Treating opioid dependence
Treatment of opioid dependence is aimed at countering the disruptive effect of dependence so that the individual can regain control of his or her life.1 Because opioid dependence is a chronic medical condition characterized by risk of relapse, successful treatment requires a comprehensive, long-term approach involving maintenance medication as well as counseling and/or psychosocial support.1

The importance of comprehensive treatment

Studies show that treatment approaches including the use of both maintenance medication and psychosocial support in an outpatient setting are critical to prevent relapse.

  • In a 1-year retention study, all detoxed patients who received only placebo and behavioral therapy (n=20) relapsed in approximately 50 days while 75% of patients treated with maintenance medication and behavioral therapy (n=20) remained on therapy (P=0.0001)2
Treating opioid dependence

Adapted with permission from Kakko J et al.

*Study design: 40 patients* >20 years of age who met the DSM-IV® criteria for opioid dependence for at least 1 year were randomized to either sublingual buprenorphine plus psychosocial therapy or psychosocial therapy alone. All patients participated in group cognitive behavioral therapy (CBT) to prevent relapse, received weekly individualized counseling sessions, and submitted supervised urine samples 3 times a week. The primary endpoint was 1-year retention in treatment. Retention was defined as remaining in treatment with a negative urine drug screen.

ZUBSOLV was not studied in this clinical trial.

 


Benefits of treatment with maintenance medication

Long-term maintenance treatment that includes buprenorphine/naloxone can provide successful results.

  • Nearly 40% of patients who had previously demonstrated significant abstinence over a 6-month period of time remained in treatment for an additional 2 years with buprenorphine/naloxone therapy and monthly counseling3

ZUBSOLV was not studied in this clinical trial.

Adapted with permission from Fiellin DA et al.

Treatment rates

Treatment rates are improving, but remain low. Although treatment of opioid dependence is effective, a majority of patients do not receive treatment.

  • Only about 40% of patients with opioid dependence received any treatment in 20114
Treating opioid dependence
  • Of patients referred for treatment of opioid dependence, only 20% are prescribed maintenance medication as part of their therapy6
  • Successful treatment for opioid dependence typically requires continual evaluation and modification as appropriate, similar to the approach taken for other chronic conditions1

Waivered physicians

The treatment of opioid dependence with Schedule III-IV medications requires trained physicians who qualify for a waiver to prescribe under the Drug Addiction Treatment Act of 2000 (DATA 2000). To receive a waiver, physicians must meet at least one of the following criteria7:

  • Subspecialty board certification in addiction psychiatry from the American Board of Medical Specialties
  • Addiction certification from the American Society of Addiction Medicine
  • Subspecialty board certification in addiction medicine from the American Osteopathic Association
  • ≥8 hours of training in the treatment and management of patients with opioid dependence, sponsored by an organization authorized in the DATA 2000
  • Participated as an investigator in clinical trials leading to the approval of a Schedule III, IV, or I narcotic drug for maintenance or detoxification treatment
  • Training or experience as the State medical licensing board considers to demonstrate the ability of the physician to treat and manage opioid-addicted patients.
  • Training or experience as the Secretary considers to demonstrate the ability of the physician to treat and manage opioid-addicted patients.

For more information on DATA 2000 or how to become waivered, visit buprenorphine.samhsa.gov.

Methadone or buprenorphine-containing medication.

Adherence

Adherence remains an important challenge to treatment success. Nonadherence to current maintenance medication formulations remains a driver of relapse.

  • In a study of compliance with buprenorphine, patients who were noncompliant with buprenorphine treatment were over 10 times more likely to relapse than patients who adhered to treatment8

References:

  1. National Institute of Drug Abuse. Principles of drug addiction treatment: a research-based guide, 3rd edition. http://www.drugabuse.gov/sites/default/files/podat_1.pdf. Accessed May 11, 2013.
  2. Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomized, placebo-controlled trial. Lancet. 2003;361:662–668.
  3. Fiellin DA, Moore BA, Sullivan LE, et al. Long-term treatment with buprenorphine/naloxone in primary care: results at 2-5 years. Am J Addict. 2008;17:116-120.
  4. Substance Abuse and Mental Health Services Administration. Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-44, HHS Publication No. (SMA) 12-4713. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012.
  5. Substance Abuse and Mental Health Services Administration. Results from the 2010 National Survey on Drug Use and Health: Summary of National Findings. NSDUH Series H-41, HHS Publication No. (SMA) 11-4658. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2011.
  6. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. Treatment Episode Data Set (TEDS): 2000-2010. National Admissions to Substance Abuse Treatment Services. DASIS Series S-61, HHS Publication No. (SMA) 12-4701. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2012.
  7. https://www.samhsa.gov/medication-assisted-treatment/buprenorphine-waiver-management/qualify-for-physician-waiver Accessed 10 Feb 2015
  8. Tkacz J, Severt J, Cacciola J, Ruetsch C. Compliance with buprenorphine medication-assisted treatment and relapse to opioid use. Am J Addict. 2011;21:55–62.
DSM-IV is a registered trademark of the American Psychiatric Association.

Indication

ZUBSOLV® (buprenorphine and naloxone) sublingual tablet (CIII) is indicated for the treatment of opioid dependence. ZUBSOLV should be used as part of a complete treatment plan that includes counseling and psychosocial support.

Treatment should be initiated under the direction of healthcare providers who meet certain qualifying requirements under the Drug Addiction Treatment Act of 2000, and who have been assigned a unique identification number (“X” number).

IMPORTANT SAFETY INFORMATION

Contraindications

  • ZUBSOLV is contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone, as serious adverse reactions, including anaphylactic shock, have been reported.

Warnings and Precautions

  • Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits.

  • Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with ZUBSOLV.

  • Unintentional Pediatric Exposure: Store ZUBSOLV safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal respiratory depression in children.

  • Neonatal Opioid Withdrawal Syndrome (NOWS): Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.

  • Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patients off of the opioid.

  • Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.

  • Risk of Hepatitis; Hepatic Events: Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events.

  • Precipitation of Opioid Withdrawal Signs and Symptoms: An opioid withdrawal syndrome is likely to occur with parenteral misuse of ZUBSOLV by individuals physically dependent on full opioid agonists or by sublingual administration before the agonist effects of other opioids have subsided.

  • Risk of Overdose in Opioid-Naïve Patients: ZUBSOLV is not appropriate as an analgesic. There have been reported deaths of opioid-naïve individuals who received a 2-mg sublingual dose of buprenorphine.

Use in Specific Populations

  • Lactation: Buprenorphine passes into mother’s milk.

  • Geriatric Patients: Monitor for sedation and respiratory depression.

  • Moderate and Severe Hepatic Impairment: Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment.

Adverse Reactions & Drug Interactions

  • Adverse events commonly observed with the sublingual administration of ZUBSOLV are headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.

  • Benzodiazepines: Use caution in prescribing ZUBSOLV for patients receiving benzodiazepines or other CNS depressants and warn patients against concomitant self-administration/misuse.

  • CYP3A4 Inhibitors and Inducers: Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing.

  • Antiretrovirals: Patients who are on chronic buprenorphine treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Monitor patients taking buprenorphine and atazanavir with and without ritonavir, and reduce dose of buprenorphine if warranted.

  • Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue ZUBSOLV if serotonin syndrome is suspected.

This is not a complete list of potential adverse events associated with buprenorphine/naloxone sublingual tablets. Please see full Prescribing Information for a complete list.

To report an adverse event associated with taking ZUBSOLV sublingual tablet, please call 1-888-ZUBSOLV (1-888-982-7658). You are encouraged to report adverse events of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see accompanying full Prescribing Information and Medication Guide.