An Introduction to Extended-Release
`
`Injectable Naltrexone for the Treatment
`
`of People With Opioid Dependence
`
`
`The U.S. Food and Drug Administration (FDA)
`approved extended-release injectable naltrexone
`(Vivitrol) in October 2010 to treat people with opioid
`dependence. This medication provides patients with
`opioid dependence the opportunity to take effective
`medication monthly, as opposed to the daily dosing
`required by other opioid dependence medications
`(i.e., methadone, buprenorphine, oral naltrexone).
`Extended-release injectable naltrexone was approved
`by FDA in 2006 to treat people with alcohol
`dependence.
`Treatment of opioid dependence remains a national
`priority. According to the 2010 National Survey
`on Drug Use and Health, approximately 359,000
`individuals reported either dependence on or abuse of
`heroin, and 1.92 million individuals reported either
`dependence on or abuse of prescribed painkillers.1
`
`The Treatment Episode Data Set (TEDS) reports that
`between 1998 and 2008 the percentage of individuals
`ages 12 and older who entered substance abuse
`treatment because of pain reliever abuse increased
`more than fourfold—from 2.2 percent to 9.8 percent.2
`This Advisory provides behavioral health
`professionals—including substance abuse treatment
`specialists—and primary care medical providers
`(who treat people with opioid dependence) with an
`introduction to extended-release injectable naltrexone.
`It includes succinct information about extended-
`release injectable naltrexone, how it compares with
`other medication-assisted treatment (MAT) options,
`and clinical strategies that may be used to select,
`initiate, and administer treatment.
`
`What Role Can Extended-
`Release Injectable Naltrexone
`Play in the Treatment of Opioid
`Dependence?
`Extended-release injectable naltrexone is another
`pharmacological tool that is approved for treatment
`of people with opioid dependence. Over the years,
`medications have been successful in treating many
`patients with opioid dependence. Methadone has been
`used to treat patients for decades and has been proven
`effective.3 However, methadone must be dispensed to
`the patient at a Substance Abuse and Mental Health
`Services Administration (SAMHSA)-certified opioid
`treatment program (OTP) facility—with daily doses
`provided at the clinic—until the patient is deemed
`stable enough to receive take-home doses. Barriers to
`accessing this treatment include limited geographical
`locations of OTPs, transportation difficulties, and
`policies that preclude the use of methadone.
`Buprenorphine, approved in 2002 by FDA to treat
`opioid dependence, is available at OTPs but is
`most often prescribed by physicians in office-based
`settings. Thus, in theory, it can be more accessible
`than methadone. However, to prescribe buprenorphine,
`
`physicians need limited special training and so all
`physicians may not currently be able to prescribe
`it. Physicians also need to be granted a waiver by
`the U.S. Drug Enforcement Agency (DEA) from
`regulations that otherwise prohibit them from treating
`
`people with opioid dependence in office settings and,
`at maximum, can only treat up to 100 patients at a
`time. Currently, mid-level practitioners (e.g., nurse
`practitioners, physician assistants) are not eligible for
`DEA waivers to prescribe buprenorphine.
`
`Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover
`
`ADVISORY
`
`Winter 2012 • Volume 11 • Issue 1
`
`ALKERMES EXHIBIT 2020
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited
`IPR2018-00943
`
`Page 1 of 8
`
`

`

`Naltrexone can be prescribed by any healthcare provider
`
`who is licensed to prescribe medications. Special training
`
`is not required; the medication can be administered in
`
`
`
`OTP clinics. Practitioners in community health centers or
`private office settings can also prescribe it for purchase
`at the pharmacy. These factors may improve access to
`treatment for opioid dependence.
`Naltrexone requires that patients be abstinent from opioids
`for a period prior to induction. Such abstinence can be
`difficult for patients to achieve. Retention in treatment
`has sometimes been problematic when patients are asked
`to adhere to daily doses of oral naltrexone.4 A monthly
`
`injection of naltrexone, instead of daily dosing, may
`improve patients’ adherence to their medication
`
`regimens.5, 6
`
`Extended-release injectable naltrexone has a higher
`pharmacy cost than buprenorphine and methadone,
`
`but some data suggest that its use may reduce inpatient
`admissions, emergency room visits, and other health
`system costs.7 Nonetheless, the higher pharmacy cost of
`extended-release injectable naltrexone may limit access
`for patients who lack health insurance or other financial
`resources.
`How Does Extended-Release
`Injectable Naltrexone Differ From
`Other Forms of MAT for Opioid
`Dependence?
`Both methadone and buprenorphine are controlled sub­
`stances, whereas naltrexone is not. Methadone is an opioid
`agonist, buprenorphine is a partial opioid agonist, and nal­
`trexone is an opioid antagonist.
`
`Different types of opioid receptors—or molecules to which
`opioid compounds attach themselves and exert their ef­
`fects—are present in the brain. Agonists are drugs that
`activate these receptors, binding to them and producing an
`effect. Opioids such as methadone, morphine, and heroin
`are full agonists and have the greatest abuse potential.
`Antagonists also bind to opioid receptors, but rather than
`producing an effect, they block the effects of opioid com­
`pounds. Partial agonists bind to the receptors and activate
`them, but not to the same degree as full agonists.8
`
`
`Naltrexone has no abuse potential, whereas methadone
`and buprenorphine do. Further information about the
`
`pharmacology of methadone can be found in Treatment
`Improvement Protocol (TIP) 43: Medication-Assisted
`Treatment for Opioid Addiction in Opioid Treatment
`
`Programs.9 Additional information about buprenorphine
`
`
`is available in TIP 40: Clinical Guidelines for the Use of
`Buprenorphine in the Treatment of Opioid Addiction.8
`Some physicians are reluctant to prescribe agonists to
`treat opioid dependence because of their treatment phi­
`losophies, difficulties in tapering patients off these medi­
`cations, or the potential for illicit diversion of agonist
`medications.5 Physicians with these concerns may be more
`
`comfortable prescribing an antagonist, such as naltrexone,
`rather than agonists.
`Exhibit 1 summarizes key differences between extended-
`release injectable naltrexone, buprenorphine, and metha­
`done.
`How Does Extended-Release
`Injectable Naltrexone Work?
`Naltrexone is an opioid antagonist, a medication that binds
`to and effectively blocks opioid receptors.8, 10 It prevents
`
`receptors from being activated by agonist compounds,
`such as heroin or prescribed opioids, and is reported to
`reduce opioid cravings and to prevent relapse.11, 12 Patients
`
`need to be informed that this medication will prevent
`them from feeling the euphoric effect or pain relief they
`previously felt when they took an opioid.10, 13, 14
`
`
`Are There Safety Concerns About
`Extended-Release Injectable
`Naltrexone?
`Risk of accidental opioid overdose
`and death
`Accidental overdoses and overdose-related deaths have
`occurred among patients who have taken opioids while
`being treated for opioid dependence with naltrexone­
`containing products—including both the extended-release
`injectable formulation and the daily oral formulation.15, 16
`
`
`Overdoses and overdose-related deaths are also a risk with
`
`2
`
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`
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`

`agonist therapies. No comprehensive mortality data are
`yet available about extended-release injectable naltrexone,
`but cases of fatal opioid overdose have been reported in
`patients who:
`● Used opioids at or near the end of the 1-month dosing
`
`interval.
`● Used opioids after missing a dose of extended-release
`
`injectable naltrexone.
`● Attempted to overcome the opioid blockade.10
`
`
`Patients who have been treated with extended-release
`injectable naltrexone may have reduced tolerance to opioids
`and may be unaware of their potential sensitivity to the
`same, or lower, doses of opioids that they used to take. If
`patients who are treated with extended-release injectable
`naltrexone relapse after a period of abstinence, it is possible
`that the dosage of opioid that was previously used may
`have life-threatening consequences, including respiratory
`arrest and circulatory collapse.10
`
`Physicians have an obligation to educate patients who are
`treated with naltrexone-containing products about mortality
`
`risks that exist during and after leaving treatment for opioid
`
` dependence.13, 17 Behavioral health providers may play a
`
`role in reminding patients of these risks. It is recommended
`that providers and patients develop a relapse prevention
`plan that includes strategies to decrease the risks if relapse
`occurs. If patients continue to use opioids during treatment,
`transition to agonist medications may be considered to
`reduce mortality risk, although these medications also have
`mortality risks.13, 17
`
`Risk of precipitating withdrawal
`Naltrexone displaces heroin or prescribed opioids
`from receptors to which they have bound, which can
`precipitate withdrawal symptoms.8, 20 Therefore, complete
`
`detoxification from opioids before initiating or resuming
`extended-release injectable naltrexone is necessary to
`prevent withdrawal. At least 7–10 days without opioid
`use is recommended before beginning extended-release
`injectable naltrexone.10,16
`
`
` Prescribing
`
`Considerations
`
` Frequency of
`Administration
`
` Route of
`Administration
`
`
` Restrictions on
`
` Prescribing or
`Dispensing
`
`
`
` Abuse and Diversion
`Potential
` Additional
`
`Requirements
`
`Sources: Adapted from 16,18,19
`
`
`
`
`
`Exhibit 1: Key Differences Between Medications Used
`
`To Treat Patients With Opioid Dependence
`
`
` Extended-Release
`Buprenorphine
`Injectable Naltrexone
`Monthly
`
`Daily
`
`Daily
`
`Methadone
`
`
` Intramuscular injection in the
`
` gluteal muscle by healthcare
`professional.
`
`
`
` Any individual who is licensed
`
` to prescribe medicine
` (e.g., physician, physician
`
`
` assistant, nurse practitioner)
`
` may prescribe and order
` administration by qualified
`
`staff.
`No
`
`
`
` None; any pharmacy can fill
`the prescription.
`
` Oral tablet or film is dissolved
`
`
` under the tongue. Can be
` taken at a physician’s office or
`
`at home.
` Only licensed physicians
`
` who are DEA registered and
`
`
` either work at an OTP or have
`
` obtained a waiver to prescribe
`buprenorphine may do so.
`
` Oral (liquid) consumption
`
` usually witnessed at an OTP,
`
`until the patient receives take-
`home doses.
`
` Only licensed physicians who
`
` are DEA registered and who
`
` work at an OTP can order
` methadone for dispensing at
`
`the OTP.
`
`Yes
`
`Yes
`
`
`
` Physicians must complete
`
` limited special training to
`
` qualify for the DEA prescribing
`
` waiver. Any pharmacy can fill
`the prescription.
`
`For opioid dependence
`
`treatment purposes,
`
`methadone can only be
`
`purchased by and dispensed
`
`at certified OTPs or hospitals.
`
`3
`
`Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover
`
`An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence
`Winter 2012, Volume 11, Issue 1
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`
`

`

`Adverse events
` The most frequently reported adverse events include hepatic
`
`enzyme abnormalities, injection site pain, common cold
`symptoms, insomnia, and toothache. Nausea, vomiting,
`muscle cramps, dizziness, sedation, decreased appetite,
`and an allergic form of pneumonia have also occurred
`in people treated with extended-release injectable
`naltrexone.10, 21
`
`
`Injection site reactions
`Injection site reactions—including pain, hardness,
`swelling, blisters, redness, bruising, abscesses, and tissue
`death—have been reported to FDA. Some reactions are
`serious enough that surgery is needed.16
`
`To reduce the risk of serious injection site reactions:
`● Extended-release injectable naltrexone should be
`
`
`administered as an intramuscular injection into
`
`the gluteal muscle using the specially designed
`
`
`administration needle provided. It should never
`
`
`be administered intravenously, subcutaneously,
`
`or inadvertently into fatty tissues.
`
`● Extended-release injectable naltrexone should be
`
`
`administered into alternating buttocks (sides of the
`
`patient) each month.
`
`● Healthcare providers should consider alternate
`
`treatments for patients whose body size, shape, or
`posture makes it impossible to administer extended-
`release injectable naltrexone in the recommended
`location. Note that the needle provided is not a
`
`standard needle (see last bullet). It is not possible
`to substitute a standard needle of a longer length.
`
` ● Patients who develop injection site reactions that
`
`
`do not improve should be referred to a surgeon.
`
`● The packaging of extended-release injectable
`
`naltrexone was changed in 2010. Both 1.5- and 2-inch
`needles are included for injecting the medication, to
`accommodate patients’ different body sizes. Use the
`2-inch needle for most patients and reserve the shorter
`needle for lean patients.10, 16
`
`
`Liver adverse effects
`The FDA requires warnings on formulations of naltrexone
`about possible liver adverse effects. The current product
`labeling for extended-release injectable naltrexone
`includes a warning about hepatotoxicity when the
`medication is given in more than the recommended
`dose. Use of the medication is contraindicated in patients
`with acute hepatitis or liver failure. The medication
`manufacturer states that the margin of separation between
`the apparently safe dose and the dose causing hepatic
`injury appears to be only fivefold or less.10 Extended-
`release injectable naltrexone should be discontinued if
`signs or symptoms of hepatitis develop (e.g., fatigue,
`loss of appetite, nausea, vomiting, abdominal pain, gray-
`colored bowel movement, joint pain, jaundice).10 Further
`research and postmarket surveillance are underway to
`
`determine any long-term effects of this formulation on
`the liver.
`Which Patients May Benefit Most
`From Treatment With Extended-
`Release Injectable Naltrexone?
`It is difficult to predict which medication will work for
`a particular patient with opioid dependence. Factors
`affecting a patient’s treatment success with a medication
`may change over time or with subsequent treatment
`attempts. Extended-release injectable naltrexone benefits
`people with opioid dependence who are at risk for opioid
`use immediately after detoxification.6 People facing
`periods of greatly increased stress or other relapse risks
`(e.g., visiting places of previous drug use, loss of spouse,
`loss of job) may find they benefit from the reassurance of
`the blockade provided by the medication.11, 13 People who
`
`have a short or less severe history of dependence may also
`want to consider injectable naltrexone.6 Still others may
`have to demonstrate to professional boards, supervisors,
`drug court judges, or other authorities that their risk of
`using a nonprescribed opioid is low and the extended-
`release formulation may provide an option that has
`reduced risk compared with other options. No definitive
`research is available that states which patients would
`most benefit from extended-release injectable naltrexone,
`but the following people may be good candidates for
`treatment.
`
`4
`
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`

`People who have not had treatment
`success with methadone or
`buprenorphine
`Depending on the reasons for treatment failure, people
`with opioid dependence who have not been successful
`with treatment with methadone or buprenorphine may
`benefit from extended-release injectable naltrexone.22
`People who have a high level of
`motivation for abstinence
`People who are highly motivated to achieve and maintain
`abstinence from opioids may be good candidates for
`
`extended-release injectable naltrexone.12, 23 This includes
`
`people who are required to demonstrate abstinence with
`drug screens, such as individuals in impaired healthcare
`provider programs, parolees, probationers, and airline
`pilots.24 Preliminary results from an ongoing study of U.S.
`healthcare professionals with opioid dependence suggest
`that this treatment can be successful for up to 1 year.25
`People successful on agonists who
`wish to change their medication or
`patients not interested in agonist
`therapy to treat their opioid
`dependence
`Some patients may be successful on agonist treatment and
`want continued pharmacologic help to prevent relapse
`but would prefer another type of treatment,22 while other
`patients may never be interested in agonist therapy. These
`types of patients could include individuals who:
`● Feel they are discriminated against, or are embarrassed
`
`or ashamed, because they are on methadone maintenance
`
`or who previously experienced these emotions while
`undergoing methadone therapy.26
`● Would like to reduce the time devoted to daily or
`
`
`multiple OTP visits per week, as is often required
`
`
`for methadone treatment.13
`
`● Prefer to receive office-based treatment in a primary
`
`medical care setting, rather than treatment in specialty
`clinics or treatment centers.24,26
`
`
`Adolescents or young adults with
`opioid dependence
`Methadone or buprenorphine are not always available
`to treat young people with opioid dependence because
`of OTP facility policies or governmental regulations.
`However, the safety and efficacy of extended-release
`injectable naltrexone have not been established for patients
`who are younger than age 18, and use for this population is
`not approved by FDA. Only limited experience in treating
`this population with extended-release injectable naltrexone
`is reported in the literature.26
`Can Extended-Release Injectable
`Naltrexone Be Used With
`Behavioral Therapies?
`For most patients with opioid dependence, medications
`alone are insufficient. Treatment in individual or group
`counseling sessions and participation in mutual-help
`programs are also needed. Patients have better treatment
`outcomes when naltrexone-based treatment is combined
`
` with behavioral therapies.4, 6, 27 The efficacy of extended-
`
`
`release naltrexone has been established when given in
`conjunction with behavioral support; it has not been
`studied as a sole component of treatment.
`Healthcare providers should be ready to offer brief
`intervention if patients relapse during treatment of opioid
`dependence. Motivational interviewing and relapse
`prevention strategies may also enhance the effectiveness
`
`of pharmacological treatments.8
`How Can Pain Be Treated During
`or After Extended-Release
`Injectable Naltrexone Treatment?
`Pain management in people receiving all forms of
`MAT, including extended-release injectable naltrexone,
`can be challenging. Some people can be safely and
`effectively treated with nonpharmacologic remedies,
`such as physical therapy, massage, or acupuncture, as
`long as the injection site is protected. Pain relief may
`
`also be obtained from nonopioid topical medications,
`nonsteroidal anti-inflammatory agents, regional blocks,
`
`5
`
`Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover
`
`An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence
`Winter 2012, Volume 11, Issue 1
`
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`
`

`

`
`and nonopioid painkillers such as gabapentin and atypical
`antidepressants.13
`Use of opioid-containing analgesics may aggravate
`
`preexisting addiction disorders and cause relapse. People
`
`with opioid dependence who require opioid therapy for
`chronic pain should be managed by pain management
`specialists. In light of its antagonist property, extended-
`release injectable naltrexone may not be appropriate for
`these patients.22
`Reversing blockade of opioid
`receptors
`There are few clinical trial data available about reversing
`
`the opioid receptor blockade. When surgeries or
`procedures are planned for patients who use extended-
`release injectable naltrexone, it may be safest to delay the
`procedure until naltrexone blood levels are low enough
`to restore opioid receptor availability. The manufacturer
`of extended-release injectable naltrexone also suggests
`considering use of regional analgesia or nonopioid
`analgesics.10
`In emergencies, it is possible for healthcare providers to
`reverse extended-release injectable naltrexone’s opioid
`receptor blockade. However, higher than usual dosages
`of a rapidly acting opioid medication may be needed
`to achieve pain relief if a patient still has a tolerance
`to opioids. These higher dosages increase the risk of
`respiratory depression. Patients administered such high
`doses should be closely monitored by professionals trained
`in the use of anesthetic drugs, management of respiratory
`depression, and the performance of cardiopulmonary
`resuscitation.10,16
`
`Patients who are treated with extended-release injectable
`naltrexone should be encouraged to wear medical alert
`jewelry or carry a disclosure card to help emergency
`personnel provide pain management safely when
`these patients are unconscious or cannot otherwise
`communicate.
`
`Resources
`Several publications are available free of charge from
`SAMHSA. The resources listed below can be ordered
`
`from SAMHSA’s Publications Ordering Web page at
`http://www.store.samhsa.gov. Or call 1-877-SAMHSA-7
`(1-877-726-4727) (English and Español). Publications
`can also be downloaded from the Knowledge Application
`Program Web site at http://www.kap.samhsa.gov.
`Resources for professionals
`Substance Abuse Treatment Advisory: Naltrexone for
`Extended-Release Injectable Suspension for Treatment
`of Alcohol Dependence. (2007). Volume 6, Issue 1. HHS
`Publication No. (SMA) 07-4267.
`Substance Abuse Treatment Advisory: Emerging Issues in
`the Use of Methadone. (2009). Volume 8, Issue 1. HHS
`Publication No. (SMA) 09-4368.
`Treatment Improvement Protocol (TIP) 40: Clinical
`Guidelines for the Use of Buprenorphine in the Treatment
`of Opioid Addiction. (2004). HHS Publication No. (SMA)
`07-3939.
`TIP 43: Medication-Assisted Treatment for Opioid
`Addiction in Opioid Treatment Programs. (2005). HHS
`Publication No. (SMA) 08-4214.
`TIP 45: Detoxification and Substance Abuse Treatment.
`(2006). HHS Publication No. (SMA) 08-4131.
`Resources for clients
`The Facts About Naltrexone for Treatment of Opioid
`Addiction. (2009). HHS Publication No. (SMA) 09-4444.
`Medication-Assisted Treatment for Opioid Addiction:
`Facts for Families and Friends. (2009). HHS Publication
`No. (SMA) 09-4443.
`
`6
`
`Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover
`
`ADVISORY
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`

`
`
`
`
`Other Web resources for medical and
`health professionals
`National Institute on Drug Abuse, NIDAMED
`http://www.drugabuse.gov/nidamed
` U.S. Food and Drug Administration
`http://www.fda.gov
`For specific information on extended-release injectable
` naltrexone: http://www.accessdata.fda.gov/drugsatfda_docs/
`
`label/2010/021897s005s010lbl.pdf
` For specific information on adverse injection site reactions:
`
`http://www.fda.gov/Drugs/DrugSafety/PostmarketDrug­
`SafetyInformationforPatientsandProviders/ucm103334.htm
`Notes
`1 Substance Abuse and Mental Health Services Administration. (2011).
`Results from the 2010 National Survey on Drug Use and Health:
`Summary of National Findings, NSDUH Series H-41, HHS
`Publication No. (SMA) 11-4658. Rockville, MD: Substance Abuse
`and Mental Health Services Administration.
`2 Substance Abuse and Mental Health Services Administration. (2010).
`TEDS report: Substance abuse treatment admissions involving
`abuse of pain relievers: 1998 and 2008. (Office of Applied
`Studies, July 15, 2010). Rockville, MD: Author.
` 3 Mattick, R. P., Breen C., Kimber J., & Davoli, M. (2009). Methadone
`maintenance therapy versus no opioid replacement therapy for
`opioid dependence. Cochrane Database of Systematic Reviews,
`Issue 3, Art. No.: CD002209. doi: 0.1002/14651858.CD002209.
`pub2
`4 Johansson, B. A., Berglund, M., & Lindgren, A. (2006). Efficacy of
`
`maintenance treatment with naltrexone for opioid dependence: A
`
`meta-analytical review. Addiction, 101(4), 491–503.
`5 Comer, S. D., Sullivan, M. A., Yu, E., Rothenberg, J. L., Kleber,
`
`H. D., Kampman, K., et al. (2006). Injectable, sustained-release
`naltrexone for the treatment of opioid dependence: A randomized,
`placebo-controlled trial. Archives of General Psychiatry, 63(2),
`210–218.
`6 Sullivan, M. A. (2011, April). Antagonist maintenance for opioid
`dependence: The naltrexone story. Presentation at the American
`Society of Addiction Medicine’s 42nd Annual Medical-Scientific
`Conference, Washington, DC.
`7 Baser, O., Chalk, M., Fiellin, D. A., & Gastfriend, D. R. (2011).
`
`Cost and utilization outcomes of opioid-dependence treatments.
`American Journal of Managed Care, 17(8), S235–S248.
`
`
`
`
`
`8 Center for Substance Abuse Treatment. (2004). Clinical guidelines
`for the use of buprenorphine in the treatment of opioid addiction.
`Treatment Improvement Protocol (TIP) Series 40. HHS
`Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse
`and Mental Health Services Administration.
`9 Center for Substance Abuse Treatment. (2008). Medication-assisted
`treatment for opioid addiction in opioid treatment programs.
`Treatment Improvement Protocol (TIP) Series 43. HHS
`Publication No. (SMA) 08-4214. Rockville, MD: Substance Abuse
`and Mental Health Services Administration.
`10 Alkermes, Inc. (2010a). Vivitrol prescribing information. Waltham,
`
`MA: Author. Retrieved February 2, 2012, from http://www.
`vivitrol.com/Content/pdf/prescribing_info.pdf
`11 Gastfriend, D. R. (2011a). Intramuscular extended-release naltrexone:
`
`Current evidence. Annals of the New York Academy of Sciences,
`1216, 144–166. doi: 10.1111/j.1749-6632.2010.05900.x
`12 Krupitsky, E., Zvartau, E., & Woody, G. (2010). Use of naltrexone
`
`to treat opioid addiction in a country in which methadone and
`buprenorphine are not available. Current Psychiatry Reports,
`12(5), 448–453. doi:10.1007/s11920-010-0135-5
`13 Bisaga, A. (2011, April). Antagonist treatment for opioid dependence:
`
`Patient selection and treatment initiation. Presentation at the
`American Society of Addiction Medicine 42nd Annual Medical-
`Scientific Conference, Washington, DC.
`
`14 O’Brien, C., & Kampman, K. M. (2008). Antagonists of opioids.
`In M. Galanter & H. D. Kleber, (Eds.), American Psychiatric
`Publishing textbook of substance abuse treatment. (Chapter 22).
`doi:10.1176/appi.books.9781585623440.352692
`
`15 Diguisto, E., Shakeshaft, A., Ritter, A., O’Brien, S., Mattick, R. P.,
`& NEPOD Research Group. (2004). Serious adverse events in the
`Australian National Evaluation of Pharmacotherapies for Opioid
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`7
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`Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover
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`An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence
`Winter 2012, Volume 11, Issue 1
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`Page 7 of 8
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`

`

`ADVISORY
`
`21 Alkermes, Inc. (2010b). Medication guide. Waltham, MA: Author.
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`25 Gastfriend, D. R. (2011b, April). Extended-release naltrexone
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`Society of Addiction Medicine 42nd Annual Medical-Scientific
`Conference, Washington, DC.
`26 Fishman, M. J., Winstanley, E. W., Curran, E., Garrett, S., &
`Subramaniam, G. (2010). Treatment of opioid dependence in
`adolescents and young adults with extended release naltrexone:
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`27 Rothenberg, J. L., Sullivan, M. A., Church, S. H., Seracini, A.,
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`
`SAMHSA Advisory
`This Advisory was written and produced under contract number 270-09-0307 by the Knowledge Application Program (KAP),
`a Joint Venture of JBS International, Inc., and The CDM Group, Inc., for the Center for Substance Abuse Treatment (CSAT),
`Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human Services
`(HHS). Christina Currier served as the Contracting Officer’s Representative (COR).
`Disclaimer: The views, opinions, and content expressed herein do not necessarily reflect the views or policies of CSAT,
`SAMHSA, or HHS. No official support of or endorsement by CSAT, SAMHSA, or HHS for these opinions or for particular
`instruments, software, or resources is intended or should be inferred.
`Public Domain Notice: All materials appearing in this document except those taken from copyrighted sources are in the
`public domain and may be reproduced or copied without permission from SAMHSA or the authors. Citation of the source
`is appreciated. However, this publication may not be reproduced or distributed for a fee without the specific, written
`authorization of the Office of Communications, SAMHSA, HHS.
`Electronic Access and Copies of Publication: This publication may be ordered from SAMHSA’s Publications Ordering
`Web page at http://www.store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727). The document
`can be downloaded from the KAP Web site at http://www.kap.samhsa.gov.
`Recommended Citation: Substance Abuse and Mental Health Services Administration. (2012). An Introduction to
`Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence. Advisory, Volume 11, Issue 1.
`Originating Office: Quality Improvement and Workforce Development Branch, Division of Services Improvement, Center
`for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 1 Choke Cherry Road,
`Rockville, MD 20857.
`
`SAMHSA Advisory
`An Introduction to Extended-Release Injectable Naltrexone
`for the Treatment of People With Opioid Dependence
`
`HHS Publication No. (SMA) 12-4682
`Printed 2012
`
`Page 8 of 8
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