VIVITROL® and Value of Medication-Assisted Treatment for Opioid Dependence Featured in Study Sponsored by National Institute on Drug Abuse

DUBLIN–(BUSINESS WIRE)–Results from a National Institute on Drug Abuse (NIDA)-funded study,
were published in The Lancet today, comparing extended-release
naltrexone (VIVITROL®) and buprenorphine-naloxone, two
options for opioid dependence. This is the second study published in the
past month comparing these two medications and it provides additional
evidence supporting the use of VIVITROL as an effective treatment option
for patients. Against the backdrop of a national opioid crisis,
Medication-Assisted Treatment (MAT) is substantially underutilized. Data
from the study reinforce the value of MAT and the distinct differences
between two important options for this devastating disease.

VIVITROL represents a different approach to treating opioid dependence.
VIVITROL is an injectable, once-monthly, extended-release form of
naltrexone, an opioid receptor antagonist. Buprenorphine-naloxone is an
opioid partial agonist. In a previously published journal article
discussing the NIDA study design, the study investigators observed,
Agonists and antagonists are diametrically opposite in domains ranging
from pharmacology to treatment philosophy. Agonists maintain physical
tolerance and opioid dependence; antagonists block any opioid effects
and are not psychoactive or habit-forming.1

VIVITROL was developed by Alkermes
(NASDAQ: ALKS). It was approved by the U.S. Food and Drug Administration
(FDA) for the treatment of alcohol dependence in 2006 and for the
prevention of relapse to opioid dependence, following opioid
detoxification, in 2010. Since its first approval, more than 350,000
patients have been treated with VIVITROL.

VIVITROL is an entirely different approach from maintenance therapies.
VIVITROL works by blocking opioid receptors in the brain and is the only
FDA-approved medication for preventing relapse to opioid dependence,
following opioid detoxification,” said Craig Hopkinson, M.D., Chief
Medical Officer and Senior Vice President of Clinical Development and
Medical Affairs at Alkermes. “This study highlights the importance of
detoxification for initiating treatment with VIVITROL. Alkermes is
working alongside prominent researchers in the field to determine
effective, safe and efficient detoxification strategies for successful
induction onto VIVITROL, in order to help healthcare providers manage
their patients through this critical transition period.”

These data confirm and build on the body of evidence supporting the
value of Medication-Assisted Treatment, and VIVITROL is an important
element of the nation’s response to treating opioid dependence.
Addiction is a highly complex disease, and no single treatment option is
right for all patients,” said Richard Pops, Chief Executive Officer of
Alkermes. “In order to address this epidemic, the treatment system for
opioid addiction must evolve to embrace data-driven, patient-centered
care customized to the clinical needs of each individual. We remain
committed to working alongside healthcare providers, policymakers and
public health officials to ensure access to all FDA-approved medications
for this underserved population. Patients need greater access to
medicines that work.”

We are in the midst of a public health crisis, and only a small
percentage of patients suffering from opioid use disorder are getting
treatment. Alkermes applauds NIDA’s commitment to advancing research
focused on treatment options, as it is effective and significantly
underutilized despite the large and growing body of evidence supporting
the use of medication to treat the disease.

About Opioid Dependence
chronic brain disease, opioid dependence is characterized by cognitive,
behavioral and physiological symptoms in which an individual continues
to use opioids despite significant harm to oneself and others.2
The use of heroin, an illegal opioid drug, and the non-medical use of
FDA-approved opioid analgesics, including prescription pain relievers,
represents a growing public health problem in the U.S. According to the
2016 U.S. National Survey on Drug Use and Health, nearly 2 million
people aged 18 or older had an opioid use disorder.3

(naltrexone for extended-release injectable suspension) is a
once-monthly medication for the treatment of alcohol dependence as well
as for the prevention of relapse to opioid dependence, following opioid
detoxification. VIVITROL is a non-narcotic, non-addictive, once-monthly
medication approved for the treatment of opioid dependence. Treatment
with VIVITROL should be part of a comprehensive management program that
includes psychosocial support.



VIVITROL® is indicated for:

  • Treatment of alcohol dependence in patients who are able to abstain
    from alcohol in an outpatient setting prior to initiation of treatment
    with VIVITROL. Patients should not be actively drinking at the time of
    initial VIVITROL administration.
  • Prevention of relapse to opioid dependence, following opioid
  • VIVITROL should be part of a comprehensive management program that
    includes psychosocial support.


VIVITROL is contraindicated in patients:

  • Receiving opioid analgesics
  • With current physiologic opioid dependence
  • In acute opioid withdrawal
  • Who have failed the naloxone challenge test or have a positive urine
    screen for opioids
  • Who have exhibited hypersensitivity to naltrexone,
    polylactide-co-glycolide (PLG), carboxymethylcellulose, or any other
    components of the diluent


Vulnerability to Opioid Overdose:

  • After opioid detoxification, patients are likely to have a reduced
    tolerance to opioids. VIVITROL blocks the effects of exogenous opioids
    for approximately 28 days after administration. As the blockade wanes
    and eventually dissipates completely, use of previously tolerated
    doses of opioids could result in potentially life-threatening opioid
    intoxication (respiratory compromise or arrest, circulatory collapse,
  • Cases of opioid overdose with fatal outcomes have been reported in
    patients who used opioids at the end of a dosing interval, after
    missing a scheduled dose, or after discontinuing treatment. Patients
    and caregivers should be told of this increased sensitivity to opioids
    and the risk of overdose.
  • Although VIVITROL is a potent antagonist with a prolonged
    pharmacological effect, the blockade produced by VIVITROL is
    surmountable. The plasma concentration of exogenous opioids attained
    immediately following their acute administration may be sufficient to
    overcome the competitive receptor blockade. This poses a potential
    risk to individuals who attempt, on their own, to overcome the
    blockade by administering large amounts of exogenous opioids.
  • Any attempt by a patient to overcome the VIVITROL blockade by taking
    opioids may lead to fatal overdose. Patients
    should be told of the serious consequences of trying to overcome the
    opioid blockade.

Injection Site Reactions:

  • VIVITROL injections may be followed by pain, tenderness, induration,
    swelling, erythema, bruising, or pruritus; however, in some cases
    injection site reactions may be very severe.
  • Injection site reactions not improving may require prompt medical
    attention, including, in some cases, surgical intervention.
  • Inadvertent subcutaneous/adipose layer injection of VIVITROL may
    increase the likelihood of severe injection site reactions.
  • Select proper needle size for patient body habitus, and use only the
    needles provided in the carton.
  • Patients should be informed that any concerning injection site
    reactions should be brought to the attention of their healthcare

Precipitation of Opioid Withdrawal:

  • When withdrawal is precipitated abruptly by
    of an opioid antagonist to
    an opioid-dependent patient
    , the resulting withdrawal syndrome
    can be severe. Some cases of withdrawal symptoms have been severe
    enough to require hospitalization, and in some cases, management in
    the ICU.
  • To prevent occurrence of precipitated withdrawal, opioid-dependent
    patients, including those being treated for alcohol dependence, should
    be opioid-free (including tramadol) before starting VIVITROL treatment:

    – An opioid-free interval of a minimum of 7–10 days is recommended
    for patients previously dependent on short-acting opioids.

    – Patients transitioning from buprenorphine or methadone may be
    vulnerable to precipitated withdrawal for as long as two weeks.

  • If a more rapid transition from agonist to antagonist therapy is
    deemed necessary and appropriate by the healthcare provider, monitor
    the patient closely in an appropriate medical setting where
    precipitated withdrawal can be managed.
  • Patients should be made aware of the risk associated with precipitated
    withdrawal and be encouraged to give an accurate account of last
    opioid use.


  • Cases of hepatitis and clinically significant liver dysfunction have
    been observed in association with VIVITROL. Warn patients of the risk
    of hepatic injury; advise them to seek help if experiencing symptoms
    of acute hepatitis. Discontinue use of VIVITROL in patients who
    exhibit acute hepatitis symptoms.

Depression and Suicidality:

  • Alcohol- and opioid-dependent patients taking VIVITROL should be
    monitored for depression or suicidal thoughts. Alert families and
    caregivers to monitor and report the emergence of symptoms of
    depression or suicidality.

When Reversal of VIVITROL Blockade Is Required for Pain Management:

  • For VIVITROL patients in emergency situations, suggestions for pain
    management include regional analgesia or use of non-opioid analgesics.
    If opioid therapy is required to reverse the VIVITROL blockade,
    patients should be closely monitored by trained personnel in a setting
    staffed and equipped for CPR.

Eosinophilic Pneumonia:

  • Cases of eosinophilic pneumonia requiring hospitalization have been
    reported. Warn patients of the risk of eosinophilic pneumonia and to
    seek medical attention if they develop symptoms of pneumonia.

Hypersensitivity Reactions:

  • Patients should be warned of the risk of hypersensitivity reactions,
    including anaphylaxis.

Intramuscular Injections:

  • As with any IM injection, VIVITROL should be administered with caution
    to patients with thrombocytopenia or any coagulation disorder.

Alcohol Withdrawal:

  • Use of VIVITROL does not eliminate nor diminish alcohol withdrawal


  • Serious adverse reactions that may be associated with VIVITROL therapy
    in clinical use include severe injection site reactions, eosinophilic
    pneumonia, serious allergic reactions, unintended precipitation of
    opioid withdrawal, accidental opioid overdose, and depression and
  • The adverse events seen most frequently in association with VIVITROL
    therapy for alcohol dependence (ie, those occurring in ≥5% and at
    least twice as frequently with VIVITROL than placebo) include nausea,
    vomiting, injection site reactions (including induration, pruritus,
    nodules, and swelling), muscle cramps, dizziness or syncope,
    somnolence or sedation, anorexia, decreased appetite or other appetite
  • The adverse events seen most frequently in association with VIVITROL
    in opioid-dependent patients (ie, those occurring in ≥2% and at least
    twice as frequently with VIVITROL than placebo) were hepatic enzyme
    abnormalities, injection site pain, nasopharyngitis, insomnia, and

You are encouraged to report side effects to the FDA.

or call 1-800-FDA-1088.

Please see Full
Prescribing Information

About Alkermes
Alkermes plc is
a fully integrated, global biopharmaceutical company developing
innovative medicines for the treatment of central nervous system (CNS)
diseases. The company has a diversified commercial product portfolio and
a substantial clinical pipeline of product candidates for chronic
diseases that include schizophrenia, depression, addiction and multiple
sclerosis. Headquartered in Dublin, Ireland, Alkermes plc has an R&D
center in Waltham, Massachusetts; a research and manufacturing facility
in Athlone, Ireland; and a manufacturing facility in Wilmington, Ohio.
For more information, please visit Alkermes’ website at

Note Regarding Forward-Looking Statements
Certain statements
set forth in this press release constitute “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, but not limited to, statements concerning
the potential therapeutic and commercial value of VIVITROL and
improvements to the treatment system for opioid dependence. The company
cautions that forward-looking statements are inherently uncertain.
Although the company believes that such statements are based on
reasonable assumptions within the bounds of its knowledge of its
business and operations, the forward-looking statements are neither
promises nor guarantees and they are necessarily subject to a high
degree of uncertainty and risk. Actual performance and results may
differ materially from those expressed or implied in the forward-looking
statements due to various risks and uncertainties. These risks and
uncertainties include, among others: whether clinical results for
VIVITROL will be predictive of commercial results and success; and those
risks and uncertainties described under the heading “Risk Factors” in
the company’s Annual Report on Form 10-K for the year ended Dec. 31,
2016 and Quarterly Reports on Form 10-Q for the quarters ended March 31,
2017 and Sept. 30, 2017 and in subsequent filings made by the company
with the U.S. Securities and Exchange Commission (SEC), which are
available on the SEC’s website at
Existing and prospective investors are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the
date hereof. Except as required by law, the company disclaims any
intention or responsibility for updating or revising any forward-looking
statements contained in this press release.

VIVITROL® is a registered trademark of Alkermes, Inc.

1 Lee, J.D., et al. (2016). “NIDA Clinical Trials Network
CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid
Treatment (X:BOT): Study design and rationale.” Contemporary Clinical
50, 253-264.

DSM-IV-TR, American Psychiatric Association.

SAMHSA. Behavioral Health Trends in the United
States: Results from the 2016 National Survey on Drug Use and Health


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