Buprenorphine for pain

Generic Name

Buprenorphine

Brand Names (Pain Indications Only)

Butrans (transdermal patch)

Buvidal (extended-release injection, Europe/Australia)

Belbuca (buccal film)

Temgesic (sublingual tablets)

Buprenex (injectable formulation)

Subutex, Suboxone (primarily for opioid dependence, not pain)

Various generics available in different formulations and countries

Drug Class

Partial opioid agonist

Schedule III controlled substance (USA)

Narcotic analgesic

Phenanthrene class of opioids

Schedule C medication in UK (Controlled Drug, Schedule 3)

Mechanism of Action

Buprenorphine is a partial agonist at the μ-opioid receptor and an antagonist at the κ-opioid receptor

Its partial agonism at μ-receptors provides effective analgesia with a ceiling effect on respiratory depression, reducing overdose risk compared to full agonists

Its κ-antagonism is believed to reduce opioid-induced hyperalgesia and dysphoria

Buprenorphine also has high receptor affinity and slow dissociation from μ-receptors, contributing to long duration of action and potential interference with full agonist opioids

Onset of action varies by route: faster with IV/IM, slower with transdermal or buccal

Indications for Pain (Non-Addiction)

Moderate to severe chronic pain requiring long-term opioid treatment

Cancer pain (including palliative care)

Neuropathic pain (off-label in some jurisdictions)

Post-operative pain (short-acting sublingual or injectable buprenorphine)

Musculoskeletal pain (e.g. osteoarthritis, low back pain)

Pain in patients with a history of opioid misuse (safer than full agonists)

Older patients or those with renal impairment requiring opioid analgesia

Off-Label Uses

Fibromyalgia (limited data)

Pain in opioid-tolerant patients who cannot tolerate other opioids

Migraines and tension headaches (rare, specialist settings)

Dosage and Administration

Transdermal Patch (Butrans)

Used for chronic pain in opioid-naïve or opioid-intolerant patients

Dose: 5 mcg/h, 7.5 mcg/h, 10 mcg/h, 15 mcg/h, 20 mcg/h

Applied once weekly to non-irritated skin (upper back, chest, upper arm)

Takes ~12–24 hours to reach therapeutic levels

Patch rotation is necessary to prevent skin irritation

Should not be used in patients requiring >80 mg oral morphine equivalents per day

Buccal Film (Belbuca)

Used for moderate to severe chronic pain

Initial dose: 75 mcg once or twice daily

Titrated up to 900 mcg twice daily

Applied to buccal mucosa, allowed to dissolve completely

Avoid eating or drinking until film dissolves

More flexible for dose titration than patch

Sublingual Tablets (Temgesic, generic buprenorphine)

Dose for pain: 200–400 mcg every 6–8 hours

Short-term use for acute or breakthrough pain

Rapid onset: ~15–30 minutes

Peak plasma concentration: ~1 hour

Not the same as high-dose sublingual formulations used for opioid dependence

Parenteral (Buprenex or generic)

IV or IM: 0.3 mg every 6–8 hours as needed

Used for post-operative pain or severe acute pain

Rapid onset within minutes

Available as single-use ampoules or vials

May be administered in palliative care or in-hospital settings

Extended-Release Injection (Buvidal, Sublocade)

Primarily used for opioid dependence

Occasionally used in chronic pain as long-acting depot under specialist guidance

Not widely approved for pain in most regulatory settings

Pharmacokinetics

Bioavailability:

– Sublingual: ~30–50%

– Buccal: ~50%

– Transdermal: ~15%

– IM: ~100%

– Oral (swallowed): <10% (ineffective)

Onset:

– IV: <5 minutes

– SL: 30–60 minutes

– TD: 12–24 hours

Duration:

– 6–12 hours (SL)

– 7 days (TD patch)

Metabolism: Hepatic via CYP3A4 and CYP2C8 to norbuprenorphine

Elimination: Biliary and renal

Half-life: 20–70 hours depending on formulation and route

Contraindications

Severe respiratory depression

Acute or severe bronchial asthma (unmonitored settings)

Paralytic ileus

Known hypersensitivity to buprenorphine or excipients

Concomitant use of full opioid agonists (risk of withdrawal)

Substance use disorder without proper assessment (when used for pain only)

Warnings and Precautions

Risk of opioid addiction, abuse, and misuse—use lowest effective dose

May precipitate withdrawal in patients on full agonists due to partial agonism

Can cause QT prolongation—avoid in patients with existing QT prolongation or on other QT-prolonging drugs

Use caution in hepatic impairment—risk of accumulation and increased sedation

Avoid abrupt discontinuation after prolonged use—taper slowly

Transdermal formulations may result in delayed respiratory depression

Not recommended for opioid-naïve patients starting at high doses

Monitor for sedation and respiratory depression in elderly

Apply patch only to intact, non-irritated skin

Avoid exposure to heat sources (increases absorption of patch)

Adverse Effects

Very Common

Constipation

Nausea

Headache

Drowsiness

Dizziness

Dry mouth

Application site irritation (with patch)

Common

Vomiting

Fatigue

Insomnia

Sweating

Itching

Hypotension

Blurred vision

Mood changes

Back pain

Less Common

Urinary retention

Respiratory depression

QT prolongation

Confusion

Bradycardia

Withdrawal symptoms (if tapered abruptly)

Rare and Serious

Severe respiratory depression

Anaphylaxis

Severe hypotension

Adrenal insufficiency

Serotonin syndrome (when used with serotonergic drugs)

Pregnancy and Lactation

Pregnancy Category C (US FDA – discontinued system)

Animal studies have shown adverse fetal effects

May be used when benefits outweigh risks—especially in opioid-dependent pregnant women

Chronic exposure during pregnancy may result in neonatal withdrawal syndrome

Lactation

Excreted in breast milk

Infants should be monitored for sedation and respiratory depression

Breastfeeding may be allowed in low-dose use with close monitoring

Drug Interactions

CNS depressants (benzodiazepines, alcohol, sedatives)

Additive CNS and respiratory depression—high overdose risk

Avoid or closely monitor

CYP3A4 inhibitors (e.g., ketoconazole, ritonavir)

May increase buprenorphine plasma levels—enhanced effects and toxicity

Monitor for increased sedation or respiratory depression

CYP3A4 inducers (e.g., rifampin, carbamazepine)

May decrease buprenorphine efficacy

Other opioids (e.g., morphine, oxycodone)

Buprenorphine may block effects of full agonists—risk of withdrawal or reduced analgesia

Avoid combining unless under specialist supervision

MAOIs

Possible risk of serotonin syndrome or CNS toxicity—use caution

QT-prolonging drugs (e.g., methadone, haloperidol)

Additive QT prolongation risk—avoid concurrent use or monitor ECG

Monitoring Parameters

Pain control assessment

Signs of sedation, respiratory depression

Signs of opioid misuse or dependence

Liver function tests

ECG in patients at risk of QT prolongation

Skin for patch site reactions

Signs of withdrawal during tapering

Constipation and bowel function

Counseling Points

Apply transdermal patch to clean, dry skin once weekly

Rotate patch sites to avoid irritation

Do not expose patch to external heat sources (heating pads, saunas)

Do not consume alcohol or sedatives while using buprenorphine

Report any breathing difficulty, extreme drowsiness, or confusion

Avoid operating heavy machinery until drug effects are known

Do not abruptly stop after prolonged use—risk of withdrawal

Dispose of patches properly—fold in half, flush, or follow local disposal regulations

Store away from children and pets

Comparative Notes

Buprenorphine vs Morphine

Buprenorphine is a partial agonist with lower overdose risk

Ceiling effect on respiratory depression unlike morphine

Less constipation than full agonists

Less effective for rapidly titrating pain compared to morphine

Buprenorphine vs Fentanyl Patch

Both transdermal, but fentanyl is a full agonist

Buprenorphine has fewer respiratory complications

Fentanyl preferred in high opioid tolerance; buprenorphine preferred in moderate chronic pain or older adults

Buprenorphine vs Methadone

Methadone is full agonist, used more for severe pain or dependence

Buprenorphine safer in terms of respiratory and cardiac toxicity

Methadone associated with higher QT prolongation risk

Regulatory Status

Controlled drug (Schedule III US, Schedule 3 UK)

Approved by FDA and EMA for chronic pain (specific formulations only)

Butrans and Belbuca require prescription and specific documentation

Requires regular re-evaluation in long-term use