BUTORPHANOL TARTRATE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUTORPHANOL TARTRATE (BUTORPHANOL TARTRATE).
| Breastfeeding | Butorphanol is excreted into human milk. The milk-to-plasma ratio (M/P) is approximately 0.7. Limited data suggest low levels; however, due to potential for serious adverse reactions in nursing infants, caution should be exercised. The manufacturer recommends avoiding use while breastfeeding. |
| 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. |
■ 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 tartrate or any component of the formulation","Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation","Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting","Known or suspected gastrointestinal obstruction","Patients who are physically dependent on mu-agonists due to risk of acute withdrawal"]
| 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"] |
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| 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. |
| 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. |