ST. LOUIS--(BUSINESS WIRE)--Aug. 27, 2012--
The U.S. Food and Drug Administration (FDA) has notified Mallinckrodt,
the pharmaceuticals business of Covidien (NYSE:COV), that it has
approved a 32 mg tablet strength of EXALGO® (hydromorphone
HCI) Extended-Release Tablets (CII) for opioid-tolerant patients with
moderate-to-severe chronic pain requiring continuous around-the-clock
opioid analgesia for an extended period of time. The FDA approved the 8,
12 and 16 mg tablets of EXALGO in March 2010 and the Supplemental New
Drug Application (sNDA) for the 32 mg tablet was submitted in January
2012 with post-marketing data to support the original application’s
compendium of clinical trials demonstrating efficacy and tolerability.
The EXALGO 32 mg tablet strength will be available in the next few weeks.
“We believe that the new 32 mg tablet - delivered by the same
extended-release OROS® technology used with the 8, 12, and 16
mg tablets - will provide an established pharmacologic profile and
analgesic potency of once-daily hydromorphone. This new EXALGO 32 mg
tablet represents an important milestone as 32 mg was the median
effective dose upon which patients were stabilized during the pivotal
trial,” said Thomas Smith, M.D., Chief Medical Officer, Mallinckrodt.
“By providing a variety of tablet strengths, we hope that physicians and
opioid-tolerant patients can work together to develop and tailor a
treatment regimen that adequately and appropriately controls their
EXALGO utilizes the OROS drug delivery system designed to
release the opioid analgesic at a controlled rate. By providing a steady
release of hydromorphone throughout the day once steady-state is
achieved after three to four days, the drug is formulated to help
minimize the peaks and valleys that are sometimes experienced by chronic
pain patients who rely on immediate-release products that are dosed at
more frequent intervals. Additionally, the physical properties of EXALGO
may make it difficult to extract the active ingredient using common
forms of physical and chemical tampering, including chewing, crushing
and dissolving. OROS technology has been used in products for various
therapeutic areas for more than 30 years.
There are an estimated 116 million Americans1 with chronic
pain. According to a survey of 1,000 patients, many people have made
life-altering changes such as taking disability leave from work,
changing jobs altogether, getting help with activities of daily living
and moving to a home that is easier to manage.2 While opioid
therapy to help reduce their pain levels is not appropriate for all of
these patients, it is critically important for all patients to work with
their physicians to find the right treatment, including the right dosing
regimen if medications are used.
“Physicians may try as many as five types of opioids before finding a
treatment plan that provides pain relief to patients,” said Dr. Joseph
Shurman, Chairman, Pain Management, at Scripps Memorial Hospital.
“Sustained release treatments like EXALGO help patients avoid
fluctuations in blood plasma levels and a new tablet strength provides
more options for physicians to use with their opioid-tolerant patients."
All EXALGO dosage strengths, including the new 32 mg tablet, are subject
to the recently approved Risk Evaluation and Mitigation Strategy (REMS)
program for all long-acting and extended-release opioids. The three
primary components of this REMS program are: training for prescribers in
the form of continuing medical education (CME) initiatives, which will
be available by March 2013; updated medication guides for each opioid
and a patient counseling document; and assessment and auditing to ensure
the reach and effectiveness of prescriber training.
Mallinckrodt fully supports the efforts coordinated by the White House
Office of National Drug Control Policy to address the abuse, misuse and
overdose of these opioid analgesics.
In order to ensure a smooth transition to the class-wide REMS program,
Mallinckrodt will maintain the current EXALGO REMS program web site at www.exalgorems.com
and continue to provide important EXALGO prescribing information, with a
focus on appropriate patient selection and dosing, to new prescribers.
In addition, Mallinckrodt continues to provide to health care
professionals, patients and caregivers more than 60 educational tools,
at no cost, on the safe and appropriate prescribing, dispensing and use
of opioids at www.caresalliance.org.
Mallinckrodt is committed to ensuring that patients have access to
medications that adequately control their pain. If a patient cannot
afford their EXALGO prescription, Mallinckrodt may be able to help. More
information about the Patient Assistance Program is available by calling
1-800-259-7765. Some rules and restrictions may apply.
Beyond the Patient Assistance Program, Mallinckrodt also offers EXALGO
Co-Pay Cards to certain eligible patients. Those eligible patients can
show their Co-Pay Card to their pharmacist and save every time they fill
their prescription for EXALGO. If a patient did not receive a Co-Pay
Card enrollment form from their physician, they can access one by
IMPORTANT RISK INFORMATION
EXALGO® (hydromorphone HCI) Extended-Release Tablets (CII) is
indicated for the management of moderate to severe pain in opioid
tolerant patients requiring continuous, around-the-clock opioid
analgesia for an extended period of time.
IMPORTANT RISK INFORMATION
WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION,
and ACCIDENTAL EXPOSURE
EXALGO contains hydromorphone, an opioid agonist and a Schedule
II controlled substance with an abuse liability similar to other
opioid agonists, legal or illicit. Assess each patient’s risk for
opioid abuse or addiction prior to prescribing EXALGO. The risk
for opioid abuse is increased in patients with a personal or
family history of substance abuse (including drug or alcohol abuse
or addiction) or mental illness (e.g., major depressive disorder).
Routinely monitor all patients receiving EXALGO for signs of
misuse, abuse, and addiction during treatment.
Life-threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with
use of EXALGO, even when the drug has been used as recommended and
not misused or abused. EXALGO is for use in opioid tolerant
patients only. Proper dosing and titration are essential and
EXALGO should be prescribed only by healthcare professionals who
are knowledgeable in the use of potent opioids for the management
of chronic pain. Monitor for respiratory depression, especially
during initiation of EXALGO or following a dose increase.
Crushing, dissolving, or chewing the tablet can cause rapid
release and absorption of a potentially fatal dose of
Accidental ingestion of EXALGO, especially in children, can
result in a fatal overdose of hydromorphone.
EXALGO is contraindicated in:
Opioid non-tolerant patients. Fatal respiratory depression could
occur in patients who are not opioid tolerant.
Patients with significant respiratory depression
Patients with acute or severe bronchial asthma in an unmonitored
setting or in the absence of resuscitative equipment
Patients with known or suspected paralytic ileus
Patients who have had surgical procedures and/or underlying
disease resulting in narrowing of the gastrointestinal tract, or
have “blind loops” of the gastrointestinal tract or
Patients with hypersensitivity (e.g., anaphylaxis) to
hydromorphone or sulfite-containing medications
EXALGO is indicated for opioid tolerant patients only. 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.
EXALGO is not intended for use as an as-needed analgesic and is not
indicated for the management of acute or postoperative pain. It is
contraindicated in patients who need management of mild pain or pain
not expected to persist.
Avoid concurrent use of alcohol and EXALGO. Concurrent use of EXALGO
with CNS 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
Not intended in patients who have received MAO 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.
Respiratory depression, which occurs more frequently in elderly or
debilitated patients, is the chief hazard with EXALGO.
Serious adverse events could also include hypotensive effects, GI
effects, cardiac arrest from overdose and precipitation of withdrawal.
Most common adverse events (>10%) seen in clinical studies (N=2474)
were: constipation (31%), nausea (28%), vomiting, somnolence,
headache, asthenia and dizziness.
Use EXALGO with extreme caution in patients susceptible to
intracranial effects of CO2 retention.
Do not abruptly discontinue EXALGO.
See Full Prescribing Information and Medication Guide at http://www.imaging.covidien.com/WorkArea/DownloadAsset.aspx?id=2147483728.
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 2011 revenue of $11.6 billion, Covidien has 43,000
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.
1 American Academy of Pain Medicine (AAPM) Facts and Figures
on Pain. American Academy of Pain Medicine website. Retrieved on April
24, 2012 http://www.painmed.org/patient/facts.html.
2 Peter D. Hart Research Associates. (2003). Americans in
Pain: A SURVEY AMONG ADULTS NATIONWIDE CONDUCTED FOR RESEARCH!AMERICA.
Retrieved on May 15, 2012 from http://www.researchamerica.org/uploads/poll2003pain.pdf.
Lynn Phillips, 314-654-3263
Manager, Media Relations
Lannum, CFA, 508-452-4343
Vice President, Communications