U.S DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Substance Abuse and Mental Health Services Administration 

Center for Substance Abuse Treatment 

www.samhsa.gov 

Substance Abuse Treatment 

ADVISORY

News for the Treatment Field 

Spring 2007 

Volume 6 

Issue 1 

Naltrexone for Extended-Release 

Injectable Suspension for Treatment
 

of Alcohol Dependence
 

What is naltrexone for extendedrelease injectable suspension? 

In April 2006, the U.S. Food and Drug 

Administration (FDA) approved a new extendedrelease injectable formulation of naltrexone 

(Vivitrol®) for the treatment of alcohol dependence. 

In 1994, the FDA had approved oral naltrexone for 

treating alcohol use disorders, based on multiple 

clinical studies that found the medication was 

generally safe and significantly reduced alcohol 

craving, alcohol consumption, and relapse. 

Table 1 provides a comparison of oral naltrexone 

and naltrexone for extended-release injectable 

suspension (injectable naltrexone). 

Not surprisingly, additional studies have 

found that the effectiveness of oral naltrexone 

varied according to patient compliance with 

the medication regimen.1 An extended-release 

preparation of naltrexone had been sought for 

more than 30 years, and injectable naltrexone was 

developed in part to help address this issue of 

patient nonadherence to treatment. 

Table 1: Comparison of Oral Naltrexone and Extended-Release Injectable Naltrexone* 

Oral Naltrexone (ReVia®, Depade®) Naltrexone for Extended-Release 

Injectable Suspension (Vivitrol®) 

Mechanism of 

Action 

Blocks brain opiate receptors, attenuates 

euphoria associated with alcohol use, 

makes alcohol use less rewarding, and 

reduces craving. 

Precise mechanism unknown. 

Same as oral naltrexone; 30-day duration 

of action. 

Usual Adult 

Dosage and 

Prescribing 

Information 

One 50-mg tablet daily. 

Available by prescription from 

pharmacies. 

380 mg given as deep intramuscular (IM) 

injection, once a month or every 4 weeks.† 

Available only to prescribing medical 

personnel as single-use cartons containing 

one 380-mg vial of naltrexone microspheres, 

one vial diluent, one syringe, and needles. 

Table 1 continues on the next page. 
Spring 2007, Volume 6, Issue 1 

Substance Substance Abuse Treatmentreatment

ADVISOR ADVISORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
 

Table 1: Comparison of Oral Naltrexone and Extended-Release Injectable Naltrexone (continued)* 

Oral Naltrexone (ReVia®, Depade®) Naltrexone for Extended-Release 

Injectable Suspension (Vivitrol®) 

Examples of 

Drugs Causing 

Interactions 

Opioids and medications containing opioids 

(naltrexone blocks the action of opioids). 

Same as oral naltrexone. 

Common Side 

Effects 

Nausea, vomiting, decreased appetite, 

somnolence, fatigue, headache, dizziness, 

and anxiety. 

Same as oral naltrexone, plus reaction at 

injection site, joint pain, muscle aches, or 

cramps. 

Contraindications Hypersensitivity to naltrexone. 

Currently using opioids or in acute opioid 

withdrawal. 

Anticipated need for opioid analgesics. 

Acute hepatitis or liver failure. 

Same as oral naltrexone, plus sensitivity to 

any components of diluent, inadequate muscle 

mass for deep IM injection, rash, or infection 

at injection site. 

Precautions Other hepatic disease. 

Boxed warning about liver toxicity, although 

naltrexone does not appear to be toxic at 

recommended doses. 

Renal impairment. 

History of suicide attempts or depression. 

If opioid analgesia is required, larger doses may be 

needed, and respiratory depression may be deeper 

and more prolonged. 

FDA pregnancy category C.‡ 

Same as oral naltrexone, plus hemophilia or 

other bleeding problems. 

Serious Adverse 

Reactions 

Will precipitate severe withdrawal if the patient is 

dependent on opioids. 

Hepatotoxicity (although naltrexone does not appear 

to be a hepatotoxin at recommended doses). 

Same as oral naltrexone, plus infection at the 

injection site, depression, and rare events 

including allergic pneumonia and suicidal 

ideation and behavior. 

* Based on information in the FDA-approved product labeling or published medical literature. 

† Because it is administered as an injection, naltrexone for extended-release injectable suspension may be covered as a medical benefit and is available only through specialty pharmacies. For 

more information, contact your specialty pharmacy provider of choice, call VIP3 (Vivitrol Information for Patients, Physicians, and Providers) at 1-800-848-4876, or visit www.vivitrol.com. 

‡ FDA pregnancy category C: Animal studies have indicated potential fetal risk OR have not been conducted and no or insufficient human studies have been done. The drug should be used 

with pregnant or lactating women only when potential benefits justify potential risk to the fetus or infant. 

2 
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How does injectable naltrexone address 

patient nonadherence? 

Patient nonadherence is a common problem with all types 

of oral medications. In addition, people with substance 

use disorders experience fluctuations in their motivation 

for abstinence, further affecting their compliance with 

taking their medication. With injectable naltrexone, one 

intramuscular injection is effective for 4 weeks, reducing 

opportunities for patients to cease their medication. 

What is the efficacy of injectable naltrexone? 

The efficacy of injectable naltrexone in the treatment 

of alcohol dependence was evaluated in a 6-month, 

randomized, double-blind, multicenter trial of outpatients 

dependent on alcohol.2 Psychosocial support in addition 

to medication was provided to all patients. Subjects were 

randomized to three groups: Vivitrol 190 mg, Vivitrol 

380 mg, or placebo. Patients treated with 380 mg of 

injectable naltrexone in conjunction with psychosocial 

support had a greater reduction in the number of heavy 

drinking days than those treated with placebo. A subset 

of 53 patients (8 percent) who abstained completely from 

drinking in the week before the first dose of Vivitrol had 

greater reductions in the number of both drinking days 

and heavy drinking days than those patients treated with 

placebo. These patients were also more likely than patients 

treated with placebo to be completely abstinent. The same 

treatment effects were not seen among the subset of 571 

patients (92 percent) who were actively drinking when 

treatment with injectable naltrexone was begun. 

How safe is injectable naltrexone? 

Before FDA approval, injectable naltrexone was studied in 

more than 900 patients.3 Injectable naltrexone appears to 

be generally well tolerated, and adverse effects tend to be 

mild.2, 4 Patients using injectable naltrexone do not develop 

tolerance for or dependence on the medication. 

Like oral naltrexone, injectable naltrexone has a boxed 

warning on its packaging regarding the possibility of 

serious injury to those with active liver disease. However, 

the warning includes the statement that naltrexone does 

not appear to be a hepatotoxin at recommended doses. 

At least one study found it to be safe for use by patients 

with mild to moderate liver impairment.5 Nonetheless, 

liver function should be monitored during treatment with 

injectable naltrexone. 

Naltrexone is an opioid antagonist; to avoid serious 

withdrawal reactions, prescribers must ensure (through 

urine screens and/or a naloxone challenge test) that 

patients have been free of all opioid or opioid-containing 

medications for at least 7 days before administering 

injectable naltrexone. Patients with opioid use disorders 

also may be tempted to try to overcome the opioidblocking effects of naltrexone by taking large amounts 

of opioids. Taking these large amounts of opioids is 

dangerous and may lead to serious injury, coma, or 

death.3 Patients who have taken opioid drugs or medicines 

before starting treatment with injectable naltrexone may 

possibly lose their tolerance for opioids and may respond 

to doses of opioids lower than those previously used. 

This could result in potentially life-threatening opioid 

intoxication. In addition, patients requiring opioids 

for pain management during treatment with injectable 

naltrexone may need an amount of opioid that is greater 

than usual, and the resulting respiratory depression 

may be deeper and more prolonged. Substance abuse 

specialty treatment providers should caution patients to 

tell physicians, dentists, and other medical professionals 

that they are being or have been treated with injectable 

naltrexone whenever an opioid analgesic might be 

indicated. 

How can substance abuse specialty 

treatment providers incorporate injectable 

naltrexone? 

Medications for alcohol use disorders do not replace 

counseling. Treatment with naltrexone for extendedrelease injectable suspension can be one part of a 

comprehensive management program that includes 

psychosocial support and participating in 12-Step or 

other mutual-help group programs. 

3 
Naltrexone for Extended-Release Injectable Suspension for Treatment of Alcohol Dependence 

ADVISORY

Substance Abuse Treatment 

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
 

If the treatment provider and patient decide that 

medication may help, the patient should be referred to a 

medical professional who can prescribe or administer it. 

The prescribing professional should assess the patient’s 

medical appropriateness for therapy with injectable 

naltrexone by conducting a medical examination, which 

may include tests to rule out opioid dependence, severe 

liver disease, or pregnancy. Injectable naltrexone should 

be administered only by a medical professional (e.g., 

physician, nurse, physician’s assistant) and is available 

only through specialty pharmacies. If the treatment team 

and patient decide that injectable naltrexone is a good 

choice for that patient, more information can be obtained 

by calling the distributor’s Vivitrol information line, 

1-800-848-4876. 

Regular communication between substance abuse 

specialty treatment providers and the prescribing medical 

professional is essential. In particular, treatment providers 

need to communicate information concerning— 

•	 Patient’s reported or detected drinking or drug use 

episodes;
 

•	 Patient’s concerns about side effects; 

•	 Issues affecting the patient’s safety (suicidal ideation, 

reported or observed increase in levels of depression or 

anxiety, or significant physical complaints); and 

•	 Patient’s expressed desire to stop taking the 

medication.
 

Substance abuse specialty treatment providers should 

encourage patients to talk directly to their prescribing 

professionals about these and other issues or questions 

they may have. 

When determining how long a patient should continue on 

injectable naltrexone therapy, an individualized assessment 

by the prescribing professional and treatment team, with 

input from the patient, is best to determine the optimal 

length of time for medication treatment. Controlled studies 

have been conducted for up to 6 months; some patients 

have been treated with injectable naltrexone therapy for a 

year or longer. 

What To Tell the Patient 

Substance abuse specialty treatment program staff can 

support patients taking injectable naltrexone by educating 

them about the drug, including— 

•	 Informing patients about the potential benefits of the 

medication; 

•	 Ensuring that patients understand that medications 

for alcohol dependence do not replace counseling 

and that treatment with injectable naltrexone should 

be part of a comprehensive treatment and recovery 

program that includes psychosocial support and 

participating in 12-Step or other mutual-help group 

programs; 

•	 Ensuring that patients understand that they will need 

to get an injection once a month or every 4 weeks; 

•	 Encouraging patients to talk to their prescribing 

professional about how long to continue therapy with 

injectable naltrexone; 

•	 Encouraging patients to talk to their prescribing 

professional about all other prescription and 

nonprescription medications they are taking;
 

•	 Encouraging patients to promptly report side effects 

(including injection site reactions that do not improve 

over time, shortness of breath or difficulty breathing, 

overwhelming sadness or suicidal ideation, 

abdominal pain, yellowing of the skin or eyes, or 

change in color of urine or stools) to their prescribing 

professional; 

•	 Encouraging women to inform all their prescribing 

professionals immediately if they become pregnant 

during therapy; 

•	 Advising patients to continue taking the medication if 

a slip or relapse occurs and to inform their counselors 

and prescribing professionals immediately; 

•	 Reminding patients to inform physicians or dentists 

of current or previous treatment with injectable 

naltrexone whenever an opioid analgesic for pain 

management might be indicated; and 

•	 Encouraging patients to carry a medication alert card 

or wear a medical alert bracelet or tag indicating 

that they are receiving treatment with injectable 

naltrexone. 

4 
Spring 2007, Volume 6, Issue 1 

Substance Abuse Treatment 

ADVISORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
 

Notes 

1. Mann, K. (2004). Pharmacotherapy of alcohol 

dependence: A review of the clinical data. CNS Drugs, 

18(8), 485–504. 

2. Garbutt, J. C., Kranzler, H. R., O’Malley, S. S., 

Gastfriend, D. R., Pettinati, H. M., Silverman, B. L., et al. 

(2005). Efficacy and tolerability of long-acting injectable 

naltrexone for alcohol dependence: A randomized 

controlled trial. JAMA, 293(13), 1617–1625. 

3. Vivitrol prescribing information, Alkermes, Inc., 

www.vivitrol.com. 

4. Kranzler, H. R., Wesson, D. R., & Billot, L. (2004). 

Naltrexone depot for treatment of alcohol dependence: A 

multicenter, randomized, placebo-controlled clinical trial. 

Alcoholism: Clinical and Experimental Research, 28(7), 

1051–1059. 

5. Turncliff, R. Z., Dunar, J. L., Dong, Q., Silverman, 

B. L., Ehrich, E. W., Dilzer, S. C., et al. (2005). 

Pharmacokinetics of long-acting naltrexone in subjects 

with mild to moderate hepatic impairment. Journal of 

Clinical Pharmacology, 45, 1259–1267. 

Resources for Additional Information 

Substance Abuse and Mental Health Services 

Administration (SAMHSA) 

1 Choke Cherry Road, Room 8-1054 

Rockville, MD 20857 

Phone: 1-240-276-2130 (Office of Communications) 

Web: www.samhsa.gov 

SAMHSA’s National Clearinghouse for Alcohol and 

Drug Information 

Phone: 1-800-729-6686 

Español: 1-877-767-8432 

TDD: 1-800-487-4889 

Web: www.ncadi.samhsa.gov 

National Institute on Alcohol Abuse and Alcoholism 

5635 Fishers Lane, MSC 9304 

Bethesda, MD 20892-9304 

Web: www.niaaa.nih.gov 

U.S. Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857-0001 

Phone: 1-888-INFO-FDA (1-888-463-6332) 

Web: www.fda.gov 

Selected Publications 

Center for Substance Abuse Treatment. (1998). Naltrexone 

and Alcoholism Treatment. Treatment Improvement 

Protocol (TIP) Series 28. DHHS Publication No. (SMA) 

98-3206. Rockville, MD: Substance Abuse and Mental 

Health Services Administration. (Available through 

NCADI and at www.kap.samhsa.gov.) 

Center for Substance Abuse Treatment, Substance Abuse 

and Mental Health Services Administration. (2005). 

Acamprosate: A new medication for alcohol use disorders. 

Substance Abuse Treatment Advisory, 4(1), Fall. (Available 

through NCADI and at www.kap.samhsa.gov.) 

Center for Substance Abuse Treatment. (2006). 

Detoxification and Substance Abuse Treatment. Treatment 

Improvement Protocol (TIP) Series 45. DHHS Publication 

No. (SMA) 06-4131. Rockville, MD: Substance Abuse and 

Mental Health Services Administration. (Available through 

NCADI and at www.kap.samhsa.gov.) 

National Institute on Alcohol Abuse and Alcoholism. 

(2005). Helping Patients Who Drink Too Much: 

A Clinician’s Guide. Bethesda, MD: National Institutes 

of Health. (Available at www.niaaa.nih.gov.) 

National Institute on Alcohol Abuse and Alcoholism. 

(2005). A Pocket Guide for Alcohol Screening and Brief 

Intervention. Bethesda, MD: National Institutes of Health. 

(Available at www.niaaa.nih.gov.) 

5 
Substance Abuse Treatment Advisory 

Substance Abuse Treatment Advisory was written and produced under contract number 270-04-7049 by the Knowledge 

Application Program, a Joint Venture of JBS International, Inc., and The CDM Group, Inc., for the Center for Substance Abuse 

Treatment, Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human 

Services (HHS). The content of this publication does not necessarily reflect the views or policies of SAMHSA or HHS. 

Public Domain Notice: All material appearing in this report is in the public domain and may be reproduced or copied without 

permission; 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 can be accessed electronically through the Internet at 

www.kap.samhsa.gov. Additional free print copies can be ordered from SAMHSA’s National Clearinghouse for Alcohol 

and Drug Information (NCADI) at 1-800-729-6686. 

Recommended Citation: Center for Substance Abuse Treatment, Substance 

Abuse and Mental Health Services Administration. (Spring 2007). Naltrexone 

for extended-release injectable suspension for treatment of alcohol dependence. 

Substance Abuse Treatment Advisory, 6(1). 

National Clearinghouse for Alcohol and Drug Information 

Substance Abuse and Mental Health Services Administration 

U.S. Department of Health and Human Services 

350 Winmeyer Road 

Odenton, MD 21113 

PRSRT STD 
 

U.S. POSTAGE
 

PAID
 

ODENTON, MD
 

PERMIT NO. 350
 

Naltrexone for Extended-Release Injectable Suspension for Treatment of Alcohol Dependence 

Substance Abuse Treatment 

ADVISORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
 

Substance Abuse Treatment Advisory 

Naltrexone for Extended-Release Injectable Suspension 

for Treatment of Alcohol Dependence 

DHHS Publication No. (SMA) 07-4267 

Printed 2007