Addressing Potential Questions Your Patients May Have About an Antagonist Treatment for Opioid Dependence

The following information is intended for U.S. healthcare providers only and should not be shared directly with patients. Further, it is for general informational purposes only and is not a substitute for your professional medical advice and judgment. See Important Safety Information for VIVITROL below. See Prescribing Information and Medication Guide. Review Medication Guide with your patients. This information does not replace the Prescribing Information.


1. “I’ve never heard of VIVITROL. Is it new?”

VIVITROL has been approved by the U.S. Food and Drug Administration (FDA) since 2010 for the prevention of relapse to opioid dependence, following opioid detoxification. In all controlled and uncontrolled trials during premarketing development, more than 1100 patients with alcohol and/or opioid dependence were treated with VIVITROL.1 Since its approval for the opioid dependence indication, VIVITROL is estimated to have been used to treat approximately 200,000 patients for this indication.2


2. “What is the typical duration of treatment with VIVITROL for opioid dependence?”

The pivotal clinical trial of VIVITROL in opioid dependence had a duration of 24 weeks.1 Consistent with patient-centered care, healthcare professionals may wish to evaluate the length of treatment on a patient-by-patient basis.


3. “What would happen if I took opioids while still taking VIVITROL or if I took opioids after I stopped taking VIVITROL?”

Because VIVITROL can block the subjective effects of opioids, patients will not perceive any effect if they attempt to self-administer heroin or any other opioid drug in small doses while on VIVITROL. Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on VIVITROL may lead to serious injury, coma, or death.1

If patients have previously used opioids, they may be more sensitive to lower doses of opioids and at risk of accidental overdose should they use opioids when their next dose is due, if they miss a dose, or after VIVITROL treatment is discontinued. It is important that patients inform family members and the people closest to the patient of this increased sensitivity to opioids and the risk of overdose.1


4. “What serious adverse reactions are associated with VIVITROL?”

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.1 To report suspected adverse reactions, contact Alkermes, Inc., at 1-800-VIVITROL (1-800-848-4876) and/or email usmedinfo@alkermes.com, or contact FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch. For complete information, please see the VIVITROL Prescribing Information.


5. "I have hepatitis C/I am HIV-positive. Can I still take VIVITROL?"

In the 6-month controlled trial of VIVITROL conducted in opioid-dependent subjects, 89% of subjects had a baseline diagnosis of hepatitis C infection, and 41% had a baseline diagnosis of HIV infection. There were frequently observed elevated liver enzyme levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and gamma-glutamyl transferase [GGT]); these were more commonly reported as adverse events in the VIVITROL 380-mg group than in the placebo group. Patients could not enroll in this trial if they had a baseline ALT or AST value that was more than 3 times the upper limit of normal.1


6. “If I have liver problems, am I still able to take VIVITROL?”

Patients enrolled in the VIVITROL pivotal trial were permitted to have liver function test values up to 3 times the upper limit of normal. Patients with hepatic failure, active hepatitis, or liver function test values greater than 3 times the upper limit of normal were excluded from the VIVITROL pivotal trial.3

Cases of hepatitis and clinically significant liver dysfunction were observed in association with VIVITROL exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period.1

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.1


7. “Why is it important to undergo opioid detoxification before starting VIVITROL?”

Patients should be off all opioids, including opioid-containing medicines, for a minimum of 7 to 10 days before starting VIVITROL in order to avoid precipitation of opioid withdrawal.1

Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Withdrawal precipitated by administration of an opioid antagonist may be severe enough to require hospitalization if patients have not been opioid-free for an adequate period of time, and is different from the experience of spontaneous withdrawal that occurs with discontinuation of an opioid in a dependent individual. Patients should not take VIVITROL if they have any symptoms of opioid withdrawal.1

Advise all patients, including those with alcohol dependence, that it is imperative to notify healthcare providers of any recent use of opioids or any history of opioid dependence before starting VIVITROL to avoid precipitation of opioid withdrawal.1


8. “I’m afraid of the detoxification process. What will it entail?”

The detoxification process is highly individualized. A variety of adjunctive medications may help minimize discomfort associated with opioid withdrawal.4 Although detoxification success rates can vary, assessing each patient’s readiness to begin treatment and developing a plan unique to them may help.1,5 See XR-Naltrexone: A Step-by-Step Guide, on the PCSS MAT Training website (funded in part by the Substance Abuse and Mental Health Services Administration).


9. “Why is VIVITROL administered as an injection?”

VIVITROL is supplied as a microsphere formulation of naltrexone for suspension, to be administered by intramuscular (IM) injection. More specifically, after IM injection of VIVITROL, the naltrexone plasma concentration time profile is characterized by a transient initial peak, which occurs approximately 2 hours after injection, followed by a second peak observed approximately 2 to 3 days later. Beginning approximately 14 days after dosing, concentrations slowly decline, with measurable levels for greater than 1 month.1


10. “How can I take VIVITROL? I’m afraid of needles.”

An estimated 10% of the general population has a fear of needles.6 One intervention shown to help manage fear of injection in some patients is exposure-based therapy.6,7 Other interventions that may help include reassurance that needle phobia is normal and common and education about the inherited, involuntary nature of the fear.6 It also may help to remind patients that VIVITROL is injected monthly.1


11. “Where do I go to get my injections, and when?”

Any healthcare provider who can prescribe medication may prescribe VIVITROL and administer it in-office.1 If you prefer that a patient receive VIVITROL from another provider, you can direct the patient to the Provider Locator Tool at www.vivitrol.com.

The recommended dose of VIVITROL is 380 mg delivered via a monthly intramuscular gluteal injection, alternating buttocks for each subsequent injection.1 Full instructions for administering VIVITROL are provided in the VIVITROL Prescribing Information.


12. “Do I still need to go to counseling if I am on VIVITROL?”

Yes. Patients need some form of behavioral therapy to help achieve treatment goals, and all types of medication-assisted treatment should be used in combination with counseling.8,9 Goals of counseling may include addressing a patient’s motivation to change, replacing drug-using activities with constructive and rewarding activities, building skills to resist drug use and prevent relapse, improving problem-solving skills, facilitating better interpersonal relationships, and providing incentives for abstinence.5

In the VIVITROL pivotal trial of opioid-dependent patients, subjects received psychosocial support every 2 weeks, along with their injections every 4 weeks.3


13. “What if I need pain medication for a medical procedure while taking VIVITROL?”

Patients taking VIVITROL may not benefit from opioid-containing medicines. Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations, and opioid analgesics.1 In an emergency situation in patients receiving VIVITROL, suggestions for pain management include regional analgesia or use of non-opioid analgesics.

Advise patients to carry documentation to alert medical personnel to the fact that they are taking VIVITROL® (naltrexone for extended-release injectable suspension). This will help to ensure that patients obtain adequate medical treatment in an emergency.1

For more information about pain management in emergency situations for patients taking VIVITROL, refer to this fact sheet.


14. “Is there a savings program to help me pay for VIVITROL?”

Patients with a prescription for VIVITROL may be eligible for the VIVITROL® Co-pay Savings Program card. Eligible participants include patients with commercial health insurance and those with no insurance or electing not to use insurance. Ninety percent of insured patients using the program had no out-of-pocket expenses for VIVITROL.2 Patients can visit www.vivitrol.com to find out if they are eligible for the VIVITROL Co-pay Savings Program.


References:

  1. VIVITROL [prescribing information]. Waltham, MA: Alkermes, Inc; rev December 2015.
  2. Data on file. Alkermes, Inc.
  3. 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.
  4. National Collaborating Centre for Mental Health. Drug Misuse: Opioid Detoxification. The NICE Guideline. National Clinical Practice Guideline Number 52. London, UK: The British Psychological Society and The Royal College of Psychiatrists; 2008. https://www.ncbi.nlm.nih.gov/books/NBK50622/pdf/Bookshelf_NBK50622.pdf. Accessed August 30, 2017.
  5. National Institute on Drug Abuse (NIDA). Principles of Drug Addiction Treatment: A Research-Based Guide. 3rd ed. NIH publication No. 12-4180. Rockville, MD: National Institute on Drug Abuse, National Institutes of Health. https://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/preface. Updated December 2012. Accessed August 7, 2017.
  6. Hamilton JG. Needle phobia: a neglected diagnosis. J Fam Pract. 1995;41(2):169-175.
  7. McMurtry CM, Noel M, Taddio A, et al. Interventions for individuals with high levels of needle fear: systematic review of randomized controlled trials and quasi-randomized controlled trials. Clin J Pain. 2015;31(10 suppl):S109-S123.
  8. Methadose [package insert]. Mallinckrodt, Inc.: Hazelwood, MO; December 2016.
  9. Suboxone (buprenorphine and naloxone) [package insert]. Reckitt Benckiser Pharmaceuticals, Inc. Richmond, VA; February 2017.

IMPORTANT SAFETY INFORMATION FOR VIVITROL®
(naltrexone for extended-release injectable suspension)

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.

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

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.
  • 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 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.

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.

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:

  • Cases of eosinophilic pneumonia requiring hospitalization have been reported. Warn patients of the risk of eosinophilic pneumonia and to seek medical attention if they develop symptoms of pneumonia.

Hypersensitivity Reactions:

  • Patients should be warned of the risk of hypersensitivity reactions, including anaphylaxis.

Intramuscular Injections:

  • As with any IM 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.

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.

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

See Prescribing Information and Medication Guide.