Butorphanol - Drug Monograph

Introduction

Butorphanol is a synthetic opioid agonist-antagonist analgesic medication with a complex pharmacological profile. First approved by the FDA in 1978, it occupies a unique position among pain management medications due to its mixed opioid receptor activity. Butorphanol is classified as a Schedule IV controlled substance due to its potential for abuse and dependence, though this risk is generally considered lower than with pure mu-opioid agonists.

Mechanism of Action

Butorphanol exerts its analgesic effects through complex interactions with multiple opioid receptors:

• Acts as a partial agonist at kappa-opioid receptors
• Functions as a weak partial agonist or antagonist at mu-opioid receptors
• Has minimal activity at delta-opioid receptors
• Also possesses some activity at nociceptin/orphanin FQ peptide receptors

This unique receptor profile results in potent analgesia with a potentially lower risk of respiratory depression and abuse liability compared to pure mu-opioid agonists. The kappa receptor activation contributes to its analgesic effects while producing less euphoria than mu agonists.

Indications

• Management of moderate to severe pain
• Pain relief during labor
• Preoperative or pre-anesthetic medication and sedation
• Balanced anesthesia adjunct

• Migraine treatment (particularly in emergency settings)
• Management of opioid-induced pruritus
• Treatment of shivering post-anesthesia

Dosage and Administration

• Adults: 1-4 mg IM every 3-4 hours as needed
• IV administration: 0.5-2 mg every 3-4 hours
• Maximum recommended dose: 4 mg per dose

• Initial dose: 1 mg (1 spray in one nostril)
• Repeat dose in 60-90 minutes if needed
• Subsequent doses: 1 mg every 3-4 hours
• Maximum: 4 mg per dose or 8 mg daily

• Renal impairment: Use with caution; consider dose reduction
• Hepatic impairment: Use with caution; significant impairment may require dose adjustment
• Elderly: Start with lower doses due to increased sensitivity
• Pediatric: Safety and effectiveness not established

Pharmacokinetics

• Nasal: Bioavailability approximately 60-70%
• IM: Rapid absorption with onset within 10-30 minutes
• IV: Immediate onset of action

• Volume of distribution: 300-400 L
• Protein binding: 80%
• Crosses placenta and blood-brain barrier

• Extensive hepatic metabolism via hydroxylation
• Primary metabolite: hydroxybutorphanol
• CYP3A4 enzyme involvement

• Half-life: 3-4 hours
• Excretion: Primarily renal (70-80%), with fecal elimination accounting for remainder
• Clearance: 30-40 L/hour

Contraindications

• Hypersensitivity to butorphanol or any component of the formulation
• Patients with significant respiratory depression or acute asthma exacerbation
• Known or suspected paralytic ileus
• Patients receiving MAO inhibitors within past 14 days

Warnings and Precautions

• Potential for abuse, addiction, and dependence similar to other opioids

• Respiratory depression: Monitor closely, especially in elderly or debilitated patients
• CNS depression: May impair mental/physical abilities required for hazardous tasks
• Head injury: Use with extreme caution due to potential for increased ICP
• Cardiovascular effects: May cause hypertension in some patients
• Pregnancy: Prolonged use during pregnancy can result neonatal opioid withdrawal syndrome
• Breastfeeding: Not recommended due to secretion in breast milk

Drug Interactions

• CNS depressants (benzodiazepines, alcohol, other opioids): Additive CNS depression
• MAO inhibitors: Risk of serotonin syndrome
• Opioid antagonists: May precipitate withdrawal in dependent patients
• CYP3A4 inhibitors/inducers: May alter butorphanol metabolism

• Anticholinergic agents: Increased risk of urinary retention and constipation
• Mixed agonist-antagonist opioids: May reduce analgesic effect or precipitate withdrawal

Adverse Effects

• Sedation (40-50%)
• Dizziness (30-40%)
• Nausea (10-15%)
• Vasodilation/flushing

• Vomiting
• Anxiety
• Confusion
• Pruritus
• Sweating
• Dry mouth

• Respiratory depression
• Hypotension/hypertension
• Dependence and withdrawal
• Anaphylaxis
• Seizures
• Hallucinations

Monitoring Parameters

• Pain intensity and relief scores
• Respiratory rate and oxygen saturation
• Blood pressure and heart rate
• Mental status and sedation level
• Signs of misuse or abuse
• Bowel function (constipation)
• Renal and hepatic function in long-term use
• Signs of withdrawal upon discontinuation

Patient Education

• Use exactly as prescribed; do not increase dose without consulting provider
• Avoid alcohol and other CNS depressants during treatment
• Do not drive or operate machinery until effects are known
• Report any difficulty breathing or excessive sedation immediately
• Store securely to prevent misuse by others
• Proper nasal spray administration technique
• Dispose of unused medication properly
• Be aware of potential for dependence with prolonged use
• Report any signs of allergic reaction
• Maintain adequate hydration and fiber intake to prevent constipation

References

1. FDA Prescribing Information: Stadol NS (butorphanol tartrate) Nasal Spray 2. American Pain Society. (2016). Guidelines on the Management of Postoperative Pain 3. Dahan A, et al. (2010). Butorphanol and morphine-induced analgesia, respiratory depression, and itch. Anesthesiology 4. Pergolizzi JV, et al. (2018). Butorphanol: a review of its pharmacology and clinical utility. Pain Practice 5. Micromedex Solutions: Butorphanol Drug Information 6. Lexicomp Online: Butorphanol Monograph 7. National Institute on Drug Abuse. (2020). Opioid Overdose Crisis 8. World Health Organization. (2018). Guidelines for the Pharmacological Management of Persisting Pain in Adults