BUPRENORPHINE HYDROCHLORIDE
Clinical safety rating: caution
Benzodiazepines and other CNS depressants increase risk of respiratory depression Can precipitate withdrawal in patients dependent on other opioids.
Partial agonist at mu-opioid receptors and antagonist at kappa-opioid receptors, producing analgesia and reducing opioid withdrawal symptoms.
| Metabolism | Primarily metabolized by CYP3A4 to norbuprenorphine; also glucuronidated by UGT1A1, UGT2B7. |
| Excretion | Primarily fecal (70%) via biliary excretion; renal excretion accounts for 20-30% as unchanged drug and metabolites (mainly norbuprenorphine glucuronide). |
| Half-life | Terminal elimination half-life is 20-73 hours (mean ~37 hours); prolonged half-life supports sublingual dosing every 24-48 hours in opioid dependence. |
| Protein binding | 96% bound primarily to alpha- and beta-globulins, with negligible binding to albumin. |
| Volume of Distribution | 2.5 L/kg (range 1.5-5 L/kg); high Vd indicates extensive tissue distribution (e.g., brain, adipose). |
| Bioavailability | Sublingual: 30-50% (range 15-55%); buccal: 30-50%; oral: <10% due to extensive first-pass metabolism; intramuscular: 90-100%; intravenous: 100%. |
| Onset of Action | Sublingual: 30-60 minutes; buccal: 30-60 minutes; intramuscular: 10-30 minutes; intravenous: 1-2 minutes. |
| Duration of Action | Sublingual/buccal: 24-36 hours at high doses (8-24 mg) due to slow dissociation from mu-opioid receptors; at low doses (<4 mg), duration is 6-12 hours. Intramuscular: 4-6 hours; intravenous: 4-6 hours. |
Sublingual: 8-16 mg once daily. Transdermal: 5-20 mcg/hour applied every 7 days. Injectable: 0.3 mg IM/IV every 6-8 hours as needed.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, use with caution and consider reducing dose or extending interval. Not dialyzable. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce starting dose by 50% (e.g., sublingual 4 mg). Child-Pugh C: Avoid use or reduce dose by 75% (e.g., sublingual 2 mg). |
| Pediatric use | Not approved for <16 years. For induction in adolescents: Sublingual 2-4 mg initially, titrated based on response. Maximum 24 mg/day. |
| Geriatric use | Reduce initial dose by 25-50% due to increased sensitivity. Titrate slowly. Monitor for respiratory depression and CNS effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Benzodiazepines and other CNS depressants increase risk of respiratory depression Can precipitate withdrawal in patients dependent on other opioids.
| FDA category | Animal |
| Breastfeeding | Buprenorphine is excreted in breast milk with a relative infant dose of 1-2% of maternal weight-adjusted dose. M/P ratio approximately 1.0 based on limited data. The American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for sedation, feeding difficulties, and withdrawal if breastfeeding is abruptly stopped. |
| Teratogenic Risk |
■ FDA Black Box Warning
WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; WARNING: RISK OF RESPIRATORY DEPRESSION, ADDICTION, ABUSE, AND MISUSE; WARNING: RISK OF NEONATAL OPIOID WITHDRAWAL SYNDROME
| Common Effects | opioid use disorder |
| Serious Effects |
Hypersensitivity to buprenorphine, severe respiratory depression, acute or severe bronchial asthma, known or suspected gastrointestinal obstruction (including paralytic ileus), concomitant use with full mu-opioid agonists (risk of precipitated withdrawal).
| Precautions | Respiratory depression (especially with benzodiazepines or other CNS depressants), neonatal opioid withdrawal syndrome during prolonged use in pregnancy, risk of hepatitis or hepatic injury, adrenal insufficiency, hypotension, QT prolongation, opioid-induced hyperalgesia, risk of withdrawal with partial agonist, misuse potential. |
| Food/Dietary |
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| FDA Pregnancy Category C. First trimester: No increased risk of major malformations based on human data, but animal studies show increased fetal loss and skeletal abnormalities at high doses. Second and third trimesters: Chronic use may lead to neonatal abstinence syndrome (NAS) requiring monitoring. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal liver function tests, respiratory rate, and signs of sedation. Fetal monitoring: non-stress test and biophysical profile in third trimester. Neonatal monitoring for NAS using Finnegan scoring for at least 72 hours after birth. |
| Fertility Effects | Buprenorphine may cause hyperprolactinemia, potentially leading to menstrual irregularities, anovulation, or galactorrhea. Reversible upon discontinuation. Animal studies show decreased fertility at high doses; human data limited. |
| No significant food interactions. Grapefruit juice may increase buprenorphine levels via CYP3A4 inhibition; concurrent use is not recommended. Avoid excessive alcohol consumption. |
| Clinical Pearls | Buprenorphine is a partial mu-opioid agonist; its ceiling effect reduces respiratory depression risk but may precipitate withdrawal in opioid-dependent patients if administered too soon after full agonists. Sublingual tablets require adequate dissolution under the tongue for 5-10 minutes; advise patient not to swallow or talk during dissolution. Naloxone is combined to deter intravenous misuse; sublingual bioavailability of naloxone is low, but intravenous injection can precipitate withdrawal. Avoid use in patients with severe hepatic impairment due to extensive first-pass metabolism. Monitor for QT prolongation, especially at high doses or with concomitant QT-prolonging drugs. |
| Patient Advice | Take buprenorphine exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not consume alcohol or sedatives (benzodiazepines, other opioids) while taking this medication, as it may cause severe drowsiness, respiratory depression, or coma. · Do not drive or operate machinery until you know how buprenorphine affects you; dizziness or drowsiness may occur. · If you miss a dose, take it as soon as remembered; if close to next dose, skip the missed dose and resume normal schedule. Do not double doses. · Store at room temperature away from moisture and heat; keep out of reach of children. · Do not stop abruptly; abrupt discontinuation may cause withdrawal symptoms. Your doctor will taper your dose gradually. · If you experience signs of allergic reaction (rash, hives, swelling, difficulty breathing) or signs of overdose (slow/shallow breathing, severe drowsiness, pinpoint pupils), seek emergency medical attention. · Inform all healthcare providers that you are taking buprenorphine; carry a medication card or alert bracelet. |