1. VIVITROL® A Brief Clinical Overview
VIV 784A VIVITROL Brief Medical Overview
Aug 2009
VIV 784A

2. Presentation Overview
Achieving recovery from Alcohol Dependence
Combining medication with psychosocial support
National consensus on the addition of medication to psychosocial support
Challenges of Current Therapies
Nonadherence
Relapse rates
VIVITROL
Mechanism of action
Safety and efficacy
Touchpoints℠ services
This is an overview of today’s presentation.
Today’s presentation will focus on alcohol dependence and strategies for achieving recovery from this chronic disease
We will discuss the rationale, the benefits, and the consensus on combining psychosocial treatments with medication
We will be discussing both the success and the challenges of current therapies, focusing on the challenge of nonadherence. We’ll also talk about ways medication can be integrated into traditional treatment models.
We will discuss VIVITROL:
- The mechanism of action, safety and efficacy of VIVITROL.
Finally, we’ll discuss the Touchpoints℠ services and clinical resources - a free, comprehensive program designed to support longterm recovery 2

3. Comprehensive Alcohol Dependence Treatment
Cortex
Role:
Decision making
Thinking
Reasoning
Rationalizing
Comprehensive treatment for alcohol dependence needs to address both the psychosocial and biological components, as well as the two areas of the brain that correspond to these components.
The brain’s cortex — the large area of the brain that makes us uniquely human—is the rational and analytical center, involved in conscious decision-making, thinking, and reasoning.
However, addiction treatment providers have known for over 100 years just how irrational this disease is. The cortex of an alcohol dependent brain can be “recruited” or “hijacked”, as some say, so that the rational brain becomes irrational, and makes rationalizations and excuses about the disease and the associated behaviors. Denial can play a baffling role in the disease.
Psychosocial treatments such as counseling, 12-step fellowships, and other faith-based support, target these conscious processes and help to strengthen a person’s positive decisions.
So what is “driving” these decisions – what is “recruiting” the Cortex to behave this way?
This is the part of the brain called the limbic system.
Psychosocial treatments
12-step fellowships
Faith-based support 3 3

4. Comprehensive Alcohol Dependence Treatment
VIVITROL
Psychosocial Treatment and Medication
Cortex
Role:
Decision making
Thinking
Reasoning
Rationalizing
Limbic Region
Role:
Drive generation
The limbic region is sometimes referred to as the “drive” center for our most basic and primitive needs: hunger, thirst, sex, and basic survival needs. The limbic system also drives our impulses, desires, rewards, and our emotional memory.
When VIVITROL is added to psychosocial treatment, BOTH the cortex and the limbic region are treated, and clients receive COMPREHENSIVE treatment.
While psychosocial treatment contributes to recovery, the combination of medicine and psychosocial treatment offers patients a better chance of recovery.
Psychosocial treatments
12-step fellowships
Faith-based support 4 4

5. Medication-Assisted Treatment A National Consensus
PLNDP
Physicians and Lawyers for National Drug Policy
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
Substance Abuse & Mental Health Services Administration
US Dept of Health & Human Services
National Council on Alcoholism and Drug Dependence
National Association of Drug Court Professionals
Support for the use of pharmacotherapy in the treatment of alcohol dependence is widespread. The recommendations from these organizations are consistent:
Medication should complement- not replace- current psychosocial treatment
Medication should be considered in all alcohol dependent clients, not just those with the
worst treatment histories or prognoses
In fact, CSAT has recently published TIP 49: Incorporating Alcohol Pharmacotherapies Into Medical Practice A Treatment Improvement Protocol TIP 49, which includes a chapter on VIVITROL
[Recommendation: All quotes are available at the end of the deck]
National Institute on Alcohol Abuse and Alcoholism. Helping Patients Who Drink Too Much: A Clinician’s Guide. May 2007 reprint. Accessed May 5, 2008.
Join Together: 10 Drug and Alcohol Policies That Will Save Lives. Available at: Accessed April 30, 2008.
Substance Abuse & Mental Health Services Administration (SAMHSA), Division of Pharmacologic Therapies (DPT). Medication-Assisted Treatment for Substance Use Disorders. Accessed May 5, 2008.
American Psychiatric Association. Practice Guideline for the Treatment of Patients With Substance Use Disorders, 2nd edition Accessed April 30, 2008.
National Quality Forum National Voluntary Consensus Standards for the Treatment of Substance Use Conditions: Evidence-Based Treatment Practices. Accessed May 5, 2008.
Institute of Medicine of the National Academies. Improving the Quality of Health Care for Mental and Substance-Use Conditions: Quality Chasm Series. Committee on Crossing the Quality Chasm: Adaptation to Mental Health and Addictive Disorders. Executive Summary Accessed May 5, 2008.
Physicians and Lawyers for National Drug Policy Objectives. Available at: Accessed May 6, 2008.
The National Council on Alcoholism and Drug Dependence. Interviews with the Experts: Robert Morse, MD on the Use of Pharmacology in Addiction Treatment. Accessed May 5, 2008.
Vivitrol Advisory, U.S. Department of Health and Human Services, SAMHSA/CSAT, Spring 2007,
Institute of Medicine Of the National Academies
National Quality Forum 5 5

6. Nonadherence Undermines Recovery1
Now let’s talk about some of the challenges with some of the current therapies, and specifically, look at the problem of medication nonadherence.
Patient nonadherence with treatment negatively affects outcomes.
In a 12-week study of nearly 200 alcohol-dependent patients treated with oral naltrexone or placebo, we see that those who did not adhere to the oral naltrexone treatment experienced 4 times greater relapse rates than those who were adherent. Only 10% of adherent patients relapsed, compared to 42.9% of nonadherent patients.
However, if patients took less than 80% of the oral naltrexone - which was the case for nearly half of the participants in this study - they did the same as those who were being treated with placebo! In other words, if you don’t take the medication, it doesn’t do any good.
1. Pettinati HM, et al. J Addict Dis. 2000;19:71-83. 6

7. Oral Naltrexone Discontinuation Rates
US Department of
Health and Human Services/SAMHSA study (2004)1
Kranzler et al., Addiction 20084
Now in the real world, we also know that discontinuation rates are high.
The graph on the left is from a SAMHSA sponsored study. Katherine Harris et al (2004) analyzed paid pharmacy claims for patients of a large, mid-Atlantic health insurer.
The consistent finding over the 3 years analyzed was that about half of all patients failed to refill beyond 30 days – and it is unknown how much of the medication is actually taken.
Two other studies (Hermos et al, 2004, and Un et al, 2008) had remarkably similar findings.
Recently, Kranzler et al (Addiction, 2008) did a similar commercial pharmacy claims analysis over a 6-month period and showed very similar findings; the majority of patients did not refill their prescriptions beyond the first 30 days. This represents four studies all demonstrating similar findings.
Pharmacy claims for NTX-PO 1,4
Guidelines recommend treatment from 3-6 months to 2 years1
The vast majority did not persist in refills for a reasonable course of treatment 1,4
Both analyses show that approximately 50% failed to refill even beyond 30 days1,4
Two additional independent studies obtained similar discontinuation rates2,3
1. Harris KM, et al. Psychiatr Serv. 2004;55:221.
2. Hermos JA, et al. Alcohol Clin Exp Res. 2004;28:
3. Un H, Addiction Health Services Research Conference, Boston 2008
4. Kranzler HR, et al. Addiction. 2008:103(11): 7 7

8. Medications for Alcohol Dependence
1951
30 tabs/month* (1 tab/day)
Antabuse® (disulfiram)1
1994
30 tabs/month* (1 tab/day)
ReVia® (naltrexone)2
2004
Campral®
(acamprosate)3
180 tabs/month* (2 tabs, 3x/day)
2006
1/month
VIVITROL® (naltrexone for
extended-release
injectable suspension)4
This slide shows the medications that have been developed and approved to treat alcohol dependence over the past 50 years.
Branded and Generic names – all FDA approved for alcohol dependence.
Antabuse (disulfiram): First medication approved in 1951 for treating alcoholism. Antabuse works as a deterrent…clients will get physically ill if they drink while on the medication – vomiting, accelerated heart rate, possibly convulsions and death. Antabuse is dosed 1 tab/day.
ReVia (naltrexone) – Approved 40 years later in 1994 for alcohol dependence. Mechanism of action for alcoholism is not entirely understood but it is an opioid receptor antagonist. Naltrexone occupies the receptor and blocks it from receiving other activity. ReVia is also dosed 1 tab/day.
Campral (acamprosate): More recently in 2004, the 3rd medication was approved. Campral’s mechanism of action is not entirely understood but is thought to stabilize the balance between neuronal excitation and inhibition that is altered by alcohol. Campral is dosed 6 tabs/day; 2 in the morning, 2 in the afternoon and 2 at night.
So all of the pharmaceutical agents approved in this therapeutic category through 2004 are administered orally. The problem of nonadherence, unfortunately, has greatly undermined how often clients take the medications as prescribed.
VIVITROL (naltrexone for extended-release injectable suspension) was approved in VIVITROL contains naltrexone, an opioid antagonist which blocks the receptors from receiving other activity. VIVITROL is administered as a gluteal IM injection once a month, which alleviates the burden of making daily medication adherence decisions.
1. Antabuse full Prescribing Information. Odyssey Pharmaceuticals, Inc.
2. ReVia full Prescribing Information. Duramed Pharmaceuticals, Inc.
3.Campral full Prescribing Information. Merck Santé s.a.s.
4.VIVITROLFull Prescribing Information. Alkermes, Inc.
*Based on a month with 30 days. 8 8

9. What is VIVITROL? VIVITROL is NOT1: Addictive
Aversive (e.g. disulfiram)
Euphorigenic (i.e. pleasure producing)
VIVITROL is1:
An opioid blocker (i.e. antagonist)
Extended-release (30 days)
Compatible with psychosocial treatments, antidepressants and Alcoholics Anonymous2
Administered by a healthcare professional
(use can be monitored)
This information comes from the VIVITROL Package Insert.
VIVITROL Full Prescribing Information. Alkermes, Inc.
Gromov, I., et al. AMERSA, Washington, DC, November 8, 2007. 9 9

10. VIVITROL Indication
VIVITROL is indicated for the 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.
Treatment with VIVITROL should be part of a comprehensive management program that includes psychosocial support.
The indication describes the FDA’s approval for the use of VIVITROL.
An outpatient setting in the VIVITROL Phase III clinical trial meant a physician’s office or an outpatient clinic (not a day program). The study population was very similar to that which is seen in real-world treatment settings.
VIVITROL is not intended to replace psychosocial support but to complement it. As you will see, when used as part of a program that includes psychosocial support, VIVITROL can significantly improve treatment outcomes in patients who are abstinent at treatment initiation.
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009. 10 10

11. Important Safety Information
VIVITROL is contraindicated in patients receiving opioid analgesics or with current physiologic opioid dependence,patients in acute opiate withdrawal, any individual who has failed the naloxone challenge test or has a positive urine screen for opioids, or in patients who have previously exhibited hypersensitivity to naltrexone, PLG, carboxymethylcellulose or any other components of the diluent.
VIVITROL patients must be opioid free for a minimum of 7-10 days before treatment.
Attempts to overcome opioid blockade due to VIVITROL may result in a fatal overdose.
In prior opioid users, use of opioids after discontinuing VIVITROL may result in a fatal overdose because patients may be more sensitive to lower doses of opioids.
Speaker should review all points on the slide
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009.

12. Important Safety Information
In an emergency situation in patients receiving VIVITROL, suggestions for pain management include regional analgesia or use of non-opioid analgesics.
If opioid therapy is required as part of anesthesia or analgesia, such patients should be continuously monitored, in an anesthesia care setting, by persons not involved in the conduct of the surgical or diagnostic procedure.
The opioid therapy must be provided by individuals specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation.
Irrespective of the drug chosen to reverse the VIVITROL blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.
Speaker should review all points on the slide
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009.

13. Important Safety Information
Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses.
Naltrexone is contraindicated in acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects.
The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only five-fold or less. VIVITROL does not appear to be a hepatotoxin at the recommended doses.
Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. Use of VIVITROL should be discontinued in the event of symptoms and/or signs of acute hepatitis.
VIVITROL has a black box warning for hepatotoxicity (causes liver damage). VIVITROL does not appear to be a hepatotoxin at the recommended doses.
The warning for oral naltrexone is based on a study that found seriously increased liver enzymes in obese patients who were given 2 to 6 times the recommended dose of daily oral naltrexone. Transient elevations in serum transaminases have been observed with high doses (several times higher; up to 300 mg/day) of oral naltrexone in disorders other than alcohol dependence; these elevations spontaneously reverse over a period of weeks, even with continued treatment. Hepatotoxicity has not been a finding in studies of alcohol dependent subjects taking the standard recommended dose of oral naltrexone—50 mg/day.
In the VIVITROL Phase III clinical trial, researchers specifically studied effects on the liver. They found that mean AST and ALT levels did not change significantly over the course of treatment or with medication.
In short-term controlled trials, the incidence of AST elevations associated with VIVITROL treatment was similar to that observed with oral naltrexone treatment (1.5% each) and slightly higher than observed with placebo treatment (0.9%). In subjects with mild to moderate hepatic impairment, no changes were noted in liver function after treatment with VIVITROL.
Speaker may remind the audience that this information is also included in the full prescribing information.
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009. 13

14. Important Safety Information
VIVITROL is administered as an intramuscular gluteal injection. Inadvertent subcutaneous injection of VIVITROL may increase the likelihood of severe injection site reactions.
VIVITROL must be injected using the customized needle provided in the carton. Because needle length may not be adequate due to body habitus, each patient should be assessed prior to each injection to assure that needle length is adequate for intramuscular administration.
VIVITROL injection site reactions 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.
Speaker should review all points on the slide
VIVITROL [full prescribing information]. Cambridge, MA: Alkermes, Inc; 2009.
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009.

15. Important Safety Information
Consider the diagnosis of eosinophilic pneumonia if patients develop progressive dyspnea and hypoxemia.
Alcohol dependent patients, including those taking VIVITROL, should be monitored for the development of depression or suicidal thoughts.
Caution is recommended in administering VIVITROL to patients with moderate to severe renal impairment.
The most common adverse events associated with VIVITROL in clinical trials were nausea, vomiting, headache, dizziness, asthenic conditions and injection site reactions.
Notes:
VIVITROL must never be injected into adipose or into a vein
VIVITROL [full prescribing information]. Cambridge, MA: Alkermes, Inc; 2009.
VIVITROL[full prescribing information]. Cambridge, MA: Alkermes, Inc; May 2009.

16. Opioid Receptors and Alcohol Dependence
It is required that this slide and the next slide be presented together.
We know that the release of dopamine in the brain is related to the reinforcing effect of alcohol and may be associated with alcohol dependence. This illustration depicts a proposed mechanism in which the ingestion of alcohol begins a neural cascade resulting in the excessive release of dopamine—the neurotransmitter that may lead to the reinforcement of alcohol’s pleasurable effects.
First, alcohol stimulates the release of ß-endorphins in the brain.
ß-endorphins are produced in the arcuate of the hypothalamus by nerve cells that extend to the other brain regions.
Next, ß-endorphins bind to µ- opioid receptors on the axons of the dopamine –producing neurons.
This leads to the excessive release of dopamine, which is associated with the reinforcing and rewarding effects of alcohol.
1.Gianoulakis C. Alcohol Health Res World. 1998;22:
2. Woodward JJ. Principles of Addiction Medicine. 3rd ed. 2003: 16

17. VIVITROL: A Targeted Approach
It is required that this slide and the previous slide be presented together.
While the mechanism by which VIVITROL exerts its effects in alcohol-
dependent patients is not entirely understood, this illustration depicts
the proposed MOA of VIVITROL involving opioid receptor blockade.
Naltrexone—the active ingredient in VIVITROL—is an opioid antagonist
with the highest affinity for the µ-opioid receptor. Thus, it can compete
with and block the binding of ß-endorphins to these receptors.
This may lead to the prevention of excessive dopamine release mitigating the
reinforcing and rewarding effects of alcohol.
The mechanism by which VIVITROL exerts its effects in alcohol-dependent patients is not entirely understood.
1. VIVITROL full Prescribing Information. Alkermes, Inc.
2. Oswald LM, et al. PhysiolBehav. 2004;81:
3.Kenna GA, et al. Am J Health Syst Pharm. 2004;61:
4.Gianoulakis C. Alcohol Health Res World. 1998;22: 17

18. VIVITROL Microspheres1,2
Hydration
Diffusion
Erosion
Early phase
Water absorption (hydration) causes the VIVITROL microspheres to swell
Small amounts of naltrexone released slowly at or near surface
Extended-release phase—diffusion and erosion
Polymer continues to break down
Internal structures collapse and erode
The polymer used with Medisorb® has a history of safe use in humans in the form of absorbable sutures, abdominal mesh, bone plates, and other extended-release pharmaceuticals, including an atypical antipsychotic agent.
Elimination: polymer eventually metabolized and eliminated as CO2 and H2O
1. Dean RL. Front Biosci. 2005;10:
2. Data on file. Alkermes, Inc. 18

19. VIVITROL Provides a Sustained-Release of Medication
Mean steady-state naltrexone concentration following monthly VIVITROL compared to daily oral dosing1
VIVITROL IM Injection
Oral naltrexone 50 mg
Data for oral naltrexone beyond day 5 have been extrapolated from a study of normal healthy volunteers (n=14) given oral naltrexone 50 mg daily for 5 days.
As you can see, looking at the gray line, daily dosing of oral naltrexone results in fluctuating plasma concentrations of the drug during the day. Naltrexone concentrations peak within the first hour of oral dosing, followed by a steady decline within 8 hours. This pattern recurs each day during treatment.
In contrast, VIVITROL provides consistent release of naltrexone
Transient initial peak occurs approximately 2 hours after injection
Peak concentrations observed in approximately 2 to 3 days
Steady state is achieved by the second dose
1 dose of VIVITROL (380 mg) is only ¼ of the cumulative dose of 1 month of oral naltrexone (1,500 mg)
Increased exposure (in terms of area under the curve)
Plasma concentrations do not necessarily correlate with clinical efficacy or side effects
Early phase
Water absorption (hydration) causes the VIVITROL microspheres to swell
Small amounts of naltrexone released slowly at or near the surface
Extended-release phase—diffusion and erosion
Polymer continues to break down
Internal structures collapse and erode
The polymer used with the Medisorb® formulation of VIVITROL, PLG, has a history of safe use in humans. It has been used in absorbable sutures, abdominal mesh, bone plates, and other extended-release pharmaceuticals, including an atypical antipsychotic agent.
1. Dunbar JL, et al. Alcohol Clin Exp Res. 2006;30: 19

20. Pharmacokinetics
Reduced first-pass hepatic metabolism vs oral naltrexone1
The cytochrome P450 system is not involved in naltrexone metabolism1
No clinical drug interaction studies have been performed
Lower total monthly dose:
380mg of VIVITROL vs 1500mg of oral naltrexone1
Total area-under-the-curve of VIVITROL
is approximately 4-times that with oral naltrexone2
The pharmacokinetic profile of VIVITROL is one feature that differentiates it from oral naltrexone. Due to the route of administration, (VIVITROL is a intramuscular gluteal injection), there is
Reduced first-pass hepatic metabolism as compared to oral naltrexone
Mediated by dihydrodioldehydrogenase
VIVITROL is not metabolized by the CYP450 system
Reduced total monthly dose
Also,the total area-under-the-curve of VIVITROL is approximately 4-times that with oral naltrexone2
Although no clinical trials have been conducted specifically to address drug-drug interactions with VIVITROL, the phase III clinical trial admitted patients with treated depression who were stable on pharmacotherapy for at least 8 weeks.
Naltrexone antagonizes the effect of opiate-containing medicines, such as cough and cold remedies, antidiarrheal preparations, and opioid analgesics. Patients should be advised that because VIVITROL can block the effects of opiates and opiate-like drugs, patients will not perceive any effect if they attempt to self-administer heroin or any other opioid drug in small doses while on VIVITROL.
VIVITROL Full Prescribing Information. Alkermes, Inc.
Dunbar, JL. Et al. Alcohol and Clin Exp Res. 2006;30(3): 20

21. VIVITROL Eliminates Daily Adherence Decisions1
VIVITROL utilizes a delivery system that
Provides a month of medication in a single dose
Adherence to any treatment program is essential for successful outcomes
Administration by a healthcare provider ensures that the patient receives the medication as directed
As a once-monthly injection, VIVITROL eliminates the need for patients to make daily adherence decisions.
One injection provides a month of medication
Adherence to any treatment program is essential for successful outcomes
In addition, VIVITROL must be administered by a healthcare provider, which ensures proper administration and dosing.
“…addressing patient adherence systematically will maximize the effectiveness of these medications.”2
–Updated NIAAA Clinician’s Guide
1. Dean RL. Front Biosci. 2005;10:
2. NIAAA NIH publication 21

22. Phase III Safety & Efficacy Trial Randomized, double-blind, placebo-controlled study1-3
899 assessed for eligibility
624 DSM-IV alcohol-dependent patients randomized
Received 24-weeks treatment
including 12 sessions of standardized counseling
Multicenter: 24 outpatient sites
Placebo Microspheres
n=209
XR-NTX 190 mg n=210
VIVITROL n=205
134 received all 6 injections
137 received all 6 injections
130 received all 6 injections
In the 24-week VIVITROL phase III trial, patients were treated in outpatient settings including physicians’ offices or outpatient clinics (not day programs). The study population was very similar to that which is seen in real-world treatment settings.
The psychosocial treatment used in the VIVITROL clinical trial was BRENDA. BRENDA is a low-intensity intervention designed to facilitate direct feedback of addiction-related consequences. It consists of
Biopsychosocial assessment
Reporting the assessment to the patient (sharing the findings and conclusions)
An Empathetic approach (which might include active listening, encouragement of open discussion, and sympathetic interaction)
Identified and stated patient Needs
Direct advice regarding drinking behavior
Assessment of treatment adherence
BRENDA sessions were administered by psychologists, nurses, therapists, counselors, and physicians.
Patients did not receive an oral naltrexone lead-in. The need for detoxification was determined by the investigator.
In the placebo group, 128 patients (61%) completed the trial; in the XR-NTX 190 mg group, 126 patients (60%) completed; and in the VIVITROL, 124 patients (60%) of patients completed the trial. These completion rates are consistent with those seen in other clinical trials in alcohol dependence.
Extended-release naltrexone 190 mg IM injection has not been approved by the FDA and will not be made commercially available.
64%
65%
63%
128 completed trial
126 completed trial
124 completed trial
61%
60%
60%
No oral naltrexone lead-in
1.Garbutt JC, et al. JAMA. 2005;293:
2.Volpicelli JR, et al. Combining Medication and Psychosocial Treatments for Addictions: The BRENDA Approach
3. Data on file. Alkermes, Inc. 22

23. VIVITROL Provided Rapid Results
When VIVITROL was added to counseling*…
Reductions were rapid1
Post hoc analysis of a randomized, double-blind, placebo-controlled study. Patients had ≥2 heavy drinking episodes/week during the month prior to screening. Inclusion did not require detoxification, abstinence or intent to abstain from alcohol1
VIVITROL is indicated for the 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 administration2
Approval of VIVITROL was based on a subset of patients who were able to abstain for 7 days prior to treatment initiation1
Communicate the text on the right.
This chart highlights an analysis that focused on the first 30 days of a 6-month VIVITROL trial:
Patient inclusion did not require detoxification, abstinence or intent to abstain from alcohol
The approval of VIVITROL was based on a subset of patients who were able to abstain for 7 days prior to treatment initiation
As the chart illustrates:
In the month prior to treatment, all patients consumed 5.6 median drinks per day
At Day 2:
Patients treated with VIVITROL and counseling consumed 0 median drinks per day
Patients treated with counseling and placebo consumed 2 median drinks per day
These results suggest the onset of therapeutic effect with VIVITROL can be anticipated within the first few days of treatment, a critical period in therapy
The potential clinical implications of the effects of early onset include early engagement of treatment, and motivation to continue treatment and to focus on the goals established in counseling
References:
Ciraulo DA, Dong Q, Silverman BL, Gastfriend DR, Pettinati HM. Early treatment response in alcohol dependence with extended-release naltrexone. J Clin Psychiatry. 2008;69(2):
2. VIVITROL Full Prescribing Information. Cambridge, MA: Alkermes, Inc; 2008.
Counseling* with PLACEBO (n=209)
Counseling* with VIVITROL (n=205)
*The counseling used with all subjects was BRENDA, a low-intensity intervention designed to facilitate direct feedback of alcohol-related consequences. BRENDA consists of biopsychosocial assessment, reporting the assessment to the patient, an empathetic approach, identified and stated patient needs, direct advice regarding drinking behavior, and assessment of treatment adherence.
Ciraulo D et al. J Clin Psychiatry. 2008;69(2):
VIVITROL Full Prescribing Information. Cambridge, MA. Alkermes, Inc.; 2008.

24. VIVITROL Significantly Reduces Drinking Days1,2
Reductions were substantial1†
Baseline
(n=56)
Counseling with
PLACEBO (n=28)
Counseling with VIVITROL (n=28)
The graph shows the 24-week, multi-center, randomized, double-blind, placebo-controlled trial of alcohol-dependent outpatients for the group who had only 4 or more days of abstinence before beginning treatment with VIVITROL plus counseling or placebo plus counseling
Patients treated with VIVITROL had significantly fewer drinking days than patients treated with placebo (4-day: P=0.005)
Treatment with VIVITROL led to a nearly 10-fold reduction in the number of days patients drank over the course of the 6-month study
The patients did not receive oral naltrexone lead-in therapy
All patients received counseling, and all patients received monthly gluteal IM injections
Note:
Results are from a post hoc subgroup analysis of a 6-month multicenter, double-blind, placebo-controlled clinical trial of alcohol dependents who were abstinent for 4 or more days prior to treatment initiation.
The approval of VIVITROL was based on a subset of patients who were able to abstain for 7 days prior to treatment initiation.
According to the SAMHSA/CSAT, 4 days is the US norm (median duration) for detoxification2
Approval of VIVITROL was based on a subset of patients who were able to abstain for 7 days prior to treatment initiation1
† These results are from a post hoc subgroup analysis of a 6-month, multicenter, double-blind, placebo-controlled clinical trial of alcohol dependent patients. This subset analysis evaluated patients who were abstinent for 4 or more days prior to treatment initiation1
O’Malley SS et al. J ClinPsychopharmacol. 2007;27(5):
Drug and Alcohol Services Information System. The DASIS report: discharges from detoxification: Published July 9, Accessed January 23, 2008. . 24 24

25. VIVITROL Sustained Abstinence1
VIVITROL prolonged initial abstinence
VIVITROL maintained 6-month abstinence
32%
11%
Nearly three times as many patients remained abstinent
This slide shows the efficacy of VIVITROL, highlighting the medicine’s impact on helping patients maintain abstinence—considered by many the most important parameter of success.
Among those who were abstinent for only 4 or more days prior to treatment initiation, the graph shows the percent of patients abstinent at different points in time, throughout the 6-month study.
This is clinically relevant, as 4 days is the US norm for completed detoxification episodes according to SAMHSA/CSAT.
This graph also shows:
Prolonged initial abstinence: The average patient on VIVITROL remained free of alcohol
until day 41 vs. day 12 for patients on placebo
The rate of continuous abstinence for the entire 6-month study was
nearly three times greater for patients treated with VIVITROL (plus counseling)
compared with those who were treated with placebo injections (plus counseling).
- VIVITROL 32%
- Placebo 11%
This difference was statistically significant (P=0.02) and clinically meaningful.
O’Malley SS, et al. J ClinPsychopharm. 2007;27:
OPTIONAL:
A dose response was observed. In this study, patients were given XR-NTX 190 mg. A “dose effect” was demonstrated, although patients receiving the 190 mg did not demonstrate efficacy.
Please note: The 190-mg dose is not available.
Counseling with VIVITROL (n=28)
Counseling with
PLACEBO (n=28)
Results are from a post hoc subgroup analysis of a 6-month multicenter, double-blind,
placebo controlled clinical trial of alcohol dependents who were abstinent for 4 or more days
prior to treatment initiation.
The approval of VIVITROL was based on a subset of patients who were able to
abstain for 7 days prior to treatment initiation.
1. O’Malley SS, et al. J ClinPsychopharm. 2007;27: 25 25

26. VIVITROL Sustained Reduction in Heavy Drinking
Among patients receiving VIVITROL or placebo in the 6-month trial
In the 6-month trial, while a reduction in heavy drinking was seen in all patients treated with VIVITROL, a statistically significant greater reduction in heavy drinking days was seen in those patients who were abstinent 7 days prior to treatment initiation.
This reduction in heavy drinking was sustained through 18 months in patients who began the trial on VIVITROL.
Placebo
( n=209)
Patients continuing
on VIVITROL
(n=115)
Patients switching from
placebo to VIVITROL
(n=60)
VIVITROL
(n=205)
Data on file. Alkermes, Inc. 26

27. VIVITROL Reduced Holiday Drinking1
Median % Drinking Days
“The public health significance of the findings by Lapham et al in this issue is huge.2”
--David Rosenbloom, Ph.D Boston University School of Public Health (2009)
Holiday periods are associated with increased risk of alcohol-related highway fatalities and injuries.
Holidays are also clinically recognized as a challenging time for alcoholics to remain sober. During holidays, people participate in more social and family events in which alcohol is served.
This slide presents an analysis of the pivotal trial’s 4-day lead-in abstinent subgroup, examined specifically during the top ten deadliest National Highway Traffic Safety Administration (NHTSA) monitored holiday periods (eg, New Year’s Eve, 4th of July) due to drunk driving vs. all other days of the year.
The scientific question was: What were the drinking outcomes for patients treated with VIVITROL (plus counseling) vs. placebo (plus counseling) during these holiday periods?
The bar graph shows the median percent days in which patients were “non-abstinent” (i.e., “any drinking days”) during the 6-month trial
Placebo 19%
VIVITROL 0.0%
These findings prompted the journal editor, Tom McLellan, to invite Dr. David Rosenbloom, Director JoinTogether (online) and now National Center on Addiction and Substance Abuse at Columbia University to write a commentary which begins:
“The public health significance of the findings by Lapham et al. in this issue is huge.”
n=27
Results are from a post hoc subgroup analysis of a 6-month multicenter, double-blind,
placebo controlled clinical trial of alcohol dependents who were abstinent for 4 or more days
prior to treatment initiation.
The approval of VIVITROL was based on a subset of patients who were able to
abstain for 7 days prior to treatment initiation.
Lapham. J Subst Abuse Treat. 2009;36:1.
Rosenbloom DL. J Subst Abuse Treat. 2009;36(1):7. 27 27

28. Summary of Efficacy Results1,2
In clients who were abstinent during the week before treatment initiation, VIVITROL and counseling, as compared to placebo and counseling, provided:
Rapid results
Substantial reduction in drinking days
Prolonged initial abstinence
Sustained continuous abstinence through the 6-month study
Sustained reduction in heavy drinking days through 18 months
Substantial reduction in holiday drinking
Review all points on the slide:
To summarize, in clients who were abstinent during the week before treatment initiation, VIVITROL and counseling, as compared to placebo and counseling, provided:
Rapid results
Substantial reduction in drinking days
Prolonged initial abstinence
Sustained continuous abstinence through the 6-month study
Sustained reduction in heavy drinking days through 18 months
Substantial reductions in holiday drinking
1. O’Malley SS, et al. J ClinPsychopharmacol. 2007;27:
2. VIVITROL Full Prescribing Information. Alkermes, Inc. 28 28

29. Safety Profile During clinical trials:
Treatment with extended-release naltrexone was generally well tolerated
Safety profile is based on more than 900 patients
Adverse events in the majority of patients were mild or moderate
Discontinuation rates due to adverse events:
9% in patients treated with VIVITROL
7% in patients treated with placebo
The safety profile of patients treated with VIVITROL concomitantly with antidepressants was similar to that of patients taking VIVITROL without antidepressants1
No significant increase in mean AST or ALT levels2
The safety profile describes how patients tolerated the medication during the clinical trials.
In all controlled and uncontrolled trials during the premarketing development of extended-release naltrexone, more than 900 patients with alcohol and/or opioid dependence have been treated with VIVITROL and XR-NTX 190 mg and 400 mg. Approximately 400 patients have been treated for 6 months or more, and 230 patients for 1 year or longer.
Adverse events leading to discontinuation in patients treated with VIVITROL were injection site reactions, nausea, pregnancy, headache, and suicide-related events.
VIVITROL Full Prescribing Information. Alkermes, Inc.
Garbutt JC, et al. JAMA. 2005;293: 29 29

30. Most Common Adverse Events
Occurring in >10% of patients
VIVITROL %
Placebo %
Injection site reaction* 69 50
Nausea 33 11
Headache 25 18
Asthenic conditions 23 12
Anorexia, appetite decreased NOS, appetite disorder NOS 14 3
Vomiting 6
Insomnia, sleep disorder
Dizziness 13 4
Diarrhea 10
Anxiety 8
Abdominal pain
Pharyngitis
The most common adverse events for VIVITROL were based on data from more than 200 patients from all studies.
Injection site reaction (ISR)
With VIVITROL, injection site reaction includes injection site tenderness, induration, pain, and pruritus.
The dropout rate attributed to injection site reaction was 3%.
*Injection site reaction (ISR) included tenderness, induration, pain,
and pruritus. The dropout rate due to ISR was 3%.
VIVITROL Full Prescribing Information. Alkermes, Inc. 30

31. Serious Adverse Events
In clinical trials, serious adverse events occurred at a rate similar to patients receiving placebo injections1
5.4% on VIVITROL vs 7.2% on placebo
Most common serious adverse event (SAE) was inpatient hospitalization for detoxification
Other SAEs seen on VIVITROL2
2 cases of pneumonia (one confirmed case of eosinophilic)
1 case of injection site induration requiring excision
In the phase III clinical trial, the percentage of patients who experienced serious adverse events during treatment was similar among the treatment groups:
11 (5.4%) in the VIVITROL group
15 (7.2%) in the placebo group
The most common serious adverse event was hospitalization for alcohol detoxification.
There were 4 (2.0%) cases of inpatient hospitalization for detoxification in the VIVITROL 380 mg group and 7 cases (3.3%) in the placebo group.
1.Garbutt JC, et al. JAMA. 2005;293:
2. VIVITROL Full Prescribing Information. Alkermes, Inc. 31

32. Emergency Pain Management
VIVITROL antagonizes the effects of opioid-containing medications.Patients receiving VIVITROL may not benefit from opioid-containing medications.
Patients should be advised to carry a patient alert card that informs medical personnel they are taking VIVITROL
A suggested plan for pain management is:
Regional analgesia
Use of non-opioid analgesics
In an emergency situation requiring opioid analgesia, the amount of opioid required may be greater than usual and the resulting respiratory depression may be deeper and more prolonged
Such patients should be continuously monitored in an anesthesia care setting by persons not involved in the conduct of the surgical or diagnostic procedure
The opioid therapy must be provided by individuals specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation
A rapidly acting opioid analgesic that minimizes the duration of respiratory depression is preferred
Patients should be closely monitored by trained personnel in a setting equipped for cardiopulmonary resuscitation.
A non-opioid analgesic should be considered for mild to moderate pain management.
In an emergency situation in patients receiving VIVITROL, suggestions for pain management include regional analgesia or use of non-opioid analgesics.
If opioid therapy is required as part of anesthesia or analgesia, such patients should be continuously monitored, in an anesthesia care setting, by persons not involved
in the conduct of the surgical or diagnostic procedure.
The opioid therapy must be provided by individuals specifically trained in the use of anesthetic drugs and the management of the respiratory effects of potent opioids, specifically the establishment and maintenance of a patent airway and assisted ventilation.
Irrespective of the drug chosen to reverse VIVITROL blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation

33. Dosage and Administration
Epidermis
Dermis
Adipose
Muscle
VIVITROL is given as an intramuscular (IM) gluteal injection every 4 weeks or once a month
VIVITROL should not be given subcutaneously or in the adipose layer
VIVITROL must not be administered intravenously
VIVITROL should be administered by a healthcare professional, into alternating buttocks each month
VIVITROL should be injected into the upper outer quadrant of the buttock, deep into the muscle-not the adipose.
If a patient misses a dose, he or she should be instructed to receive the missed dose as soon as possible.
It is essential to locate the proper injection site.
VIVITROL should be injected into the dorsogluteal site—the upper outer quadrant of the buttock. To locate the dorsogluteal site, draw an imaginary line from the top of the cleft in the buttocks to the greater trochanter. Draw another line vertically midway along the first line. The injection site is in the upper outer quadrant of this imaginary grid.
Location of anatomical landmarks is very important for identifying the proper injection site. The sciatic nerve and superior gluteal arteries are located within a couple of centimeters of the intended injection site. Relying on visual estimating can result in an injection that is placed too low, possibly resulting in injury to underlying structures.
VIVITROL injections must be given deep into the muscle to ensure optimal drug delivery.
VIVITROL should not be given subcutaneously or in the adipose layer
It is not necessary for a patient to completely disrobe for a VIVITROL injection.
VIVITROL must be suspended only in the diluent supplied in the carton, and must be administered with the needle supplied in the carton. Do not make any substitutions for components of the carton.
VIVITROL Full Prescribing Information. Alkermes, Inc. 33

34. Connecting people with care in recovery.
Introducing…
Connecting people with care in recovery.
A free service for patients and treatment providers
designed to:
Promote long-term recovery
Improve access to treatment
Support continuity of care
A brief overview of the new VIVITROL Touchpoints Program. It was introduced in April of 2009, and is designed to help connect people with care in recovery.

35. www.vivitrol.com 1-800-VIVITROL (1-800-848-4876)
Specializing in supporting continuity of therapy for VIVITROL patients transitioning between settings of care
Offering patients a free start on the path to recovery
Connecting customers to reimbursement and distribution services
An integrated network of providers supporting VIVITROL assisted recovery
Enhancing knowledge of VIVITROL assisted recovery and offering tools to aid in treatment
Touchpoints offers:
A single access point for healthcare providers and patients to facilitate reimbursement, distribution, follow-on therapy and adherence and persistency support
Expert staff specializing in all aspects of reimbursement and distribution services
Trained, dedicated staff, with a background in social work and addiction treatment, focused on supporting continuity of therapy and transitioning patients between settings of care
Confidential supportive recovery programs for patients
Providing confidential, supportive help for patients during recovery
1-800-VIVITROL
( )

36. VIVITROL Carton Components
Each VIVITROL carton includes the following components:
Two 1½ inch 20 gauge administration needles
One vial containing VIVITROL microsphere powder
One vial containing diluent
One single-use 5 mL syringe
One ½ inch 20 gauge preparation needle
Do not substitute carton components.
The entire carton should be stored in the refrigerator (2 – 8ºC, 36 – 46ºF).
VIVITROL can be stored at temperatures not exceeding 25ºC (77ºF) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 25ºC (77ºF). 36

37. APPENDIX 37

38. Alcohol Dependence: An Ancient Problem
After the flood, Noah plants a vineyard, makes wine and gets drunk. (Genesis 9:21)
“Who hath woe? Who hath sorrow? Who is always fighting? Who is always complaining? Who hath wounds without cause? Who has bloodshot eyes?
They who tarry long at the wine; when it sparkles in the cup.
Don't let the smooth taste deceive you. For in the end it bites like a poisonous serpent. And you will say, ‘They hit me, but I didn't feel it.’
Your eyes will see strange visions and you will say strange thoughts. Yet when you awaken, you seek it yet again.”
Alcohol dependence is an ancient problem. We begin with the story of Noah’s Ark and the flood. This is one of the oldest stories in the Old Testament, from the Book of Genesis.
Immediately following the flood, the very next thing Noah did was plant a vineyard … he planted a vineyard and then got drunk. This story is one of the first accounts of drunkenness.
His children later found him, naked. Ashamed, they covered him up – shame is associated here with drunkenness.
“Alcohol dependence” begins to be written about in the Proverbs–it is an old disease–one that’s been around for thousands of years.
Through the years, all we’ve been able to do is TALK to the disease … or lock it up in prison. We haven’t had more than good advice, good intentions, prayer, meditation, spirituality, and punishment.
This has worked for some people – but not for enough.
Proverbs 23:29 (~1,000 BC) 38

39. Medication-Assisted Treatment: A National Consensus
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism. Helping Patients Who Drink Too Much: A Clinician’s Guide. May 2007 reprint. Accessed May 5, 2008.
“Consider adding medication whenever you are treating someone with active alcohol dependence.”
National Institute on Alcohol Abuse and Alcoholism. Helping Patients Who Drink Too Much: A Clinician’s Guide. Available at: May 2007 reprint. Accessed May 5, 2008. 39 39

40. Medication-Assisted Treatment: A National Consensus
“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 injectable naltrexone, one intramuscular injection is effective for 4 weeks, reducing opportunities for patients to cease their medication.”
The U.S. Department of Health and Human Services, SAMHSA/CSAT issued this Advisory on VIVITROL, Spring 2007.
To read the full Advisory go to the SAMHSA website:
U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment Advisory (Spring 2007) 40 40

41. Medication-Assisted Treatment: A National Consensus
Substance Abuse & Mental Health Services Administration
U.S. Department of Health and Human Services
“A combination of medication and behavioral therapies is most successful.”
Substance Abuse & Mental Health Services Administration (SAMHSA), Division of Pharmacologic Therapies Medication-Assisted Treatment for Substance Use Disorders. Accessed May 5, 2008.
Substance Abuse & Mental Health Services Administration, Division of Pharmacologic Therapies. Medication-Assisted Treatment for Substance Use Disorders. Available at: Accessed May 5, 2008. 41 41

42. Medication-Assisted Treatment: A National Consensus
National Quality Forum
“Pharmacotherapy should be … available to all adult patients diagnosed with alcohol dependence … [and] should be provided in addition to … psychosocial treatment/support.”
National Quality Forum National Voluntary Consensus Standards for the Treatment of Substance Use Conditions: Evidence-Based Treatment Practices. Accessed May 5, 2008.
National Quality Forum National Voluntary Consensus Standards for the Treatment of Substance Use Conditions: Evidence-Based Treatment Practices. Available at: Accessed May 5, 2008. 42 42

43. Medication-Assisted Treatment: A National Consensus
Institute of Medicine of the National Academies
“[There is] a spectrum of evidence-based pharmacologic & psychosocial treatments … Naltrexone [shows] efficacy in treating [alcohol dependence].”
Institute of Medicine of the National Academies. Improving the Quality of Health Care for Mental and Substance-Use Conditions: Quality Chasm Series. Committee on Crossing the Quality Chasm: Adaptation to Mental Health and Addictive Disorders. Executive Summary Accessed May 5, 2008.
Institute of Medicine of the National Academies. Improving the Quality of Health Care for Mental and Substance-Use Conditions: Quality Chasm Series. Committee on Crossing the Quality Chasm: Adaptation to Mental Health and Addictive Disorders. Executive Summary Available at: Accessed May 5, 2008. 43 43

44. Medication-Assisted Treatment: A National Consensus
National Council on Alcoholism and Drug Dependence
“Integrate biological, psychosocial, and pharmacological approaches. All are helpful and necessary.”
The National Council on Alcoholism and Drug Dependence. Interviews with the Experts: Robert Morse, MD on the Use of Pharmacology in Addiction Treatment. Accessed May 5, 2008.
The National Council on Alcoholism and Drug Dependence. Interviews with the Experts: Robert Morse, MD on the Use of Pharmacology in Addiction Treatment. Accessed May 5, 2008. 44 44

45. Alcoholics Anonymous (AA) and Use of Medication
Alcoholics Anonymous published a booklet for AA members (1984)
Booklet supports appropriately prescribed medications
Booklet is being updated to address new medications
Many people in recovery mistakenly believe that Alcoholics Anonymous is anti-medication
AA is not anti-medication
Their booklet actually supports appropriate use of medications for mental health problems
At the time the booklet was published (1984) there was only disulfiram (Antabuse®)
In light of the new medications, including VIVITROL, AA’s General Service Office in New York has initiated a process to update the booklet
A little later in this presentation, data will be presented showing the compatibility of VIVITROL treatment and AA participation
Alcoholics Anonymous World Service, Inc. The AA Member – Medications and Other Drugs 45

46. Typical Clinical Team Roles
Counselor (psychosocial treatment provider)
Provides psychosocial treatment
Monitors response to medication
Communicates patient status with treatment team
Physician (prescriber/injector)
Assesses appropriateness of medication for patient
Monitors medical response to medication
Nurse (injector)
Administers medication
Provides psychosocial treatment
Assesses appropriateness of medication for patient
Administers medication
Treatment with VIVITROL brings together a clinical team composed of the counselor, the prescriber, and an individual who administers the injection (either a nurse, physician assistant, or physician).
Each member of the clinical team:
a) Monitors the patient’s response to the medication
b) Communicates the status of the patient to the others on the clinical team
Additionally, each team member has one role that is unique, which contributes to the treatment plan and care of the client.
Importantly, VIVITROL provides an opportunity for medical personnel and treatment providers to collaborate in the care of alcohol dependent patients. 46

47. Development of VIVITROL
Problem of nonadherence was well understood by 19751
NIAAA and NIDA awarded grants that led to development of Medisorb®* technology
VIVITROL uses the Medisorb extended-release properties, first introduced in Risperdal®Consta®†
More than 30 years ago, it was already well understood that adherence to naltrexone therapy is poor. The federal government (both NIAAA and NIDA) encouraged pharmaceutical companies to develop a long-acting formulation. The initial work on VIVITROL was conducted with grant support from the federal government.
The Medisorb® extended-release technology is described on the next slide.
* Medisorb is a registered trademark of Alkermes, Inc.
† Risperdal and Consta are registered trademarks of Janssen Pharmaceutica.
1. NIDA Monograph. Narcotic Antagonists: The Search for Long-Acting Preparations. 47 47

48. Pharmacokinetics
Minimal accumulation (<15%) of naltrexone or 6-naltrexol upon repeat administration of VIVITROL
Elimination
Primarily via urine for naltrexone and its metabolites
Minimal excretion of unchanged naltrexone
Half-life 5 to 10 days (dependent on erosion of polymer)
There is minimal accumulation of naltrexone or its primary metabolite with repeat administration of VIVITROL.
Elimination of naltrexone and its metabolites takes place via the urine.
The half-life of VIVITROL is 5 to 10 days, depending on the erosion of the polymer.
VIVITROL Full Prescribing Information. Alkermes, Inc. 48

49. VIVITROL Prolongs Abstinence1,2
Among patients who were abstinent for 7 days prior to treatment initiation
VIVITROL prolonged initial abstinence
VIVITROL maintained 6-month abstinence
41%
17%
More than twice as many patients remained abstinent
In this slide, we see those patients who were abstinent for 7 days prior to treatment initiation. All patients in this subgroup, therefore, start out abstinent.
The graph also shows us the following:
That VIVITROL prolonged initial abstinence: The average patient on VIVITROL
remained free of alcohol until day 84 vs day 28 for patients on placebo
Also, the rate of continuous abstinence for the entire 6-month study was more than
two times greater for patients treated with VIVITROL (plus counseling) compared with those who were treated with placebo injections (plus counseling)
- VIVITROL 41%
- Placebo %
This difference was statistically significant (P=0.02) and clinically meaningful.
OPTIONAL:
In a post hoc analysis of a 6-month multicenter, double-blind, placebo controlled clinical trial of 624 alcohol dependents, when VIVITROL was added to psychosocial treatment, results were rapid. By day 2, a significant reduction in the median number of drinks per day was observed. In fact, the median number of drinks per day was zero on day Ciraulo DA, et al. J Clin Psychiatry. 2008;69:
A dose response was observed. In this study, patients were given XR-NTX mg. A “dose effect” was demonstrated although patients receiving the 190mg
did not demonstrate efficacy.
Please note: The 190-mg dose is not available.
(n=17)
1. Garbutt JC, et al. JAMA. 2005;293:
2. Data on file. Alkermes, Inc. . 49 49

50. Subjects With Nausea by Month
Mild in the majority of reports
Occurred in the first month in the majority of cases
Median duration of a few days
Trial dropout rate due to nausea was 2% in the VIVITROL group
Nausea
Nausea was mild in the majority of reports. With VIVITROL, it usually occurred in the first month, and the median duration was a few days. Two percent of patients dropped out of the trial due to nausea
Concomitant medications used to treat nausea were bismuth subsalicylate, loperamide, aluminum hydroxide, metoclopramide, famotidine, and simethicone.
The VIVITROL group included all studied doses.
Data on file. Alkermes, Inc. 50