• Addiction, Abuse, and Misuse: Buprenorphine can be abused in a manner similar to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors.
• Respiratory Depression: Significant respiratory depression and death have occurred in association with buprenorphine particularly when taken by the intravenous (IV) route in combination with benzodiazepines or other CNS depressants (including alcohol). Consider dose reduction of CNS depressants when used concomitantly. Life-threatening respiratory depression and death have occurred in association with buprenorphine use. Warn patients of potential danger of self-administration of benzodiazepines or other CNS deprssants while under treatment with Probuphine.
• Neonatal Opioid Withdrawal Syndrome: 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 patient off of the opioid.
• Unintentional Pediatric Exposure: In the event an implant protrudes or comes out, keep the implant away from children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children.
• 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.
• Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that patient is clinically stable on transmucosal buprenorphine and not dependent on full agonists before inserting Probuphine.
• Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect.

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe opioid use disorder who began treatment with buprenorphine/naloxone sublingual film. Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. (MAT is a comprehensive approach that combines approved medications, currently methadone, buprenorphine or naltrexone, with counseling and other behavioral therapies to treat patients with opioid use disorder.) Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group. The most common side effects from treatment with Sublocade included constipation, nausea, vomiting, headache, drowsiness, injection site pain, pruritus at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

Prescription use of Sublocade is limited under the Drug Addiction Treatment Act. Sublocade should only be prepared and administered by a healthcare provider. It is administered monthly only by subcutaneous injection in the abdominal region. Do not administer intravenously or intramuscularly. The recommended dose is two monthly initial doses of 300 mg followed by 100 mg monthly maintenance doses. Increasing the maintenance dose to 300 mg monthly may be considered for patients in whom the benefits outweigh the risks. Administer Sublocade monthly with a minimum of 26 days between doses. Initiating treatment with Sublocade as the first buprenorphine product has not been studied; initiate treatment only following induction and dose-adjustment with a transmucosal buprenorphine-containing product. Sublocade dosage forms and strengths include 100 mg/0.5 mL and 300 mg/ 1.5 mL provided in a prefilled syringe with a 19 Gauge 5/8-inch needle.

Warnings and precautions in the package insert of Sublocade include:

• Addiction, abuse, and misuse: Buprenorphine can be abused in a manner similar to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors
• Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with Sublocade.
• Neonatal Opioid Withdrawal Syndrome: 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 patient off of the opioid.
• Risk of Opioid Withdrawal With Abrupt Discontinuation: If treatment with Sublocade is discontinued, monitor patients for several months for withdrawal and treat appropriately.
• Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to and during treatment.
• Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that patient is clinically stable on transmucosal buprenorphine before injecting Sublocade.
• Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect.

[INFORMATIONAL NOTE: Pursuant to the New Jersey State Mandate on substance use disorder (P.L.2017, c.28, effective May 16, 2017), health benefit plans are required to provide unlimited benefits for medically necessary inpatient (IP) and outpatient (OP) treatment of substance use disorder at in-network facilities and from in-network providers. It also prohibits any prior authorization or prospective utilization management for the first 180 days per plan year of medically necessary IP and OP treatment of substance use disorder, including outpatient prescription drugs. In addition, it places restrictions on prescription of opioids, such as a 5-day supply limit on initial prescriptions for treatment of acute pain.

For additional information and specific provisions, please refer to the mandate.]


I. Probuphine (buprenorphine) implant for subdermal administration is medically necessary when the following criteria have been met:

A. The member has a diagnosis of opioid dependence, AND
B. The member has achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (i.e., doses of <8 mg per day of Subutex or Suboxone sublingual tablet or generic equivalent) for a period of 3 months of more without any need for supplemental dosing or adjustments, AND
C. The member is currently on a maintenance dose of 8 mg per day or less of a sublingual Subutex or Suboxone tablet or its transmucosal buprenorphine product equivalent to achieve sustained prolonged clinical stability on transmucosal buprenorphine, AND
D. The member will not be on a transmucosal buprenorphine-containing product in addition to the requested agent, AND
E. Buprenorphine implants are used as part of a comprehensive substance use disorder treatment program that includes counseling and psychosocial support, AND
F. The member is abstinent from illicit drug use (includes all addictive substances) confirmed by a urine drug screen, AND
G. The prescriber meets the qualification certification criteria in the Drug Addiction Treatment Act (DATA) of 2000 and has been issued a unique DEA identification number by the DEA, indicating that he/she is a qualified physician under the DATA to prescribe buprenorphine, AND
H. The prescriber has reviewed the patient’s records in the state’s prescription drug monitoring program (PDMP) as attestation that, to the best of the provider’s knowledge, the patient is not diverting the requested medication, AND
I. One of the following:
1. The member is not currently taking an opioid agent, including tramadol and tapentadol, OR
2. If the member is receiving any other opioid medication, including tramadol and tapentadol, the prescriber has submitted information supporting the medical necessity of the opioid, including the specific pain that the current opioid is being used to treat and the expected duration of therapy with the opioid (e.g., dental procedure with dates, surgery with dates, acute injury with dates), AND
J. One of the following:
1. The patient is not currently taking other addictive medications (e.g. muscle relaxants, benzodiazepines, sedative/hypnotics, non-prescription drugs of abuse or alcohol), OR
2. The prescriber has submitted documentation indicating benefits of treatment/use of the listed prescription agents outweighs risk associated with concomitant buprenorphine use, AND
K. The member does not have any FDA labeled contraindication(s) to therapy with the requested agent

A. Four Probuphine implants (74.2 mg of buprenorphine) inserted subdermally in the inner side of the upper arm

A. The request is the first renewal request (the request will only be renewed once/ the requested agent will only be approved for 1 course of therapy up to 2 times per lifetime- 1 course of therapy in each arm), AND
B. The requested medication must be inserted subdermally in the upper arm that has not been previously used
C. Periodic assessment is done by the prescriber to evaluate for injection site infections or evidence of tampering or attempts to remove the implant.
D. Periodic assessment is done by the prescriber to evaluate the effectiveness of this drug, the member’s overall treatment plan, and overall progress.

• Subutex (buprenorphine) sublingual tablet (generic equivalent) 8 mg or less per day.
• Suboxone (buprenorphine and naloxone) sublingual tablet (generic equivalent) 8 mg/2 mg or less per day.
• Bunavail™ (buprenorphine and naloxone) buccal film 4.2 mg/0.7 mg or less per day.
• Zubsolv® (buprenorphine and naloxone) sublingual tablets 5.7 mg/1.4 mg or less per day.

• Period free from illicit opioid drug use.
• Stability of living environment.
• Participation in a structured activity/job.
• Consistent participation in recommended behavioral therapy/peer support program.
• Consistent compliance with clinic visit requirements.
• Minimal to no desire or need to use illicit opioids.
• Period without episodes of hospitalizations (addiction or mental health issues), emergency, room visits, or crisis interventions.
• Social support system.]

A. The member has a diagnosis of opioid dependence and meets DSM-5 criteria for moderate or severe opioid use disorder, AND
B. The member does not have a current diagnosis other than opioid use disorder requiring chronic opioid treatment, AND
C. The member does not meet DSM-5 criteria for moderate or severe alcohol use disorder, AND
D. The member has initiated treatment on a transmucosal buprenorphine-containing product delivering the equivalent of 8 to 24 mg of buprenorphine daily for a minimum of 7 days, AND

[INFORMATIONAL NOTE: One SUBOXONE® (buprenorphine and naloxone) 8 mg/2 mg sublingual tablet provides equivalent buprenorphine exposure to one SUBUTEX® (buprenorphine HCl) 8 mg sublingual tablet or one Bunavail® (buprenorphine and naloxone) 4.2mg/0.7 mg buccal film or one Zubsolv® (buprenorphine and naloxone) 5.7 mg/1.4 mg sublingual tablet.]

E. The member will not be on a transmucosal buprenorphine-containing product in addition to the requested agent, AND
F. Buprenorphine, extended-release subcutaneous injection is used as part of a comprehensive substance use disorder treatment program that includes counseling and psychosocial support, AND
G. The member is abstinent from illicit drug use (includes all addictive substances) confirmed by a urine drug screen, AND
H. The prescriber meets the qualification certification criteria in the Drug Addiction Treatment Act (DATA) of 2000 and has been issued a unique DEA identification number by the DEA, indicating that he/she is a qualified physician under the DATA to prescribe buprenorphine, AND
I. The prescriber has reviewed the patient’s records in the state’s prescription drug monitoring program (PDMP) as attestation that, to the best of the provider’s knowledge, the patient is not diverting the requested medication, AND
J. One of the following:
1. The member is not currently taking an opioid agent, including tramadol and tapentadol, OR
2. If the member is receiving any other opioid medication, including tramadol and tapentadol, the prescriber has submitted information supporting the medical necessity of the opioid, including the specific pain that the current opioid is being used to treat and the expected duration of therapy with the opioid (e.g., dental procedure with dates, surgery with dates, acute injury with dates), AND
K. One of the following:
1. The patient is not currently taking other addictive medications (e.g. muscle relaxants, benzodiazepines, sedative/hypnotics, non-prescription drugs of abuse or alcohol), OR
2. The prescriber has submitted documentation indicating benefits of treatment/use of the listed prescription agents outweighs risk associated with concomitant buprenorphine use, AND
L. The member does not have any FDA labeled contraindication(s) to therapy with the requested agent. (Contraindication includes hypersensitivity to buprenorphine or any component of the ATRIGEL® delivery system.)

A. 300 mg of Sublocade monthly for the first two months followed by a maintenance dose of 100 mg monthly, injected subcutaneously in the abdominal region

A. Periodic assessment is done by the prescriber to evaluate the patient for injection site infections or evidence of tampering or attempts to remove the depot.
B. Periodic assessment is done by the prescriber to evaluate the effectiveness of this drug, the member’s overall treatment plan, and overall patient progress.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage will follow the Horizon Policy.

Medicaid Coverage:

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies covered under the Medicare portion of the member’s benefit package, the above Medicaid; and (2) to the extent the service is not Coverage statement applies.

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Probuphine (Buprenorphine) Implant for Subdermal Administration
Buprenorphine (Probuphine) Implant
Opioid Dependence, Probuphine (Buprenorphine) Implant for
Sublocade (Buprenorphine, extended-release) Injection for Subcutaneous Use
Buprenorphine, extended-release (Sublocade) Injection
Opioid Dependence, Sublocade (Buprenorphine, extended-release) Injection for

References:
1. Probuphine prescribing information. Braeburn Pharmaceuticals, Inc. October 2019.

2. Rosenthal RN, Lofwall MR, Kim S, et al. Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: a randomized clinical trial. JAMA. 2016 Jul 19;316(3):282-90. doi: 10.1001/jama.2016.9382.

3. Center for Substance Abuse Treatment. Clinical guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004. Available at: http://www.naabt.org/documents/TIP40.pdf. Accessed November 2016.

4. U.S. Department of Justice: Drug Enforcement Administration Office of Diversion Control

5. Sublocade prescribing information. Indivior, Inc. October 2019.

6. U.S. Food and Drug Administration. FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm587312.htm (Accessed 1/17/18)

7. Randomized, Double-Blind, Placeb-Controlled, Multicenter Study to Assess Efficacy of Multiple Subcutaneous Injections of Depot Buprenorphine (RBP 6000) Over 24 Weeks in Treatment-Seeking Participants With Opioid Use Disorder. (2015). Retrieved from https://clinicaltrials.gov/ct2/show/NCT02357901 (Identification No. NCT02357901)

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

J0570
Q9991
Q9992