Usual Adult Dose for Opiate Dependence - Induction

All doses expressed as BUPRENORPHINE/NALOXONE

INDUCTION: For those Dependent on Heroin or Other Short-acting Opioid Products:

• INITIAL DOSES should begin when objective signs of moderate opioid withdrawal appear and not less than 6 hours after the patient last used opioids to avoid precipitating an opioid withdrawal syndrome:

Suboxone Sublingual Film:
Day 1: up to 8 mg/2 mg sublingually; administer as an initial dose of 2 mg/0.5 mg or 4 mg/1 mg with titration in 2 or 4 mg increments of buprenorphine at approximately 2-hour intervals
Day 2: 16 mg/4 mg sublingually as a single dose

Bunavail Buccal Film:
Day 1: up to 4.2 mg/0.7 mg buccally; administer as an initial dose of 2.1 mg/0.3 mg and repeat in approximately 2 hours
Day 2: up to 8.4 mg/1.4 mg buccally as a single dose

Zubsolv Sublingual Tablets:
Day 1: up to 5.7 mg/1.4 mg sublingually; administer as an initial dose of 1.4 mg/0.36 mg and then up to 4.2 mg/1.08 mg should be divided into doses 1.4 mg/0.36 mg or 2.8 mg/0.72 mg and administered in 1.5 to 2 hour intervals (some patients with recent exposure to buprenorphine may tolerate a single second dose of 4.2 mg/1.08 mg)
Day 2: 11.4 mg/2.9 mg sublingually as a single dose

Comments:

• Patients dependent on heroin or other short-acting opioid products may be inducted with combination buprenorphine/naloxone or buprenorphine monotherapy; to avoid precipitating withdrawal during induction, initiation should occur when clear signs of withdrawal are evident, preferably when moderate objective signs of opioid withdrawal appear, and no sooner than 6 hours after last use of heroin or other short-acting opioid.
• Suboxone sublingual tablets are not indicated for induction therapy; Suboxone sublingual film for sublingual or buccal use should only be administered sublingually for induction to minimize exposure to naloxone.
• Cassipa film is not indicated for induction, it is indicated only for maintenance treatment of opioid dependence.
• In some studies, too-gradual induction over several days has led to a high dropout; it is recommended that an adequate treatment dose, titrated to clinical effectiveness, be achieved as rapidly as possible.
• For patient's dependent on methadone or long-acting opioid products, buprenorphine monotherapy should be used during the induction phase as naloxone may be absorbed in small amounts and could precipitate or prolong withdrawal during induction.
• Maintenance treatment begins on day 3.

Use: For the treatment of opioid dependence as part of a complete treatment plan to include counseling and psychosocial support.

Usual Adult Dose for Opiate Dependence - Maintenance

All doses expressed as BUPRENORPHINE/NALOXONE

MAINTENANCE Treatment:

• Doses of buprenorphine/naloxone should be adjusted to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms; doses should be titrated to clinical effectiveness as rapidly as possible as gradual titration may lead to higher drop-out rates.

SUBOXONE Sublingual Film and Sublingual Tablets:

• Progressively adjust in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
• Recommended target dose: 16 mg/4 mg sublingually (film, tablet) or buccally (film) once a day; dose range 4 mg/1 mg to 24 mg/6 mg
• Maximum dose: 24 mg/6 mg per day

ZUBSOLV Sublingual Tablets:

• Progressively adjust in increments/decrements of 1.4 mg/0.36 mg or 2.9 mg/0.71 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
• Recommended target dose: 11.4 mg/2.9 mg sublingually once a day; dose range 2.9 mg/0.71 mg to 17.2 mg/4.2 mg
• Maximum dose: 17.2 mg/4.2 mg per day

BUNAVAIL Buccal Film:

• Progressively adjust in increments/decrements of 2.1 mg/0.3 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
• Recommended target dose: 8.4 mg/1.4 mg buccally once a day; range 2.1 mg/0.3 mg to 12.6 mg/2.1 mg

Maximum dose: 12.6 mg/ 2.1 mg per day

CASSIPA Sublingual Film:

• After induction and stabilization to a dose of buprenorphine 16 mg, initiate at 16 mg/4 mg sublingually once a day

Maximum dose: 16 mg/4 mg per day

Comments:

• Following induction, maintenance therapy is provided to hold a patient in treatment and suppress opioid withdrawal signs and symptoms; there is no maximum recommended duration for maintenance treatment and some patients may require treatment indefinitely.
• There are multiple buprenorphine/naloxone products available for maintenance treatment; these products are not bioequivalent and dose adjustments may be necessary when switching products; e.g., Zubsolv 4.2 mg/0.7 mg buccal film provides equivalent buprenorphine exposure as Suboxone 8 mg/2 mg sublingual tablet.

Use: For the treatment of opioid dependence as part of a complete treatment plan to include counseling and psychosocial support.

Renal Dose Adjustments

Use with caution; no dose adjustments recommended

Liver Dose Adjustments

Mild hepatic impairment: Use with caution; no dose adjustments recommended
Moderate Hepatic Impairment: Not recommended for induction due to increased risk of precipitated withdrawal; may be used cautiously for maintenance treatment; monitor for opioid withdrawal.
Severe Hepatic impairment: Use not recommended

Dose Adjustments

Elderly: Clinical studies have not included a sufficient number of subjects 65 years or older to determine whether they respond differently than younger subjects; use caution and monitor for signs and symptoms of toxicity or overdose.

Patients switching between buprenorphine-naloxone products must be monitored for over-medication or under-dosing, i.e., signs of withdrawal.

For patients switching between sublingual FILM and sublingual TABLETS:

• Start on the same dose as the previously administered product, however, due to greater relative bioavailability of FILM compared to TABLET, closely monitor.

Due to differences in bioavailability, ZUBSOLV sublingual tablets require a different strength:

• Zubsolv 1.4 mg/0.36 mg tablet provides equivalent buprenorphine exposure as buprenorphine-naloxone 2 mg/0.5 mg sublingual tablet
• Zubsolv 2.9 mg/0.71 mg tablet provides equivalent buprenorphine exposure as buprenorphine-naloxone 4 mg/1 mg (taken as two 2 mg/0.5 mg sublingual tablets)
• Zubsolv 5.7 mg/1.4 mg tablet provides equivalent buprenorphine exposure as buprenorphine-naloxone 8 mg/2 mg sublingual tablet
• Zubsolv 8.6 mg/2.1 mg tablet provides equivalent buprenorphine exposure as buprenorphine-naloxone 12 mg/3 mg (taken as one 8 mg/2 mg plus two 2 mg/0.5 mg

sublingual tablets)

• Zubsolv 11.4 mg/2.9 mg tablet provides equivalent buprenorphine exposure as buprenorphine-naloxone 16 mg/4 mg (taken as two 8 mg/2 mg sublingual tablets)

• Patients initiating or stopping CYP450 3A4 inhibitors or inducers should be monitored for potential over-medication or under-dosing of buprenorphine

REDUCING DOSAGE AND STOPPING TREATMENT:

• As part of a comprehensive treatment plan, a decision may be made to lower the maintenance dose or discontinue therapy; gradual dose reduction is recommended to avoid opioid withdrawal signs and symptoms. Following discontinuation, patients should be monitored for potential relapse.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Buprenorphine Transmucosal Products for Opioid Dependence (BTOD), Suboxone, and Subutex. It includes a medication guide, elements to assure safe use, and implementation system. For additional information: www.fda.gov/REMS

CONTRAINDICATIONS:

• Hypersensitivity to buprenorphine or naloxone or to any of the excipients

Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C 823 (g), prescription use of this product in the treatment of opioid dependence is 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 this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Safety and efficacy of sublingual or buccal film have not been established in patients younger than 18 years; safety and efficacy of sublingual tablets have not been established in patients younger than 16 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule lll

Dialysis

Data not available

Other Comments

Administration advice:

• Proper administration technique should be demonstrated to the patient
• Do not cut, chew, or swallow
• Do not eat or drink anything until the dose is completely dissolved
• Do not move product after placement
• To ensure consistency, follow the same manner of dosing with continued use
• If a dose is missed, take it as soon as remembered; if it is almost time for the next dose, skip the missed dose and take the next dose at the regular time

• SUBLINGUAL TABLET:
• Place under tongue until dissolved
• For doses requiring multiple tablets, place all tablets in different locations under tongue, minimize overlapping; alternatively, divide into multiple portions, taking second and subsequent portions directly after previous portion has dissolved
• Median dissolution time for Zubsolv(R) was 5 minutes

SUBLINGUAL FILM:

• Before administration, rinse mouth with a small volume of room temperature water to moisten mouth
• Place film under tongue close to the base on the left or right side; keep under tongue until completely dissolved; on average dissolution takes 4 to 8 minutes
• For doses requiring multiple films, place additional film on the opposite side minimizing overlap as much as possible; alternatively, divide into multiple portions, taking second and subsequent portions directly after previous portion has dissolved

BUCCAL FILM:

• Use tongue to wet inside of the cheek or rinse mouth with water to moisten application area
• Apply to inside of the cheek; press and hold for 5 seconds
• Allow film to completely dissolve; avoid manipulating film with tongue or fingers
• If multiple films are needed, immediately apply the next film in the same manner to the opposite cheek; up to 2 films can be applied to one cheek at a time

Preparation techniques:

• FILM: Wait to open foil pack until ready to use; protect from freezing and moisture
• TABLET: Wait to open blister until ready for use: do not push tablet through blister pack as it may break

General:

• Treatment should be under the supervision of a physician experienced in the management of opiate dependence/addiction.
• Medication treatment should be used as part of a complete treatment plan to include counseling and psychosocial support.
• To avoid precipitating withdrawal, buprenorphine monotherapy is generally used for induction, especially when there is doubt about the level of dependence or previous drug use.
• Multiple refills should not be provided early in treatment or without appropriate follow-up.
• The decision to discontinue treatment should be made as part of a comprehensive treatment plan; abrupt discontinuation is not recommended.

Monitoring:

• Monitor for under and over dosing
• Hepatic: Regular monitoring of liver function tests is recommended.
• If treatment goals are not being achieved, patients should be re-evaluated to determine the appropriateness of treatment or need for more intensive and structured treatment.

Patient advice:

• Advise patients to store this drug safely out of the sight and reach of children; accidental use by children is a medical emergency and can result in death.
• Advise patients that abusing this product by injecting it may cause serious withdrawal symptoms due to the presence of naloxone.
• Patients should understand the risk of life-threatening respiratory depression, and be informed as to when this risk is greatest.
• Patients should be instructed to discuss all concomitant medication use with their healthcare provider; use with benzodiazepine or other CNS depressants including alcohol may cause potentially fatal additive effects.
• This drug may cause drowsiness, dizziness, or impair thinking, or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.
• Patients should be instructed in proper disposal.

Frequently asked questions

• What are the different types of buprenorphine/naloxone?
• Can Bunavail (buprenorphine/naloxone) be cut in half?
• How long does Bunavail block opiates?
• Are Bunavail and Suboxone the same thing?
• How long does Bunavail (buprenorphine/naloxone) take to dissolve?
• What is the difference between Cassipa and Suboxone sublingual film?
• How long does Bunavail (buprenorphine/naloxone) last?