Buprenorphine

Pronunciation: byoo-pre-NOR-feen.

Generic name: buprenorphine
Drug class: Partial opioid (mu-receptor) agonist and kappa-receptor antagonist
Form: Sublingual tablet (Subutex, generic buprenorphine, and buprenorphine/naloxone combinations e.g. Suboxone); oral lyophilisate (Espranor, UK); buccal film (Belbuca, US); transdermal patch (Butrans, US); prolonged-release/extended-release subcutaneous injection (Buvidal, EU/UK; Sublocade, US/Canada/Australia/New Zealand); subdermal implant (Probuphine, Canada)
Route: Sublingual tablet/film, buccal film, transdermal patch, subcutaneous depot injection, or subdermal implant, depending on the specific formulation and its clinical purpose
Legal status: Controlled/restricted prescription medicine in all six markets reviewed (e.g. Schedule 8 in Australia); some formulations additionally require a restricted distribution program (e.g. Sublocade's REMS in the US)

Availability and supply rules vary by country

Trade names by country: United States · United Kingdom · Canada · Australia · New Zealand

Australia: Subutex (8), Suboxone Film (8), Sublocade (8) · Full directory

Boxed warning: Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome

Buprenorphine carries a boxed warning (the US FDA's strongest safety warning) on its pain-management formulations (Butrans transdermal patch, Belbuca buccal film): buprenorphine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Serious, life-threatening, or fatal respiratory depression may occur, especially when starting treatment or after a dose increase. Accidental exposure to even one dose, especially in children, can result in a fatal overdose. Concomitant use of buprenorphine with benzodiazepines or other central nervous system depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Pregnant women using an opioid for an extended period should be advised of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognised and treated by the neonatal care team. Separately, for the opioid-use-disorder (medication-assisted treatment) formulations, an additional buprenorphine-specific point applies: because buprenorphine binds very tightly to opioid receptors, naloxone may not fully reverse respiratory depression caused by buprenorphine, and deaths have occurred when buprenorphine has been misused by injection, usually together with benzodiazepines. Sublocade, the extended-release injectable formulation, carries a further specific warning: serious harm or death can result if it is injected intravenously rather than given as intended by a healthcare professional, and it is available only through a restricted REMS program. (1) (2) (3) (4)

What buprenorphine is and how it works

Buprenorphine is a controlled prescription opioid medicine used in two genuinely different ways, depending on the formulation: as part of medically supervised treatment for opioid use disorder (sublingual tablets/film, extended-release injection, or an implant), and as a long-acting analgesic for severe, persistent pain that other options cannot adequately control (a transdermal patch or a buccal film). It is a partial opioid agonist, meaning it activates opioid receptors less strongly than a full opioid like morphine or fentanyl, which underlies both its treatment role and a ceiling on some of its effects -- but it still carries real, serious opioid risks. (1) (3)

Buprenorphine carries a genuine FDA boxed warning on its pain-management formulations covering addiction, abuse, and misuse risk; life-threatening respiratory depression, especially when starting treatment or after a dose increase; a serious risk of fatal overdose from accidental exposure to even a single dose, especially in children; and Neonatal Opioid Withdrawal Syndrome with extended use in pregnancy. A further buprenorphine-specific point applies to the opioid-use-disorder formulations: naloxone (the standard opioid-overdose reversal medicine) may not fully reverse breathing problems caused by buprenorphine, and injecting it (misuse) has been linked to deaths, especially combined with benzodiazepines. All buprenorphine formulations should only be used exactly as directed by the prescriber or treatment program managing your care.

Mechanism of action: how buprenorphine works

Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor, with very high receptor-binding affinity and slow dissociation. This underlies both its 'ceiling effect' on some opioid effects (relevant to its use in OUD treatment) and the real safety point that naloxone may not fully displace buprenorphine from the receptor, limiting naloxone's ability to reverse buprenorphine-induced respiratory depression. (3) (5)

What buprenorphine is used for

Medication-assisted treatment of opioid use disorder (OUD)

Used as part of a supervised treatment program, alongside counselling and psychosocial support, to treat opioid use disorder. Formulations used for this include sublingual tablets/film (buprenorphine alone, or combined with naloxone as in Suboxone, used for induction and/or maintenance), an extended-release subcutaneous injection (Sublocade, for patients already stabilised on a transmucosal buprenorphine product), and a subdermal implant (Probuphine, in Canada, for patients stabilised on a low sublingual dose). This is a real, distinct clinical role, honestly described here as medication-assisted treatment rather than downplayed. (3) (4) (7)

Management of severe and persistent pain

Used as a long-acting analgesic for severe, persistent pain that requires an opioid and cannot be adequately managed with alternative options, including immediate-release opioids. Formulations used for this include a 7-day transdermal patch (Butrans) and a buccal film that dissolves against the inside of the cheek (Belbuca). Neither is approved for as-needed (prn) pain relief -- both are for continuous, around-the-clock pain management under a prescriber's supervision. (1) (2)

Before taking buprenorphine

Do not take / not appropriate for

Do not use any buprenorphine pain-management formulation (Butrans, Belbuca) if you have significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting, or a known or suspected gastrointestinal obstruction including paralytic ileus. (United States) (1) (2)
Do not use buprenorphine if you have a known serious allergic reaction to buprenorphine or its ingredients. (all countries) (1) (5)
Do not use buprenorphine sublingual tablets if you have severe hepatic (liver) insufficiency, severe respiratory insufficiency, acute alcoholism or delirium tremens, or if you are under 15 years old, or if you are breastfeeding -- confirmed as contraindications in the UK source reviewed. (United Kingdom) (5)
Never inject the Sublocade extended-release depot intravenously -- this can cause serious harm or death; it must be given only by a certified healthcare professional as intended. (United States) (4)

Tell your clinician about

Any history of opioid use disorder, substance use, or previous buprenorphine/methadone treatment.
Any breathing problems, including sleep apnoea, asthma, or COPD.
Any liver problems -- buprenorphine has been linked to rare but serious liver injury.
Any history of head injury, increased pressure in the brain, or seizures.
Whether you are pregnant, plan to become pregnant, or are breastfeeding.
All other medicines and substances you take, especially benzodiazepines, other sedatives, alcohol, and any strong CYP3A4 inhibitor or inducer.

(1) (5)

How to take buprenorphine

Use exactly as directed by your prescriber or treatment program -- buprenorphine formulations differ significantly in how they are administered, and following the wrong instructions for your specific product can be dangerous.
For the Butrans patch: apply to the upper outer arm, upper chest, upper back, or side of chest; wear each patch for 7 days; rotate to a different site each time and wait at least 21 days before reusing the same site; avoid direct heat sources (heating pads, hot tubs, electric blankets, sunbathing) over the patch, which can increase how much medicine you absorb.
For the Belbuca buccal film: wet the inside of your cheek first, place the film against the moist mucosa, hold it in place with clean, dry fingers for about 5 seconds, then leave it to dissolve fully (usually about 30 minutes) without eating or drinking; do not use if the pouch seal is broken or the film is cut or damaged.
For sublingual tablets/film used in opioid use disorder treatment: let the tablet or film dissolve completely under the tongue as instructed by your treatment program; do not chew or swallow it whole.
Never change your dose, switch formulations, or ask the prescriber about stopping it on your own -- always work with your prescriber or treatment program.

(1) (2) (5)

Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (5) (6) (7) (8) (9)

Missed dose

Contact your prescriber or treatment program for guidance if you miss a dose or a scheduled patch change/injection -- do not apply an extra patch, take an extra film, or attempt to make up a missed dose yourself, given the serious overdose risk with opioid medicines.

Overdose

Seek emergency medical help immediately if an overdose is suspected -- signs include severe drowsiness, slow or stopped breathing, pinpoint pupils, or unresponsiveness. Naloxone may be given by emergency responders, but because buprenorphine binds very tightly to opioid receptors, naloxone may not fully reverse the breathing problems it causes, so emergency medical care is essential even if naloxone is given. Accidental exposure to even one dose, especially in a child, can be fatal -- seek emergency help immediately. (1) (3)