John Coleman Comment on DEA-319

Comment: It is recommended that, pursuant to 21 CFR 1308.45, the Administrator of the Drug Enforcement Administration (DEA) expedite the issuance and effective date of the Final Order placing tapentadol in Schedule II of the Controlled Substances Act. The conditions of public health that necessitate and justify this request are described as follows: According to the Drug Shortage website of the Food and Drug Administration (FDA), updated March 16, 2009, there exists a shortage of oxycodone immediate release tablets (5 mg, 15 mg, and 30 mg). The reason for this shortage, according to the FDA, is an “increase in demand related to product recalls by other manufacturers.” (see: http://www.fda.gov/cder/drug/shortages/default.htm#Current) One of the other manufacturers identified by the FDA report is KV Pharmaceutical Company of St. Louis, MO, (KV) a leading specialty pharmaceutical company that develops, manufactures, and markets branded, generic/non-branded, and specialty ingredient products, including oxycodone tablets in the above-cited dosage strengths. On or about January 28, 2009, the FDA published a notice of Recall-Firm Press Release reporting a nationwide voluntary recall of products by the ETHEX Corporation, a division of KV. (See: http://www.fda.gov/oc/po/firmrecalls/ethex01_09.html) The following scheduled opioids are among the products recalled by the ETHEX Corporation: Products Recalled to WHOLESALE Level: Hydrocodone Bitartrate & Acetaminophen Liquid (58177-909-07) Hydrocodone Bitartrate/Guaifenesin Liquid (58177-881-07) Meperidine/Promethazidne Capsules (58177-027-04) Morphine InveAmp, 20mg x 1mL (58177-886-56) Morphine InveAmp, 5mg/.25mL (58177-888-80) Morphine Sulfate Concentrated Oral Solution 20mg/1ml (58177-886-01, 886-03 &886-05) Morphine Sulfate Concentrated Oral Solution, 20mg/1ml (58177-886-57) Morphine Sulfate ER Tablets, 100mg (58177-340-04) Morphine Sulfate ER Tablets, 15mg (58177-310-04) Morphine Sulfate ER Tablets, 200mg (58177-380-04) Morphine Sulfate ER Tablets, 30mg (58177-320-04) Morphine Sulfate ER Tablets, 60mg (58177-330-04) Morphine Sulfate IR Tablets, 15mg (58177-313-04) Morphine Sulfate IR Tablets, 30mg (58177-314-04) Oxycodone HCl Capsules, 5mg (58177-041-04 & 041-11) Oxycodone HCl IR Tablets, 10mg (58177-461-04) Oxycodone HCl IR Tablets, 15mg, (58177-445-04) Oxycodone HCl IR Tablets, 20mg (58177-462-04) Oxycodone HCl IR Tablets, 30mg (58177-446-04) Oxycodone HCl IR Tablets, 5mg (58177-625-04 & 625-11) Products Recalled to RETAIL PHARMACY Level: Hydromorphone HCl Tablets, 2mg (58177-620-04 & 620-11) Hydromorphone HCl Tablets, 4mg (58177-621-04 & 621-11) Hydromorphone HCl Tablets, 8mg (58177-449-04) On March 2, 2009 KV entered into a consent decree with the FDA regarding the company’s drug manufacturing and distribution services. According to a company statement, “The decree provides a series of measures that, when satisfied, will permit KV to resume the manufacture and distribution of products marketed by its subsidiaries, ETHEX and Ther-Rx.” (See: http://www.kvpharmaceutical.com/news_center_article.aspx?articleid=284) Based on a description of the measures required to be taken by KV to satisfy the consent decree, it is likely that this major source of Schedule II and III opioids will not resume manufacturing and distribution services for a considerable amount of time. As a result, it also is likely that the current shortage of immediate release oxycodone tablets will continue. Moreover, although not yet declared by the FDA, shortages in morphine and hydromorphone immediate release tablets may result from KV’s recent recalls of its morphine and hydromorphone immediate release products, especially in view of the already increased demand for these products occasioned by the shortage of oxycodone. Tapentadol is a new molecular entity with centrally-acting analgesic properties. In its clinical assessment of tapentadol’s analgesic activity, the FDA review states the following: "In clinical trials, tapentadol has been demonstrated to be a very effective analgesic at comparable levels of analgesia as other Schedule II opioids, e.g. morphine and oxycodone. In a trial evaluating the effectiveness of tapentadol IR (50 and 100 mg) to oxycodone IR (10 mg) in bunionectomy patients, both doses of tapentadol were as effective as oxycodone over a 4-day evaluation period (Stegmann and Webber 2008). The analgesic efficacy of tapentadol ER (100 or 200 mg) and oxycodone CR (20 mg) was compared in patients with moderate-to- severe pain resulting from osteoarthritis in the knee. Both doses of tapentadol were comparable to oxycodone in effectively providing pain relief over the 28-day observation period (Rauschkolb-Loeffler and Okamoto 2008)." (See: p. 4 of Docket DEA-2009-002, Schedules of Controlled Substances: Placement of Tapentadol Into Schedule II; Tapentadol 8-factor 12192008 final draft.) Because of the current FDA-declared shortage of oxycodone and a potential future shortage of morphine and hydromorphone immediate release products, I believe that conditions of public health justify this request for an expedited Final Order with an effective date on the date of issuance. Permitting tapentadol to enter the market as soon as possible will minimize the effect of the current shortage of oxycodone on the patient population in need of immediate release Schedule II analgesics. It will provide a safe and effective substitute with equivalent analgesic properties. It also may help to prevent further disruptions in the supply of important analgesic drug products that may occur as a result of the above-described recent opioid product recalls.