Subject: Buprenorphine-Naloxone Limit 1553-H 12-2021

Drug

BUNAVAIL  (buprenorphine and naloxone buccal film)

CASSIPA  (buprenorphine and naloxone sublingual film)

SUBOXONE  (buprenorphine and naloxone sublingual tablet and film)

ZUBSOLV  (buprenorphine and naloxone sublingual tablet)

Policy:

FDA-approved Indications 
Bunavail
Bunavail is indicated for the treatment of opioid dependence.  Bunavail should be used as part of a complete treatment plan that includes counseling and psychosocial support.

Cassipa
Cassipa is indicated for the maintenance treatment of opioid dependence. Cassipa should be used as part of a complete treatment plan to include counseling and psychosocial support.

Suboxone Film
Suboxone sublingual film is indicated for treatment of opioid dependence.  Suboxone sublingual film should be used as part of a complete treatment plan that includes counseling and psychosocial support.

Suboxone Tablet
Buprenorphine and Naloxone sublingual tablets are indicated for the maintenance treatment of opioid dependence.   Buprenorphine and Naloxone sublingual tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support.

Zubsolv
Zubsolv is indicated for treatment of opioid dependence.  Zubsolv should be used as part of a complete treatment plan that includes counseling and psychosocial support.

RATIONALE
Bunavail (buprenorphine/naloxone buccal film), Cassipa (buprenorphine/naloxone sublingual film), Suboxone (buprenorphine/naloxone sublingual tablet and film), and Zubsolv (buprenorphine/naloxone sublingual tablet) are indicated for the treatment of opioid dependence and should be used as part of a complete treatment plan that includes counseling and psychosocial support; however, treatment can be initiated prior to these additional services starting.^1-7

When using buprenorphine/naloxone products for induction, consideration should be given to the type of opioid use disorder (i.e., long- or short-acting opioid products), the time since last opioid use, concomitant non-pharmaceutical fentanyl use, and the severity of opioid use disorder.^1-7

At initiation, the risk of precipitated withdrawal can be reduced by using a lower initial dose of buprenorphine. An initial dose of 2-4 mg and observation of the patient for signs of precipitated withdrawal is recommended. If 60-90 minutes have passed without the onset of withdrawal symptoms, then additional dosing can be done in increments of 2-8 mg. Once it has been established that the initial dose is well tolerated, the buprenorphine dose can be increased fairly rapidly to a dose that provides stable effects for 24 hours and is clinically effective.⁸

After initiation, evidence suggests that buprenorphine doses of 16 mg or more per day or more may be more effective than lower doses at suppressing illicit opioid use. The FDA generally recommends dosing to a limit of 24 mg per day, noting that there is limited evidence regarding the relative efficacy of higher doses. In addition, the use of higher doses may increase the risk of diversion. There is no recommended time limit for treatment with buprenorphine. Clinicians should not encourage patients to discontinue and detoxification only strategies should not be used as a standard. While research is limited, available research generally suggests that longer duration of treatment results in better outcomes.⁸

Bunavail
The maintenance dose of Bunavail is generally in the range of 2.1 mg/0.3 mg buprenorphine/naloxone to 12.6 mg/2.1 mg buprenorphine/naloxone per day depending on the individual patient and clinical response.  The recommended target dosage of Bunavail during maintenance is 8.4 mg/1.4 mg buprenorphine/naloxone as a single daily dose.  Dosages higher than 12.6 mg/2.1 mg buprenorphine/naloxone have not been demonstrated to provide any clinical advantage.^1,6,7 

Cassipa
Cassipa (16 mg/4 mg) should only be used after induction and stabilization of the patient, and when the patient has been titrated to a dose of 16 mg of buprenorphine using another marketed product. The dosage of buprenorphine and naloxone sublingual film may need to be adjusted to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. Cassipa comes in a single dose and cannot be adjusted.^3,6,7

Suboxone
The maintenance dose of Suboxone is generally in the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day depending on the individual and clinical response.  The recommended target dosage of Suboxone during maintenance is 16 mg/4mg buprenorphine/naloxone per day as a single daily dose.  Dosages higher than 24 mg/6 mg buprenorphine/naloxone daily have not been demonstrated to provide a clinical advantage.^2,4,6,7  

Zubsolv
The maintenance dose of Zubsolv is generally in the range of 2.9 mg/0.71 mg buprenorphine/naloxone to 17.2 mg/4.2 mg buprenorphine/naloxone per day depending on the individual patient and clinical response. The recommended target dosage of Zubsolv during maintenance is 11.4 mg/2.9 mg buprenorphine/naloxone as a single daily dose.  Dosages higher than 17.2 mg/4.2 mg buprenorphine/naloxone have not been demonstrated to provide any clinical advantage.^5-7  

If the patient is requesting more than the initial quantity limit, then the claim will reject with a message indicating that quantity limits are exceeded. 

LIMIT CRITERIA   This limit is coded for daily dose. Limits do not accumulate together.  Patient is allowed the  maximum limit for each drug and strength.
Drug	Daily Limit
Bunavail 2.1 mg/0.3 mg, 4.2 mg/0.7 mg	3 units/day
Bunavail 6.3 mg/1 mg	2 units/day
Cassipa 16 mg/4 mg	1 unit/day
Suboxone 2 mg/0.5 mg, 4 mg/1 mg,   8 mg/2 mg	3 units/day
Suboxone 12 mg/3 mg	2 units/day
Zubsolv 0.7 mg/0.18 mg, 1.4 mg/0.36 mg,  2.9 mg/0.71 mg, 5.7 mg/1.4 mg	3 units/day
Zubsolv 8.6 mg/2.1 mg	2 units/day
Zubsolv 11.4 mg/2.9 mg	1 unit/day

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. Bunavail [package insert]. Raleigh, NC: BioDelivery Sciences International, Inc.; October 2019.
2. Buprenorphine and Naloxone tablets [package insert]. Philadelphia, PA: Lannett Company, Inc.; August 2020.
3. Cassipa [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; October 2019.
4. Suboxone films [package insert]. North Chesterfield, VA: Indivior, Inc.; October 2019.
5. Zubsolv [package insert]. Morristown, NJ: Orexo US, Inc.; April 2019.
6. Lexicomp Online, AHFS DI (Adult and Pediatric) Online. Hudson, OH: Wolters Kluwer Clinical Drug Information, Inc. http://online.lexi.com/. Accessed November 2020.
7. Micromedex (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. http://www.micromedexsolutions.com/. Accessed November 2020.
8. American Society of Addiction Medicine National Practice Guideline For the Treatment of Opioid Use Disorder. https://www.asam.org/docs/default-source/quality-science/npg-jam-supplement.pdf?sfvrsn=a00a52c2_2.  Accessed November 2020.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

April 09, 2022