Buprenorphine (Subutex®, Suboxone®, Butrans®)
| Buprenorphine |  |
|---|---|
| Brand Names | Subutex®, Suboxone®, Butrans®, Sublocade® |
| Drug Class | Opioid (Partial μ-agonist) |
| Primary Indication | Opioid Use Disorder, Chronic Pain |
| Receptor Activity | Partial μ agonist; κ antagonist |
| Ceiling Effect | Yes (respiratory depression) |
| Relative Potency | High receptor affinity |
| Controlled Substance | Schedule III |
| FDA Approval | 1985 (analgesic), 2002 (OUD) |
Overview
Buprenorphine is a partial μ-opioid receptor agonist with very high receptor affinity and slow dissociation.
It is used for both chronic pain and treatment of opioid use disorder (MOUD).
Because it is a partial agonist, it produces a ceiling effect on respiratory depression and euphoria, making it safer than full μ agonists.
However, its high receptor affinity can displace full agonists and precipitate withdrawal.
Mechanism of Action
Receptor Activity
- Partial μ-opioid receptor agonist
- κ-opioid receptor antagonist
- Very high receptor affinity
Clinical Consequences
- Produces analgesia
- Ceiling effect on respiratory depression
- Can displace morphine, heroin, fentanyl
High receptor affinity explains precipitated withdrawal risk.
Indications
- Opioid Use Disorder (MOUD)
- Chronic pain (transdermal or buccal formulations)
- Acute pain (limited use)
Common formulations:
- Sublingual (Subutex®, Suboxone®)
- Transdermal patch (Butrans®)
- Monthly injection (Sublocade®)
Suboxone® = buprenorphine + naloxone (to deter misuse).
Contraindications
Absolute:
- Severe respiratory depression
- Acute severe bronchial asthma
Relative / Caution:
- Hepatic impairment
- Concurrent CNS depressants
- Initiation too soon after full opioid use (withdrawal risk)
Dosing
Opioid Use Disorder (sublingual):
- Initial: 2–4 mg
- Titrate to 8–16 mg/day (typical maintenance)
Chronic pain (transdermal):
- Applied every 7 days
Initiation requires mild withdrawal state to avoid precipitated withdrawal.
Pharmacokinetics
Absorption:
- Sublingual
- Buccal
- Transdermal
- Injectable
Metabolism:
- Hepatic (CYP3A4)
Half-life:
- ~24–42 hours
Elimination:
- Biliary and renal
Long half-life supports once-daily dosing in OUD.
Adverse Effects
Common:
- Nausea
- Headache
- Constipation
- Insomnia
Serious:
- Respiratory depression (less than full agonists)
- Precipitated withdrawal
- Hepatic enzyme elevation
Lower abuse potential compared to full agonists.
Drug Interactions
CNS depressants:
- Benzodiazepines
- Alcohol
- Other opioids
CYP3A4 inhibitors:
- Azoles
- Macrolides
Risk:
- Increased sedation
- Respiratory depression
Monitoring
Clinical:
- Withdrawal symptoms during induction
- Cravings (OUD patients)
- Sedation and respiratory status
Laboratory:
- Liver function tests (periodically)
Clinical Pearls
- Partial μ agonist → ceiling effect on respiratory depression.
- High receptor affinity → can precipitate withdrawal.
- Must initiate when patient is in mild withdrawal.
- Suboxone® contains naloxone to deter IV misuse.
- Schedule III (lower abuse potential than Schedule II opioids).
- First-line therapy for opioid use disorder.
Toxicity
Overdose:
- Less severe respiratory depression than full agonists
- May require higher naloxone doses due to receptor affinity
Treatment:
- Naloxone (may need repeated dosing)
Comparison Within Class
Compared to Morphine:
- Partial agonist vs full agonist
- Ceiling effect
- Safer respiratory profile
Compared to Methadone:
- Lower overdose risk
- Less QT prolongation
- Requires withdrawal before initiation
Compared to Naltrexone:
- Partial agonist vs pure antagonist
- Does not block all opioid effects