Plain-language summary, compiled from the cited regulatory records
Buprenorphine is an opioid medication classified as an oripavine derivative [1]. It is approved for the treatment of opioid dependence and is specifically noted as being preferred for the induction phase of treatment [1]. Buprenorphine should be utilized within a comprehensive treatment program that includes counseling and psychosocial support [1].
This medication is available under various brand names [1]. In the past 12 months, there have been 5,323 adverse event reports associated with buprenorphine [2]. The most frequently reported events include off-label use, drug withdrawal syndrome, drug ineffectiveness, death, and nausea [2].
This is not medical advice. Consult a qualified healthcare professional.
GBOfficial regulatory label· revised May 29, 2026[1]
Moderate to severe cancer pain and severe pain which does not respond to non-opioid analgesics. Bupeaze is not suitable for the treatment of acute pain.
How to take
GB
CACanada· Health Canada
20 products
Uses
CAOfficial regulatory label· revised December 31, 2025[2]
SUBLOCADE (buprenorphine solution (extended-release) for injection) is indicated for the management of moderate to severe opioid use disorder in adult patients. SUBLOCADE should be used as part of a complete treatment plan that includes counselling and psychosocial support.
SUBLOCADE must only be administered subcutaneously by a healthcare professional (see 4 DOSAGE AND ADMINISTRATION). 1 Pediatrics Pediatrics (˂18 years of age): No data are available in patients under 18 years of age. SUBLOCADE is not indicated in pediatric patients.
2 Geriatrics Geriatrics (≥ 65 years of age): There were no patients ≥ 65 years of age in the controlled clinical trial of SUBLOCADE. In general, drug use for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, respiratory and/or cardiac function, concomitant disease or other drug therapies.
If the decision is made to prescribe SUBLOCADE to individuals 65 years of age or older, patients should be monitored for signs and symptoms of toxicity or overdose.
USUnited States· FDA
9 products
Uses
USOfficial regulatory label· revised May 22, 2026[3]
1 INDICATIONS AND USAGE Buprenorphine and naloxone sublingual tablets are indicated for 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.
Buprenorphine and naloxone sublingual tablets contain buprenorphine, a partial opioid agonist, and naloxone, an opioid antagonist, and is indicated for the maintenance treatment of opioid dependence. ( 1 ) Buprenorphine and naloxone sublingual tablets should be used as part of a complete treatment plan that includes counseling and psychosocial support.
( 1 )
How to take
EUEuropean Union· EMA
4 products
Uses
EUOfficial regulatory label· revised January 29, 2026[4]
Substitution treatment for opioid drug dependence, within a framework of medical, social and psychological treatment. The intention of the naloxone component is to deter intravenous misuse. Zubsolv is indicated in adults and adolescents over 15 years of age who have agreed to be treated for addiction.
How to take
Drug interactions
Known interactions involving Buprenorphine. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[2]Health Canada (DPD) · 02483084 · revised December 31, 2025
[3]FDA DailyMed · 072b2c2e-a564-4b… · revised May 22, 2026 [PDF]
[4]European Medicines Agency · EMEA/H/C/004407 · revised January 29, 2026
[5]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Posology Patients over 18 years of age The lowest possible dosage providing adequate pain relief should be given. 5 micrograms/h and Bupeaze 70 micrograms/h. Initial dose selection: patients who have previously not received any analgesics should start with the lowest transdermal patch strength (Bupeaze 35 micrograms/h).
Patients previously given a WHO step-I analgesic (non-opioid) or a step-II analgesic (weak opioid) should also begin with Bupeaze 35 micrograms/h. According to the WHO recommendations, the administration of a non-opioid analgesic can be continued, depending on the patient's overall medical condition.
When switching from a step-III analgesic (strong opioid) to Bupeaze and choosing the initial transdermal patch strength, the nature of the previous medication, administration and the mean daily dose should be taken into account in order to avoid the recurrence of pain.
In general it is advisable to titrate the dose individually, starting with the lowest transdermal patch strength (Bupeaze 35 micrograms/h). 1). To allow for individual dose adaptation in an adequate time period sufficient supplementary immediate release analgesics should be made available during dose titration.
The necessary strength of Bupeaze must be adapted to the requirements of the individual patient and checked at regular intervals. After application of the first Bupeaze transdermal patch the buprenorphine serum concentrations rise slowly both in patients who have been treated previously with analgesics and in those who have not.
Therefore initially, there is unlikely to be a rapid onset of effect. Consequently, a first evaluation of the analgesic effect should only be made after 24 hours. The previous analgesic medication (with the exception of transdermal opioids) should be given in the same dose during the first 12 hours after switching to Bupeaze and appropriate rescue medication on demand in the following 12 hours.
Dose titration and maintenance therapy Bupeaze should be replaced after 96 hours (4 days) at the latest. g. always on Monday morning and Thursday evening. The dose should be titrated individually until analgesic efficacy is attained. If analgesia is insufficient at the end of the initial application period, the dose may be increased, either by applying more than one transdermal patch of the same strength or by switching to the next transdermal patch strength.
At the same time no more than two transdermal patches regardless of the strength should be applied. e. the total amount of opioids required, and the dosage adjusted accordingly. g. 2 mg buprenorphine sublingual tablets every 24 hours in addition to the transdermal patch.
6 mg sublingual buprenorphine is necessary, the next strength should be used. Paediatric population As buprenorphine has not been studied in patients under 18 years of age, the use of the medicinal product in patients below this age is not recommended.
Elderly patients No dosage adjustment of Bupeaze is required for elderly patients. Patients with renal insufficiency Since the pharmacokinetics of buprenorphine is not altered during the course of renal failure, its use in patients with renal insufficiency, including dialysis patients, is possible.
Patients with hepatic insufficiency Buprenorphine is metabolised in the liver. The intensity and duration of its action may be affected in patients with impaired liver function. Therefore patients with liver insufficiency should be carefully monitored during treatment with Bupeaze.
Method of administration Treatment goals and discontinuation Before initiating treatment with Bupeaze, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.
During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with Bupeaze, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.
4). Bupeaze should be applied to non-irritated, clean skin on a non-hairy flat surface, but not to any parts of the skin with large scars. Preferable sites on the upper body are: upper back or below the collar-bone on the chest. Any remaining hairs should be cut off with a pair of scissors (not shaved).
If the site of application requires cleansing, this should be done with water. Soap or any other cleansing agents should not be used. Skin preparations that might affect adhesion of the transdermal patch to the area selected for application of Bupeaze should be avoided.
The skin must be completely dry before application. Bupeaze is to be applied immediately after removal from the sachet. Following removal of the release liner, the transdermal patch should be pressed firmly in place with the palm of the hand for approximately 30 seconds.
The transdermal patch will not be […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised May 29, 2026[1]
The following adverse reactions were reported after administration of buprenorphine in clinical studies and from postmarketing surveillance. The most commonly reported local adverse reactions were erythema and pruritus. g. g. pricking or burning skin sensation) Very rare muscle fasciculation, parageusia Not known Seizures Eye disorders Rare visual disturbance, blurring of vision, eyelid oedema Very rare miosis Ear and labyrinth disorders Very rare ear pain Cardiac/Vascular disorders Uncommon circulatory disorders (such as hypotension or, rarely, even circulatory collapse) Rare hot flushes Respiratory, thoracic and mediastinal disorders Common dyspnoea Rare respiratory depression Very rare hyperventilation, hiccups Gastrointestinal disorders Very common nausea Common vomiting, constipation Uncommon dry mouth Rare pyrosis Very rare retching Skin and subcutaneous tissue disorders Very common erythema, pruritus Common exanthema, diaphoresis Uncommon rash Rare urticaria Very rare pustules, vesicles Not known dermatitis contact, application skin discolouration Renal and urinary disorders Uncommon urinary retention, micturition disorders Reproductive system and breast disorders Rare decreased erection General disorders and administration site conditions Common oedema, tiredness Uncommon weariness Rare withdrawal symptoms*, administration site reactions Very rare thoracic pain * see section c) c) In some cases delayed allergic reactions occurred with marked signs of inflammation.
In such cases treatment with buprenorphine should be terminated. Drug dependence Repeated use of Bupeaze can lead to drug dependence, even at therapeutic doses. 4). Buprenorphine has a low risk of dependence. After discontinuation of buprenorphine, withdrawal symptoms are unlikely.
This is due to the very slow dissociation of buprenorphine from the opiate receptors and to the gradual decrease of buprenorphine serum concentrations (usually over a period of 30 hours after removal of the last transdermal patch).
However, after long-term use of buprenorphine withdrawal symptoms, similar to those occurring during opiate withdrawal, cannot be entirely excluded. These symptoms include: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastro-intestinal disorders.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised May 29, 2026[1]
Buprenorphine must only be used with particular caution in acute alcohol intoxication, convulsive disorders, in patients with head injury, shock, a reduced level of consciousness of uncertain origin, increased intracranial pressure without the possibility of ventilation.
Buprenorphine occasionally causes respiratory depression. Therefore care should be taken when treating patients with impaired respiratory function or patients receiving medicinal products which can cause respiratory depression. Buprenorphine has a substantially lower dependence liability than pure opioid agonists.
In healthy volunteer and patient studies with buprenorphine, withdrawal reactions have not been observed. 8). These symptoms are: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disorders. In patients abusing opioids, substitution with buprenorphine may prevent withdrawal symptoms.
This has resulted in some abuse of buprenorphine and caution should be exercised when prescribing it to patients suspected of having drug abuse problems. Buprenorphine may lower the seizure threshold in patients with a history of seizure disorder.
Post-operative opioid use (PPOU) and opioid-induced ventilatory impairment (OIVI) Do not use for acute post-operative pain owing to the increased risk of persistent post- operative opioid use (PPOU) and opioid-induced ventilatory impairment (OIVI).
Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as Bupeaze. Repeated use of Bupeaze can lead to OUD.
A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. Abuse or intentional misuse of Bupeaze may result in overdose and/or death. g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD.
If these signs occur, patients should be advised to contact their physician. g. too early requests for refills). This includes the review of concomitant opioids and psycho- active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised May 29, 2026[1]
5) - patients suffering from myasthenia gravis - patients suffering from delirium tremens. 6)
This is not medical advice. Consult a qualified healthcare professional.
CAOfficial regulatory label· revised December 31, 2025[2]
). 1 Pediatrics Pediatrics (˂18 years of age): No data are available in patients under 18 years of age. SUBLOCADE is not indicated in pediatric patients. 2 Geriatrics Geriatrics (≥ 65 years of age): There were no patients ≥ 65 years of age in the controlled clinical trial of SUBLOCADE.
In general, drug use for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, respiratory and/or cardiac function, concomitant disease or other drug therapies. If the decision is made to prescribe SUBLOCADE to individuals 65 years of age or older, patients should be monitored for signs and symptoms of toxicity or overdose.
2 CONTRAINDICATIONS SUBLOCADE is contraindicated in patients: • who are hypersensitive to this drug or any ingredient in the formulation, including any non- medicinal ingredient, or any component of Indivior’s proprietary delivery system.
For a complete listing, see
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised December 31, 2025[2]
, Clinical Trial Findings, Liver Enzyme Abnormalities). Prior to initiation of SUBLOCADE, liver function tests should be conducted to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. An etiological evaluation should be performed when a hepatic event is suspected.
Use in Patients with Impaired Hepatic Function The effect of hepatic impairment on the pharmacokinetics of SUBLOCADE has not been studied. In a pharmacokinetic study with sublingual buprenorphine, compared to control subjects, buprenorphine plasma levels were found to be notably higher and the half-life was found to be notably longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment.
Because of the long-acting nature of the product, adjustments to SUBLOCADE dosing are not rapidly reflected in plasma buprenorphine levels. Because buprenorphine levels cannot be rapidly decreased, caution should be exercised in treating patients with pre-existing moderate hepatic impairment with SUBLOCADE.
SUBLOCADE should not be given to patients with pre- existing severe hepatic impairment (see 2 CONTRAINDICATIONS). Patients with moderate hepatic impairment or those who develop moderate hepatic impairment while being treated with SUBLOCADE should be monitored for several months for signs and symptoms of toxicity or overdose caused by increased levels of buprenorphine.
3 Pharmacokinetics, Special Populations and Conditions). SUBLOCADE (buprenorphine) Page 22 of 64 Immune Allergic Reactions Cases of hypersensitivity to buprenorphine-containing products have been reported both in clinical trials and in the post-marketing experience.
Cases of bronchospasm, angioneurotic oedema, and anaphylactic shock have been reported. The most common signs and symptoms include rashes, hives, and pruritus. A history of hypersensitivity to buprenorphine is a contraindication to the use of SUBLOCADE (see 2 CONTRAINDICATIONS).
Monitoring and Laboratory Tests Baseline liver function tests and documentation of viral hepatitis status should be performed prior to commencing therapy. Regular monitoring of liver function is also recommended. Patients who are positive for viral hepatitis, on concomitant medicinal products and/or have existing liver dysfunction are at greater risk of liver injury.
Neonatal Opioid Withdrawal Syndrome Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medically-authorized or illicit. Unlike opioid withdrawal syndrome in adults, NOWS may be life threatening if not recognized and treated in the neonate.
1 Pregnant Women). NOWS may present as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth.
The duration and severity of NOWS may vary. Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered to minimize the risk of respiratory depression or withdrawal syndrome in neonates. Based on the currently available data, the incidence of NOWS is not clear and there does not appear to be a dose-response relationship.
1 Pregnant Women). This risk of NOWS and the risk of exposure to SUBLOCADE during pregnancy must be balanced against the risk of untreated opioid addiction. 1 Pregnant Women). Neurologic Interactions with Central Nervous System Depressants (including benzodiazepines and alcohol) Buprenorphine should be used with caution during concomitant administration of other opioids, general anesthetics, phenothiazines and other tranquilizers, sedative-hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, benzodiazepines, gabapentin, pregabalin, baclofen, centrally active antiemetics and other CNS depressants.
Respiratory depression, hypotension and profound sedation, coma or death may result. Alcohol should not be consumed with SUBLOCADE as it may increase the chance of experiencing dangerous side effects, including death (see 2 CONTRAINDICATIONS, 8 ADVERSE REACTIONS and
CAOfficial regulatory label· Warnings and precautions· revised December 31, 2025[2]
). • Limitations of Use SUBLOCADE should never be handed to patients and should only be administered by a healthcare professional. • Addiction, Abuse, and Misuse Abuse and diversion of buprenorphine component of SUBLOCADE is possible.
All patients should be monitored regularly for the development of these behaviours or conditions (see 7 WARNINGS AND PRECAUTIONS). • Use During Pregnancy o Women of childbearing potential should use reliable and effective birth control o Inform patients to tell their physician immediately should they become pregnant.
1 Special Populations, 16 NON-CLINICAL TOXICOLOGY). • Life-threatening Respiratory Depression: OVERDOSE Serious, life-threatening, or fatal respiratory depression may occur with use of SUBLOCADE. Infants exposed in-utero or through breast milk are at risk of life- threatening respiratory depression upon delivery or when nursed.
Patients should be monitored for respiratory depression, especially immediately after SUBLOCADE injection and following a dose increase. Misuse or abuse of SUBLOCADE may pose a significant risk of overdose and death (see 7 WARNINGS AND PRECAUTIONS).
Further instruct patients of the hazards related to taking opioids including fatal overdose. • Accidental Exposure Accidental exposure to even one dose of SUBLOCADE by individuals not physically dependent on opioids, especially children, can result in a fatal overdose of buprenorphine (see 4 DOSAGE AND ADMINISTRATION, 12 SPECIAL HANDLING INSTRUCTIONS for instructions on proper disposal).
• Interaction with Alcohol The co-ingestion of alcohol with SUBLOCADE should be avoided as it may result in dangerous additive effects, causing serious injury or death (see 7 WARNINGS AND PRECAUTIONS and 9 DRUG INTERACTIONS). • Neonatal Opioid Withdrawal Syndrome Prolonged maternal use of SUBLOCADE during pregnancy can result in a neonatal opioid withdrawal syndrome, which may be life threatening (see 7 WARNINGS AND PRECAUTIONS).
2 Breast-feeding). • Interaction with other Central Nervous System Depressants SUBLOCADE (buprenorphine) Page 6 of 64 Risks from concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see 7 WARNINGS AND PRECAUTIONS, Neurologic and DRUG INTERACTIONS).
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised December 31, 2025[2]
SUBLOCADE is contraindicated in patients: • who are hypersensitive to this drug or any ingredient in the formulation, including any non- medicinal ingredient, or any component of Indivior’s proprietary delivery system. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
g. acute or severe bronchial asthma, chronic obstructive airway, status asthmaticus, acute respiratory depression and/or cor pulmonale. • with severe hepatic impairment. • with acute alcoholism or delirium tremens. g. g. ileus of any type).
g. acute appendicitis or pancreatitis). Patients with severe central nervous system (CNS) depression, increased cerebrospinal or intracranial pressure, and head injury. • taking monoamine oxidase (MAO) inhibitors (or within 14 days of such therapy).
• with convulsive or seizure disorders. • with congenital Long QT Syndrome or QT prolongation at baseline. • with uncorrected hypokalemia, hypomagnesemia, or hypocalcemia. SUBLOCADE (buprenorphine) Page 5 of 64
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised May 22, 2026[3]
2 DOSAGE AND ADMINISTRATION Administer buprenorphine and naloxone sublingual tablet sublingually as a single daily dose. , naloxone, nalmefene) at the time buprenorphine and naloxone sublingual tablet are initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose.
2 ) To avoid precipitating withdrawal, induction with buprenorphine sublingual tablets should be undertaken when objective and clear signs of withdrawal are evident. 3 ) The maintenance dose of buprenorphine and naloxone sublingual tablets is generally in the range of 4 mg/1 mg to 24 mg/6 mg per day and should be based on clinical response.
3 ) Administer buprenorphine and naloxone sublingual tablets as directed in the Full Prescribing Information. 4 ) When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal. 1 Important Dosage and Administration Information Buprenorphine and naloxone sublingual tablet is administered sublingually as a single daily dose.
Buprenorphine and naloxone sublingual tablets should be used in patients who have been initially inducted using buprenorphine sublingual tablets. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits.
, naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider recommending or prescribing an overdose reversal agent for the emergency treatment of opioid overdose, both when initiating and renewing treatment with buprenorphine and naloxone sublingual tablets.
2) ]. 2) ] . There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.
Advise patients and caregivers that opioid overdose reversal agents, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with buprenorphine and naloxone sublingual tablets itself. Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of buprenorphine and naloxone sublingual tablets and its affinity for the mu‐opioid receptor [see Overdosage (10) ].
5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms. After treatment induction to the recommended dose of 16 mg/4 mg buprenorphine/naloxone, dosing should be further adjusted based on the individual patient and clinical response.
The maintenance dose of buprenorphine and naloxone sublingual tablets is generally in the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day. Dosages higher than 24 mg/6 mg daily have not been investigated in randomized clinical trials but may be appropriate for some patients.
When determining the prescription quantity for unsupervised administration, consider the patient's level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.
There is no maximum recommended duration of maintenance treatment. Patients may require treatment indefinitely and should continue for as long as patients are benefiting and the use of buprenorphine and naloxone sublingual tablets contributes to the intended treatment goals.
4 Method of Administration Buprenorphine and naloxone sublingual tablets must be administered whole. Do not cut, chew, or swallow buprenorphine and naloxone sublingual tablets. Advise patients not to eat or drink anything until the tablet is completely dissolved.
Buprenorphine and naloxone sublingual tablet should be placed under the tongue until it is dissolved. For doses requiring the use of more than two tablets, patients are advised to either place all the tablets at once or alternatively (if they cannot fit in more than two tablets comfortably), place two tablets at a time under the tongue.
Either way, the patients should continue to hold the tablets under the tongue until they dissolve; swallowing the tablets reduces the bioavailability of the drug. To ensure consistency in bioavailability, patients should follow the same manner of dosing with continued use of the product.
Proper administration technique should be demonstrated to the patient. Advise patients to do the following after the product has completely dissolved in the oral mucosa: take a sip of water, swish gently around the teeth and gums, and swallow.
2) , Information for Patients (17) , and the Medication Guide ]. 5 Clinical Supervision Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient's clinical stability permits.
Buprenorphine and naloxone sublingual tablets are subject to diversion and abuse. When determining the prescription quantity for unsupervised administration, consider the patient's level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.
, at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits.
Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress. , urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate.
A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the healthcare provider's evaluation of treatment outcomes and objectives such as: Absence of medication toxicity Absence of medical or behavioral adverse effects Responsible handling of medications by the patient Patient's compliance with all elements of the treatment plan (including recovery-oriented activities, psychotherapy, and/or other psychosocial modalities) Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use) If treatment goals are not being achieved, the healthcare provider should re-evaluate the appropriateness of continuing the current treatment.
6 Unstable Patients Healthcare providers will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the healthcare provider does not feel that he/she has the expertise to manage the patient.
In such cases, the healthcare provider may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.
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. 7 Discontinuing Treatment The decision to discontinue therapy with buprenorphine and naloxone sublingual tablets after a period of maintenance should be made as part of a comprehensive treatment plan.
Advise patients of the potential to relapse to illicit drug use following discontinuation of opioid agonist/partial agonist medication-assisted treatment. 7) ] . 8 Switching between Buprenorphine and Naloxone Sublingual Film and Buprenorphine and Naloxone Sublingual Tablets Patients being switched between buprenorphine and naloxone sublingual tablets and buprenorphine and naloxone sublingual film should be started on the same dosage as the previously administered product.
However, dosage adjustments may be necessary when switching between products. Because of the potentially greater relative bioavailability of buprenorphine and naloxone sublingual film compared to buprenorphine and naloxone sublingual tablets, patients switching from buprenorphine and naloxone sublingual tablets to buprenorphine and naloxone sublingual film should be monitored for over-medication.
Those switching from buprenorphine and naloxone sublingual film to buprenorphine and naloxone sublingual tablets should be monitored for withdrawal or other indications of under dosing. In clinical studies, pharmacokinetics of buprenorphine and naloxone sublingual film was similar to the respective dosage strengths of buprenorphine and naloxone sublingual tablets; although not all doses and dose combinations met bioequivalence criteria.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 5,323 reports total. [5]
Off Label Use 558
Drug Withdrawal Syndrome 381
Drug Ineffective 367
Death 365
Nausea 363
Maternal Exposure During Pregnancy 335
Pain 319
Dizziness 304
Confusional State 302
Asthenia 301
Dental Caries 300
Headache 299
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised May 22, 2026[3]
18) ] Adverse events commonly observed with administration of buprenorphine/naloxone are oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.
1 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 buprenorphine and naloxone sublingual tablets was evaluated in 497 opioid-dependent subjects. The prospective evaluation of buprenorphine and naloxone sublingual tablets was supported by clinical trials using buprenorphine tablets without naloxone and other trials using buprenorphine sublingual solutions.
In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction. Few differences in adverse event profile were noted between buprenorphine and naloxone sublingual tablets and buprenorphine sublingual tablets or buprenorphine administered as a sublingual solution.
The following adverse events were reported to occur by at least 5% of patients in a 4-week study (Table 1). Table 1. 3%) The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solution, 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 Sublingual solution.
2 Postmarketing Experience The following adverse reactions have been identified during post approval use of buprenorphine/naloxone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most frequently reported postmarketing adverse event not observed in clinical trials was peripheral edema.
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 buprenorphine and naloxone sublingual tablets. 2) ] . Local reactions : dental decay (including caries, tooth fracture, and tooth loss), glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis.
Hypoglycemia :
Cases of hypoglycemia have been reported in patients taking opioids. , diabetes). 2) ] .
USOfficial regulatory label· Warnings and precautions· revised May 22, 2026[3]
5 WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids. Clinical monitoring appropriate to the patient's level of stability is essential. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors.
Multiple refills should not be prescribed early in treatment or without appropriate patient follow-up visits. 1 ) Respiratory Depression: Life-threatening respiratory depression and death have occurred in association with buprenorphine use.
Warn patients of the potential danger of self-administration of benzodiazepine or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets. 3 ).
Unintentional Pediatric Exposure:
Store buprenorphine and naloxone sublingual tablets safely out of the sight and reach of children. Buprenorphine can cause severe, possibly fatal, respiratory depression in children. 4 ) Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
5 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. 6 ) Risk of Opioid Withdrawal with Abrupt Discontinuation: If treatment is temporarily interrupted or discontinued, monitor patients for withdrawal and treat appropriately.
7 ) Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to initiation and during treatment and evaluate suspected hepatic events. 8 ) Precipitation of Opioid Withdrawal Signs and Symptoms: An opioid withdrawal syndrome is likely to occur with parenteral misuse of buprenorphine and naloxone sublingual tablets by individuals physically dependent on full opioid agonists, or by sublingual administration before the agonist effects of other opioids have subsided.
10 ) Risk of Overdose in Opioid-Naïve Patients: Buprenorphine and naloxone sublingual tablet is not appropriate as an analgesic. There have been reported deaths of opioid naïve individuals who received a 2 mg sublingual dose. 1 Addiction, Abuse, and Misuse Buprenorphine and naloxone sublingual tablets contain buprenorphine, a schedule III controlled substance that can be abused in a manner similar to other opioids, legal or illicit.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised May 22, 2026[3]
9) ] . Hypersensitivity to buprenorphine or naloxone. ( 4 )
This is not medical advice. Consult a qualified healthcare professional.
Treatment must be under the supervision of a physician experienced in the management of opioid dependence/addiction. Zubsolv is not interchangeable with other buprenorphine products, as different buprenorphine products have different bioavailability.
Therefore, the dose in mg can differ between products. Once the appropriate dose has been identified for a patient with a specific buprenorphine product, that product should not be exchanged with another product. 2). 2). e. long- or short-acting opioid), the time since last opioid use and the degree of opioid dependence.
g. by 4 a score indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS). • For patients dependent upon heroin or short-acting opioids, the first dose of buprenorphine/naloxone must be taken when signs of withdrawal appear, but not less than 6 hours after the patient last used opioids.
• For patients receiving methadone, the dose of methadone must be reduced to a maximum of 30 mg/day before beginning buprenorphine/naloxone therapy. The long half-life of methadone should be considered when starting buprenorphine/naloxone.
The first dose of buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone.
71 mg a day. 71 mg may be administered on day one depending on the individual patient’s requirement. During the initiation of treatment, daily supervision of dosing is recommended to ensure proper sublingual placement of the dose and to observe patient response to treatment as a guide to effective dose titration according to clinical effect.
Dosage stabilisation and maintenance therapy Following treatment induction on day 1, the patient must be rapidly stabilised on an adequate maintenance dose by titrating to achieve a dose that holds the patient in treatment and suppresses opioid withdrawal effects and is guided by reassessment of the clinical and psychological status of the patient.
g. 7 mg). During maintenance therapy, it may be necessary to periodically restabilise the patient on a new maintenance dose in response to changing patient needs. 18 mg strength is intended to be used to fine tune the dose for patients especially during tapering of treatment or in case of tolerability issues during titration.
Physicians are encouraged to prescribe a single tablet once daily regimen where possible to minimise risk of diversion. Less than daily dosing After a satisfactory stabilisation has been achieved the frequency of Zubsolv dosing may be decreased to dosing every other day at twice the individually titrated daily dose.
In some patients, after a satisfactory stabilisation has been achieved, the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and Friday. 2 mg buprenorphine. 7 mg buprenorphine /day may not find this regimen adequate.
Medical withdrawal After a satisfactory stabilisation has been achieved, if the patient agrees, the dose may be reduced gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The availability of six different tablet strengths supports individual dose titration and tapering.
Patients should be monitored following medical withdrawal because of the potential for relapse. Special populations 5 Elderly The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not been established.
No recommendation on posology can be made. 2). 2). Renal impairment Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 2). Paediatric population The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not been established.
No data are available. 4). The tablet is to be placed […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised January 29, 2026[4]
e. insomnia, headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious. 5%) reported adverse reactions and adverse reactions reported during post-marketing surveillance.
The frequency of possible adverse reactions listed below is defined using the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1 000 to <1/100), Rare (≥/10 000 to <1/1 000), Very rare (<1/10 000), Not known (cannot be estimated from available data).
4). 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
EUOfficial regulatory label· Warnings and precautions· revised January 29, 2026[4]
Misuse, abuse and diversion Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some risks of misusers and abusers include overdose, spread of blood borne viral or localised and systemic infections, respiratory depression and hepatic injury.
Buprenorphine misuse by someone other than the intended patient poses the additional risk of new drug dependent individuals using buprenorphine as the primary drug of abuse, and may occur if the medicinal product is distributed for illicit use directly by the intended patient or if the medicinal product is not safeguarded against theft.
Sub-optimal treatment with buprenorphine/naloxone may prompt medicinal product misuse by the patient, leading to overdose or treatment dropout. A patient who is under-dosed with buprenorphine/naloxone may continue responding to uncontrolled withdrawal symptoms by self- 6 medicating with opioids, alcohol or other sedative-hypnotics such as benzodiazepines.
To minimize the risk of misuse, abuse and diversion, appropriate precautions should be taken when prescribing and dispensing buprenorphine, such as to avoiding prescribing multiple refills early in treatment, and to conducting patient follow-up visits with clinical monitoring that is appropriate to the patient's needs.
Combining buprenorphine with naloxone in Zubsolv is intended to deter misuse and abuse of the buprenorphine. Intravenous or intranasal misuse of Zubsolv is expected to be less likely than with buprenorphine alone since the naloxone in Zubsolv can precipitate withdrawal in individual’s dependent on heroin, methadone, or other opioid agonists.
Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep- related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.
5) or when buprenorphine was not used according to the prescribing information. Deaths have also been reported in association with concomitant administration of buprenorphine and other depressants such as alcohol or other opioids. If buprenorphine is administered to some non-opioid dependent individuals, who are not tolerant to the effects of opioids, potentially fatal respiratory depression may occur.
g. chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, pre-existing respiratory depression or kyphoscoliosis (curvature of spine leading to potential shortness of breath)). Buprenorphine/naloxone may cause severe, possibly fatal, respiratory depression in children and non-dependent persons in case of accidental or deliberate ingestion.
Patients must be warned to store the blister safely, to never open the blister in advance, to keep them out of the reach of children and other household members, and not to take this medicinal product in front of children. An emergency unit should be contacted immediately in case of accidental ingestion or suspicion of ingestion.
7). Risk from concomitant use of sedative medicinal products such as benzodiazepines or related medicinal products Concomitant use of buprenorphine/naloxone and sedative medicinal products such as benzodiazepines or related medicinal products may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing with these sedative medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe buprenorphine/naloxone concomitantly with sedative medicinal products, the lowest effective dose of the sedative medicines should be used, and the duration of treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). 5). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.
Dependence Buprenorphine is a partial agonist at the μ (mu)-opiate receptor and chronic administration produces dependence of the opioid type. g. morphine. Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal syndrome that may be delayed in onset.
Hepatitis and hepatic events Cases of acute hepatic injury have been reported in opioid-dependent addicts both in clinical trials and in post […]
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised January 29, 2026[4]
1. Severe respiratory insufficiency. Severe hepatic impairment. Acute alcoholism or delirium tremens. Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of alcohol or opioid dependence.
This is not medical advice. Consult a qualified healthcare professional.
Risk from concomitant use of sedating medicinal product such as benzodiazepines or related substances Concomitant use of Bupeaze and sedating medicinal products such as benzodiazepines or related substances may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing with these sedating medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Bupeaze concomitantly with sedating medicinal product, the lowest effective dose should be used, and the duration of the concomitant treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5). Buprenorphine is metabolised in the liver. The intensity and duration of effect may be altered in patients with liver function disorders.
Therefore such patients should be carefully monitored during buprenorphine treatment. Athletes should be aware that this medicine may cause a positive reaction to sports doping control tests. 5). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.
Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose- dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.
Paediatric population As buprenorphine has not been studied in patients under 18 years of age, the use of the medicinal product in patients below this age is not recommended. Patients with fever / external heat Fever and the presence of heat may increase the permeability of the skin.
Theoretically in such situations buprenorphine serum concentrations may be raised during buprenorphine treatment. Therefore on treatment with buprenorphine, attention should be paid to the increased possibility of opioid reactions in febrile patients or those with increased skin temperature due to other causes.
o Reserve concomitant prescribing of SUBLOCADE and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. o Consider dose reduction of CNS depressants in situations of concomitant prescribing.
o Follow patients for signs and symptoms of respiratory depression and sedation. • Cardiac QTc prolongation (see 2 CONTRAINDICATIONS, 7 WARNINGS AND PRECAUTIONS, 9 DRUG INTERACTIONS, 10 CLINICAL PHARMACOLOGY). 1 Dosing Considerations • FOR SUBCUTANEOUS INJECTION ONLY.
SUBLOCADE must NOT be administered intravenously, intramuscularly OR intradermally. • SUBLOCADE should never be handed to patients and should only be administered by a healthcare professional. • SUBLOCADE is available only through a controlled distribution process and should only be prescribed by healthcare professionals who have completed the SUBLOCADE Certification Program.
ca/. More information is available by calling this toll-free phone number: 1-877-782-6966. • Women of childbearing potential should use reliable and effective birth control. Patients should tell their physician immediately should they become pregnant.
The use of a formulation allowing for dosage adjustment may be considered during pregnancy. 1 Special Populations, 16 NON-CLINICAL TOXICOLOGY). • SUBLOCADE should be administered monthly only by subcutaneous injection in the abdomen, thigh, buttock, or back of the upper arm (see 4 DOSAGE AND ADMINISTRATION).
Each injection should be administered only using the syringe and safety needle included with the product. 1 Patient Selection Patients appropriate for SUBLOCADE are adults who have agreed to be treated for opioid use disorder (See below and 1 INDICATIONS).
Periodic assessment is necessary to determine effectiveness of the treatment plan and overall patient progress. When evaluating the patient, examine the injection site for signs of infection or evidence of tampering or attempts to remove the depot (see 7 WARNINGS AND PRECAUTIONS, Addiction, Abuse and Misuse).
SUBLOCADE (buprenorphine) Page 7 of 64 Due to the chronic nature of opioid use disorder, the need for continuing medication-assisted treatment plan should be re-evaluated periodically. If considering stopping treatment plan, the clinical status of the patient should be considered.
If SUBLOCADE is discontinued, patient should be monitored for several months for signs and symptoms of withdrawal and treated appropriately. 3 Pharmacokinetics). 2 Recommended Dose and Dosage Adjustment Induction in patients not already receiving buprenorphine: Treatment with buprenorphine should be initiated when objective and clear signs […]
Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home. Clinical monitoring appropriate to the patient's level of stability is essential.
2) ] . 2 Life-Threatening Respiratory Depression and Central Nervous System (CNS) Depression Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol.
3) , Drug Interactions (7) ] . , chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17) ].
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. 7) ]. , naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent.
Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider recommending or prescribing an opioid overdose reversal agent for the emergency treatment of an opioid overdose, both when initiating and renewing treatment with buprenorphine and naloxone sublingual tablets.
2) ]. , prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.
Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Advise patients and caregivers that an opioid overdose reversal agent, such as naloxone or nalmefene, may also be administered for a known or suspected overdose with buprenorphine and naloxone sublingual tablets itself.
Higher than normal doses and repeated administration of an opioid overdose reversal agent may be necessary due to the long duration of action of buprenorphine and naloxone sublingual tablets and its affinity for the mu‐opioid receptor [see Overdosage (10) ] .
Educate patients and caregivers on how to recognize respiratory depression, and how to use an opioid overdose reversal agent for the emergency treatment of opioid overdose. Emphasize the importance of calling 911 or getting emergency medical help, even if an opioid overdose reversal agent is administered.
, alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids) increases the risk of adverse reactions including overdose, respiratory depression, and death.
Medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs. Prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone.
As a routine part of orientation to buprenorphine treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol. Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment.
Adjustments to induction procedures and additional monitoring may be required. There is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients.
However, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate. 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. For patients in buprenorphine treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia.
Before co-prescribing benzodiazepines, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments to address anxiety or insomnia. Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient's buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use.
2) , Overdosage (10) ] . In addition, take measures to confirm that patients are taking their medications as prescribed and are not diverting or supplementing with illicit drugs. Toxicology screening should test for prescribed and illicit benzodiazepines [see Drug Interactions (7) ].
4 Unintentional Pediatric Exposure Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Store buprenorphine-containing medications safely out of the sight and reach of children and destroy any unused medication appropriately [see Patient Counseling Information (17) ] .
5 Neonatal Opioid Withdrawal Syndrome Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medically-authorized or illicit. Unlike opioid withdrawal syndrome in adults, NOWS may be life-threatening if not recognized and treated in the neonate.
1) ] . 1) ] . This risk must be balanced against the risk of untreated opioid addiction which often results in continued or relapsing illicit opioid use and is associated with poor pregnancy outcomes. Therefore, prescribers should discuss the importance and benefits of management of opioid addiction throughout pregnancy.
6 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
7 Risk of Opioid Withdrawal with Abrupt Discontinuation Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid-type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper.
3) ] . 6) ]. 8 Risk of Hepatitis, Hepatic Events Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through postmarketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy.
In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role.
In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary.
The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline.
Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, buprenorphine and naloxone sublingual tablets may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.
9 Hypersensitivity Reactions Cases of hypersensitivity to buprenorphine and naloxone containing products have been reported both in clinical trials and in the postmarketing experience. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported.
The most common signs and symptoms include rashes, hives, and pruritus. A history of hypersensitivity to buprenorphine or naloxone is a contraindication to the use of buprenorphine and naloxone sublingual tablets. 10 Precipitation of Opioid Withdrawal Signs and Symptoms Because it contains naloxone, buprenorphine and naloxone sublingual tablet is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone.
Because of the partial agonist properties of buprenorphine, buprenorphine and naloxone sublingual tablets may precipitate opioid withdrawal signs and symptoms in such persons if administered sublingually before the agonist effects of the opioid have subsided.
11 Risk of Overdose in Opioid Naïve Patients There have been reported deaths of opioid naïve individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. Buprenorphine and naloxone sublingual tablets are not appropriate as an analgesic.
12 Use in Patients with Impaired Hepatic Function Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. The doses of buprenorphine and naloxone in this fixed-dose combination product cannot be individually titrated, and hepatic impairment results in a reduced clearance of naloxone to a much greater extent than buprenorphine.
Therefore, patients with severe hepatic impairment will be exposed to substantially higher levels of naloxone than patients with normal hepatic function. This may result in an increased risk of precipitated withdrawal at the beginning of treatment (induction) and may interfere with buprenorphine's efficacy throughout treatment.
In patients with moderate hepatic impairment, the differential reduction of naloxone clearance compared to buprenorphine clearance is not as great as in subjects with severe hepatic impairment. However, buprenorphine/naloxone products are not recommended for initiation of treatment (induction) in patients with moderate hepatic impairment due to the increased risk of precipitated withdrawal.
Buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone. 6) ] . , tooth fracture, tooth loss), have been reported following the use of transmucosal buprenorphine-containing products.
Reported events include cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss. , fillings, crowns, implants, dentures). Multiple cases were reported in individuals without any prior history of dental problems.
Refer patients to dental care services and encourage them to have regular dental checkups while taking buprenorphine and naloxone sublingual tablets. Educate patients to seek dental care and strategies to maintain or improve oral health while being treated with transmucosal buprenorphine-containing products.
Strategies include, but are not limited to, gently rinsing the teeth and gums with water and then swallowing after buprenorphine and naloxone sublingual tablets have been completely dissolved in the oral mucosa. 4) , Information for Patients (17) , Medication Guide ].
14 QTc Prolongation Thorough QT studies with buprenorphine products have demonstrated QTc prolongation ≤15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors.
The risk of combining buprenorphine with other QT-prolonging agents is not known. Consider these observations in clinical decisions when prescribing buprenorphine and naloxone sublingual tablets to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia.
15 Impairment of Ability to Drive or Operate Machinery Buprenorphine and naloxone sublingual tablets may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery, especially during treatment induction and dose adjustment.
Caution patients about driving or operating hazardous machinery until they are reasonably certain that buprenorphine and naloxone sublingual tablet therapy does not adversely affect his or her ability to engage in such activities. 16 Orthostatic Hypotension Like other opioids, buprenorphine and naloxone sublingual tablets may produce orthostatic hypotension in ambulatory patients.
17 Elevation of Cerebrospinal Fluid Pressure Buprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased.
Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation. 18 Elevation of Intracholedochal Pressure Buprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract.
19 Effects in Acute Abdominal Conditions As with other opioids, buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions.