BUTRANS
Clinical safety rating
cautionComprehensive clinical and safety monograph for BUTRANS (BUTRANS).
Buprenorphine is a partial mu-opioid receptor agonist and a weak kappa-opioid receptor antagonist. It binds with high affinity to mu-opioid receptors, producing analgesic and opioid effects with a ceiling effect on respiratory depression.
| Metabolism | Primarily metabolized by CYP3A4 to norbuprenorphine; also undergoes conjugation with glucuronic acid. Norbuprenorphine is active and further glucuronidated. |
| Excretion | Renal: 60-70% as unchanged drug and metabolites; biliary/fecal: 20-30% |
| Half-life | Terminal half-life: 4-6 hours in healthy adults; prolonged to 12-18 hours in elderly or renal impairment |
| Protein binding | 96% bound primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 2-5 L/kg, indicating extensive tissue distribution |
| Bioavailability | Transdermal: 15-25%; buccal: 60-70% |
| Onset of Action | Transdermal: 2-4 hours; buccal: 30-60 minutes |
| Duration of Action | Transdermal: 7 days (patch replacement every 7 days); buccal: 12-24 hours |
| Molecular Weight | 504.4 |
Apply one BUTRANS (buprenorphine) transdermal system to a clean, dry, non-irritated, and non-hairy area of the chest, back, flank, or upper arm. Initial dose: 5 mcg/h for opioid-naïve patients; titrate based on pain control and tolerability. Maximum dose: 20 mcg/h. Replace every 7 days. Rotate application sites.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution and consider starting at the lowest dose (5 mcg/h) with close monitoring for adverse effects. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Start at the lowest dose (5 mcg/h) and titrate cautiously; consider reducing dose by 50%. Child-Pugh Class C: Avoid use due to increased risk of toxicity. |
| Pediatric use | Not recommended for use in pediatric patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | Initiate at the lowest dose (5 mcg/h) and titrate slowly with careful monitoring for respiratory depression, sedation, and falls. Consider age-related reductions in renal and hepatic function. |
| 1st trimester | Buprenorphine is not recommended in first trimester due to potential teratogenic effects; limited data. Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; may cause neonatal withdrawal syndrome if used near term. Monitor for fetal growth and development. |
| 3rd trimester | Use in third trimester may cause neonatal opioid withdrawal syndrome (NOWS). Taper if possible; avoid high doses near delivery. |
Clinical note
Comprehensive clinical and safety monograph for BUTRANS (BUTRANS).
| Placental transfer | Buprenorphine crosses the placenta with a fetal-to-maternal plasma concentration ratio of approximately 0.5-0.7, indicating moderate transfer. Norbuprenorphine, its metabolite, crosses to a lesser extent. |
| Breastfeeding | Buprenorphine is excreted in breast milk in low concentrations. In mothers on maintenance therapy, benefits of breastfeeding generally outweigh risks; however, monitor infant for sedation, respiratory depression, and withdrawal. Avoid in mothers with high-dose or illicit use. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Inadequate human data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimester: Prolonged use can cause neonatal opioid withdrawal syndrome (NOWS); avoid chronic use near term due to risk of respiratory depression. Generally, buprenorphine is considered lower risk than full agonists but still requires careful risk-benefit assessment. |
| Fetal Monitoring | Maternal: monitor respiratory rate, sedation level, blood pressure, and signs of withdrawal or overdose. Fetal: nonstress test or biophysical profile if prolonged use after 28 weeks. Neonatal: monitor for NOWS (irritability, poor feeding, tremors) for at least 48 hours after birth. |
| Fertility Effects | Buprenorphine may cause hyperprolactinemia, leading to menstrual irregularities and reduced fertility in females. In males, it may decrease libido and cause erectile dysfunction. These effects are reversible upon discontinuation. |
■ FDA Black Box Warning
Risk of respiratory depression, addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome; risk of potentially fatal respiratory depression when used with benzodiazepines or other CNS depressants; and risk of life-threatening respiratory depression in children with accidental ingestion.
| Serious Effects |
Hypersensitivity to buprenorphineSevere respiratory insufficiencySevere hepatic impairment (Child-Pugh C)
| Precautions | Addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; risk with benzodiazepines or other CNS depressants; severe hypotension; gastrointestinal obstruction; seizures; biliary tract disease; use in elderly and debilitated patients; hepatic impairment; renal impairment; pregnancy; lactation. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4, potentially increasing buprenorphine levels. No other significant food interactions documented. |
| Clinical Pearls | BUTRANS (buprenorphine transdermal system) is a Schedule III partial mu-opioid agonist used for chronic pain. Do not apply to irritated skin; rotate application sites to minimize skin reactions. Onset of analgesia is delayed (12-24 hours), so titrate with immediate-release analgesics as needed. Avoid concurrent use with full mu-opioid agonists (e.g., morphine) due to risk of precipitated withdrawal. The 5, 7.5, 10, 15, and 20 mcg/h patches are approved; 20 mcg/h is the maximum single dose. Reserve for patients tolerant to around-the-clock opioids (≥30 mg oral morphine equivalents/day). Monitor for respiratory depression (less than full agonists, but still a risk) and serotonin syndrome with other serotonergic agents. |
| Patient Advice | Apply the patch to clean, dry, hairless skin on the upper arm, chest, back, or side of the chest. Remove immediately if it falls off. · Wear the patch for 7 days; replace with a new patch at the same time of day. Do not cut or damage the patch. · Avoid exposure to direct heat (heating pads, saunas, hot tubs, prolonged sun) as it increases absorption and overdose risk. · Do not drink alcohol while using Butrans; it can cause dangerous side effects. · Keep all patches away from children and pets; used patches should be folded and flushed down the toilet immediately. · Do not stop abruptly or change dose without consulting your doctor; withdrawal may occur. · Common side effects include nausea, constipation, headache, and application site redness. |
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