New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 Through 2015

Grace Chai, Pharm.D.; Jing Xu, Ph.D., M.A.; James Osterhout, Ph.D.; Mark A. Liberatore, Pharm.D., R.A.C.; Kathleen L. Miller, Ph.D.; Carolyn Wolff, Ph.D.; Marisa Cruz, M.D.; Peter Lurie, M.D., M.P.H. and Gerald Dal Pan, M.D., M.H.S.

Disclosures

Anesthesiology. 2018;128(5):953-966. 

In This Article

Results

New Product Approvals

From 1997 through 2015, 263 new opioid analgesic applications were approved, including 222 abbreviated new drug applications and 41 new drug applications (Figure 1). Thirty-three (33) of the 41 new drug applications approvals were for brand products. The annual number of approvals, which generally increased over time, was higher in the second half of the study period (2007 through 2015; median, 20 approvals/yr; range, 10 to 27) than in the first half (1997 through 2006; median, 9 approvals/yr; range, 5 to 15).

Figure 1.

Number of U.S. Food and Drug Administration (FDA) approvals of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for opioid analgesic products by year of approval from 1997 through 2015.

National Prescription Trends

The nationally estimated number of prescriptions dispensed for opioid analgesics initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015 (Table 1). Adjusted for the total U.S. Census population, the overall trends were similar, but the peak in population-adjusted utilization during the study period was in years 2010 to 2012 (Figure 2). Total morphine milligram equivalents dispensed increased from 70 billion dispensed in 1997 to a peak of 244 billion in 2010 before decreasing by 16% to 206 billion morphine milligram equivalents dispensed in 2015. Morphine milligram equivalents per prescription dispensed nearly doubled from 486 in 1997 to a peak of 950 in 2010 before decreasing to 905 morphine milligram equivalents per prescription in 2015. Generic products accounted for 96% of opioid analgesic prescriptions dispensed in 2015, compared to 68% of total prescriptions in 1997.

Figure 2.

Nationally estimated annual number of opioid analgesics dispensed in number of morphine milligram equivalents (MME, right axis, line graph) and in number of prescriptions (left axis, bar graph), by brand (brand and branded generics) and generic product, adjusted for the U.S. population, from U.S. outpatient retail pharmacies. Estimates were derived from the following sources: Total U.S. Census Population projections and estimates and IQVIA, National Prescription Audit. Brand: All trade name products including Brand and Branded Generic products. Excludes injectable formulations, opioid containing cough/cold products, and opioid-containing medication assistance therapy products.

New Brand Product Approvals

Of the 33 brand products approved as new drug application between 1997 and 2015, 23 brand products were dispensed in 2015. The annual combined market share of the 23 brand products accounted for 3% of all opioid analgesic prescriptions dispensed in 2015 (Figure 3 and Appendix 3), largely dispensed for a single brand product (OxyContin); the combined market share of the other 22 brand products accounted for only 1% of the total opioid analgesic market in 2015. Tapentadol (Nucynta, 2008, and Nucynta ER, 2011; Ortho-McNeil, USA), the only new molecular entity approved during the study period, accounted for 0.3% of the total opioid analgesic market in 2015.

Figure 3.

Nationally estimated annual number of prescriptions dispensed for the top 10 newly approved opioid analgesic brand products (left axis, bar graph) and the combined market share of all newly approved opioid analgesic brand products (right axis, line graph) in the U.S. outpatient retail pharmacy setting from 1997 through 2015. Source: IQVIA, National Prescription Audit. Individual brand products represent the brand opioid analgesics dispensed in 2015 that were introduced into the market from 1997 to 2015. Only brand utilization is shown—does not include generic utilization. Solid line represents the combined market share for all brand products approved between 1997 and 2015, out of the total opioid analgesic market. Opana ER includes original formulation (approved 2006) and reformulation (approved 2011). OxyContin includes original formulation (approved 1995) and reformulation (approved 2010). Utilization excludes injectable formulations, opioid-containing cough/cold products, and opioid-containing medication assistance therapy products. *All Others includes all brand opioid analgesic products approved between 1997 and 2015 that are not individually shown. ER = extended-release formulation.

Figure 4 shows prescriptions dispensed for OxyContin and generic extended-release oxycodone increased from nearly 1 million prescriptions dispensed in 1997 to about 7 to 7.5 million prescriptions dispensed annually between 2001 and 2010 (the year reformulated OxyContin was introduced and original OxyContin marketing ceased), before decreasing by 39% from approximately 7 million prescriptions in 2010 to nearly 4.5 million prescriptions 2015. In terms of morphine milligram equivalents dispensed, approximately 33 billion morphine milligram equivalents were dispensed for extended-release oxycodone at its peak in 2010, accounting for 14% of total morphine milligram equivalents dispensed for the total opioid analgesic market.

Figure 4.

Nationally estimated annual number of dispensed prescriptions and morphine milligram equivalents (MME) dispensed for extended-release oxycodone (brand and generic products, left axis, bar graph) and their market share of total opioid analgesic prescriptions or MME dispensed (right axis, line graph) from U.S. outpatient retail pharmacies. Source: IQVIA, National Prescription Audit. ER = extended-release formulation.

Generic Product Approvals

The six most frequently dispensed opioid analgesic products in 2015 were oral immediate-release formulations of hydrocodone/acetaminophen (40% of total opioid analgesic prescriptions), single-ingredient tramadol (17%), oxycodone/acetaminophen (15%), single-ingredient oxycodone (8%), codeine/acetaminophen (7%), and extended-release morphine (3%), together accounting for nearly 90% of all opioid analgesic prescriptions dispensed in 2015. The majority of these prescriptions were dispensed as generics throughout the examined time (Figure 5). For the examined drugs, the number of prescriptions dispensed generally increased as the cumulative number of generic product approvals increased with the exceptions of hydrocodone/acetaminophen and codeine/acetaminophen. Prescriptions dispensed for hydrocodone/acetaminophen more than doubled from 53 million prescriptions in 1997 to a peak of 129 million prescriptions in 2011 to 2012 before decreasing 29% to 91 million prescriptions in 2015. Prescriptions generally declined for codeine/acetaminophen throughout the examined time before a 27% increase in prescriptions dispensed from 11 million prescriptions in 2013 to 15 million prescriptions in 2015.

Figure 5.

Cumulative number of new U.S. Food and Drug Administration generic product approvals (right axis, line graph) and the nationally estimated annual number of prescriptions dispensed (left axis, bar graph) from U.S. outpatient retail pharmacies for the six most frequently dispensed opioid analgesics from 1997 through 2015. Source: IQVIA, National Prescription Audit. *Branded: All trade name products including Brand and Branded Generic products. Excludes injectable formulations, opioid-containing cough/cold products, and opioid-containing medication assistance therapy products. ER = extended release formulations; IR = immediate-release formulations.

Generic versions of six opioid analgesics, which were dispensed for the first time during years 2006 through 2015, are shown in Figure 6. Four of the six opioid analgesic products with initial generic approvals between 2006 and 2015 (extended-release hydromorphone, extended-release tramadol, transmucosal immediate-release fentanyl products [excluding sprays], and oxycodone/ibuprofen) showed declines in total dispensing after generic introduction, while two (oxymorphone and extended-release oxymorphone) showed essentially stable total dispensing. In some cases, the decrease in prescriptions began before the introduction of generics.

Figure 6.

Cumulative number of U.S. Food and Drug Administration generic approvals (right axis, line graph) and the nationally estimated annual number of prescriptions dispensed (left axis, bar graph) from U.S. outpatient retail pharmacies for opioid analgesics with "newly marketed generics," stratified by brand (brand and branded generic) and generic products from 2006 through 2015. Source: IQVIA, National Prescription Audit. *Branded: All trade name products including Brand and Branded Generic products. **Newly marketed generics: Generic versions for opioid analgesics, where the generics were dispensed for the first time during 2006–2015. Excludes injectable formulations, opioid-containing cough/cold products, and opioid-containing medication assistance therapy products. Oral solid products for Transmucosal Immediate-Release Fentanyl (TIRFs) were included. Brand TIRF products include Abstral, Actiq, Fentora, Onsolis (does not include sprays). Brand product of hydromorphone ER includes Exalgo. Brand products of tramadol include Ultram ER, Conzip, and Ryzolt. ER = extended release formulation; IR = immediate-release formulation.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....