Drug class: Opiate Partial Agonists
VA class: CN101
CAS number: 58786-99-5

Medically reviewed by Drugs.com on Apr 19, 2023. Written by ASHP.

Introduction

Opiate partial agonist; phenanthrene derivative.^{a b d}

Uses for Butorphanol

Pain

Relief of pain that is severe enough to require an opiate analgesic and for which alternative treatment options (e.g., nonopiate analgesics) have not been, or are not expected to be, adequate or tolerated.⁷⁰⁴

Preoperative sedation and analgesia and as a supplement to surgical anesthesia.^a

Obstetric analgesia during labor.^a

Management of pain associated with migraine headache.^{113 114 116 122}

In equianalgesic doses, parenteral butorphanol is as effective as morphine, meperidine, and pentazocine, but relative potential for abuse reportedly is less than that of codeine or propoxyphene.^d

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.^{431 432 433 435} Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435} Optimize concomitant use of other appropriate therapies.^{432 434 435} (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Butorphanol Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

• Optimize concomitant use of other appropriate therapies.^{432 434 435}

• When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Effects under Cautions.)

• When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.⁴³²

• For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435} Do not prescribe larger quantities for use in case pain continues longer than expected;^{411 432} instead, reevaluate patient if severe acute pain does not remit.^{411 431 435}

• For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.^{430 431 432}

• Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.^{430 431}

• Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.^{430 432} When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.^{430 431}

Administration

Administer IM, by IV injection, or by nasal inhalation.¹¹³

Nasal Administration

Assemble the nasal solution spray pump according to the manufacturer’s instructions.¹¹³ Prior to initial use, fully prime the spray pump; reprime pump whenever it has not been used for ≥48 hours.¹¹³

Consult the manufacturer’s patient instructions regarding use of the nasal solution spray pump.^{113 124}

The nasal solution spray pump is an open delivery system; aim the pump spray away from the patient, other individuals, or animals to minimize environmental exposure.¹¹³

IV Administration

For drug compatibility information, see Compatibility under Stability.

Dosage

Available as butorphanol tartrate; dosage expressed in terms of the salt.^{a b}

After initial priming, the nasal solution spray pump delivers about 14–15 metered doses containing 1 mg per spray.^a If repriming of the pump is necessary, the spray pump will deliver about 8–10 metered doses, depending on the extent of repriming.¹¹³

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.^{411 413 431 432 435}

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.^{700 703} (See Specific Drugs under Interactions.)

Adults

Pain

IV

Initially, 1 mg; may repeat dose every 3–4 hours as necessary.^a Usual effective dosage, depending on severity of pain, is 0.5–2 mg repeated every 3–4 hours.^a

IM

Initially, 2 mg in patients able to remain recumbent; may repeat dose every 3–4 hours as necessary.^a Usual effective dosage, depending on severity of pain, is 1–4 mg repeated every 3–4 hours.^a

Intranasal

Initially, 1 mg (1 spray in 1 nostril); if adequate analgesia is not achieved, may give an additional 1-mg dose within 60–90 minutes.¹¹³ May repeat this initial dose sequence in 3–4 hours, if needed.¹¹³

For management of severe pain: Initially, 2 mg (1 spray in each nostril) in patients who can remain recumbent if drowsiness or dizziness occurs.¹¹³ Do not administer additional 2-mg doses at intervals <3–4 hours, since the incidence of adverse effects may be increased.¹¹³

Preoperative Sedation and Analgesia

IM

Usual dosage is 2 mg administered 60–90 minutes before surgery.^a

Supplement to Surgical Anesthesia

IV

2 mg shortly before induction of anesthesia and/or 0.5–1 mg administered during anesthesia in increments up to 0.06 mg/kg (depending on previous administration of sedatives, analgesics, and hypnotic agents).^a Usual total dose is 4–12.5 mg (approximately 0.06–0.18 mg/kg).^a

Obstetric Analgesia

IV or IM

1–2 mg administered in patients at full term in early labor; may repeat after 4 hours.^a Use alternative analgesia if delivery expected within 4 hours.^a

Prescribing Limits

Adults

Pain

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435}

Some states have set prescribing limits for opiate analgesics (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).^{411 420 421 423}

IM

Maximum 4 mg as a single dose.^a

Special Populations

Hepatic Impairment

Pain

IV

Initially, 0.5 mg.¹¹³ If necessary, repeat dose at an interval of ≥6 hours.¹¹³

IM

Initially, 1 mg.¹¹³ If necessary, repeat dose at an interval of ≥6 hours.¹¹³

Intranasal

Initially, 1 mg (1 spray in 1 nostril); may give an additional 1-mg dose within 90–120 minutes, if necessary.¹¹³ May repeat this initial dose sequence at an interval of ≥6 hours.¹¹³

Renal Impairment

Patients with renal impairment may receive the same IV, IM, or intranasal dosages as patients with hepatic impairment.¹¹³

Geriatric Patients

Geriatric patients may receive the same IV, IM, or intranasal dosages as patients with hepatic impairment.¹¹³

Cautions for Butorphanol

Contraindications

• Known hypersensitivity to butorphanol or benzethonium chloride (contained in the multiple-dose vials of the injection or in the nasal solution).^{a b}

Warnings/Precautions

Warnings

Abuse Potential

Possible tolerance, psychologic dependence, and physical dependence.^{a b d} Episodes of abuse associated with all routes of administration, especially nasal administration.^{a b}

Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence; use only with careful surveillance in such patients.^{a b}

Respiratory Effects

Possible respiratory depression, especially in patients with impaired respiration caused by other drugs, uremia, severe infection, severely limited respiratory reserve, bronchial asthma, respiratory obstruction, or cyanosis.^{a b d} Use with caution and in lower dosages in these patients.^{a b d}

Routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics, including butorphanol.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of opiate use disorder [OUD], those who have experienced a prior opiate overdose).⁷⁵⁰

Patients Dependent on Opiates

Partial opiate antagonist; not recommended for use in patients physically dependent on opiates^a because of the potential to precipitate symptoms of withdrawal (e.g., anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, diarrhea).^{128 129}

Use with caution in patients who recently received repeated doses of opiate analgesics; allow an adequate period of withdrawal from opiates before initiation of butorphanol therapy.^{128 129}

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiate agonists or opiate partial agonists, including butorphanol, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiates, alcohol) may result in profound sedation, respiratory depression, coma, and death.^{416 417 418 700 701 702 703} Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{416 417 418 435 700 701}

Reserve concomitant use of butorphanol and other CNS depressants for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs under Interactions.)

General Precautions

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.^{a b}

Concurrent use of other CNS depressants may potentiate CNS depression^{a b} and may result in profound sedation, respiratory depression, coma, or death.^{700 703} (See Concomitant Use with Benzodiazepines or Other CNS Depressants under Cautions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.⁴⁰⁰ Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.⁴⁰⁰

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.⁴⁰⁰ If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.⁴⁰⁰ In some patients, switching to a different opiate improved symptoms.⁴⁰⁰

Head Injury and Increased Intracranial Pressure

Adverse effects of opiates may obscure the existence, extent, or course of intracranial pathology.¹¹³ Use in patients with head injury only if the potential benefits justify the possible risks.¹¹³

Cardiovascular Effects

Possible increased myocardial workload; use in patients with AMI, ventricular dysfunction, or coronary insufficiency only if the potential benefits justify the possible risks.^{a b}

Severe hypertension reported rarely.^{a b} If hypertension occurs, discontinue and administer a hypotensive agent as necessary; butorphanol-induced hypertension reportedly has been managed with naloxone in patients who were not opiate dependent.¹¹³

Use cautiously before surgery or anesthesia in hypertensive patients.^d

Possible hypotension associated with syncope in patients receiving nasal solution; caution patients against performing activities that may pose risks if hypotension were to occur.¹¹³

Biliary Tract Surgery

Safe use in patients about to undergo biliary tract surgery has not been established; use with caution.^d

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;^{400 401 402 403 404} causality not established.⁴⁰⁰ Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.⁴⁰⁰ Perform appropriate laboratory testing in patients with manifestations of hypogonadism.⁴⁰⁰

Specific Populations

Pregnancy

Category C.^{a b}

Use of intranasal spray not recommended during labor and delivery.

Lactation

Distributed into milk following parenteral administration, but not in clinically important amounts at usual therapeutic dosages.¹¹³

No experience with use of nasal solution in nursing women; estimated that amount of drug distributed into milk will be similar to that when administered parenterally.^{113 b}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{a b}

Geriatric Use

Select dosage with caution.¹¹³ (See Geriatric Patients under Dosage and Administration.)

Possible increased sensitivity to the drug in some geriatric individuals.¹¹³

Insufficient experience with the nasal solution in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^b

Hepatic Impairment

Use with caution.^{a b} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Use with caution.^{a b} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Sedation, dizziness, nausea and/or vomiting.^{a b}

Drug Interactions

Not known whether drugs that affect hepatic microsomal enzymes may interfere with metabolism of butorphanol.¹¹³

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.⁴⁰⁰ May occur at usual dosages.⁴⁰⁰ Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.⁴⁰⁰ (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.⁴⁰⁰

If serotonin syndrome is suspected, discontinue butorphanol, other opiate therapy, and/or any concurrently administered serotonergic agents.⁴⁰⁰

Specific Drugs

Butorphanol Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following IM injection; peak plasma concentrations usually attained within 30–60 minutes.^{a d}

Following nasal inhalation, peak blood concentrations are achieved in about 30–60 minutes.^{113 114} Absolute bioavailability of nasally administered butorphanol is 60–70% and appears to be unchanged in patients with allergic rhinitis.^a

Completely absorbed from the GI tract following oral administration; however, after first-pass metabolism, bioavailability is only 5–17%.^{a b}

Onset

Onset of analgesic activity occurs in a few minutes after IV administration or within 15 minutes after IM administration;^{a b} peak analgesic effect achieved within 30–60 minutes after IV or IM administration.^a

After nasal inhalation in postoperative patients, onset of analgesia occurs within 15 minutes;^{113 114 125} peak analgesic effect achieved within 1–2 hours.^b

Duration

After IV or IM administration, duration of analgesia is 3–4 hours.^{a b}

After nasal inhalation in postoperative patients, duration of analgesia is approximately 2.5–5 hours.^{113 114 125}

Distribution

Extent

Highest concentrations of butorphanol and its metabolites in animals are found in the liver, kidneys, and intestine; drug concentrations are higher in the lungs, spleen, heart, endocrine tissues, blood cells, and fat tissue than in plasma; brain concentrations are lower than plasma concentrations.^d

Rapidly crosses the placenta and is distributed into milk.^{a b}

Plasma Protein Binding

About 80%.^{a b}

Elimination

Metabolism

Extensively metabolized in the liver, principally by hydroxylation; N-dealkylation and conjugation of butorphanol and its metabolites also occur.^{a b d} Metabolites have no analgesic activity.^d

Elimination Route

Excreted principally in urine (70–80%) mainly as metabolites; also excreted in feces (15%).^{a b}

Half-life

About 4.6–4.7 hours following intranasal or IV administration.^{113 114}

Special Populations

In patients with hepatic impairment, elimination half-life of 16.8 hours reported.^b

In patients with renal impairment (Cl_cr <30 mL/minute), elimination half-life of 10.5 hours reported.¹¹³

In geriatric individuals, elimination half-life reported to be about 5.6 hours (range 3.3–8.8 hours) or 6.6 hours (range: 3.8–9.2 hours) following IV or intranasal administration, respectively.¹¹³

Stability

Storage

Nasal

Solution

25°C.^b

Parenteral

Injection

15–30°C; protect from light.^a

Compatibility

Drug Compatibility

Actions

• Analgesic effect is believed to result from an interaction with an opiate receptor site in the CNS (probably in or associated with the limbic system).^a

• Opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but other mechanisms probably also are involved.^d Butorphanol exerts antagonistic^{114 115 126} or partially antagonistic¹¹³ effects at μ opiate receptor sites; it appears to exerts agonistic effects principally at κ and Σ opiate receptors.^{101 102 103 104}

• Produces respiratory depression, sedation, miosis and, in animals, antitussive effect.^a

• Slightly increases pulmonary artery pressure, pulmonary wedge pressure, left ventricular end-diastolic pressure, systemic arterial pressure, pulmonary vascular resistance, and cardiac index.^a

• In animals, inhibits GI motility slightly, causes little increase in duodenal smooth muscle activity, and has little or no effect on bile duct flow.^d

Advice to Patients

• Potential for butorphanol to impair mental alertness or physical coordination; do not drive or operate machinery for ≥1 hour after receiving the drug or until effects on individual are known.^{a b}

• Patients receiving the nasal solution should not perform activities that may pose risks if hypotension were to occur.¹¹³

• Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.^{a b}

• Risk of respiratory depression following overdosage.⁷⁵⁰ Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.⁷⁵⁰

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.^{700 703} Importance of informing patients that butorphanol should not be combined with alcohol.^{700 a b}

• Potential risk of serotonin syndrome with concurrent use of butorphanol and other serotonergic agents.⁴⁰⁰ Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.⁴⁰⁰

• Potential risk of adrenal insufficiency.⁴⁰⁰ Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.⁴⁰⁰

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.⁴⁰⁰ Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.⁴⁰⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption.^{a b}

• Importance of women informing their clinician if they are or plan to become pregnant or to breast-feed.^{a b}

• Importance of advising patients of other important precautionary information.^{a b} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.^{127 128 129}

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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