Tanum Study

Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence¹

Tanum study design¹

A Norway-based, 12-week, open-label, randomized clinical trial in which patients recruited from outpatient addiction clinics and detoxification units were randomized to oral BUP-NX (n=79) or XR-NTX (n=80) after detoxification. Participants were asked to attend standard drug counseling, but no behavioral interventions could be initiated

73 individuals were excluded due to: refusal to
participate (51), not meeting inclusion criteria (9),
failing detoxification (6), or other reasons (7).

Demographics and clinical baseline characteristics¹

ITT POPULATION (n=159)

Lifetime Characteristic	XR-NTX^† (n=80)	BUP-NX^† (n=79)
Age, mean (SD), years	36.4 (8.8)	35.7 (8.5)
Male, n (%)	61 (76.3)	54 (68.4)
White, n (%)	72 (90.0)	70 (88.6)
Injecting (intravenous) users, n (%)	72 (90.0)	64 (81.0)
HIV positive, n (%)	2 (2.5)	2 (2.5)
Hepatitis C seropositive, n (%)	44 (55.0)	42 (53.2)
Years of substance use, mean (SD)
Heavy opioid use	8.9 (7.8)	9.6 (10.5)
Heroin	6.9 (5.8)	6.7 (5.2)
Other illicit opioids	2.4 (5.1)	3.2 (7.0)
Use during past 30 days (baseline), mean (SD)
Heroin	7.6 (11.0)	12.0 (12.9)
Other illicit opioids	8.2 (11.1)	14.5 (13.2)

^†Naltrexone, naloxone, and buprenorphine were all administered as the hydrochloride form. Data are mean (SD) or number (%).

PRIMARY ENDPOINTS¹

The number of days of use of heroin and other illicit opioids
Trial completion rate
Proportion of illicit opioid-negative UDTs^†

^†The weekly urine drug tests (UDTs) were calculated as the number of opioid-negative UDTs divided by the total number of attended tests. Missing UDTs were considered as testing positive for opioids in all participants.

DAYS OF USE OF HEROIN AND OTHER ILLICIT OPIOIDS FOR XR-NTX VS BUP-NX¹

XR-NTX was noninferior to BUP-NX in helping opioid-dependent patients decrease the number of days in which they used heroin and other illicit opioids

Mean 3.2 fewer days of heroin use (95% CI, -4.9 to -1.5)
Mean 2.7 fewer days of other illicit opioids use (95% CI, -4.6 to -0.9)

Retention time

69.3 days [SD 25.9] with XR-NTX vs 63.7 days [SD 29.9] with BUP-NX

Retention time on XR-NTX vs BUP-NX at the conclusion of the 12-week study

Illicit opioid-negative UDTs

90% opioid-free urine drug tests (UDTs) with XR-NTX

80% opioid-free urine drug tests (UDTs) with BUP-NX

Mean (SD), 0.9 (0.3) and 0.8 (0.4), respectively; mean difference, 0.1 with 95% CI, -0.04 to 0.2

Study limitations¹

The study was not blinded. Participants in each treatment group knew which medication they were receiving during the trial.

For the study to have been blinded, it would have required placebo injections like the XR-NTX kits or placebo tablets for BUP-NX
Patients would be able to determine their respective treatment quite quickly, given their long experience with opioid use
Due to an increased risk of overdose in newly detoxified opioid users, the use of placebo and the masking of medications were considered unethical

DISCLOSURES:

Funding/Support: The study was supported by unrestricted grants from the Research Council of Norway and the Western Norway Regional Health Authority. Financial support was also received from the Norwegian Centre for Addiction Research, University of Oslo, and from Akershus University Hospital.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication; however, Alkermes, Inc. was allowed to comment on the manuscript before submission for publication.

Alkermes, Inc. supplied extended-release naltrexone for the study.

View the open-label, head-to-head study in the treatment of opioid dependence.

Download the Tanum Study

VIVITROL is not right for everyone. There are significant risks from VIVITROL treatment, including risk of opioid overdose, injection site reactions, and sudden opioid withdrawal. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose. See Important Safety Information below. See Prescribing Information. Review Medication Guide with your patients.

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Important safety information MORE

Important safety information

Contraindications

VIVITROL is contraindicated in patients:

Receiving opioid analgesics
With current physiologic opioid dependence
In acute opioid withdrawal
Who have failed the naloxone challenge test or have a positive urine screen for opioids
Who have exhibited hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose, or any other components of the diluent

Indications

VIVITROL is indicated for:

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.
Prevention of relapse to opioid dependence, following opioid detoxification.
VIVITROL should be part of a comprehensive management program that includes psychosocial support.

Warnings and precautions

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. Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver, at the initial VIVITROL injection and with each subsequent injection. Strongly consider prescribing naloxone for the emergency treatment of opioid 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.

Injection Site Reactions:

VIVITROL must be prepared and administered by a healthcare provider.
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.
In the clinical trials, one patient developed an area of induration that continued to enlarge after 4 weeks, with subsequent development of necrotic tissue that required surgical excision.
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.

Precipitation of Opioid Withdrawal:

When withdrawal is precipitated abruptly by administration of an opioid antagonist to an opioid-dependent patient, the resulting withdrawal syndrome can be severe. Some cases of withdrawal symptoms have been severe enough to require hospitalization, and in some cases, management in the ICU.
To prevent occurrence of precipitated withdrawal, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting VIVITROL treatment:
- An opioid-free interval of a minimum of 7–10 days is recommended for patients previously dependent on short-acting opioids.
- Patients transitioning from buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as two weeks.
If a more rapid transition from agonist to antagonist therapy is deemed necessary and appropriate by the healthcare provider, monitor the patient closely in an appropriate medical setting where precipitated withdrawal can be managed.
Patients should be made aware of the risk associated with precipitated withdrawal and be encouraged to give an accurate account of last opioid use.
Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.

Hepatotoxicity:

Cases of hepatitis and clinically significant liver dysfunction have been observed in association with VIVITROL. Warn patients of the risk of hepatic injury; advise them to seek help if experiencing symptoms of acute hepatitis. Discontinue use of VIVITROL in patients who exhibit acute hepatitis symptoms.

Depression and Suicidality:

Alcohol- and opioid-dependent patients taking VIVITROL should be monitored for depression or suicidal thoughts. Alert families and caregivers to monitor and report the emergence of symptoms of depression or suicidality.

When Reversal of VIVITROL Blockade Is Required for Pain Management:

For VIVITROL patients in emergency situations, suggestions for pain management include regional analgesia or use of non-opioid analgesics. If opioid therapy is required to reverse the VIVITROL blockade, patients should be closely monitored by trained personnel in a setting staffed and equipped for CPR.

Eosinophilic Pneumonia:

Patients who develop dyspnea and hypoxemia should seek medical attention immediately. Consider the possibility of eosinophilic pneumonia in patients who do not respond to antibiotics.

Hypersensitivity Reactions including Anaphylaxis:

Cases of urticaria, angioedema, and anaphylaxis have been observed with the use of VIVITROL.
Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis.
In the event of a hypersensitivity reaction, patients should be advised to seek immediate medical attention in a healthcare setting prepared to treat anaphylaxis. The patient should not receive any further treatment with VIVITROL.

Intramuscular Injections:

As with any intramuscular injection, VIVITROL should be administered with caution to patients with thrombocytopenia or any coagulation disorder.

Alcohol Withdrawal:

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

Interference with Laboratory Tests:

VIVITROL may be cross-reactive with certain immunoassay methods for the detection of drugs of abuse (specifically opioids) in urine.
For further information, reference to the specific immunoassay instructions is recommended.

Adverse reactions

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), arthralgia, arthritis, or joint stiffness, 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.

You are encouraged to report side effects to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Reference: 1. Tanum L, Solli KK, Latif ZE, et al. Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: a randomized clinical noninferiority trial. JAMA Psychiatry. 2017;74(12):1197-1205.

^‡Terms and Conditions

Eligibility for Alkermes-Sponsored Co-pay Savings. This offer is only available to patients 18 years or older, with a prescription consistent with the Prescribing Information and the patient is not enrolled in, or covered by, any local, state, federal or other government program that pays for any portion of medication costs, including but not limited to Medicare, including Medicare Part D or Medicare Advantage plans; Medicaid, including Medicaid Managed Care and Alternative Benefit Plans under the Affordable Care Act; Medigap; VA; DOD; TRICARE; or a residential correctional program.

Additional Terms of Use: This offer is not conditioned on any past, present, or future purchase, including refills. Alkermes reserves the right to rescind, revoke, or amend this offer, program eligibility, and requirements at any time without notice. This offer is limited to one per patient, may not be used with any other offer, is not transferable and may not be sold, purchased or traded, or offered for sale, purchase or trade. Void where prohibited by law. Program Administrator or its designee will have the right upon reasonable prior written notice, during normal business hours, and subject to applicable law, to audit compliance with this program.

TANUM: AN INVESTIGATIONAL HEAD-TO-HEAD STUDY

Tanum Study

Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence1

Tanum study design1

Demographics and clinical baseline characteristics1

PRIMARY ENDPOINTS1

DAYS OF USE OF HEROIN AND OTHER ILLICIT OPIOIDS FOR XR-NTX VS BUP-NX1

Retention time

Illicit opioid-negative UDTs

Study limitations1

DISCLOSURES:

View the open-label, head-to-head study in the treatment of opioid dependence.

REQUEST AREPRESENTATIVE

LEARN ABOUT THE VIVITROL®CO-PAY SAVINGS PROGRAM

Important safety information

Important safety information

Contraindications

Indications

Warnings and precautions

Adverse reactions

You are encouraged to report side effects to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

TANUM: AN INVESTIGATIONAL
HEAD-TO-HEAD STUDY

Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence¹

Tanum study design¹

Demographics and clinical baseline characteristics¹

PRIMARY ENDPOINTS¹

DAYS OF USE OF HEROIN AND OTHER ILLICIT OPIOIDS FOR XR-NTX VS BUP-NX¹

Study limitations¹

REQUEST A
REPRESENTATIVE

LEARN ABOUT THE VIVITROL^®
CO-PAY SAVINGS PROGRAM