DUBLIN and EMERYVILLE, Calif., Sept. 22, 2016 /PRNewswire/ -- Allergan plc
(NYSE: AGN), a leading global pharmaceutical company, and Adamas
Pharmaceuticals, Inc. (Nasdaq: ADMS) announced today that all
four dosage strengths of NAMZARIC® (memantine and donepezil
hydrochlorides) extended-release capsules that allow patients on
donepezil 10 mg to start directly on NAMZARIC are now available by
prescription in pharmacies throughout the U.S. NAMZARIC is a
once-daily, fixed-dose combination of memantine hydrochloride (a
NMDA receptor antagonist) and donepezil hydrochloride (an
acetylcholinesterase inhibitor, AChEI) for the treatment of
moderate to severe Alzheimer's Disease in patients stabilized on 10
mg of donepezil hydrochloride once daily. NAMZARIC'S new indication
and dosage strengths were approved by the U.S. Food and Drug
Administration (FDA) in July
2016.
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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 significantly
superior improvement in cognition and global function verses an
AChEI alone.
"We are excited that with the new available dosage strengths
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.
NAMZARIC offers these patients the benefits of combining two
products that each work differently to treat moderate to
severe Alzheimer's disease, without increasing the number of pills
a patient and their caregiver need to administer each day," said
Gavin Corcoran, M.D., chief medical
officer at Allergan. "This launch reinforces Allergan's commitment
to development of treatments for Alzheimer's Disease and other
neurological disorders."
NAMZARIC will be commercially available in 30 count bottles in 7
mg/10 mg, 14 mg/10 mg, 21 mg/10 mg and 28 mg/10 mg. NAMZARIC is
covered broadly by Medicare Part D prescription plans.
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 Namzaric; 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 (Nasdaq: ADMS) will
retain exclusive commercialization rights outside of the U.S.
Adamas is eligible to receive royalties from Allergan on the U.S.
sales of NAMZARIC beginning in May of 2020.
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 Pharmaceuticals, Inc.
Adamas
Pharmaceuticals, Inc. 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 walking impairment in
patients with multiple sclerosis. The company is also evaluating
ADS-4101, an extended-release version of an FDA-approved
single-agent compound for the treatment of epilepsy. 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 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 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 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 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). Except as expressly required by law,
Allergan disclaims any intent or obligation to update these
forward-looking statements.
CONTACTS:
Investor:
Allergan
Lisa
Defrancesco
(862) 261 7152
Media:
Allergan
Fran
DeSena
(973) 517-3132
Mark Marmur
(862) 261-7558
Media & IR
Adamas
Martin Forrest
(510)-944-1112
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SOURCE Allergan plc