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Study Characterizes Extractability Properties of Once-Daily Extended-Release Hydromorphone

^{Published on 2011-05-19 05:11:11 - Market Wire}
 

AUSTIN, Texas--([ BUSINESS WIRE ])--Covidien (NYSE: COV), a leading global provider of healthcare products, announced the results of two studies that compare the physical and pharmacological properties of once-daily hydromorphone extended-release (ER) tablets to immediate-release (IR) hydromorphone and other ER opioids. The studies will be presented at the American Pain Societya™s Annual Scientific Meeting being held here May 19-21.

"As a supplier of opioid pain medications in the United States, Covidiena™s Mallinckrodt business is dedicated to safe and appropriate use of these important pain treatments"

In the United States, once-daily hydromorphone ER is approved by the U.S. Food and Drug Administration (FDA) under the brand name EXALGO^® (hydromorphone HCl) Extended-Release Tablets (CII). It is indicated for opioid-tolerant patients with moderate-to-severe pain requiring continuous, around-the-clock analgesia for an extended period of time. It is not intended to be used for as-needed pain relief and is not indicated for the management of acute or postoperative pain. EXALGO is designed using the OROS^® drug delivery system,which releases hydromorphone at a controlled rate.

The intentional manipulation of long-acting opioids by chewing or crushing to achieve a rapid onset of effect, or high, is a growing problem in the United States. In an in vitro study, once-daily hydromorphone ER tablets (32 mg) were evaluated versus other ER opioids for certain physical properties related to manipulation, including hardness, tablet milling and dissolution/extraction. Results of hardness testing demonstrated that once-daily hydromorphone ER withstood significantly more force before cracking than the active comparator (>80-125 lb_f vs. <20 lb_f, respectively). Milling the tablets yielded approximately 30 percent of active ingredient from once-daily hydromorphone ER in the smallest particle-size fraction versus approximately 65 percent from the active comparator. The 32 mg formulation is not FDA approved.

A component that physicians consider when monitoring patients for the risks of abuse during pain management is adrug likability.a A rapid peak in euphoric or pleasurable effect a patient may experience soon after the administration of some drugs is a significant factor in determining adrug likability.a Separately, in a previously reported open-label, repeat-dose study of 22 patients, once-daily hydromorphone ER was shown to provide predictable, consistent 24-hour blood plasma levels of hydromorphone at steady state (four days after administration is started), reducing peaks and troughs compared to those levels seen with IR hydromorphone. At steady state, the mean peak-to-trough fluctuation in plasma levels was 60.5 percent 41.1 percent with once-daily hydromorphone ER versus 172 percent 57.6 percent with hydromorphone IR. Further, the current analysis demonstrated that once-daily hydromorphone mean concentrations remained above 50 percent of the maximum plasma concentration (C_max) substantially longer than hydromorphone IR (20.5 hours vs. 7.5 hours).

aAs a supplier of opioid pain medications in the United States, Covidiena™s Mallinckrodt business is dedicated to safe and appropriate use of these important pain treatments,a said Herbert Neuman, M.D., Vice President, Medical Affairs and Chief Medical Officer, Pharmaceuticals, Covidien. aAlthough once-daily hydromorphone ER can still be misused or abused, these studies indicate that the pharmacological and physical properties of this formulation are performing as designed to make it less susceptible to blood plasma level peaks and troughs and potentially difficult to manipulate.a

Key clinical poster presentations at the meeting include:

• Characterization of the Pharmacokinetic Profile of Single-Dose Once-Daily Hydromorphone ER (OROS Hydromorphone ER) Versus IR Hydromorphone Administered Over 24 Hours in Healthy Subjects
• Tamper-Resistant Properties of Once-Daily Hydromorphone ER (OROS Hydromorphone ER)
• Characterization of the Steady-State Pharmacokinetic Profile of Once-Daily Hydromorphone ER (OROS Hydromorphone ER) Versus IR Hydromorphone in Healthy Subjects
• Sustained Safety and Efficacy of Once-Daily Hydromorphone ER (OROS Hydromorphone ER) Compared With Twice-Daily Oxycodone CR Over 52 Weeks in Patients With Moderate to Severe Chronic Noncancer Pain
• A Repeat-Dose, Steady-State Pharmacokinetic Evaluation of Once-Daily Hydromorphone ER (OROS Hydromorphone ER) in Patients With Chronic Cancer or Noncancer Pain

• EXALGO is also contraindicated in patients who:
  • have significant impaired respiratory function including those with acute or severe bronchial asthma or hypercarbia
  • have or are suspected to have paralytic ileus
  • have narrowed or obstructed gastrointestinal (GI) tract including those from previous surgery or ablind loopsa in the GI tract
  • have known hypersensitivity to any components including hydromorphone hydrochloride and sulfites
• Avoid concurrent use of EXALGO and alcohol. Concurrent use of EXALGO with central nervous system depressants, including alcohol, increases risk of respiratory depression, hypotension, and profound sedation, potentially resulting in coma or death. EXALGO may impair the ability to drive a car or operate machinery.
• EXALGO is not intended for use in patients who have received monoamine oxidase inhibitors within 14 days of starting EXALGO.
• Use with caution and in reduced doses in older or debilitated patients, as well as patients with renal or hepatic insufficiency, Addisona™s disease, delirium tremens, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, toxic psychosis. May aggravate convulsions in patients with convulsive disorders; may induce or aggravate seizures in some clinical settings. Consider use of an alternate analgesic in patients with severe renal impairment.
• Use EXALGO with extreme caution in patients susceptible to the intracranial effects of CO₂ retention.
• Respiratory depression, which occurs more frequently in elderly or debilitated patients, is the chief hazard with EXALGO.
• EXALGO should not be abruptly discontinued. Administer no more frequently than every 24 hours. Titrate doses no more often than every 3-4 days to achieve steady state plasma levels.
• Do not abruptly discontinue EXALGO.
• Serious adverse events could also include hypotensive effects, GI effects, cardiac arrest from overdose and precipitation of withdrawal. Most common adverse events (>10%) are: constipation (31%), nausea (28%), vomiting, somnolence, headache and dizziness.

See Full Prescribing Information for additional Important Risk Information.
[ http://www.exalgo.com/media/pdf/EXALGO_FullPrescribingInformation.pdf ]

EXALGO is a registered trademark of Mallinckrodt Inc.

OROS is a registered trademark of ALZA Corporation.

ABOUT COVIDIEN

Covidien is a leading global healthcare products company that creates innovative medical solutions for better patient outcomes and delivers value through clinical leadership and excellence. Covidien manufactures, distributes and services a diverse range of industry-leading product lines in three segments: Medical Devices, Pharmaceuticals and Medical Supplies. With 2010 revenue of $10.4 billion, Covidien has 41,000 employees worldwide in more than 65 countries, and its products are sold in over 140 countries. Please visit [ www.covidien.com ] to learn more about our business.