BUTORPHANOL TARTRATE PRESERVATIVE FREE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUTORPHANOL TARTRATE PRESERVATIVE FREE (BUTORPHANOL TARTRATE PRESERVATIVE FREE).
Butorphanol is a mixed agonist-antagonist opioid analgesic acting at mu- and kappa-opioid receptors; it exerts its analgesic effects primarily via kappa-opioid receptor agonism and partial mu-opioid receptor agonism/antagonism.
| Metabolism | Primarily hepatic via CYP3A4; undergoes N-dealkylation and hydroxylation; metabolites include norbutorphanol (active) and other inactive metabolites. |
| Excretion | Primarily renal (70-80% as unchanged drug and metabolites; 5% unchanged), biliary/fecal (15-20%), with enterohepatic recirculation. |
| Half-life | Terminal elimination half-life: 2.5-3.5 hours (IV); 4-6 hours (IM). In hepatic impairment, half-life may increase to 5-9 hours; in renal impairment, minimal change unless severe. |
| Protein binding | ~80% bound, primarily to alpha-1 acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | Vd: 4-7 L/kg (range 4.2-7.5 L/kg). Large Vd indicates extensive tissue distribution (e.g., brain, lungs, liver) with slow redistribution. |
| Bioavailability | IM: 80-100%; Intranasal: 60-70% (due to first-pass metabolism); Oral: <5% (extensive first-pass). |
| Onset of Action | IV: 1-2 minutes; IM: 10-15 minutes; Intranasal: 15-30 minutes. |
| Duration of Action | IV/IM: 3-4 hours (analgesic); Intranasal: 4-5 hours. Ceiling effect limits additional analgesia at higher doses. |
Adults: 1-2 mg intramuscularly or intravenously every 3-4 hours as needed for pain; alternatively, 0.5-1 mg intravenously every 3-4 hours. For epidural administration: 1-2 mg at the lumbar level, may repeat once after 60 minutes if needed.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-50 mL/min: Use with caution, consider dose reduction by 25-50%. GFR <30 mL/min: Avoid use or reduce dose by 50% and monitor for prolonged effects. Hemodialysis: Not dialyzable; use with caution. |
| Liver impairment | Child-Pugh A: No adjustment needed. Child-Pugh B: Reduce dose by 50% and monitor. Child-Pugh C: Avoid use or reduce dose by 75% and monitor closely. |
| Pediatric use | Children <18 years: Safety and efficacy not established. For acute pain in children ≥2 years: 0.05-0.1 mg/kg intramuscularly or intravenously every 3-4 hours; maximum single dose 2 mg. Epidural use not recommended in pediatrics. |
| Geriatric use | Elderly patients (≥65 years): Consider starting dose at 50% of adult dose (0.5-1 mg IM/IV) and titrate carefully due to increased sensitivity and risk of respiratory depression. Monitor renal function and adjust dose accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUTORPHANOL TARTRATE PRESERVATIVE FREE (BUTORPHANOL TARTRATE PRESERVATIVE FREE).
| Breastfeeding | Butorphanol is excreted into breast milk in low concentrations. M/P ratio not established. The relative infant dose is estimated to be low (<2% of maternal weight-adjusted dose). Monitor infant for drowsiness, respiratory depression, and withdrawal symptoms if used repeatedly. The American Academy of Pediatrics considers butorphanol compatible with breastfeeding with caution. |
| Teratogenic Risk | Butorphanol is an opioid agonist-antagonist. Data on human pregnancy are limited. Animal studies show no teratogenicity at clinically relevant doses. However, opioid use in pregnancy is associated with risks of neonatal opioid withdrawal syndrome (NOWS) with third-trimester exposure. Avoid use in first trimester unless necessary. Late pregnancy use may cause respiratory depression in the neonate. |
■ FDA Black Box Warning
Risk of respiratory depression; risk of addiction, abuse, and misuse; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; CYP3A4 interactions affecting metabolism.
| Serious Effects |
["Hypersensitivity to butorphanol or any component","Significant respiratory depression","Acute or severe bronchial asthma","Known or suspected gastrointestinal obstruction (including paralytic ileus)","Concurrent use of MAOIs or within 14 days"]
| Precautions | ["Respiratory depression risk, especially in elderly/debilitated/COPD patients","Risk of hypotension and bradycardia","May increase intraocular pressure in glaucoma patients","Dependence and withdrawal with prolonged use","Serotonin syndrome risk with serotonergic drugs","Avoid in patients with head injury or increased intracranial pressure","Use caution in patients with biliary tract disease"] |
| Food/Dietary | No specific food interactions. Avoid grapefruit juice as it may increase butorphanol levels via CYP3A4 inhibition. Maintain adequate hydration to prevent constipation. |
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| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and fetal heart rate if used during labor. For chronic use or near term, assess for fetal growth restriction and preterm labor. Newborns should be observed for signs of NOWS (irritability, poor feeding, respiratory distress) for at least 48 hours after delivery if exposed in the third trimester. |
| Fertility Effects | Based on animal studies and limited human data, butorphanol may impair fertility by altering hormonal regulation (e.g., decreased LH, prolactin, and testosterone). Reversible after discontinuation. No specific human fertility studies available. |
| Clinical Pearls | Butorphanol tartrate preservative-free is indicated for intranasal or parenteral use. It has a ceiling effect for respiratory depression, making it safer than full agonists in equianalgesic doses. Onset of action is rapid (within 15 minutes intranasally). Use with caution in patients with hepatic or renal impairment; reduce dose. Avoid in patients with opioid dependence due to risk of precipitated withdrawal. Monitor for sedation and dizziness, especially in ambulatory patients. |
| Patient Advice | Use exactly as prescribed; do not exceed recommended dose or frequency. · Avoid driving or operating heavy machinery until you know how this medication affects you. · Do not consume alcohol or other central nervous system depressants while using this medication. · Report any difficulty breathing, excessive sedation, or signs of allergic reaction immediately. · Store at room temperature away from light and moisture; keep out of reach of children. |