FRAZER, Pa., July 21, 2011 /PRNewswire/ -- Cephalon, Inc.
(Nasdaq: CEPH) announced today that the U.S. Food and Drug
Administration (FDA) approved the Risk Evaluation and Mitigation
Strategy (REMS) for FENTORA® (fentanyl buccal tablet) [C-II] and
ACTIQ® (oral transmucosal fentanyl citrate) [C-II]. Both
products are indicated for the management of breakthrough pain in
opioid-tolerant patients with cancer. Under this REMS,
pharmacies and healthcare professionals who prescribe FENTORA and
ACTIQ will enroll by completing an education module and knowledge
assessment focused on safety information including appropriate
patient selection. Healthcare professionals who prescribe
these products will also educate patients as part of the program.
Cephalon expects that enrollment in the REMS program will
begin in September 2011.
The goals of the REMS are to ensure proper patient selection, to
prevent accidental exposure and inappropriate conversion between
fentanyl products, as well as to mitigate the potential risks of
misuse, abuse, addiction, and overdose. The newly-approved
REMS will replace the existing risk management programs for ACTIQ
and FENTORA.
"The FENTORA and ACTIQ REMS demonstrate Cephalon's commitment to
patient safety while maintaining access to these medicines for the
often debilitating breakthrough pain experienced by many
opioid-tolerant patients with cancer," said Dr. Lesley Russell, Chief Medical Officer, Cephalon.
"The program provides education and systems to support safe use of
FENTORA and ACTIQ, preserving availability of the medicines to
patients through retail pharmacies and using other systems already
familiar to prescribers and pharmacists."
When implemented, the FENTORA and ACTIQ REMS will provide checks
and balances within the distribution channel to provide safeguards
to help assure dispensing to patients appropriate for the
medications. All stakeholders can enroll in the system any
time beginning in September 2011.
There will be a transition period of about six months
following launch of the REMS after which no prescription may be
dispensed unless the prescriber and pharmacy are enrolled.
Cephalon will provide regular updates to FDA regarding the
effectiveness of the REMS. Based on these evaluations,
Cephalon plans to open discussions with FDA regarding the Company's
pending supplemental New Drug Application for FENTORA as a
treatment for opioid-tolerant patients with non-cancer breakthrough
pain.
Important Safety Information
WARNING: IMPORTANCE OF PROPER PATIENT
SELECTION, DOSING, and POTENTIAL FOR ABUSE
Reports of serious adverse events,
including deaths in patients treated with
ACTIQ® have been reported. Deaths
occurred as a result of improper patient selection (e.g., use in
opioid non-tolerant patients) and/or improper dosing. The
substitution of ACTIQ for any other fentanyl product may result
in fatal overdose.
ACTIQ is indicated only for the
management of breakthrough cancer pain in patients with
malignancies who are already receiving and who are tolerant to
around-the-clock opioid therapy for their underlying persistent
cancer pain. Patients considered opioid tolerant are those who
are taking around-the-clock medicine consisting of at least 60 mg
of oral morphine daily, at least 25 mcg of transdermal
fentanyl/hour, at least 30 mg of oral oxycodone daily, at least 8
mg oral hydromorphone daily or an equianalgesic dose of another
opioid for a week or longer.
ACTIQ is not indicated for use in opioid
non-tolerant patients including those with only as needed (PRN)
prior exposure.
Life-threatening respiratory depression
could occur at any dose in opioid non-tolerant patients. Deaths
have occurred in opioid non-tolerant patients.
ACTIQ is contraindicated in the
management of acute or postoperative pain including
headache/migraine.
When prescribing, do not convert
patients on a mcg per mcg basis to ACTIQ from other fentanyl
products.
When dispensing, do not substitute an
ACTIQ prescription for other fentanyl products. Substantial
differences exist in the pharmacokinetic profile of ACTIQ compared
to other fentanyl products that result in clinically important
differences in the extent of absorption of fentanyl. As a result of
these differences, the substitution of ACTIQ for any other fentanyl
product may result in fatal overdose.
Special care must be used when dosing
ACTIQ. If the breakthrough pain episode is not relieved 15 minutes
after completion of the ACTIQ unit, patients may take ONLY
ONE additional dose using the same strength and then must wait
at least 4 hours before taking another dose [see Dosage And
Administration (2.2)].
ACTIQ contains fentanyl, an opioid
agonist and a Schedule II controlled substance, with an abuse
liability similar to other opioid analgesics. ACTIQ can be
abused in a manner similar to other opioid agonists, legal or
illicit. This should be considered when prescribing or
dispensing ACTIQ in situations where the physician or pharmacist is
concerned about an increased risk of misuse, abuse or diversion.
Schedule II opioid substances which include morphine,
oxycodone, hydromorphone, oxymorphone, and methadone have the
highest potential for abuse and risk of fatal overdose due to
respiratory depression.
Patients and their caregivers must be
instructed that ACTIQ contains a medicine in an amount which
can be fatal to a child. Death has been reported in children who
have accidentally ingested ACTIQ. All units must be kept out of the
reach of children and opened units properly discarded
[see Warnings And Precautions (5.3), Patient Counseling
Information (17.5, 17.6), and How
Supplied/Storage And Handling (16.2)].
ACTIQ is intended to be used only in the
care of cancer patients and only by oncologists and pain
specialists who are knowledgeable of and skilled in the use of
Schedule II opioids to treat cancer pain.
The concomitant use of ACTIQ with strong
and moderate cytochrome P450 3A4 inhibitors may result in an
increase in fentanyl plasma concentrations, and may cause
potentially fatal respiratory depression [see Drug Interactions
(7)].
WARNINGS: IMPORTANCE OF PROPER PATIENT
SELECTION, DOSING, and POTENTIAL FOR ABUSE
Reports of serious adverse events,
including deaths in patients treated with FENTORA have been
reported. Deaths occurred as a result of improper patient
selection (e.g., use in opioid non-tolerant patients) and/or
improper dosing. The substitution of FENTORA
for any other fentanyl product may result in fatal
overdose.
FENTORA is indicated only for the
management of breakthrough pain in patients with cancer who are
already receiving and who are tolerant to around-the-clock
opioid therapy for their underlying persistent cancer pain.
Patients considered opioid tolerant are those who are taking
around-the-clock medicine consisting of at least 60 mg of oral
morphine daily, at least 25 mcg/hour of transdermal fentanyl, at
least 30 mg of oral oxycodone daily, at least 8 mg of oral
hydromorphone daily or an equianalgesic dose of another opioid
daily for a week or longer.
FENTORA is contraindicated in the
management of acute or postoperative pain including
headache/migraine. FENTORA is not indicated
for use in opioid non-tolerant patients including those with
only as needed (PRN) prior exposure to opioids.
Life-threatening respiratory depression
could occur at any dose in opioid non-tolerant patients. Deaths
have occurred in opioid non-tolerant patients.
When prescribing, do not convert
patients on a mcg per mcg basis from any other fentanyl products
to FENTORA. Carefully consult the Initial
Dosing Recommendations table. [See Dosage and
Administration (2.1)]
When dispensing, do not substitute a
FENTORA prescription for other fentanyl products. Substantial
differences exist in the pharmacokinetic profile of FENTORA
compared to other fentanyl products that result in clinically
important differences in the extent of absorption of fentanyl.
As a result of these differences, the substitution of FENTORA
for any other fentanyl product may result in fatal
overdose.
Special care must be used when dosing
FENTORA. If the breakthrough pain episode is not relieved after 30
minutes, patients may take ONLY one additional dose using the same
strength and must wait at least 4 hours before taking another dose.
[See Dosage and Administration (2.1)]
FENTORA contains fentanyl, an opioid
agonist and a Schedule II controlled substance, with an abuse
liability similar to other opioid analgesics. FENTORA can be
abused in a manner similar to other opioid agonists, legal or
illicit. This should be considered when prescribing or
dispensing FENTORA in situations where the physician or pharmacist
is concerned about an increased risk of misuse, abuse or diversion.
Schedule II opioid substances which include morphine,
oxycodone, hydromorphone, oxymorphone, and methadone have the
highest potential for abuse and risk of fatal overdose due to
respiratory depression.
Patients and their caregivers must be
instructed that FENTORA contains a medicine in an amount
which can be fatal to a child. Patients and their caregivers must
be instructed to keep all tablets out of the reach of children.
[See Patient Counseling Information (17.1) and How
Supplied/Storage and Handling (16.1)]
FENTORA is intended to be used only in
the care of opioid tolerant cancer patients and only by healthcare
professionals who are knowledgeable of and skilled in the use of
Schedule II opioids to treat cancer pain.
The concomitant use of FENTORA with CYP3A4
inhibitors may result in an increase in fentanyl plasma
concentrations, and may cause potentially fatal respiratory
depression [see Drug Interactions (7)].
Contraindications:
- ACTIQ and FENTORA must not be used in opioid
non-tolerant patients because life-threatening respiratory
depression and death can occur at any dose in opioid non-tolerant
patients
- ACTIQ and FENTORA are contraindicated in the management
of acute or postoperative pain, including headache/migraine
- ACTIQ and FENTORA are contraindicated in patients with
known hypersensitivity to any of the components or the drug
fentanyl
Warnings and Precautions:
- Clinically significant respiratory and CNS depression can
occur. Monitor patients accordingly
- Use with other CNS depressants and cytochrome P450 3A4
inhibitors may increase depressant effects including
hypoventilation, hypotension and profound sedation. Consider
dosage adjustments if warranted
- Titrate ACTIQ and FENTORA cautiously in patients with
chronic obstructive pulmonary disease or preexisting medical
conditions predisposing them to respiratory depression
- Administer ACTIQ and FENTORA with extreme caution in
patients susceptible to intracranial effects of CO2 retention
- Application site reactions occurred in 10% of patients in
FENTORA clinical trials and ranged from paresthesia to
ulceration and bleeding
- Full and partially consumed ACTIQ units contain medicine that
can be fatal to a child. Ensure proper storage and disposal.
Interim safe storage container available (ACTIQ Child Safety
Kit)
Adverse Reactions:
- For ACTIQ, most common adverse reactions during
titration phase (frequency greater than or equal to 5%): nausea,
dizziness, somnolence, vomiting, asthenia and headache. Most
common adverse reactions during longer-term treatment (frequency
greater than or equal to 5%): dyspnea, constipation, anxiety,
confusion, depression, rash and insomnia
- For FENTORA, most common adverse reactions during
titration phase (frequency greater than or equal to 10%): nausea
and dizziness. Most common adverse reactions during longer-term
treatment (frequency greater than or equal to 10%): nausea,
vomiting, fatigue, anemia, dizziness, peripheral edema,
constipation, asthenia, dehydration and headache
Drug Interactions:
- Monitor patients who begin therapy with, or increase dose of,
inhibitors of CYP 3A4 for signs of opioid toxicity
- Monitor patients who stop therapy with, or decrease dose of,
inducers of CYP 3A4 for signs of opioid toxicity
Use in Specific Populations:
- Administer FENTORA with caution to patients with severe hepatic
or renal disease. Please see accompanying full prescribing
information.
Please see full prescribing information, including boxed
warning, at www.actiq.com and www.fentora.com.
About Cephalon, Inc.
Cephalon is a global biopharmaceutical company dedicated to
discovering, developing and bringing to market medications to
improve the quality of life of individuals around the world. Since
its inception in 1987, Cephalon has brought first-in-class and
best-in-class medicines to patients in several therapeutic areas.
Cephalon has the distinction of being one of the world's
fastest-growing biopharmaceutical companies, now among the Fortune
1000 and a member of the S&P 500 Index, employing approximately
4,000 people worldwide. The company sells numerous branded and
generic products around the world. In total, Cephalon sells more
than 180 products in more than 100 countries. More information on
Cephalon and its products is available at
http://www.cephalon.com/.
In addition to historical facts or statements of current
condition, this press release may contain forward-looking
statements. Forward-looking statements provide the Cephalon current
expectations or forecasts of future events. These may include
statements regarding anticipated scientific progress on its
research programs; development of potential pharmaceutical
products; interpretation of clinical results; prospects for
regulatory approval; manufacturing development and capabilities;
market prospects for its products; and other statements regarding
matters that are not historical facts. You may identify some
of these forward-looking statements by the use of words in the
statements such as "anticipate," "estimate," "expect," "project,"
"intend," "plan," "believe" or other words and terms of similar
meaning. Cephalon performance and financial results could differ
materially from those reflected in these forward-looking statements
due to general financial, economic, regulatory and political
conditions affecting the biotechnology and pharmaceutical
industries as well as more specific risks and uncertainties facing
Cephalon, such as those set forth in its reports on Form 8-K, 10-Q
and 10-K filed with the U.S. Securities and Exchange Commission.
Given these risks and uncertainties, any or all of these
forward-looking statements may prove to be incorrect.
Therefore, you should not rely on any such factors or
forward-looking statements. Furthermore, Cephalon does not
intend to update publicly any forward-looking statement, except as
required by law. The Private Securities Litigation Reform Act
of 1995 permits this discussion.
Contacts:
Media:
Jenifer Antonacci
610-738-6674 (office)
jantonacci@cephalon.com
Investor Relations:
Chip Merritt
610-738-6376 (office)
cmerritt@cephalon.com
Joseph Marczely
610-883-5894 (office)
jmarczely@cephalon.com
SOURCE Cephalon, Inc.