DUBLIN, July 19, 2016 /PRNewswire/ -- Allergan plc (NYSE:
AGN) and Adamas Pharmaceuticals, Inc. (NASDAQ: ADMS), today
announced that the U.S. Food and Drug Administration (FDA) has
approved a new, expanded label for NAMZARIC®
(memantine and donepezil hydrochlorides) extended-release, a
once-daily, fixed-dose combination of memantine hydrochloride (a
NMDA receptor antagonist) and donepezil hydrochloride (an
acetylcholinesterase inhibitor, AChEI).
With the new indication, patients with moderate to severe
Alzheimer's disease, who are currently stabilized on Aricept,
donepezil hydrochloride (10 mg), can now start combination therapy
directly with NAMZARIC. Approximately 75% of patients
diagnosed with Alzheimer's Disease are in the moderate to severe
stage of the disease and yet only about one-third of these patients
are treated with combination therapy.
"Clinical studies have shown that combination therapy with
Namenda XR and an AChEI such as Aricept demonstrated greater
improvement in cognition and global function verses an AChEI
alone. NAMZARIC offers the benefits of combining two products
that each work differently to treat moderate to severe
Alzheimer's disease while at the same time reducing the number of
pills a patient and their caregivers need to administer each day,"
says Gavin Corcoran, M.D., chief
medical officer at Allergan. "At Allergan, we're proud to continue
developing products and supporting new programs that can help
patients and their caregivers as they navigate this complex
disease."
With the new, expanded indication, NAMZARIC will be available in
four dosage strengths which allows patients currently taking
Aricept 10mg to start on NAMZARIC the very next day. Namzaric is
covered broadly by Medicare Part D prescription plans.
In addition to the two currently available dosage strengths, the
two new NAMZARIC dosage strengths will be available in pharmacies
in September.
For more information about NAMZARIC, visit www.Namzaric.com.
About the Clinical Trial
The efficacy and safety of
the coadministration of memantine HCl extended release and
acetylcholinesterase inhibitors (AChEIs), including donepezil HCl,
was based on the results of a randomized, double-blind,
placebo-controlled trial of 677 patients with moderate to severe
Alzheimer's Disease on a stable dose of AChEIs. The clinical study
was not conducted with Namazaric; however, bioequivalence of
Namzaric with coadministered memantine HCl extended release and
donepezil HCl was demonstrated. Approximately 68% of the patients
randomized to receive either memantine HCl extended release 28 mg
or placebo were taking donepezil as the AchEI at Baseline and
throughout the study. The results of this study, demonstrated
statistically significant improvement in cognition and global
function for patients treated with NAMENDA XR (memantine HCl
extended release) 28 mg plus an AChEI compared to placebo plus an
AchEI at 24 weeks.
About NAMZARIC®
NAMZARIC is a once-daily,
fixed-dose combination of memantine hydrochloride, a NMDA receptor
antagonist, and donepezil hydrochloride, an acetylcholinesterase
inhibitor indicated for the treatment of moderate to severe
dementia of the Alzheimer's type in patients stabilized on 10 mg of
donepezil HCl once daily
Memantine hydrochloride extended-release is the active
ingredient in the currently marketed NAMENDA XR®, which
is indicated for the treatment of moderate to severe dementia of
the Alzheimer's type. Donepezil is the active ingredient in
ARICEPT® (donepezil hydrochloride), which is indicated
for the treatment of mild to severe dementia of the Alzheimer's
type. Allergan and Adamas collaborated on the development of the
fixed-dose combination and Allergan owns the exclusive U.S.
commercialization rights, while Adamas will retain exclusive
commercialization rights outside of the U.S.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
NAMZARIC is contraindicated in
patients with known hypersensitivity to memantine
hydrochloride,donepezil hydrochloride, piperidine derivatives, or
to any excipients used in the formulation.
WARNINGS AND PRECAUTIONS
Anesthesia
NAMZARIC is likely to exaggerate
succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions
NAMZARIC may have
vagotonic effects on the sinoatrial and atrioventricular nodes
manifesting as bradycardia or heart block. Bradycardia or heart
block may manifest in patients both with and without known
underlying cardiac conduction abnormalities. Syncopal episodes have
been reported in association with the use of donepezil
hydrochloride, an active ingredient in NAMZARIC.
Peptic Ulcer Disease and Gastrointestinal
Bleeding
Patients treated with NAMZARIC should be monitored
closely for symptoms of active or occult
gastrointestinal bleeding, especially those at increased risk for
developing ulcers, those with a history of ulcer disease, or those
receiving concurrent nonsteroidal anti-inflammatory drugs
(NSAIDs).
Nausea and Vomiting
NAMZARIC can cause
diarrhea, nausea, and vomiting. Although in most cases, these
effects have been mild and transient, sometimes lasting one to
three weeks, and have resolved during continued use of donepezil
hydrochloride, patients should be observed closely at the
initiation of treatment.
Genitourinary Conditions
NAMZARIC may cause
bladder outflow obstructions. Conditions that raise urine pH may
decrease the urinary elimination of memantine, an active ingredient
in NAMZARIC, resulting in increased plasma levels of memantine.
Seizures
Cholinomimetics, including donepezil
hydrochloride, are believed to have some potential to cause
generalized convulsions. However, seizure activity also may be a
manifestation of Alzheimer's disease.
Pulmonary
Conditions
Cholinesterase inhibitors should be prescribed
with care to patients with a history of asthma or obstructive
pulmonary disease.
ADVERSE REACTIONS
- The most common adverse reactions, occurring at a frequency of
at least 5% in patients taking memantine hydrochloride
extended-release 28 mg/day, and greater than placebo, were headache
(6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
- The most common adverse reactions, occurring at a frequency of
at least 5% in patients taking donepezil, and at twice or more the
rate of placebo, were diarrhea (10% vs 4%), anorexia (8% vs 4%),
vomiting (8% vs 4%), nausea (6% vs 2%), and ecchymosis (5% vs
2%).
DRUG INTERACTIONS
- Alterations of urine pH toward the alkaline condition may lead
to an accumulation of memantine with a possible increase in adverse
reactions. NAMZARIC should be used with caution under conditions
that may be associated with increased urine pH including
alterations by diet, drugs, and the clinical state of the
patient.
- The combined use of memantine hydrochloride with other NMDA
antagonists (amantadine, ketamine, and dextromethorphan) has not
been systematically evaluated and such use should be approached
with caution.
- Inhibitors of CYP450, 3A4 (eg,
ketoconazole) and 2D6 (eg, quinidine), inhibit donepezil metabolism
in vitro. Whether there is a clinical effect of quinidine is
not known.
- Inducers of CYP3A4 (eg, phenytoin, carbamazepine,
dexamethasone, rifampin, and phenobarbital) could increase the rate
of elimination of donepezil.
- Cholinesterase inhibitors, including donepezil hydrochloride,
have the potential to interfere with the activity of
anticholinergic medications.
- A synergistic effect may be expected when cholinesterase
inhibitors, including donepezil hydrochloride, are given
concurrently with succinylcholine, similar neuromuscular blocking
agents, or cholinergic agonists such as bethanechol.
DOSAGE AND ADMINISTRATION
For patients stabilized on donepezil and not currently on
memantine:
For patients stabilized on donepezil hydrochloride 10 mg and not
currently on memantine hydrochloride, the recommended starting dose
of NAMZARIC is 7 mg/10 mg, taken once a day in the evening. The
dose should be increased in 7 mg increments of the memantine
hydrochloride component to the recommended maintenance dose of 28
mg/10 mg once daily. The minimum recommended interval between dose
increases is one week. The dose should only be increased if the
previous dose has been well tolerated. The maximum dose is 28 mg/10
mg once daily.
For patients with severe renal impairment (creatinine clearance
5-29 mL/min, based on the Cockcroft-Gault equation) stabilized on
donepezil hydrochloride 10 mg once daily and not currently on
memantine hydrochloride the recommended starting dose of NAMZARIC
is 7 mg/10 mg taken once a day in the evening. The dose should be
increased to the recommended maintenance dose of 14 mg/10 mg once
daily in the evening after a minimum of one week.
For patients stabilized on both donepezil and
memantine:
Patients stabilized on memantine hydrochloride (10 mg twice
daily or 28 mg extended-release once daily) and donepezil
hydrochloride 10 mg once daily can be switched to NAMZARIC 28 mg/10
mg, taken once a day in the evening. Patients should start NAMZARIC
the day following the last dose of memantine hydrochloride and
donepezil hydrochloride administered separately.
Patients with severe renal impairment, stabilized on memantine
hydrochloride (5 mg twice daily or 14 mg extended-release once
daily) and donepezil hydrochloride 10 mg once daily, can be
switched to NAMZARIC 14 mg/10 mg, taken once daily in the
evening.
For Full Prescribing Information, visit
www.namzaric.com
About Allergan
Allergan plc (NYSE: AGN), headquartered
in Dublin, Ireland, is a unique,
global pharmaceutical company and a leader in a new industry model
– Growth Pharma. Allergan is focused on developing,
manufacturing and commercializing innovative branded
pharmaceuticals, high-quality generic and over-the-counter
medicines and biologic products for patients around the world.
Allergan markets a portfolio of best-in-class products that
provide valuable treatments for the central nervous system, eye
care, medical aesthetics, gastroenterology, women's health,
urology, cardiovascular and anti-infective therapeutic categories,
and operates the world's third-largest global generics business,
providing patients around the globe with increased access to
affordable, high-quality medicines. Allergan is an industry leader
in research and development, with one of the broadest development
pipelines in the pharmaceutical industry and a leading position in
the submission of generic product applications globally.
With commercial operations in approximately 100 countries,
Allergan is committed to working with physicians, healthcare
providers and patients to deliver innovative and meaningful
treatments that help people around the world live longer, healthier
lives.
For more information, visit Allergan's website at
www.allergan.com.
About Adamas
Adamas Pharmaceuticals, Inc.
(NASDAQ: ADMS) is driven to improve the lives of those
affected by chronic disorders of the central nervous system.
The company seeks to achieve this by modifying the pharmacokinetic
profiles of approved drugs to create novel therapeutics for use
alone and in fixed-dose combination products. Adamas is
currently developing ADS-5102, its lead wholly-owned product
candidate, for the treatment of levodopa-induced dyskinesia
associated with Parkinson's disease and for the treatment of major
symptoms associated with multiple sclerosis in patients with
walking impairment. The company is also evaluating ADS-4101,
an extended-release version of an FDA-approved single-agent
compound for the treatment of epilepsy. In addition, under a
license agreement with Forest Laboratories Holdings Limited, an
indirect wholly-owned subsidiary of Allergan plc., the company is
eligible to receive royalties from Forest on sales of Namenda XR®
and Namzaric™ beginning in June of 2018 and May of 2020,
respectively.
For more information, please visit Adamas's website at
www.adamaspharma.com.
Forward-Looking Statement
Statements contained in
this press release that refer to future events or other
non-historical facts are forward-looking statements that reflect
Allergan's and Adamas's current perspective of existing trends and
information as of the date of this release. Except as expressly
required by law, Allergan disclaims any intent or obligation to
update these forward-looking statements. Actual results may differ
materially from Allergan's or Adamas's current expectations
depending upon a number of factors affecting Allergan's business.
These factors include, among others, the difficulty of predicting
the timing or outcome of FDA approvals or actions, if any; the
impact of competitive products and pricing; market acceptance of
and continued demand for Allergan's and Adamas's products;
difficulties or delays in manufacturing; and other risks and
uncertainties detailed in Allergan's periodic public filings with
the Securities and Exchange Commission, including but not limited
to Allergan's Annual Report on Form 10-K for the year ended
March 31, 2016(certain of such
periodic public filings having been filed under the "Actavis plc"
name). Other risks and uncertainties regarding Adamas are
detailed in its periodic public filings with the Securities and
Exchange Commission, including but not limited to Adamas's
Quarterly Report on Form 10-Q for the quarter ended March 31, 2016. Except as expressly
required by law, Allergan or Adamas disclaims any intent or
obligation to update these forward-looking statements.
CONTACTS: Investor:
Allergan
Lisa Defrancesco
(862)
261 7152
Adamas
Julie Wood
(510) 450
3528
Media:
Allergan
Fran DeSena
(973) 517-3132
Mark Marmur
(862) 261-7558
Adamas
(510) 450 3567
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