Efficacy and Safety

CLINICAL STUDIES OF VIVITROL

Researchers conducted 2 separate clinical trials to evaluate the efficacy and safety of VIVITROL. One study was conducted among those with opioid dependence and the other study among those with alcohol dependence. In both studies, 2 groups of patients were studied for 6 months.1

VIVITROL AND OPIOID DEPENDENCE

In this double-blind, placebo-controlled, randomized clinical study, opioid-dependent patients were treated with VIVITROL (n=126) or placebo (n=124) and counseling following opioid detoxification.2*

*Sessions of individual drug counseling, adapted for opioid dependence, occurred biweekly.

STUDY DESIGN2

  • Initial screening of 335 participants
  • 250 participants randomized into 2 groups
  • 126 patients received VIVITROL 380 mg
  • All groups received psychosocial support*
*Psychosocial support consisted of biweekly counseling sessions of individual drug counseling, adapted for opioid dependence.

Primary ENDPOINT

CONFIRMED OPIOID ABSTINENCE

Weeks 1-4 were omitted from this endpoint to allow for stabilization of abstinence. Patients treated with VIVITROL and counseling:
Placebo
23%
Vivitrol
36%

Had higher rate of complete abstinence2

36% of VIVITROL patients were opioid-free at all visits from week 5–24 vs 23% of placebo patients. P=0.0224


Placebo
35%
Vivitrol
90%

Had signiFIcantly higher percentage of opioid-free weeks2

The median VIVITROL patient was opioid-free for 90% of weeks 5–24 vs 35% for placebo patients. P=0.0002

IMPORTANT SAFETY INFORMATION

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 provider.
Confirmed abstinence = negative urine drug test and no self-reported opioid use.

Secondary Endpoints

Patients treated with VIVITROL and counseling:
Patients treated with VIVITROL and counseling for opioid dependence had a 55% decrease in self-reported opioid cravings

Had a sustained decrease IN OPIOID CRAVING2‡

VIVITROL patients had a mean change from baseline of -10.1 points vs. a mean change of +0.7 points for patients in the placebo group over 6 months (baseline mean VAS score for VIVITROL vs. placebo was 18 and 22 respectively). Patients given VIVITROL had a 55% decrease in self-reported opioid craving from baseline to week 24. Patients given a placebo had a 3% increase in craving from baseline to week 24.

Patients treated with VIVITROL and counseling for opioid dependence stayed in treatment longer vs placebo patients

Stayed in treatment longer

At the end of the study period (168 days), the median VIVITROL patient had not dropped out vs. 96 days in treatment for placebo patients (P=0.0042 [adjusted]).

Patients treated with VIVITROL and counseling for opioid dependence were 17x less likely to relapse compared to placebo

Were less likely to relapse to PHYSICAL OPIOID DEPENDENCE2

Only 1 patient on VIVITROL (<1%) discontinued due to positive naloxone challenge, indicating physical dependence had been re-established, compared to 17 patients on placebo (14%, P<0.0001)

IMPORTANT SAFETY INFORMATION

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, etc.).
  • 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.
Craving was measured by self-reported "need for opioids" using the visual analog scale. §2% of people discontinued treatment.1

VIVITROL and ALCOHOL DEPENDENCE

In this double-blind, placebo-controlled, randomized clinical study, alcohol-dependent patients were treated with VIVITROL 380 mg (n=205), VIVITROL 190 mg (n=210) or placebo (n=209) and counseling.3,||

STUDY DESIGN1,3

VIVITROL and alcohol dependence study
design
  • Initial screening of 899|| participants
  • 627 participants randomized into 3 groups||
  • 210 patients received VIVITROL 190 mg
  • All groups received psychosocial support||

Primary Endpoint

Patients treated with VIVITROL and counseling for alcohol dependence had 25% fewer heavy-drinking days
Patients treated with VIVITROL and counseling:

Had fewer heavy-drinking days

In the overall population, patients treated with VIVITROL 380 mg and psychosocial support (n=205) had 25% fewer heavy-drinking days (P=0.02) than patients treated with placebo and psychosocial support (n=209).

IMPORTANT SAFETY INFORMATION

Alcohol Withdrawal:

  • Use of VIVITROL does not eliminate nor diminish alcohol withdrawal symptoms.

Subset Population

92% of patients in the study had fewer heavy-drinking days in the subset population

A prespecified subset of patients (n=53, or 8% of the total study population) who were able to abstain from drinking for the week prior to receiving VIVITROL (380 mg) were studied.4

VIVITROL and alcohol dependence study
subset population

Patients treated with VIVITROL and counseling:

HAD FEWER HEAVY-DRINKING DAYS

The median number of heavy-drinking days for patients treated with VIVITROL (380 mg) and psychosocial support was 0.2 days vs. 2.5 days for patients treated with placebo and psychosocial support (P=0.05).3

The same results were not seen in patients (n=571, or 92% of the total study population) who were actively drinking at the time of treatment initiation.

ADVERSE REACTIONS

  • 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 suicidality.
  • 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 disorders.
  • 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 toothache.
||Psychosocial support consisted of biweekly counseling. Patients with treated depression and stable pharmacotherapy for at least 8 weeks were not excluded. Heavy drinking was defined as a self-report of 5 or more standard drinks consumed on a given day for male patients and 4 or more drinks for female patients.

HOW VIVITROL WORKS

VIVITROL is an opioid antagonist.3 Learn what this means and how VIVITROL works inside the body to help reinforce recovery.

Find out how VIVITROL works

Considering Vivitrol treatment for your pragram

Learn more about incorporating VIVITROL and counseling into your program.

See if VIVITROL is right for your program

VIVITROL Q&A

Have questions about VIVITROL? Check out our Q&A section for answers that may help.

See VIVITROL Q&A

VIVITROL is not right for everyone. There are significant risks from VIVITROL treatment, including but not limited to, risk of opioid overdose, injection site reaction and sudden opioid withdrawal. See Important Safety Information below.

References:

  1. VIVITROL [prescribing information]. Waltham, MA: Alkermes, Inc.; rev December 2015.
  2. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506-1513.
  3. Garbutt JC, Kranzler HR, O'Malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-1625.
  4. Data on file. Alkermes, Inc.