Effective Date

Date of Origin 

04-01-2024            

buprenorphine

Sublingual tablet^a

Treatment of opioid dependence and is preferred for induction.

Should be used as part of a complete treatment plan that includes counseling and psychosocial support.

a – generic available

1-5

buprenorphine/naloxone

Sublingual tablet^a

Maintenance treatment of opioid dependence.

Should be used as part of a complete treatment plan that includes counseling and psychosocial support.

a - generic available and included in the quantity limit program.

1-5

Suboxone^®

(buprenorphine/naloxone)

Sublingual film^a

Treatment of opioid dependence.

Should be used as part of a complete treatment plan that includes counseling and psychosocial support.

a - generic available and included in the quantity limit program.

1-5

Zubsolv^®

(buprenorphine/naloxone)

Sublingual tablet

Treatment of opioid dependence.

Should be used as part of a complete treatment plan that includes counseling and psychosocial support.

1-5

Opioid Use Disorder

Opioid use disorder requires continuing care for effectivder (OUD) is defined as a disorder characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. It is estimated that 1.8 million Americans have OUD related to opioid painkillers. Opioid addiction is considered a moderate to severe form of OUD. The Substance Abuse and Mental Health Services Administration (SAMHSA) and the National Institute on Drug Abuse indicate addiction is a lifelong, treatable illness and oftene treatment. OUD treatment does not have a “one size fits all” approach and patients should receive information from their healthcare team regarding OUD and the options for treatment, including treatment with FDA approved medications. Patient’s receiving OUD treatment should have access to medical, mental health, addiction counseling, and recovery support services to supplement medication assisted treatment (MAT).(7,8) Under the Drug Addiction Treatment Act (DATA) codified at 21 United States Code (U.S.C.) 823(g), use of these products in the treatment of opioid dependence are limited to healthcare providers who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe or dispense these products for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.(1-4)

To expand access to medication-assisted treatment, including buprenorphine that can be prescribed in office-based settings, Congress eliminated the "DATA-Waiver Program," with the signing of Section 1262 of the Consolidated Appropriations Act of 2023. Current DEA registrants are able to prescribe buprenorphine for opioid use disorder, no longer requiring a DATA-Waiver registration.(15)

For induction treatment, single-agent buprenorphine is preferred. For patients dependent on short-acting opioid products who are in opioid withdrawal, single agent buprenorphine or Suboxone (buprenorphine/naloxone) may be used for induction. For patients dependent on methadone or long-acting opioid products, single-agent buprenorphine is recommended.  Single-agent buprenorphine should be limited to a maximum of 5 days, except in pregnant women and patients with a documented allergy to naloxone or naltrexone. These patients should be allowed treatment with single-agent buprenorphine beyond 5 days.6-8 When determining treatment initiation, consider the opioid's duration of action, time since last opioid use, and degree of opioid dependence. Administer first dose of buprenorphine at least 4 hours after the last used opioid or preferably when early signs of opioid withdrawal appear. Use of buprenorphine/naloxone during induction may result in more withdrawal symptoms than if single-agent buprenorphine is used.(1-4)

For maintenance treatment, patients should be transitioned from single-agent buprenorphine to buprenorphine/naloxone after 2 days of induction, except in pregnant women and patients with a documented allergy to naloxone or naltrexone.(1-4) Buprenorphine/naloxone is preferred over single-agent buprenorphine for maintenance treatment, especially when drug administration will not be supervised. Buprenorphine is indicated for daily administration; however, administering the total weekly dose over three days (roughly every other day) may be effective in decreasing opioid dependence.(1-4) Buprenorphine has a long elimination half-life, due to a slow dissociation rate from the mu opioid receptor, which gives rise to its prolonged suppression of opioid withdrawal and blockade of exogenous opioids. This enables buprenorphine dosing to occur on a less frequent basis than full opioid agonists.6  The half-life varies from 24 to 69 hours, with a mean of 24 to 42 hours. For example, a patient stabilized on 12 mg daily of buprenorphine/naloxone could be treated with 24 mg every other day or 24 mg on Mondays and Wednesdays and 36 mg on Fridays. These types of schedules allow for reduced travel burden for patients wanting supervised dosing at an OPT or may be useful for patients who must spend weekends in a jail that does not allow buprenorphine dosing.(8) Doses up to 32 mg per day are needed by some patients, but this should be rare.(14)

According to the Substance Abuse and Mental Health Services Administration (SAMHSA), dosing can vary between 2 mg/0.5 mg (buprenorphine/naloxone) to 8mg/2mg (Suboxone) on the first and second day of induction, with a recommended target dose of 16 mg/4 mg, and up to 32 mg/8 mg per day during maintenance therapy. Dosing depends on the stabilization of withdrawal symptoms.(6) There is limited evidence regarding the relative efficacy of doses higher than 24 mg/6 mg per day and the use of higher doses may increase the risk of diversion.(6-8) Dosages higher than 24mg/6mg have not been demonstrated to provide a clinical advantage.(1-8) Evidence used to gain the FDA approval demonstrated efficacy in doses up to 16 mg/4 mg per day through clinical trial data with safety being supported in open label extensions in doses up to 24 mg/6 mg per day of the tablets. Justification for approval of the 24 mg/6 mg dose is based on data extrapolations comparing the pharmacokinetic profiles of the tablet and sublingual solutions.(1)

Buprenorphine dosing for buprenorphine tablets and Suboxone is considered interchangeable. Buprenorphine equivalency amongst available products is as follows: 8 mg buprenorphine is equivalent to 5.7 mg buprenorphine (1.4 mg naloxone) within Zubsolv. When switching between buprenorphine/naloxone sublingual tablets and buprenorphine/naloxone (Suboxone) sublingual film, start on the same dosage as the previously administered product. However, dosage adjustments may be necessary when switching between products because of the potentially greater relative bioavailability of sublingual film compared to sublingual tablet. Patients switching from sublingual film to sublingual tablet should be monitored for withdrawal or other indications of under-dosing.(1-3) When switching between buprenorphine/naloxone sublingual tablet/film and Zubsolv sublingual tablets, the difference in bioavailability of Zubsolv compared to buprenorphine/naloxone sublingual tablet requires a different dosage strength to be administered to the patient.(4)

Efficacy

Buprenorphine is a partial opioid agonist and mixed opioid agonist-antagonist. As a partial mu-receptor agonist, buprenorphine exhibits a ceiling to its pharmacological effects; thus, the danger of overdose, abuse liability, and toxicity from buprenorphine may be less than with full opioid agonists. Naloxone is a full opiate antagonist. Since buprenorphine may be given outside of an opiate-treatment clinic, a formulation with naloxone (Suboxone, at a ratio of 4:1 buprenorphine: naloxone) was developed in an effort to decrease the potential for abuse of the combination product via the injection route. In this formulation, the naloxone component produces no clinical effect when administered sublingually; however, when dissolved in water and injected, the full opiate antagonist effect of naloxone occurs and will induce withdrawal symptoms. As a result, the buprenorphine with naloxone combination product is preferred for maintenance therapy in patients with unsupervised drug administration.(6-8)

Clinical practice guidelines indicate goals of the initial medical assessment of a patient who is addicted to opioids are to:(6-8)

• Establish the diagnosis or diagnoses
• Determine appropriateness for treatment
• Make initial treatment recommendations
• Formulate an initial treatment plan
• Plan for engagement in psychosocial treatment
• Ensure that there are no contraindications to the recommended treatments
• Assess other medical problems or conditions that need to be addressed during early treatment
• Assess other psychiatric or psychosocial problems that need to be addressed during early treatment 

A careful evaluation of current and past use of alcohol and drugs, including nonmedical use of prescription medications, is required to diagnose opioid use disorder. Because opioid use disorder may co-occur with other use disorders, the evaluator should assess frequency and quantity of use. Prescription Drug Monitoring Programs (PDMPs) offer information about prescription opioid use. They can serve as important resources for clinicians’ use in completing full patient clinical assessments of opiate and other controlled substance use history, and it is recommended that they be utilized. Concurrent use of other drugs or active engagement in other addictive behaviors should lead to consideration of other treatment plan components for the patient. Psychosocial treatment should be implemented in conjunction with the use of buprenorphine in the treatment of opioid use disorder. Urine drug testing, or other reliable biological tests for the presence of drugs, during the initial evaluation and frequently throughout treatment, is highly recommended.(6-8)

Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress. Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow‐up visits may be appropriate.(1-4)

There is no recommended time limit for treatment with buprenorphine. Providers and their patients should base decisions about discontinuing OUD medication on knowledge of the evidence base for the use of these medications, individualized assessments, and an individualized treatment plan they collaboratively develop and agree upon.8 Buprenorphine taper and discontinuation is a slow process and close monitoring is recommended. Buprenorphine tapering is generally accomplished over several months and patients should be encouraged to remain in treatment for ongoing monitoring past the point of discontinuation.(7)

The Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction issued by the US Dept of Health and Human Services recommends the following: 

“The consensus panel recommends that the buprenorphine/naloxone combination be used for induction treatment (and for stabilization and maintenance) for most patients. However, pregnant women who are determined to be appropriate candidates for buprenorphine treatment should be inducted and maintained on buprenorphine monotherapy. In addition, patients who desire to change from long-acting opioids (e.g., methadone) to buprenorphine should be inducted using buprenorphine monotherapy. Patients and their physicians together need to reach agreement on the goals of treatment and develop a treatment plan based on the patient’s particular problems and needs. During the stabilization phase, patients receiving maintenance treatment should be seen on at least a weekly basis. Once a stable buprenorphine dose is reached and toxicologic samples are free of illicit opioids, the physician may determine that less frequent visits (biweekly or longer, up to 30 days) are acceptable. During opioid addiction treatment with buprenorphine, toxicology tests for relevant illicit drugs should be administered at least monthly."(6)

The American Society of Addiction Medicine National Practice Guideline For the Use of Medications in the Treatment of Addiction Involving Opioid Use recommends the following:(7)

• Buprenorphine mono-product is a reasonable and recommended alternative to methadone for pregnant women.
• Methadone is recommended for patients who may benefit from daily dosing and supervision in an opioid treatment program (OTP), or for patients for whom buprenorphine for the treatment of opioid use disorder has been used unsuccessfully in an OTP or office based opioid treatment (OBOT) setting.

The occurrence of acute and chronic pain among patients with an opioid use disorder is not uncommon. Temporarily increasing buprenorphine dosing or dividing the dose may be effective for acute pain management. Patients’ pain may not be adequately addressed with buprenorphine and may require a full opioid agonist. In situations when a full opioid agonist is needed for pain control, patients may be taken off buprenorphine and switched to a full opioid agonist until analgesia is no longer necessary, such as elective surgery. However, there are data to suggest that the discontinuation of buprenorphine is unnecessary and that adequate analgesia may be possible by simply adding non-narcotic and narcotic analgesics to the patient’s baseline buprenorphine dose.(6-7)

Continuation or modification of pharmacotherapy should be based on the physician’s evaluation of treatment outcomes and objectives such as:(1-4)

1. Absence of medication toxicity
2. Absence of medical or behavioral adverse effects
3. Responsible handling of medications by the patient
4. Patient’s compliance with all elements of the treatment plan (including recovery-oriented activities, psychotherapy, and/or other psychosocial modalities)
5. Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use)

If treatment goals are not being achieved, the physician should re-evaluate the appropriateness of continuing the current treatment.(1-4)

Safety(1-4)

Buprenorphine-containing products are contraindicated in patients with a history of hypersensitivity to buprenorphine or naloxone as serious adverse reactions, including anaphylactic shock, have been reported.

1

Buprenorphine prescribing information. Hikma Pharmaceuticals USA Inc. September 2023.

2

Buprenorphine/naloxone tablet prescribing information. Amneal Pharmaceuticals LLC. September 2023.

3

Suboxone sublingual film prescribing information. Indivor Inc. December 2023.

4

Zubsolv prescribing information. Orexo US, Inc. December 2023.

5

Bunavail buccal film prescribing information. BioDelivery Sciences International. June 2020. Reference no longer used.

6

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.

7

National Practice Guideline for the Treatment of Opioid Use Disorder. The American Society of Addiction Medicine. Available at: https://www.asam.org/quality-care/clinical-guidelines/national-practice-guideline. Accessed December 2022.

8

Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63 Publication No. PEP21-02-01-002. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2021.

9

Statutes, Regulations, and Guidelines. U.S. Department of Health & Human Services. Substance Abuse and Mental Health Services Administration. Available at: https://www.samhsa.gov/medication-assisted-treatment/statutes-regulations-guidelines. Accessed December 2022.

10

Johnson RE, Chutuape MA, Strain EC, et al. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000;343:1290-1297.

11

Fudala PJ, Bridge T, Herbert S, et al. Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone. N Engl J Med. 2003;349(10):949-958.

12

Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database of Syst Rev 2009;July 8;(3)CD002025.

13

Fareed et al. Treatment Outcome for Flexible Dosing Buprenorphine during Maintenance Treatment. Am. J. Drug Alcohol Abuse. 2012 Mar;38(2):155-160.

14

Strain, E, MD. Pharmacotherapy for Opioid Use Disorder. UpToDate, Post, TW (Ed), UpToDate, Waltham. Last updated November 2023. Literature review current through December 2023. Accessed December 2023.

15

Removal of DATA Waiver (X-Waiver) Requirement. Substance Abuse and Mental Health Services Administration. Available at: https://www.samhsa.gov/medication-assisted-treatment/removal-data-waiver-requirement Accessed January 2023.

Buprenorphine HCl SL Tab 2 MG (Base Equiv)

2  ; 2 MG

5

Tablets

90

DAYS

Buprenorphine HCl SL Tab 8 MG (Base Equiv)

8  ; 8 MG

5

Tablets

90

DAYS

Buprenorphine HCl-Naloxone HCl SL Tab 2-0.5 MG (Base Equiv)

2-0.5 MG

90

Tablets

30

DAYS

Buprenorphine HCl-Naloxone HCl SL Tab 8-2 MG (Base Equiv)

8-2 MG

60

Tablets

30

DAYS

Suboxone

buprenorphine hcl-naloxone hcl sl film

12-3 MG ; 2-0.5 MG ; 4-1 MG ; 8-2 MG

30

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 2-0.5 MG (Base Equiv)

2-0.5 MG

90

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 2-0.5 MG (Base Equiv)

2-0.5 MG

90

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 4-1 MG (Base Equiv)

4-1 MG

60

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 4-1 MG (Base Equiv)

4-1 MG

60

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 8-2 MG (Base Equiv)

8-2 MG

60

Films

30

DAYS

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 8-2 MG (Base Equiv)

8-2 MG

60

Films

30

DAYS

Zubsolv

buprenorphine hcl-naloxone hcl sl tab

0.7-0.18 MG ; 1.4-0.36 MG ; 11.4-2.9 MG ; 2-0.5 MG ; 2.9-0.71 MG ; 5.7-1.4 MG ; 8-2 MG ; 8.6-2.1 MG

30

Tablets

30

DAYS

Zubsolv

Buprenorphine HCl-Naloxone HCl SL Tab 1.4-0.36 MG (Base Eq)

1.4-0.36 MG

90

Tablets

30

DAYS

Buprenorphine HCl SL Tab 2 MG (Base Equiv)

2  ; 2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Buprenorphine HCl SL Tab 8 MG (Base Equiv)

8  ; 8 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Buprenorphine HCl-Naloxone HCl SL Tab 2-0.5 MG (Base Equiv)

2-0.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Buprenorphine HCl-Naloxone HCl SL Tab 8-2 MG (Base Equiv)

8-2 MG

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Suboxone

buprenorphine hcl-naloxone hcl sl film

12-3 MG ; 2-0.5 MG ; 4-1 MG ; 8-2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 2-0.5 MG (Base Equiv)

2-0.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 2-0.5 MG (Base Equiv)

2-0.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 4-1 MG (Base Equiv)

4-1 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 4-1 MG (Base Equiv)

4-1 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 8-2 MG (Base Equiv)

8-2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Suboxone

Buprenorphine HCl-Naloxone HCl SL Film 8-2 MG (Base Equiv)

8-2 MG

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Zubsolv

buprenorphine hcl-naloxone hcl sl tab

0.7-0.18 MG ; 1.4-0.36 MG ; 11.4-2.9 MG ; 2-0.5 MG ; 2.9-0.71 MG ; 5.7-1.4 MG ; 8-2 MG ; 8.6-2.1 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zubsolv

Buprenorphine HCl-Naloxone HCl SL Tab 1.4-0.36 MG (Base Eq)

1.4-0.36 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Buprenorphine for Opioid Dependence Prior Authorization with Quantity Limit

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. ONE of the following:
   1. The requested quantity (dose) is less than or equal to the program quantity limit OR
   2. The requested quantity (dose) is within FDA-approved labeling and the prescriber has submitted documentation in support of therapy with a higher dose for the requested indication OR
   3. The patient is pregnant OR
   4. The patient has an intolerance or hypersensitivity to naloxone or naltrexone OR
   5. The patient has an FDA labeled contraindication to naloxone or naltrexone

Length of Approval:

Initial: Allow for a single course of induction treatment within the quantity limit OR as requested and approved, based on submitted information up to 2 months OR duration of pregnancy if less than 2 months to term

Renewal: 6 months, or duration of pregnancy if less than 6 months to term

Buprenorphine/Naloxone for Opioid Dependence Quantity Limit

OBJECTIVE

The intent of the Buprenorphine/Naloxone for Opioid Dependence Quantity Limit (QL) program is to ensure appropriate selection of patients for treatment of opioid dependence in appropriate quantities according to product labeling and/or clinical guidelines and/or clinical studies. These products will not be covered for the treatment of pain. Claims for opioids during buprenorphine/naloxone therapy will only be covered with prior authorization and only in the event of acute pain/surgery not to exceed a 5-day course of treatment (see separate criteria below “Concomitant Use of Opioid Products with Buprenorphine and Buprenorphine/Naloxone”).

TARGET AGENT(S)

buprenorphine/naloxone
Bunavail™ (buprenorphine/naloxone)
Suboxone® (buprenorphine/naloxone)
Zubsolv® (buprenorphine/naloxone)

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Evaluation

Please provide clinical notes to support information below.

Quantities above the program set limit for Bunavail, buprenorphine/naloxone, Suboxone, Zubsolv (buprenorphine/naloxone) will be approved when ALL of the following are met and supported by medical records (e.g., chart notes, physician letter of attestation):

1. The patient has an active diagnosis of opioid dependence AND
2. ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age AND
3. The patient will NOT be using the requested agent in combination with another buprenorphine or buprenorphine/naloxone agent (including implantable and injectable buprenorphine) for the requested indication AND
4. ONE of the following:
   1. The requested quantity (dose) is less than or equal to the program quantity limit OR
   2. The requested quantity (dose) is within FDA-approved labeling and the prescriber has submitted documentation in support of therapy with a higher dose for the requested indication

Length of Approval: 6 months