Actavis Confirms Appeals Court Ruling Requiring Continued Distribution of NAMENDA IR

DUBLIN, May 22, 2015 /PRNewswire/ -- Actavis plc (NYSE: ACT) today confirmed that a panel of the U.S. Court of Appeals for the Second Circuit has issued a ruling upholding a December 15, 2014 preliminary injunction requiring the Company to continue distribution of NAMENDA^® (memantine HCl) immediate-release tablets.

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"While we are disappointed by the Court's decision to uphold this ruling, we intend to continue our strong efforts to convey the significant benefits of NAMENDA XR® to physicians, patients and caregivers," said Brent Saunders, CEO and President of Actavis.  "Patient demand for NAMENDA XR® is currently trending at more than 50 percent of the total product line's days of therapy and growing, underscoring the strong physician, patient and caregiver demand for our once-daily product."

"We have also recently launched once-daily NAMZARIC®, a fixed-dose combination of NAMENDA XR® and donepezil that provides another treatment option for patients with moderate to severe Alzheimer's disease.  Since the launch of NAMENDA XR® in 2013, the two medications, NAMENDA XR® and donepezil, have been commonly prescribed in combination with one another to treat the symptoms of moderate to severe Alzheimer's disease. NAMZARIC® offers an option with the benefits of both treatments, while reducing the number of pills a patient and their caregivers need to administer each day, to treat this disease."

Actavis noted that the Company will continue to manage sales and R&D expenses to ensure that the Appeals court's decision will have minimal to no impact on its 2015 NAMENDA^® franchise contribution to earnings and longer term company earnings aspirations. 

About NAMENDA XR®

NAMENDA XR® (memantine HCl) extended release capsules are a higher dose, once-daily formulation of NAMENDA® immediate release indicated for the treatment of moderate to severe dementia of the Alzheimer's type. Its mechanism of action focuses on the glutamate pathway, a target for the treatment of Alzheimer's disease. The efficacy and safety of NAMENDA XR® was established in a 24 week, randomized, double-blind, placebo-controlled trial of 677 outpatients on a stable dose of acetylcholinesterase inhibitors (AChEl).

NAMENDA XR® 28 mg plus an AChEI demonstrated statistically significant improvement in cognition and global function compared to placebo plus an AChEI. Cognition was measured by the Severe Impairment Battery Scale (2.6 unit mean difference). Global function was measured by the Clinician's Interview-Based Impression of Change Scale (0.3. unit mean difference).

There is no evidence that NAMENDA XR® or an AChEI prevents or slows the underlying disease process in patients with Alzheimer's disease.

Dosing and Administration

• The recommended starting dose of NAMENDA XR® is 7 mg once daily. The recommended target dose is 28 mg once daily. The dose should be increased in 7 mg increments to 28 mg once daily. The minimum recommended interval between dose increases is one week and only if the previous dose has been well tolerated. The maximum recommended dose is 28 mg once daily.
• It is recommended that a patient who is on a regimen of 10 mg twice daily of NAMENDA tablets be switched to NAMENDA XR® 28 mg once-daily capsules the day following the last dose of a 10 mg NAMENDA® tablet. There is no study addressing the comparative efficacy of these 2 regimens.
• It is recommended that a patient with severe renal impairment who is on a regimen of 5 mg twice daily of NAMENDA® tablets be switched to NAMENDA XR 14 mg once-daily capsules the day following the last dose of a 5 mg NAMENDA® tablet.

Special Populations

• NAMENDA XR® should be administered with caution to patients with severe hepatic impairment.
• A target dose of 14 mg/day is recommended in patients with severe renal impairment (creatinine clearance of 5-29 mL/min, based on the Cockcroft-Gault equation).

IMPORTANT SAFETY INFORMATION

Contraindications

• NAMENDA XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.

Warnings and Precautions

• NAMENDA XR should be used with caution under conditions that raise urine pH (including alterations by diet, drugs and the clinical state of the patient). Alkaline urine conditions may decrease the urinary elimination of memantine, resulting in increased plasma levels and a possible increase in adverse effects.
• NAMENDA XR has not been systematically evaluated in patients with a seizure disorder.

Adverse Reactions

• The most commonly observed adverse reactions seen in patients administered NAMENDA XR (28 mg/day) in a controlled clinical trial, defined as those occurring at a frequency of at least 5% in the NAMENDA XR group and at a higher frequency than placebo were headache (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).

Drug Interactions

• No drug-drug interaction studies have been conducted with NAMENDA XR, specifically. The combined use of NAMENDA XR with other NMDA antagonists (amantadine, ketamine, or dextromethorphan) has not been systematically evaluated and such use should be approached with caution.

Please visit www.NamendaXR.com for more information and full prescribing information.

About NAMZARIC™

NAMZARIC is a once-daily, fixed-dose combination of memantine hydrochloride extended-release, a NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor. NAMZARIC will be available in two dosage strengths, 28/10 mg (memantine HCl extended-release/donepezil HCl) and 14/10mg (memantine HCl extended-release/donepezil HCl) for patients with severe renal impairment. 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. Actavis and Adamas collaborated on the development of the fixed-dose combination and Actavis will have 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.
• 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, and have resolved during continued treatment.
• Genitourinary Conditions: NAMZARIC may cause bladder outflow obstructions. Conditions that raise urine pH may decrease the urinary elimination of memantine 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, include 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 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 (e.g., ketoconazole) and 2D6 (e.g., quinidine), inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known.
• Inducers of CYP3A4 (e.g., 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.

DOSAGE AND ADMINISTRATION

• Patients stabilized on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily and donepezil hydrochloride 10 mg) 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 (creatinine clearance 5-29 mL/min, based on the Cockcroft-Gault equation), stabilized on memantine hydrochloride (5 mg twice daily or 14 mg extended-release once daily) and donepezil hydrochloride 10 mg, can be switched to NAMZARIC 14 mg/10 mg, taken once daily.

About Actavis
Actavis plc (NYSE: ACT), headquartered in Dublin, Ireland, is a unique, global pharmaceutical company and a leader in a new industry model – Growth Pharma.  Actavis 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. 

Actavis 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. Actavis 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, Actavis 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.

Actavis intends to adopt a new global name – Allergan – pending shareholder approval in 2015.

For more information, visit Actavis' website at www.actavis.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 Actavis' current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Actavis' current expectations depending upon a number of factors affecting Actavis' 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 Actavis' products; risks associated with acquisitions, mergers and joint ventures; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Actavis' periodic public filings with the Securities and Exchange Commission, including but not limited to Actavis' Quarterly Report on Form 10-Q for the quarter ended March 31, 2015. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements.

Actavis
Investors:
Lisa DeFrancesco
(862) 261-7152

Media:
David Belian
(862) 261-8141  

SOURCE Actavis plc

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