Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover

ADVISORY

Winter 2012 • Volume 11 • Issue 1

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 extendedrelease 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 ExtendedRelease 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 

2 

ADVISORY

 

 

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 substances, whereas naltrexone is not. Methadone is an opioid 

agonist, buprenorphine is a partial opioid agonist, and naltrexone is an opioid antagonist. 

Different types of opioid receptors—or molecules to which 

opioid compounds attach themselves and exert their effects—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 compounds. 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 philosophies, difficulties in tapering patients off these medications, 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 extendedrelease injectable naltrexone, buprenorphine, and methadone. 

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 naltrexonecontaining 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 
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

 

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 

Exhibit 1: Key Differences Between Medications Used 

To Treat Patients With Opioid Dependence
 

Prescribing 

Considerations 

Extended-Release 

Injectable Naltrexone 

Buprenorphine Methadone 

Frequency of 

Administration 

Monthly Daily Daily 

Route of 

Administration 

Intramuscular injection in the 

gluteal muscle by healthcare 

professional. 

Oral tablet or film is dissolved 

under the tongue. Can be 

taken at a physician’s office or 

at home. 

Oral (liquid) consumption 

usually witnessed at an OTP, 

until the patient receives takehome doses. 

Restrictions on 

Prescribing or 

Dispensing 

Any individual who is licensed 

to prescribe medicine 

(e.g., physician, physician 

assistant, nurse practitioner) 

may prescribe and order 

administration by qualified 

staff. 

Only licensed physicians 

who are DEA registered and 

either work at an OTP or have 

obtained a waiver to prescribe 

buprenorphine may do so. 

Only licensed physicians who 

are DEA registered and who 

work at an OTP can order 

methadone for dispensing at 

the OTP. 

Abuse and Diversion 

Potential 

No Yes Yes 

Additional 

Requirements 

None; any pharmacy can fill 

the prescription. 

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. 

Sources: Adapted from 16,18,19 

3 
Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover 

4 

ADVISORY

 

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 extendedrelease 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 Extendedrelease injectable naltrexone should be discontinued if 

signs or symptoms of hepatitis develop (e.g., fatigue, 

loss of appetite, nausea, vomiting, abdominal pain, graycolored 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 ExtendedRelease 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 extendedrelease 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. 
Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover

5 

An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence

Winter 2012, Volume 11, Issue 1

 

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 extendedrelease 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, 
Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover 

6 

ADVISORY

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, extendedrelease 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 extendedrelease 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. 
Behavioral Health Is Essential To Health • Prevention Works • Treatment Is Effective • People Recover

7 

An Introduction to Extended-Release Injectable Naltrexone for the Treatment of People With Opioid Dependence

Winter 2012, Volume 11, Issue 1

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/PostmarketDrugSafetyInformationforPatientsandProviders/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 MedicalScientific 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 

Dependence (NEPOD). Addiction, 99(4), 450–460. 

16 U.S. Food and Drug Administration. (2010, Sept.). VIVITROL 

(naltrexone for extended-release injectable suspension): 

NDA 21-897C—Briefing document/background package. 

Psychopharmacologic Drugs Advisory Committee Meeting, Silver 

Spring, MD. 

17 Gibson, A. E., & Degenhardt, L. J. (2007). Mortality related to 

pharmacotherapies for opioid dependence: A comparative analysis 

of coronial records. Drug and Alcohol Review, 26, 405–410. 

18 Clark, L., Haram, E., Johnson, K., & Molfenter, T. (2010). Getting 

started with medication-assisted treatment. University of 

Wisconsin–Madison: Network for the Improvement of Addiction 

Treatment (NIATx). 

19 Physician Clinical Support System-Buprenorphine. (2009). PCSS 

Guidance: Buprenorphine induction. Retrieved February 2, 2012, 

from http://www.pcssb.org/wp-content/uploads/2010/09/PCSS-BBuprenorphine-induction.pdf 

20 Fishman, M. (2008). Precipitated withdrawal during maintenance 

opioid blockade with extended release naltrexone. Addiction, 

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ADVISORY

21 Alkermes, Inc. (2010b). Medication guide. Waltham, MA: Author. 

Retrieved February 2, 2012, from http://www.vivitrol.com/pdf_

docs/Vivitrol%20Approved%20PPI.pdf 

22 Comer, S. D. (2011, April). Oral naltrexone for opioid dependence. 

Presentation at the American Society of Addiction Medicine 42nd 

Annual Medical-Scientific Conference, Washington, DC.

23 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A., Gastfriend, 

D. R., & Silverman, B. L. (2011). Injectable extended-release 

naltrexone for opioid dependence: A double-blind, placebocontrolled, multicentre randomized trial. Lancet, 377(9776), 

1506–1513. doi:10.1016/S0140-6736(11)60358-9

24 National Institute on Drug Abuse. (2009). Principles of drug 

addiction treatment: A research-based guide (2nd ed.). NIH 

Publication No. 09–4180. Washington, DC: National Institutes of 

Health.

25 Gastfriend, D. R. (2011b, April). Extended-release naltrexone 

(XR-NTX) for opioid dependence. Presentation at the American 

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: 

Preliminary case-studies and feasibility. Addiction, 105(9), 1669–

1676.

27 Rothenberg, J. L., Sullivan, M. A., Church, S. H., Seracini, A., 

Collins, E., Kleber, H. D., et al. (2002). Behavioral naltrexone 

therapy: An integrated treatment for opiate dependence. Journal of 

Substance Abuse Treatment, 23(4), 351–360. doi:10.1016/S0740-

5472(02)00301-X

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 

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Electronic Access and Copies of Publication: This publication may be ordered from SAMHSA’s Publications Ordering 

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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