BUTORPHANOL TARTRATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for BUTORPHANOL TARTRATE (BUTORPHANOL TARTRATE).
Butorphanol tartrate is a mixed agonist-antagonist opioid analgesic that exerts its effects primarily through partial agonism at the mu-opioid receptor and full agonism at the kappa-opioid receptor. This results in analgesia with a ceiling effect for respiratory depression. It also has weak antagonistic activity at the mu receptor.
| Metabolism | Butorphanol is extensively metabolized in the liver via hydroxylation and N-dealkylation, primarily by CYP3A4. The major metabolite is hydroxybutorphanol, which has some analgesic activity but is less potent. |
| Excretion | Primarily hepatic metabolism to inactive metabolites; renal excretion accounts for approximately 70-80% of elimination (mostly metabolites), with 15-20% via feces (biliary). Less than 5% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is 2.5-3.5 hours (mean ~3 hours) in adults; prolonged in hepatic impairment (up to 5-6 hours) and renal impairment (variable, may increase). |
| Protein binding | Approximately 80% bound to plasma proteins (mainly alpha-1-acid glycoprotein and albumin). |
| Volume of Distribution | Vd: 4-5 L/kg (range 3-6 L/kg), indicating extensive tissue distribution, including CNS. |
| Bioavailability | Intranasal: 60-70% (range 48-80%); IM: 80-100% (complete but variable); Oral: very low (<5%) due to extensive first-pass metabolism; not used orally. |
| Onset of Action | IV: 1-2 minutes; IM: 10-15 minutes; Intranasal: 15-30 minutes. |
| Duration of Action | Analgesic effect lasts 2-4 hours (IV/IM); 4-5 hours (intranasal). Duration may be shorter with repeated dosing due to tolerance. Respiratory depression effects may outlast analgesia. |
| Molecular Weight | 327.5 Da (as butorphanol free base; tartrate salt: 477.5 Da) |
1-2 mg intravenously or intramuscularly every 3-4 hours as needed; alternatively, 1-2 mg intranasally as a single dose (for migraine, may repeat after 60 minutes). For patient-controlled analgesia (PCA): 0.5-1 mg intravenous bolus with lockout interval of 10-15 minutes. Epidural: 0.5-2 mg as a single dose.
| Dosage form | INJECTABLE |
| Renal impairment | No specific guidelines for dose adjustment in renal impairment; use with caution. For severe renal impairment (eGFR <30 mL/min), consider reducing dose and/or extending dosing interval due to potential accumulation of active metabolites. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 25-50% and monitor for excessive sedation. Class C: Avoid use or reduce dose to 25% of normal and monitor closely. |
| Pediatric use | Weight-based: 0.01-0.02 mg/kg intravenously or intramuscularly every 3-4 hours as needed; maximum single dose 1 mg. For intranasal: 1 mg as a single dose in patients ≥18 kg (for migraine). Not recommended for PCA in children. |
| Geriatric use | Reduce initial dose by 50% (e.g., 0.5-1 mg IV/IM every 4-6 hours); titrate cautiously due to increased sensitivity to opioid effects and risk of respiratory depression. For intranasal, consider lower dose (0.5 mg). Monitor renal function. |
| 1st trimester | Avoid use; limited data suggest potential teratogenic effects in animal studies. Use only if clearly needed. |
| 2nd trimester | Use only if benefit outweighs risk; may cause fetal respiratory depression and withdrawal in utero. |
| 3rd trimester | Avoid near term; can cause neonatal respiratory depression and withdrawal. Prolonged use may lead to neonatal opioid withdrawal syndrome. |
Clinical note
Comprehensive clinical and safety monograph for BUTORPHANOL TARTRATE (BUTORPHANOL TARTRATE).
| Placental transfer | Butorphanol crosses the placenta readily, with maternal-fetal transfer ratio of about 0.5-0.9. Can cause fetal respiratory depression and decreased fetal heart rate variability. |
| Breastfeeding | Butorphanol is excreted into breast milk in low concentrations. Peak milk levels occur 1-2 hours after administration. Potential for infant sedation and respiratory depression. Consider monitoring for adverse effects. Alternative analgesics preferred. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Butorphanol tartrate is pregnancy category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, butorphanol administered during organogenesis produced increased fetal resorptions and decreased fetal weights at doses 3-6 times the human therapeutic dose. In the first trimester, risks cannot be ruled out. In the second and third trimesters, prolonged use may cause neonatal opioid withdrawal syndrome. Use near term may cause respiratory depression in the neonate. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and blood pressure. Fetal monitoring should include heart rate and variability if used during labor. Prolonged use requires monitoring for neonatal withdrawal syndrome. |
| Fertility Effects | Butorphanol may suppress menstrual cyclicity via opioid-mediated inhibition of gonadotropin-releasing hormone. No human studies on fertility; animal studies show no impairment at therapeutic doses. |
■ FDA Black Box Warning
Concomitant use of opioids with benzodiazepines or other CNS depressants may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
| Serious Effects |
Hypersensitivity to butorphanol or any componentPatients with significant respiratory depressionAcute or severe bronchial asthma in unmonitored settingsSuspected or known gastrointestinal obstructionUse in patients taking or within 14 days of MAO inhibitors
| Precautions | Respiratory depression: especially in patients with compromised respiratory function or when used with other CNS depressants, Dependence and abuse liability: Schedule IV controlled substance, Increases in intracranial pressure: may exacerbate in patients with head injury, Cardiovascular effects: may increase cardiac workload and should be avoided in acute MI, Biliary tract spasm: may cause spasm of the sphincter of Oddi, Withdrawal: may precipitate withdrawal in opioid-dependent patients if given shortly after other mu-agonists |
| Food/Dietary | Avoid alcohol and grapefruit juice (may increase butorphanol levels). No specific food restrictions. |
| Clinical Pearls | Butorphanol is a mixed agonist-antagonist opioid; may precipitate withdrawal in opioid-dependent patients. Ceiling effect on respiratory depression. Higher risk of psychotomimetic effects (dysphoria, hallucinations) compared to morphine. Onset: 1-2 min IV, 5-10 min IM; duration 3-4 hours. Nasal spray has bioavailability ~70%. |
| Patient Advice | May cause drowsiness or dizziness; avoid driving or operating machinery. · Do not take with alcohol or other CNS depressants. · Can cause nausea, vomiting, or sweating; report severe reactions. · Use exactly as prescribed; risk of dependence with long-term use. · If you are dependent on opioids, this drug may cause withdrawal symptoms. · Notify your doctor if you have a history of head injury, asthma, or liver/kidney disease. |
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