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 Americans 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. 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.