Opioid use disorder: Note:  Prior to induction, consider type of opioid use (ie, long- or short-acting opioid) and time since last use of opioid. 
Patients on heroin or short-acting prescription opioids should initiate buprenorphine/naloxone when signs of opioid withdrawal occur, but no sooner than 6 hours after the last use of heroin or other short-acting opioid (SAMHSA 2018; manufacturer’s labeling).
Patients on methadone should have their methadone maintenance dose reduced to the minimum tolerable dose and remain on that dose for ≥7 days; initiate buprenorphine/naloxone only when early signs of withdrawal appear but no sooner than 24 hours after the last methadone dose. Waiting ≥36 hours after last use of methadone and initiating at lower doses (eg, buprenorphine 2 mg/naloxone 0.5 mg) decreases risk of precipitated methadone withdrawal (SAMHSA 2018). Despite the manufacturer’s recommendation to use buprenorphine instead of buprenorphine/naloxone during the induction period for long-acting opioid dependence due to the risk of withdrawal caused by naloxone, some experts recommend the combination product or buprenorphine for induction for long- and short-acting opioids (SAMHSA 2018).
US labeling:
 Induction:
Note:
Titrate induction dose carefully to control acute withdrawal symptoms while avoiding sedation and monitoring for onset of precipitated withdrawal symptoms (SAMHSA 2018).
Buccal film (Bunavail: Buprenorphine 2.1 mg/naloxone 0.3 mg; buprenorphine 4.2 mg/naloxone 0.7 mg; buprenorphine 6.3 mg/naloxone 1 mg):
Day 1 induction dose: Initial: Buccal: Buprenorphine 2.1 mg/naloxone 0.3 mg; may repeat dose after ~2 hours, based on control of acute withdrawal symptoms; maximum total dose: buprenorphine 4.2 mg/naloxone 0.7 mg.
Day 2 induction dose: Up to buprenorphine 8.4 mg/naloxone 1.4 mg as a single dose.
Sublingual film (Suboxone: Buprenorphine 2 mg/naloxone 0.5 mg; buprenorphine 4 mg/naloxone 1 mg; buprenorphine 8 mg/naloxone 2 mg; buprenorphine 12 mg/naloxone 3 mg):
Day 1 induction dose: Initial: Sublingual: Buprenorphine 2 mg/naloxone 0.5 mg or buprenorphine 4 mg/naloxone 1 mg; may titrate dose, based on control of acute withdrawal symptoms, in buprenorphine 2 mg/naloxone 0.5 mg or buprenorphine 4 mg/naloxone 1 mg increments approximately every 2 hours up to a total dose of buprenorphine 8 mg/naloxone 2 mg.
Day 2 induction dose: Sublingual: Up to buprenorphine 16 mg/naloxone 4 mg as a single dose
Sublingual tablet (Zubsolv: Buprenorphine 0.7 mg/naloxone 0.18 mg, buprenorphine 1.4 mg/naloxone 0.36 mg, buprenorphine 2.9 mg/naloxone 0.71 mg, buprenorphine 5.7 mg/naloxone 1.4 mg, buprenorphine 8.6 mg/naloxone 2.1 mg, or buprenorphine 11.4 mg/naloxone 2.9 mg):
Day 1 induction dose: Sublingual: Start with an initial dose of buprenorphine 1.4 mg/naloxone 0.36 mg; based on control of acute withdrawal symptoms, may administer additional doses in increments of 1 to 2 buprenorphine 1.4 mg/naloxone 0.36 mg tablets every 1.5 to 2 hours to a total day 1 dose up to buprenorphine 5.7 mg/naloxone 1.4 mg. Some patients (eg, those with recent exposure to buprenorphine) may tolerate up to buprenorphine 4.2 mg/naloxone 1.08 mg as a single, second dose.
Day 2 induction dose: Sublingual: Up to buprenorphine 11.4 mg/naloxone 2.9 mg as a single dose
Maintenance: 
Buccal film (Bunavail: Buprenorphine 2.1 mg/naloxone 0.3 mg, buprenorphine 4.2 mg/naloxone 0.7 mg, buprenorphine 6.3 mg/naloxone 1 mg): Buccal: Target dose: Buprenorphine 8.4 mg/naloxone 1.4 mg once daily; dosage should be adjusted in increments/decrements of buprenorphine 2.1 mg/naloxone 0.3 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: Buprenorphine 2.1 to 12.6 mg/naloxone 0.3 to 2.1 mg once daily.
Sublingual film (Suboxone: Buprenorphine 2 mg/naloxone 0.5 mg; buprenorphine 4 mg/naloxone 1 mg; buprenorphine 8 mg/naloxone 2 mg; buprenorphine 12 mg/naloxone 3 mg): Sublingual or buccal: Target dose: Buprenorphine 16 mg/naloxone 4 mg once daily; dosage should be adjusted in increments/decrements of buprenorphine 2 mg/naloxone 0.5 mg or buprenorphine 4 mg/naloxone 1 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: Buprenorphine 4 to 24 mg/naloxone 1 to 6 mg once daily.
Sublingual film (Cassipa: Buprenorphine 16 mg/naloxone 4 mg): Sublingual: Buprenorphine 16 mg/naloxone 4 mg once daily; dosage should be adjusted to a level that maintains treatment and suppresses opioid withdrawal symptoms. Note: Buprenorphine 16 mg/naloxone 4 mg sublingual film is only for use following titration from lower doses.
Sublingual tablet (buprenorphine 2 mg/naloxone 0.5 mg or buprenorphine 8 mg/naloxone 2 mg): Sublingual: Target dose: Buprenorphine 16 mg/naloxone 4 mg once daily; dosage should be adjusted in increments/decrements of buprenorphine 2 mg/naloxone 0.5 mg or buprenorphine 4 mg/naloxone 1 mg to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: Buprenorphine 4 to 24 mg/naloxone 1 to 6 mg once daily. Doses higher than buprenorphine 24 mg/naloxone 6 mg have not been demonstrated to provide any clinical advantage.
Sublingual tablet (Zubsolv: Buprenorphine 0.7 mg/naloxone 0.18 mg, buprenorphine 1.4 mg/naloxone 0.36 mg, buprenorphine 2.9 mg/naloxone 0.71 mg, buprenorphine 5.7 mg/naloxone 1.4 mg, buprenorphine 8.6 mg/naloxone 2.1 mg, or buprenorphine 11.4 mg/naloxone 2.9 mg): Sublingual: Target dose: Buprenorphine 11.4 mg/naloxone 2.9 mg once daily; dosage should be adjusted in increments/decrements of buprenorphine 2.9 mg/naloxone 0.71 mg or lower to a level that maintains treatment and suppresses opioid withdrawal symptoms; usual range: Buprenorphine 2.9 to 17.2 mg/naloxone 0.71 to 4.2 mg once daily. Doses higher than buprenorphine 17.2 mg/naloxone 4.2 mg have not been demonstrated to provide any clinical advantage.
Switching between sublingual tablets and sublingual film: Same dosage should be used as the previous administered product. Note: Potential for greater bioavailability with certain sublingual film strengths compared to the same strength of the sublingual tablet; monitor closely for either over- or underdosing when switching patients from one formulation to another.
Switching between buccal film and sublingual tablets or films: Due to differences in the bioavailability of Bunavail buccal films compared to other buprenorphine/naloxone sublingual tablets, different strengths must be given to achieve equivalent doses. When switching between Bunavail and other sublingual tablets, corresponding dosage strengths are as follows:
Bunavail buprenorphine 2.1 mg/naloxone 0.3 mg = buprenorphine 4 mg/naloxone 1 mg sublingual tablets or films
Bunavail buprenorphine 4.2 mg/naloxone 0.7 mg = buprenorphine 8 mg/naloxone 2 mg sublingual tablets or films
Bunavail buprenorphine 6.3 mg/naloxone 1 mg = buprenorphine 12 mg/naloxone 3 mg sublingual tablets or films
Switching between sublingual film strengths:
Systemic exposure may be different with various combinations of sublingual film strengths; pharmacists should not substitute one or more film strengths for another (eg, switching from three buprenorphine 4 mg/naloxone 1 mg films to a single buprenorphine 12 mg/naloxone 3 mg film, or vice-versa) without health care provider approval, and patients should be monitored closely for either over- or underdosing when switching between film strengths.
Cassipa: Patients may switch from two buprenorphine 8 mg/naloxone 2 mg sublingual films to a single buprenorphine 16 mg/ naloxone 4 mg sublingual film.
Switching between sublingual and buccal sites of administration (Suboxone): Systemic exposure between buccal and sublingual administration of buprenorphine/naloxone sublingual film is similar. Once induction is complete, patients can switch between buccal and sublingual administration without significant risk of under or overdosing.
Switching between sublingual tablet products: Due to differences in the bioavailability of Zubsolv sublingual tablets compared to other buprenorphine/naloxone sublingual tablets, different strengths must be given to achieve equivalent doses. When switching between Zubsolv and other sublingual tablets, corresponding dosage strengths are as follows:
Zubsolv buprenorphine 1.4 mg/naloxone 0.36 mg sublingual tablets = buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets
Zubsolv buprenorphine 2.9 mg/naloxone 0.71 mg sublingual tablets = buprenorphine 4 mg/naloxone 1 mg (as two buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets)
Zubsolv buprenorphine 5.7 mg/naloxone 1.4 mg sublingual tablets = buprenorphine 8 mg/naloxone 2 mg sublingual tablets
Zubsolv buprenorphine 8.6 mg/naloxone 2.1 mg sublingual tablet = buprenorphine 12 mg/naloxone 3 mg sublingual tablets (as one buprenorphine 8 mg/naloxone 2 mg sublingual tablets and two buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets)
Zubsolv buprenorphine 11.4 mg/naloxone 2.9 mg sublingual tablet = buprenorphine 16 mg/naloxone 4 mg sublingual tablets (as two buprenorphine 8 mg/naloxone 2 mg sublingual tablets)
Canadian labeling: Sublingual tablet: Note: Dose based on buprenorphine content.
Induction: Day 1: Initial: 4 mg as single dose; may repeat dose if necessary depending on patient's requirement; target dose: 8 to 12 mg.
Maintenance: Day 2 and beyond: Titrate per response in increments or decrements of 2 to 8 mg; usual maintenance dose: 12 to 16 mg once daily (maximum: 24 mg/day). Upon stabilization, may consider less frequent administration of corresponding equivalent dose (eg, 16 mg every other day instead of 8 mg/day or 3 times/week dosing [eg, Monday-Wednesday-Friday] with twice the maintenance dose on Monday and Wednesday and three times the maintenance dose on Friday); continue to limit maximum dose to 24 mg/day on any single day. Note: When switching dosing to less than once daily, monitor all patients for at least 90 minutes following the initial dose of the new regimen. The less frequent dosing regimen is not recommended in patients dependent on concurrent CNS-active drugs, including ethanol.
Missed doses: Reassess patients who have missed multiple doses; initial induction doses may be required when resuming therapy.
Discontinuation of therapy: When discontinuing buprenorphine/naloxone for long-term treatment of opioid use disorder, gradually decrease the dose over several months (SAMHSA 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
 Detailed Buprenorphine/naloxone dosage information
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Sublingual tablets and film contain a free-base ratio of buprenorphine:naloxone of 4:1. Not all sublingual dosage forms are bioequivalent and dosing adjustment or additional monitoring may be necessary when switching products; refer to specific dosing sections below. Doses based on buprenorphine content; titrate to appropriate effect.
Opioid dependence, maintenance treatment (heroin or short-acting opioid) (ASAM [Kampman 2015]): Note: Buprenorphine alone (without naloxone) is preferred over the combination product for use during the induction period for long-acting opioids or methadone.
Adolescents: Limited data available: Sublingual: Tablets or Film:
Induction: Note: Combination products should only be administered for induction in patients dependent on short-acting opioids (eg, heroin, oxycodone) who have begun to show mild to moderate opioid withdrawal signs (to avoid precipitated withdrawal) and whose last dose of opioids was at least 6 to 12 hours prior to induction.
Initial: 2 to 4 mg; if no signs of precipitated withdrawal after 60 to 90 minutes, may increase in increments of 2 to 4 mg. Once initial dose is tolerated, may increase to a dose that is clinically effective and provides 24 hours of stabilization.
After induction and titration, daily doses usually ≥8 mg/day are necessary. In patients continuing to use opioids, consider increasing the dose by 4 to 8 mg to a daily dose of 12 to 16 mg/day. Maximum daily dose: 24 mg/day.
Switching between sublingual tablets and sublingual film: The same dosage should be used as the previous administered product with close patient monitoring. Note: Potential for greater bioavailability with certain sublingual film strengths compared to the same strength of the sublingual tablet; monitor closely for either over- or underdosing when switching patients from one formulation to another (ASAM [Kampman 2015]).
Switching between sublingual film strengths: Systemic exposure may be different with various combinations of sublingual film strengths; pharmacists should not substitute one or more film strengths for another (eg, switching from three buprenorphine 4 mg/naloxone 1 mg films to a single buprenorphine 12 mg/naloxone 3 mg film, or vice-versa) without health care provider approval, and patients should be monitored closely for either over- or underdosing when switching between film strengths.
Cassipa: Patients may switch from two buprenorphine 8 mg/naloxone 2 mg sublingual films to a single buprenorphine 16 mg/ naloxone 4 mg sublingual Cassipa film.
Switching between sublingual tablet products: Due to differences in the bioavailability of Zubsolv sublingual tablets compared to other buprenorphine/naloxone sublingual tablets, different strengths must be given to achieve equivalent doses. When switching between Zubsolv and other sublingual tablets, corresponding dosage strengths are as follows:
Zubsolv buprenorphine 1.4 mg/naloxone 0.36 mg sublingual tablets = buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets.
Zubsolv buprenorphine 2.9 mg/naloxone 0.71 mg sublingual tablets = buprenorphine 4 mg/naloxone 1 mg (as two buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets).
Zubsolv buprenorphine 5.7 mg/naloxone 1.4 mg sublingual tablets = buprenorphine 8 mg/naloxone 2 mg sublingual tablets.
Zubsolv buprenorphine 8.6 mg/naloxone 2.1 mg sublingual tablet = buprenorphine 12 mg/naloxone 3 mg sublingual tablets (as one buprenorphine 8 mg/naloxone 2 mg sublingual tablets and two buprenorphine 2 mg/naloxone 0.5 mg sublingual tablets).
Zubsolv buprenorphine 11.4 mg/naloxone 2.9 mg sublingual tablet = buprenorphine 16 mg/naloxone 4 mg sublingual tablets (as two buprenorphine 8 mg/naloxone 2 mg sublingual tablets).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Administration
Film:
Bunavail: Buccal: Although the manufacturer recommends administering the film whole without cutting, chewing, or swallowing, one stability study (using Suboxone brand) suggested that films split in half have uniform content and maintain stability for up to 7 days (Reindel 2019). Immediately before placing the film, moisten inside of cheek with tongue or water. Apply film with a dry finger immediately after removing it from packaging. Place film with the text (BN2, BN4, or BN6) against the inside of the moistened cheek; press and hold the film in place for 5 seconds with finger (film should stay in place after this period). Keep film in place until it dissolves completely. Do not chew, swallow or move film after placement. Liquids and food can be consumed after film dissolves. If using more than 1 film simultaneously, the additional film should be placed on the inside of the other cheek; no more than 2 films should be applied to the inside of one cheek at a time.
Cassipa: Sublingual: Although the manufacturer recommends administering the film whole without cutting, chewing, or swallowing, one stability study (using Suboxone brand) suggested that films split in half have uniform content and maintain stability for up to 7 days (Reindel 2019). Prior to film placement, rinse mouth with a small volume of room temperature water; avoid beverages with a high pH prior to dosing. Place one film under the tongue until the film completely dissolves, close to the base on the left or right side. Do not move film after placement. Liquids and food should not be consumed until after film completely dissolves.
Suboxone: May be used buccally or sublingually.
Buccal: Although the manufacturer recommends administering the film whole without cutting, chewing, or swallowing, one stability study suggested that films split in half have uniform content and maintain stability for up to 7 days (Reindel 2019). Place one film on the inside of the right or left cheek. If more than one film is needed, the additional film should be placed on the inside of the opposite cheek. Keep the film on the inside of the cheek until completely dissolved. Do not move film after placement. If a third film is necessary, place it on the inside of the right or left cheek after the first 2 films have dissolved.
Sublingual film: Although the manufacturer recommends administering the film whole without cutting, chewing, or swallowing, one stability study suggested that films split in half have uniform content and maintain stability for up to 7 days (Reindel 2019). Place one film under the tongue until the film completely dissolves, close to the base on the left or right side. If more than one film is needed, the additional film should be placed under the tongue on the opposite side from the first film. Place the film in a manner to minimize overlapping as much as possible. Do not move film after placement. If a third film is necessary to achieve the prescribed dose, place it under the tongue on either side after the first 2 films have dissolved.
Sublingual tablet: Immediately after removal from blister pack, tablet should be placed under the tongue until dissolved (can take up to 10 minutes to fully dissolve [SAMHSA 2018]). If 2 or more tablets are needed per dose, all may be placed under the tongue at once, or 2 at a time. In patients requiring more than one sublingual tablet, place all tablets in different places under the tongue at the same time. To ensure consistent bioavailability, subsequent doses should always be taken the same way. Patients should not eat or drink anything until the tablet(s) are completely dissolved. If a sequential mode of administration is preferred, patients should follow the same manner of dosing with continued use of the product, to ensure consistency in bioavailability. Do not chew or swallow sublingual tablets.
