Bunavail Generic Name: buprenorphine and naloxone buccal film Brand Name: Bunavail Bunavail (Buprenorphine and Naloxone Buccal Film) side effects drug center Related Drugs Cassipa Dolophine Methadone Hydrochloride Methadose Methadose Oral Concentrate Probuphine Revia Suboxone Subutex Vivitrol Health Resources Drug Abuse Teen Drug Abuse PROFESSIONAL CONSUMER SIDE EFFECTS Overview Professional Information Bunavail Side Effects Center What Is Bunavail? Bunavail (buprenorphine and naloxone) Buccal Film is a combination of an opioid partial agonist-antagonist and an opioid receptor antagonist used for the maintenance treatment of opioid dependence and should be used as part of a complete treatment plan to include counseling and psychosocial support. What Are Side Effects of Bunavail? Common side effects of Bunavail include: headache, drug withdrawal syndrome, lethargy (lack of energy), weakness, increased sweating, constipation, sleep problems (insomnia), fatigue and sleepiness, tongue pain or redness, numbness inside your mouth, runny or stuffy nose, watery eyes, nausea, vomiting, depression, anxiety, swelling in your arms or legs, abscess, chills, fever, flu symptoms, infection, back pain, diarrhea, indigestion, dizziness, insomnia, nervousness, cough, and sore throat. Dosage for Bunavail Bunavail buccal film is applied to the buccal mucosa as a single daily dose. What Drugs, Substances, or Supplements Interact with Bunavail? Bunavail may interact with azole antifungals such as ketoconazole, macrolide antibiotics such as erythromycin, HIV protease inhibitors, efavirenz, phenobarbital, carbamazepine, phenytoin, rifampicin, NNRTIs such as efavirenz and delavirdine, and benzodiazepines. Tell your doctor all medications and supplements you use. Bunavail During Pregnancy and Breastfeeding Tell your doctor if you are pregnant or plan to become pregnant before taking Bunavail. If you become pregnant while taking this drug, tell your doctor as there may be significant risks to you and your baby; your baby may have withdrawal symptoms at birth. This drug can pass into your breast milk and may harm a nursing baby. Monitor your baby for increased sleepiness and breathing problems. Consult your doctor before breastfeeding. Withdrawal symptoms may occur if you suddenly stop taking this medication. Additional Information Our Bunavail (buprenorphine and naloxone) Buccal Film Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication. Bunavail Consumer Information Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up. Call your doctor at once or seek emergency medical attention if you have: weak or shallow breathing, breathing that stops during sleep; a light-headed feeling, like you might pass out; confusion, loss of coordination, extreme weakness; blurred vision, slurred speech; liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); high levels of serotonin in the body--agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea; low cortisol levels--nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness; or opioid withdrawal symptoms--shivering, goose bumps, increased sweating, feeling hot or cold, runny nose, watery eyes, diarrhea, muscle pain. Serious breathing problems may be more likely in older adults and those who are debilitated or have wasting syndrome or chronic breathing disorders. Common side effects may include: dizziness, drowsiness, blurred vision, feeling drunk, trouble concentrating; withdrawal symptoms; tongue pain, redness or numbness inside your mouth; nausea, vomiting, constipation; headache, back pain; fast or pounding heartbeats, increased sweating; or sleep problems (insomnia). This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Read the entire detailed patient monograph for Bunavail (Buprenorphine and Naloxone Buccal Film) Bunavail Professional Information SIDE EFFECTS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS] Respiratory and CNS Depression [see WARNINGS AND PRECAUTIONS] Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS] Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS] Opioid Withdrawal [see WARNINGS AND PRECAUTIONS] Hepatitis, Hepatic Events [see WARNINGS AND PRECAUTIONS] Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS] Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS] Elevation of Cerebrospinal Fluid Pressure [see WARNINGS AND PRECAUTIONS] Elevation of Intracholedochal Pressure [see WARNINGS AND PRECAUTIONS] 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 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. 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 to 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 mg/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 a 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 5 (3%) 37 (21%) 49 (26%) 44 (24%) 177 (24%) Pain Back 18 (10%) 29 (16%) 28 (15%) 27 (15%) 102 (14%) 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. 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 BUNAVAIL. Androgen Deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY]. Local Reactions: Glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis DRUG INTERACTIONS Table 3 includes clinically significant drug interactions with BUNAVAIL. Table 3. Clinically Significant Drug Interactions Benzodiazepine and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines and other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments [see WARNINGS AND PRECAUTIONS]. If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in treatment for opioid use disorder [see WARNINGS AND PRECAUTIONS]. Examples: Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids. Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of BUNAVAIL is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see CLINICAL PHARMACOLOGY], potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. Intervention: If concomitant use is necessary, consider dosage reduction of BUNAVAIL until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the BUNAVAIL dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see CLINICAL PHARMACOLOGY], potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the BUNAVAIL dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider BUNAVAIL dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects. Intervention: Patients who are on chronic BUNAVAIL treatment should have their dose monitored if NNRTIs are added to their treatment regimen. Examples: efavirenz, nevirapine, etravirine, delavirdine Antiretrovirals: Protease inhibitors (PIs) Clinical Impact: Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetics and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post-marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. Intervention: Monitor patients taking BUNAVAIL and atazanavir with and without ritonavir, and reduce dose of BUNAVAIL if warranted. Examples: atazanavir, ritonavir Antiretrovirals: Nucleoside reverse transcriptase inhibitors (NRTIs) Clinical Impact: Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected. Intervention: None Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue BUNAVAIL if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS AND PRECAUTIONS] Intervention: The use of BUNAVAIL is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Muscle Relaxants Clinical Impact: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients receiving muscle relaxants and BUNAVAIL for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of BUNAVAIL and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, strongly consider prescribing naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS]. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when BUNAVAIL is used concomitantly with anticholinergic drugs. Drug Abuse And Dependence Controlled Substance BUNAVAIL contains buprenorphine, a Schedule III substance under the Controlled Substances Act. 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. Abuse Buprenorphine, like morphine and other opioids, has the potential for being abused and is subject to criminal diversion. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion. Healthcare professionals should contact their state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment. Abuse of buprenorphine poses a risk of overdose and death. This risk is increased with the abuse of buprenorphine and alcohol and other substances, especially benzodiazepines. The healthcare provider may be able to more easily detect misuse or diversion by maintaining records of medication prescribed including date, dose, quantity, frequency of refills, and renewal requests of medication prescribed. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper handling and storage of the medication are appropriate measures that help to limit abuse of opioid drugs. Dependence Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by moderate withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset [see WARNINGS AND PRECAUTIONS]. Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy [see WARNINGS AND PRECAUTIONS]. Read the entire FDA prescribing information for Bunavail (Buprenorphine and Naloxone Buccal Film) &Copy; Bunavail Patient Information is supplied by Cerner Multum, Inc. and Bunavail Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
