Buprenorphine and Naloxone Buccal Film

Name: Buprenorphine and Naloxone Buccal Film

Indications

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

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 physicians 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.

What do I need to tell my doctor BEFORE I take Buprenorphine and Naloxone Buccal Film?

  • If you have an allergy to buprenorphine, naloxone, or any other part of buprenorphine and naloxone buccal film.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have liver disease.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.

This is not a list of all drugs or health problems that interact with buprenorphine and naloxone buccal film.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some other side effects of Buprenorphine and Naloxone Buccal Film?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Dizziness.
  • Feeling sleepy.
  • Upset stomach or throwing up.
  • Hard stools (constipation).
  • Headache.
  • Belly pain.
  • Not able to sleep.
  • Feeling tired or weak.
  • Sweating a lot.
  • Flushing.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

How do I store and/or throw out Buprenorphine and Naloxone Buccal Film?

  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Do not freeze.
  • Store in foil pouch until ready for use.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Side effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of BUNAVAIL buccal film is supported by clinical trials using buprenorphine and naloxone sublingual tablets, and other trials using buprenorphine tablets and buprenorphine sublingual solutions, as well as an open-label study in 249 patients treated with BUNAVAIL buccal film. In total, safety data from clinical studies are available from over 3000 opioid-dependent subjects exposed to buprenorphine at doses in the range used in the treatment of opioid addiction. Few differences in the adverse event profile were noted among buprenorphine and naloxone sublingual tablets, buprenorphine sublingual tablets and a buprenorphine ethanolic sublingual solution.

The safety and tolerability of BUNAVAIL was evaluated in a 12-week clinical study of BUNAVAIL in 249 opioid-dependent subjects stabilized on buprenorphine and naloxone sublingual tablet or film dosages of buprenorphine 8-32 mg/day.

The following adverse reactions were reported to occur by at least 5% of patients in a 12-week study with BUNAVAIL: drug withdrawal syndrome, lethargy and headache.

The adverse reactions listed below represent those that were reported by >1%, but less than 5% of patients from the 12-week clinical trial while receiving BUNAVAIL. Events are classified by system organ class.

  • General disorders and administration site conditions: fatigue and chills
  • Nervous system disorders: somnolence
  • Psychiatric disorders: drug dependence and insomnia
  • Gastrointestinal disorders: constipation and oral mucosal erythema
  • Respiratory, thoracic and mediastinal disorders: rhinorrhea
  • Skin and subcutaneous tissue disorders: hyperhidrosis

The following adverse events were reported to occur by at least 5% of patients in a 4-week study with buprenorphine and naloxone sublingual tablets (Table 1).

Table 1 Adverse Events (> 5%) by Body System and Treatment Group in a 4-week Study

Body System/ Adverse
Event (COSTART)
Terminology
Buprenorphine/ naloxone sublingual tablets 16/4 mg/day N=107
n (%)
Placebo
N=107
n (%)
Body as a Whole
Asthenia 7 (6.5%) 7 (6.5%)
Chills 8 (7.5%) 8 (7.5%)
Headache 39 (36.4%) 24 (22.4%)
Infection 6 (5.6%) 7 (6.5%)
Pain 24 (22.4%) 20 (18.7%)
Pain abdomen 12 (11.2%) 7 (6.5%)
Pain back 4 (3.7%) 12 (11.2%)
Withdrawal syndrome 27 (25.2%) 40 (37.4%)
Cardiovascular System
Vasodilation 10 (9.3%) 7 (6.5%)
Digestive System
Constipation 13 (12.1%) 3 (2.8%)
Diarrhea 4 (3.7%) 16 (15.0%)
Nausea 16 (15.0%) 12 (11.2%)
Vomiting 8 (7.5%) 5 (4.7%)
Nervous System
Insomnia 15 (14.0%) 17 (15.9%)
Respiratory System
Rhinitis 5 (4.7%) 14 (13.1%)
Skin and Appendages
Sweating 15 (14.0%) 11 (10.3%)

The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solutions, over a range of doses in four months of treatment. Table 2 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study.

Table 2 Adverse Events (> 5%) by Body System and Treatment Group in a 16-week Study

Body System /Adverse Event
(COSTART Terminology)
Buprenorphine Dose*
Very Low*
(N=184)
n (%)
Low*
(N=180)
n (%)
Moderate*
(N=186)
n (%)
High*
(N=181)
n (%)
Total*
(N=731)
n (%)
Body as a Whole
Abscess 9 (5%) 2 (1%) 3 (2%) 2 (1%) 16 (2%)
Asthenia 26 (14%) 28 (16%) 26 (14%) 24 (13%) 104 (14%)
Chills 11 (6%) 12 (7%) 9 (5%) 10 (6%) 42 (6%)
Fever 7 (4%) 2 (1%) 2 (1%) 10 (6%) 21 (3%)
Flu Syndrome 4 (2%) 13 (7%) 19 (10%) 8 (4%) 44 (6%)
Headache 51 (28%) 62 (34%) 54 (29%) 53 (29%) 220 (30%)
Infection 32 (17%) 39 (22%) 38 (20%) 40 (22%) 149 (20%)
Injury Accidental 5 (3%) 10 (6%) 5 (3%) 5 (3%) 25 (3%)
Pain 47 (26%) 37 (21%) 49 (26%) 44 (24%) 177 (24%)
Withdrawal Syndrome 45 (24%) 40 (22%) 41 (22%) 36 (20%) 162 (22%)
Digestive System
Constipation 10 (5%) 23 (13%) 23 (12%) 26 (14%) 82 (11%)
Diarrhea 19 (10%) 8 (4%) 9 (5%) 4 (2%) 40 (5%)
Dyspepsia 6 (3%) 10 (6%) 4 (2%) 4 (2%) 24 (3%)
Nausea 12 (7%) 22 (12%) 23 (12%) 18 (10%) 75 (10%)
Vomiting 8 (4%) 6 (3%) 10 (5%) 14 (8%) 38 (5%)
Nervous System
Anxiety 22 (12%) 24 (13%) 20 (11%) 25 (14%) 91 (12%)
Depression 24 (13%) 16 (9%) 25 (13%) 18 (10%) 83 (11%)
Dizziness 4 (2%) 9 (5%) 7 (4%) 11 (6%) 31 (4%)
Insomnia 42 (23%) 50 (28%) 43 (23%) 51 (28%) 186 (25%)
Nervousness 12 (7%) 11 (6%) 10 (5%) 13 (7%) 46 (6%)
Somnolence 5 (3%) 13 (7%) 9 (5%) 11 (6%) 38 (5%)
Respiratory System
Cough Increase 5 (3%) 11 (6%) 6 (3%) 4 (2%) 26 (4%)
Pharyngitis 6 (3%) 7 (4%) 6 (3%) 9 (5%) 28 (4%)
Rhinitis 27 (15%) 16 (9%) 15 (8%) 21 (12%) 79 (11%)
Skin and Appendages
Sweat 23 (13%) 21 (12%) 20 (11%) 23 (13%) 87 (12%)
Special Senses
Runny Eyes 13 (7%) 9 (5%) 6 (3%) 6 (3%) 34 (5%)
*Sublingual solution. Doses in this table cannot necessarily be delivered in film form, but for comparison purposes: “very low” dose (1 mg solution) would be less than a tablet dose of 2 mg; “low” dose (4 mg solution) approximates a 6 mg tablet dose; “moderate” dose (8 mg solution) approximates a 12 mg tablet dose; “high” dose (16 mg solution) approximates a 24 mg tablet dose.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of buprenorphine and naloxone sublingual tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate a causal relationship to drug exposure.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in ZUBSOLV.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Bunavail (Buprenorphine and Naloxone Buccal Film)

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