59,000 pharmacies throughout the US. The pharmacies in the data base account for nearly all retail pharmacies and represent nearly half of retail prescriptions dispensed nationwide. Verispan receives all prescriptions from approximately one-third of the stores and a significant sample of prescriptions from the remaining stores. For prescription drug sales data and market share, IMS Health, IMS National Sales Perspectives was utilized. These data are based on national projections and the outlets within the retail market included the following pharmacy settings: chain drug stores, independent drug stores, mass merchandisers, food stores, and mail service. Outlets within the non-retail market include clinics, non-federal hospitals, federal facilities, HMOs, long-term care facilities, home health care, and other miscellaneous settings. When viewing these data, it�s also important to keep in mind the overall increase in U.S. population. In 1998, the U.S. population was approximately 270 million, and in 2006, the U.S. population was approximately 299 million. This equates to an overall increase of 29 million or a 10.7 percent increase in 9 years. The slides being presented contain a fair amount of information and given the presentation time limits, I�m going to hit upon major points of interests. At the same time, keep in mind that when looking at prescription volume for each of these drugs on each of these slides, it�s the volume dispensed that impacts the consumer directly. That�s the biggest focus. And the slides reflecting actual drug volume dispensed will come at the end of this presentation along with a slide representing each drug ranked nationally out of a possible total of 7,500 prescriptions drugs on the U.S. market. The first set of slides focuses on the total number of prescriptions for each of the previous mentioned prescription drugs; the actual increase or decrease in prescription drug volume; and the percent increase or decrease in prescription drug volume.Good morning. Today, I�m presenting on prescribing trends for 15 commonly prescribed controlled drugs that fall within the pharmacologic classes: opioid analgesics; benzodiazepines; stimulants; and barbiturates. All these products are further classified as scheduled controlled substances with a rating of CII through CV. The 15 drugs chosen for this analysis were based on their use relative to all other prescribed controlled drugs, potential for abuse, and potential for diversion from individuals for whom the prescriptions were intended. I would like to thank in advance Nick Reuter from the Division of Pharmacologic Therapies, CSAT, for his assistance in this presentation and a very special thanks to Dr. Hina Mehta and Dr. Vicky Borders-Hemphill, both Pharm.Ds from the Office of Surveillance and Epidemiology, FDA, for completing all the requests for compiling and analyzing the data for this presentation. This presentation could not have been completed without their assistance and the cooperation and partnership that exists between FDA and SAMHSA. Several types of analyses were performed that looked at prescription drug data spanning the last 10 years from 1998 through 2007. The drugs analyzed were oxycodone, hydrocodone, methadone, fentanyl, codeine, propoxyphene, alprazolam, lorazepam, diazepam, clonazepam, temazepam, amphetamine, methamphetamine, butalbital, and phenobarbital. To make the analyses more accurate and complete, we combined brand and generic drug data for each drug to give a more complete picture, e.g., Percocet, Oxycontin, Endocet, Percodan, Tylox, Oxy-IR, and Oxy-Fast, are several brand names containing Oxycodone in addition to firms manufacturing generic Oxycodone.� Some of these brands (and generics) contain not only Oxycodone alone but also contain acetaminophen or aspirin in combination. �Thus, to be complete and accurate, all products containing Oxycodone (brand and generic or combination products, e.g. Oxycodone plus Acetaminophen) have to be combined and accounted for to give a more accurate and complete picture. We created a break down of each drug prescribed by strength. For example, hydrocodone comes as 2.5, 3.5, 4.5, 5, 7, 7.5, and 10mg strengths. We then analyzed the total number of prescriptions dispensed for each drug; for each year; over the last 10 years from 1998 through 2007. We also analyzed the demographics by breaking down each drug into how many prescriptions were filled for men; how many for women; and how many prescriptions were filled for various age ranges using 10 year intervals to get a sense of which age range the drug product was most utilized. Finally, to give a more complete picture, we further analyzed the total number of tablets, capsules, patches, mls, etc., which we refer to as �extended units�, that were dispensed for each drug; for each year, from 1998 through 2007. This would reflect the volume of just how much drug product was being dispensed on a year to year basis. Now, what this presentation does not attempt to do is draw any conclusions or explain the reasons behind the prescribing trends over the last 10 years. I�m deferring to Dr. Wesley Clark, CSATs Center Director, to help shed light on this issue. He will be presenting in the afternoon session at 1:45 pm. The analyses conducted utilized Verispan�s Vector One� National data base, also known as VONA, and IMS Health, IMS National Sales Perspectives: Retail and Non-Retail data base, both of which were utilized to compile and analyze the data. Vector One� database measures retail dispensing of prescriptions or the frequency with which drugs move out of retail pharmacies into the hands of consumers via formal prescriptions. Information on the physician specialty, the patient�s age and gender, and estimates for the numbers of patients that are continuing on or beginning new therapy is available. Vector One� integrates prescription activity from a variety of sources including national retail chains, mass merchandisers, mail order pharmacies, pharmacy benefits managers and their data systems, and provider groups. Vector One� receives over 2.0 billion prescription claims per year, representing over 160 million unique patients. Since 2002, Vector One� has captured information on over 8 billion prescriptions representing 200 million unique patients. Prescriptions are captured from a sample of approximately 59,000 pharmacies throughout the US. The pharmacies in the data base account for nearly all retail pharmacies and represent nearly half of retail prescriptions dispensed nationwide. Verispan receives all prescriptions from approximately one-third of the stores and a significant sample of prescriptions from the remaining stores. For prescription drug sales data and market share, IMS Health, IMS National Sales Perspectives was utilized. These data are based on national projections and the outlets within the retail market included the following pharmacy settings: chain drug stores, independent drug stores, mass merchandisers, food stores, and mail service. Outlets within the non-retail market include clinics, non-federal hospitals, federal facilities, HMOs, long-term care facilities, home health care, and other miscellaneous settings. When viewing these data, it�s also important to keep in mind the overall increase in U.S. population. In 1998, the U.S. population was approximately 270 million, and in 2006, the U.S. population was approximately 299 million. This equates to an overall increase of 29 million or a 10.7 percent increase in 9 years. The slides being presented contain a fair amount of information and given the presentation time limits, I�m going to hit upon major points of interests. At the same time, keep in mind that when looking at prescription volume for each of these drugs on each of these slides, it�s the volume dispensed that impacts the consumer directly. That�s the biggest focus. And the slides reflecting actual drug volume dispensed will come at the end of this presentation along with a slide representing each drug ranked nationally out of a possible total of 7,500 prescriptions drugs on the U.S. market. The first set of slides focuses on the total number of prescriptions for each of the previous mentioned prescription drugs; the actual increase or decrease in prescription drug volume; and the percent increase or decrease in prescription drug volume.

2. Verispan, LLC: Vector One�: National, Years 1998-2007, Extracted 7/08 In the next set of slides, Figures 1 through 5, focus on the total number of prescriptions for each of the previous mentioned prescription drugs, the actual increase or decrease in prescription volume, and the percent increase or decrease in prescription volume. Figure #1 shows the total number of propoxyphene and codeine prescriptions from 1998 through 2007. Here, volume decreased year to year for a total decrease of 11.6 million codeine prescriptions and 8.4 million propoxyphene prescriptions, representing a 36.5% decrease for codeine and 27% decrease for propoxyphene.In the next set of slides, Figures 1 through 5, focus on the total number of prescriptions for each of the previous mentioned prescription drugs, the actual increase or decrease in prescription volume, and the percent increase or decrease in prescription volume. Figure #1 shows the total number of propoxyphene and codeine prescriptions from 1998 through 2007. Here, volume decreased year to year for a total decrease of 11.6 million codeine prescriptions and 8.4 million propoxyphene prescriptions, representing a 36.5% decrease for codeine and 27% decrease for propoxyphene.

3. Dispensed prescriptions for methadone have increased by approximately 794% from 1998 to 2007. 463% increase for amphetamine, 409% increase for Fentanyl, 114% increase for clonazepam, 30% increase for temazepam, 24% increase for lorazepam, and 17% increase for diazepam. 65% decrease for methamphetamines, 61% decrease for butalbital, and 22% decrease for phenobarbital. Verispan, LLC: Vector One�: National, Years 1998-2007, Extracted 7/08 I recognize Figure #2 is a very busy slide, so bear with me here. What can not be emphasized enough in this slide and the following slides are both the rapid, and very significant increase in prescription volume for the majority of these drugs in the last 10 reportable years. Here, you can see total methadone increased by 3.7 million prescriptions from 1998 through 2007 which equates to a percent increase of nearly 800%. Amphetamine prescription volume increased by 463% or 11.7 million prescriptions, and there was a 409% increase for Fentanyl or 4.5 million prescriptions for the same time period. As for the benzodiazepines, there was a 114% increase in clonazepam which represents 10.9 million prescriptions, 30% increase in temazepam or 1.9 million prescriptions, a 24% increase in lorazepam which represents 4.2 million prescriptions, and a 17% increase in diazepam represented by 2.1 million prescriptions. Those drug prescriptions that decreased in this slide were phenobarbital, which decreased by 22% or 820 thousand prescriptions, butalbital which went down 61% or 381 thousand prescriptions, and finally, methamphetamines which decreased by 65% or approximately 36 thousand prescriptions. Methamphetamine prescriptions have greatly fallen out of favor over the decades and have since been replaced by a dramatic rise in amphetamine prescriptions.I recognize Figure #2 is a very busy slide, so bear with me here. What can not be emphasized enough in this slide and the following slides are both the rapid, and very significant increase in prescription volume for the majority of these drugs in the last 10 reportable years. Here, you can see total methadone increased by 3.7 million prescriptions from 1998 through 2007 which equates to a percent increase of nearly 800%. Amphetamine prescription volume increased by 463% or 11.7 million prescriptions, and there was a 409% increase for Fentanyl or 4.5 million prescriptions for the same time period. As for the benzodiazepines, there was a 114% increase in clonazepam which represents 10.9 million prescriptions, 30% increase in temazepam or 1.9 million prescriptions, a 24% increase in lorazepam which represents 4.2 million prescriptions, and a 17% increase in diazepam represented by 2.1 million prescriptions. Those drug prescriptions that decreased in this slide were phenobarbital, which decreased by 22% or 820 thousand prescriptions, butalbital which went down 61% or 381 thousand prescriptions, and finally, methamphetamines which decreased by 65% or approximately 36 thousand prescriptions. Methamphetamine prescriptions have greatly fallen out of favor over the decades and have since been replaced by a dramatic rise in amphetamine prescriptions.

4. Oxycodone prescriptions increased by 166% from 1998 to 2007 and alprazolam increased by 71% in the same period. Verispan, LLC: Vector One�: National, Years 1998-2007, Extracted 7/08 In Figure #3, from 1998 to 2007, alprazolam increased overall by 17.6 million prescriptions or 71%, from 24.8 million to 42.4 million prescriptions in 2007, and oxycodone increased by 26.4 million prescriptions or 166%, to 42.2 million prescriptions in 2007.In Figure #3, from 1998 to 2007, alprazolam increased overall by 17.6 million prescriptions or 71%, from 24.8 million to 42.4 million prescriptions in 2007, and oxycodone increased by 26.4 million prescriptions or 166%, to 42.2 million prescriptions in 2007.

5. 94% increase in prescriptions of hydrocodone being dispensed from 1998 to 2007. Verispan, LLC: Vector One�: National, Years 1998-2007, Extracted 7/08 Finally, in Figure #4, hydrocodone prescription volume tops the list by increasing from 63.6 million prescriptions in 1998 to 123.3 million prescriptions in 2007, which is a net increase in 59.7 million prescriptions by 2007 compared to 1998, a 94% increase.Finally, in Figure #4, hydrocodone prescription volume tops the list by increasing from 63.6 million prescriptions in 1998 to 123.3 million prescriptions in 2007, which is a net increase in 59.7 million prescriptions by 2007 compared to 1998, a 94% increase.

6. Of the selected agents, products containing hydrocodone were the top dispensed in the U.S. from 1998-2007. Dispensed prescriptions for methadone have increased by approximately 794% followed by amphetamine, Fentanyl, oxycodone, clonazepam, and hydrocodone at 463%, 409%, 166%, 114%, and 94%, respectively from 1998 to 2007. Verispan, LLC: Vector One�: National, Years 1998-2007, Extracted 7/08 Figure #5 is a summation of Figures #1 through #4. It�s important to keep in mind that when looking at any of these slides, one has to view them by considering the increase or decrease in prescription volume, together with the percent change, to get a more complete perspective of the prescribing trends. You can not show prescription volume alone without percent change, and vice versa, without skewing the overall perspective relative to prescription and drug volume trending.Figure #5 is a summation of Figures #1 through #4. It�s important to keep in mind that when looking at any of these slides, one has to view them by considering the increase or decrease in prescription volume, together with the percent change, to get a more complete perspective of the prescribing trends. You can not show prescription volume alone without percent change, and vice versa, without skewing the overall perspective relative to prescription and drug volume trending.

7. Channels of Distribution for Selected Prescription Drugs Sales data for oxycodone, hydrocodone, methadone, codeine, propoxyphene, alprazolam, lorazepam, diazepam, clonazepam, temazepam, amphetamine, methamphetamine, butalbital, and phenobarbital by number of tablets, capsules, and mL sold in year 2007 indicate that the majority of distribution is toward outpatient pharmacy settings* (80% or greater). The only exception is with Fentanyl in which 21% of distribution is toward outpatient pharmacy settings while 78% is toward inpatient settings.