|Properties of OROS(R)
technology also shown to provide predictable, consistent blood plasma
levels of hydromorphone at steady-state, reducing peaks and troughs|
AUSTIN, Texas, May 19, 2011 (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 Society's
Annual Scientific Meeting being held here May 19-21.
In the United States, once-daily hydromorphone ER is approved by the
U.S. Food and Drug Administration (FDA) under the brand name EXALGO(R)
(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(R) 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 lbf vs. <20 lbf, 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 "drug likability." 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
"drug likability." 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 (Cmax) substantially longer than
hydromorphone IR (20.5 hours vs. 7.5 hours).
"As a supplier of opioid pain medications in the United States,
Covidien's Mallinckrodt business is dedicated to safe and appropriate
use of these important pain treatments," said Herbert Neuman, M.D., Vice
President, Medical Affairs and Chief Medical Officer, Pharmaceuticals,
Covidien. "Although 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."
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
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
IMPORTANT RISK INFORMATION FOR EXALGO
WARNING: POTENTIAL FOR ABUSE, IMPORTANCE OF PROPER PATIENT
AND LIMITATIONS OF USE
Potential for Abuse
contains hydromorphone, an opioid agonist and a Schedule II
controlled substance with an abuse liability similar to other
opioid analgesics. EXALGO can be abused in a manner similar to
other opioid agonists, legal or illicit. These risks should be
considered when administering, prescribing, or dispensing EXALGO
in situations where the healthcare professional is concerned about
the risks of misuse, abuse or diversion. Schedule II opioid
substances which include hydromorphone, morphine, oxycodone,
fentanyl, oxymorphone and methadone have the highest potential for
abuse and risk of fatal overdose due to respiratory depression.
EXALGO is an extended-release
formulation of hydromorphone hydrochloride indicated for the
management of moderate to severe pain in opioid tolerant patients
when a continuous around-the-clock opioid analgesic is needed for
an extended period of time. Patients considered opioid tolerant
are those who are taking at least 60 mg oral morphine per day, 25
mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral
hydromorphone/day, 25 mg oral oxymorphone/day or an equianalgesic
dose of another opioid, for a week or longer.
is for use in opioid tolerant patients only.
respiratory depression could occur in patients who are not opioid
Accidental consumption of EXALGO,
especially in children, can result in a fatal overdose of
EXALGO is not indicated for the
management of acute or postoperative pain.
is not intended for use as an as-needed analgesic.
tablets are to be swallowed whole and are not to be broken,
chewed, dissolved, crushed or injected. Taking broken, chewed,
dissolved or crushed EXALGO or its contents leads to rapid release
and absorption of a potentially fatal dose of hydromorphone.
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 "blind loops" 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,
Addison'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
EXALGO is a registered trademark of Mallinckrodt Inc.
OROS is a registered trademark of ALZA Corporation.
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.
Coleman Lannum, CFA