Butorphanol (injection)

Butorphanol (injection)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Overview

Butorphanol (injection) is an opioid agonist-opioid antagonist, analgesic that is FDA approved for the treatment of management of pain when the use of an opioid analgesic is appropriate.. Common adverse reactions include nausea, vomiting, dizziness, Insomnia, Sedation, Somnolence, nasal congestion and a long-term use of intranasal product.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and surgical procedure involved. Use in the elderly and in patients with hepatic or renal disease requires extra caution. The following doses are for patients who do not have impaired hepatic or renal function and who are not on CNS active agents:

Management of Pain

• Dosage:
  • The usual recommended dose for initial nasal administration of butorphanol tartrate nasal solution is 1 mg (1 spray in one nostril). Adherence to this dose reduces the incidence of drowsiness and dizziness. If adequate pain relief is not achieved within 60 to 90 minutes, an additional 1 mg dose may be given.
  • The initial dose sequence outlined above may be repeated in 3 to 4 hours as required after the second dose of the sequence.
  • Depending on the severity of the pain, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent in the event drowsiness or dizziness occurs. In such patients single additional 2 mg doses should not be given for 3 to 4 hours.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Butorphanol in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Butorphanol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Butorphanol (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Butorphanol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Butorphanol in pediatric patients.

Contraindications

Butorphanol tartrate nasal solution is contraindicated in patients hypersensitive to butorphanol tartrate or the preservative benzethonium chloride.

Warnings

Patients Dependent on Narcotics

Because of its opioid antagonist properties, butorphanol is not recommended for use in patients dependent on narcotics. Such patients should have an adequate period of withdrawal from opioid drugs prior to beginning butorphanol therapy. In patients taking opioid analgesics chronically, butorphanol has precipitated withdrawal symptoms such as anxiety, agitation, mood changes, hallucinations, dysphoria, weakness and diarrhea.

Because of the difficulty in assessing opioid tolerance in patients who have recently received repeated doses of narcotic analgesic medication, caution should be used in the administration of butorphanol to such patients.

Drug Abuse and Dependence

Drug Abuse: Butorphanol tartrate, by all routes of administration, has been associated with episodes of abuse. Of the cases received, there were more reports of abuse with the nasal solution formulation than with the injectable formulation.

Physical Dependence, Tolerance and Withdrawal

Prolonged, continuous use of butorphanol tartrate may result in physical dependence or tolerance (a decrease in response to a given dose). Abrupt cessation of use by patients with physical dependence may result in symptoms of withdrawal.

Note: Proper patient selection, dose and prescribing limitations, appropriate directions for use, and frequent monitoring are important to minimize the risk of abuse and physical dependence (see DRUG ABUSE AND DEPENDENCE).

Adverse Reactions

Clinical Trials Experience

A total of 2446 patients were studied in premarketing clinical trials of butorphanol. Approximately half received butorphanol tartrate injection with the remainder receiving butorphanol tartrate nasal solution. In nearly all cases the type and incidence of side effects with butorphanol by any route were those commonly observed with opioid analgesics.

The adverse experiences described below are based on data from short-term and long-term clinical trials in patients receiving butorphanol by any route. There has been no attempt to correct for placebo effect or to subtract the frequencies reported by placebo-treated patients in controlled trials. The most frequently reported adverse experiences across all clinical trials were somnolence (43%), dizziness (19%), nausea and/or vomiting (13%). In long-term trials with butorphanol tartrate nasal solution only, nasal congestion (13%) and insomnia (11%) were frequently reported.

The following adverse experiences were reported at a frequency of 1% or greater in clinical trials, and were considered to be probably related to the use of butorphanol:

Body as a Whole

• Asthenia/lethargy
• Headache
• Sensation of heat

Cardiovascular

• Vasodilation
• Palpitations

Digestive

• Anorexia
• Constipation
• Dry mouth
• Nausea and/or vomiting
• Stomach pain

Nervous

• Anxiety
• Confusion
• Dizziness
• Euphoria
• Floating feeling
• Insomnia
• Nervousness
• Paresthesia
• Somnolence
• Tremor

Respiratory

• Bronchitis
• Cough
• Dyspnea
• Epistaxis
• Nasal congestion
• Nasal irritation
• Pharyngitis
• Rhinitis
• Sinus congestion
• Sinusitis
• Upper respiratory infection

Skin and Appendages

• Sweating/clammy
• Pruritus

Special Senses

• Blurred vision
• Ear pain
• Tinnitus
• Unpleasant taste

The following adverse experiences were reported with a frequency of less than 1% in clinical trials, and were considered to be probably related to the use of butorphanol:

Cardiovascular

• Hypotension
• Syncope

Nervous

• Abnormal dreams
• Agitation
• Dysphoria
• Hallucinations
• Hostility
• Withdrawal symptoms

Skin and Appendages

• Rash/hives

Urogenital

• Impaired urination

Postmarketing Experience

Postmarketing experience with butorphanol tartrate nasal solution has shown an adverse event profile similar to that seen during the premarketing evaluation of butorphanol by all routes of administration. Adverse experiences that were associated with the use of butorphanol tartrate nasal solution and that are not listed above have been chosen for inclusion below because of their seriousness, frequency of reporting, or probable relationship to butorphanol. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse experiences include apnea, convulsion, delusion, drug dependence, excessive drug effect associated with transient difficulty speaking and/or executing purposeful movements, overdose, and vertigo. Reports of butorphanol overdose with a fatal outcome have usually but not always been associated with ingestion of multiple drugs.

Drug Interactions

Concurrent use of butorphanol with central nervous system depressants (e.g., alcohol, barbiturates, tranquilizers, and antihistamines) may result in increased central nervous system depressant effects. When used concurrently with such drugs, the dose of butorphanol should be the smallest effective dose and the frequency of dosing reduced as much as possible when administered concomitantly with drugs that potentiate the action of opioids.

In healthy volunteers, the pharmacokinetics of a 1 mg dose of butorphanol administered as butorphanol tartrate nasal solution were not affected by the co-administration of a single 6 mg subcutaneous dose of sumatriptan. However, in another study in healthy volunteers, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in Cmax) when a 1 mg dose of butorphanol tartrate nasal solution was administered 1 minute after a 20 mg dose of sumatriptan nasal solution. (The two drugs were administered in opposite nostrils.) When butorphanol tartrate nasal solution was administered 30 minutes after the sumatriptan nasal solution, the AUC of butorphanol increased 11% and Cmax decreased 18%. In neither case were the pharmacokinetics of sumatriptan affected by co-administration with butorphanol tartrate nasal solution. These results suggest that the analgesic effect of butorphanol tartrate nasal solution may be diminished when it is administered shortly after sumatriptan nasal solution, but by 30 minutes any such reduction in effect should be minimal.

• The safety of using butorphanol tartrate nasal solution and IMITREX® (sumatriptan) Nasal Spray during the same episode of migraine has not been established. However, it should be noted that both products are capable of producing transient increases in blood pressure.
• The pharmacokinetics of a 1 mg dose of butorphanol administered as butorphanol tartrate nasal solution were not affected by the co-administration of cimetidine (300 mg QID). Conversely, the administration of butorphanol tartrate nasal solution (1 mg butorphanol QID) did not alter the pharmacokinetics of a 300 mg dose of cimetidine.
• It is not known if the effects of butorphanol are altered by other concomitant medications that affect hepatic metabolism of drugs (erythromycin, theophylline, etc.), but physicians should be alert to the possibility that a smaller initial dose and longer intervals between doses may be needed.
• The fraction of butorphanol tartrate nasal solution absorbed is unaffected by the concomitant administration of a nasal vasoconstrictor (oxymetazoline), but the rate of absorption is decreased. Therefore, a slower onset can be anticipated if butorphanol tartrate nasal solution is administered concomitantly with, or immediately following, a nasal vasoconstrictor.
• No information is available about the use of butorphanol concurrently with MAO inhibitors.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C Reproduction studies in mice, rats and rabbits during organogenesis did not reveal any teratogenic potential to butorphanol. However, pregnant rats treated subcutaneously with butorphanol at 1 mg/kg (5.9 mg/m2) had a higher frequency of stillbirths than controls. Butorphanol at 30 mg/kg/oral (360 mg/m2) and 60 mg/kg/oral (720 mg/m2) also showed higher incidences of post-implantation loss in rabbits.

There are no adequate and well-controlled studies of butorphanol tartrate in pregnant women before 37 weeks of gestation. Butorphanol tartrate should be used during pregnancy only if the potential benefit justifies the potential risk to the infant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Butorphanol (injection) in women who are pregnant.

Labor and Delivery

Butorphanol tartrate nasal solution is not recommended during labor or delivery because there is no clinical experience with its use in this setting.

Nursing Mothers

Although there is no clinical experience with the use of butorphanol tartrate nasal solution in nursing mothers, it should be assumed that butorphanol will appear in the milk in similar amounts following the nasal route of administration.

Pediatric Use

Butorphanol is not recommended for use in patients below 18 years of age because safety and efficacy have not been established in this population.

Geriatic Use

Of the approximately 1700 patients treated with butorphanol tartrate nasal solution in clinical studies, 8% were 65 years of age or older and 2% were 75 years or older. Due to changes in clearance, the mean half-life of butorphanol is increased by 25% (to over 6 hours) in patients over the age of 65 years. Elderly patients may be more sensitive to the side effects of butorphanol. In clinical studies of butorphanol tartrate nasal solution, elderly patients had an increased frequency of headache, dizziness, drowsiness, vertigo, constipation, nausea and/or vomiting, and nasal congestion compared with younger patients. There are insufficient efficacy data for patients ≥ 65 years to determine whether they respond differently from younger patients.

Initially a 1 mg dose of butorphanol tartrate nasal solution should generally be used in geriatric patients and 90 to 120 minutes should elapse before administering a second 1 mg dose, if needed (see CLINICAL PHARMACOLOGY, INDIVIDUALIZATION OF DOSAGE).

Butorphanol and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection.

Gender

There is no FDA guidance on the use of Butorphanol (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Butorphanol (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Butorphanol (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Butorphanol (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Butorphanol (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Butorphanol (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Butorphanol (injection) Administration in the drug label.

Monitoring

There is limited information regarding Butorphanol (injection) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Butorphanol (injection) and IV administrations.

Overdosage

Clinical Manifestations

The clinical manifestations of butorphanol overdose are those of opioid drugs in general. Consequences of overdose vary with the amount of butorphanol ingested and individual response to the effects of opiates. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death. Butorphanol overdose may be associated with ingestion of multiple drugs. Overdose can occur due to accidental or intentional misuse of butorphanol, especially in young children who may gain access to the drug in the home.

Treatment

The management of suspected butorphanol overdosage includes maintenance of adequate ventilation, peripheral perfusion, normal body temperature, and protection of the airway. Patients should be under continuous observation with adequate serial measures of mental state, responsiveness and vital signs. Oxygen and ventilatory assistance should be available with continual monitoring by pulse oximetry if indicated. In the presence of coma, placement of an artificial airway may be required. An adequate intravenous portal should be maintained to facilitate treatment of hypotension associated with vasodilation. The use of a specific opioid antagonist such as naloxone should be considered. As the duration of butorphanol action usually exceeds the duration of action of naloxone, repeated dosing with naloxone may be required. In managing cases of suspected butorphanol overdosage, the possibility of multiple drug ingestion should always be considered.

Pharmacology

Butorphanol (injection)
Systematic (IUPAC) name
(4bR,8aR,9S)-11-(cyclobutylmethyl)-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene-3,8a-diol
Identifiers
CAS number	42408-82-2
ATC code	N02AF01 Template:ATCvet
PubChem	5361092
DrugBank	DB00611
Chemical data
Formula	Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass	327.473 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	Nasal: 60-70%
Metabolism	Hepatic hydroxylated & glucuronidated
Half life	4-7 hours
Excretion	Renal, 75% Biliary, 11-14% Fecal, 15%
Therapeutic considerations
Pregnancy cat.	C/D (United States)
Legal status	Controlled (S8)(AU) Schedule IV(US)
Routes	IV, intranasal, oral

Mechanism of Action

Butorphanol is a mixed agonist-antagonist with low intrinsic activity at receptors of the µ-opioid type (morphine-like). It is also an agonist at K -opioid receptors. Its interactions with these receptors in the central nervous system apparently mediate most of its pharmacologic effects, including analgesia.

In addition to analgesia, CNS effects include depression of spontaneous respiratory activity and cough, stimulation of the emetic center, miosis and sedation. Effects possibly mediated by non-CNS mechanisms include alteration in cardiovascular resistance and capacitance, bronchomotor tone, gastrointestinal secretory and motor activity and bladder sphincter activity.

In an animal model, the dose of butorphanol tartrate required to antagonize morphine analgesia by 50% was similar to that for nalorphine, less than that for pentazocine and more than that for naloxone.The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity. In human studies of butorphanol (see CLINICAL TRIALS), sedation is commonly noted at doses of 0.5 mg or more. Narcosis is produced by 10 to 12 mg doses of butorphanol administered over 10 to 15 minutes intravenously.

Butorphanol, like other mixed agonist-antagonists with a high affinity for the ĸ-receptor, may produce unpleasant psychotomimetic effects in some individuals. Nausea and/or vomiting may be produced by doses of 1 mg or more administered by any route.

Structure

Butorphanol tartrate is a synthetically derived opioid agonist-antagonist analgesic of the phenanthrene series. The chemical name is (-)-17-(cyclobutylmethyl)morphinan-3,14-diol[S-(R*,R*)]-2,3-dihydroxy-butanedioate (1:1) (salt). The molecular formula is C21H29NO2•C4H6O6, which corresponds to a molecular weight of 477.55 and the following structural formula:

Pharmacodynamics

The analgesic effect of butorphanol is influenced by the route of administration. Onset of analgesia is within a few minutes for intravenous administration, within 15 minutes for intramuscular injection, and within 15 minutes for the nasal solution doses. Peak analgesic activity occurs within 30 to 60 minutes following intravenous and intramuscular administration and within 1 to 2 hours following the nasal spray administration.

The duration of analgesia varies depending on the pain model as well as the route of administration, but is generally 3 to 4 hours with IM and IV doses as defined by the time 50% of patients required remedication. In postoperative studies, the duration of analgesia with IV or IM butorphanol was similar to morphine, meperidine, and pentazocine when administered in the same fashion at equipotent doses. Compared to the injectable form and other drugs in this class, butorphanol tartrate nasal solution has a longer duration of action (4 to 5 hours).

Pharmacokinetics

Absorption

After nasal administration, mean peak blood levels of 0.9 to 1.04 ng/mL occur at 30 to 60 minutes after a 1 mg dose (see Table 1). The absolute bioavailability of butorphanol tartrate nasal solution is 60% to 70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. The peak plasma concentrations were approximately half those achieved in the absence of the vasoconstrictor.

Following its initial absorption/distribution phase, the single dose pharmacokinetics of butorphanol by the intravenous, intramuscular, and nasal routes of administration are similar (see Figure 1).

Distribution

Serum protein binding is independent of concentration over the range achieved in clinical practice (up to 7 ng/mL) with a bound fraction of approximately 80%. The volume of distribution of butorphanol varies from 305 to 901 liters and total body clearance from 52 to 154 liters/hour (see Table 1).

Dose proportionality for butorphanol tartrate nasal solution has been determined at steady state in doses up to 4 mg at 6 hour intervals. Steady state is achieved within 2 days. The mean peak plasma concentration at steady state was 1.8-fold (maximal 3-fold) following a single dose. The drug is transported across the blood brain and placental barriers and into human milk.

Metabolism

Butorphanol is extensively metabolized in the liver. Metabolism is qualitatively and quantitatively similar following intravenous, intramuscular, or nasal administration. Oral bioavailability is only 5 to 17% because of extensive first pass metabolism of butorphanol.

The major metabolite of butorphanol is hydroxybutorphanol, while norbutorphanol is produced in small amounts. Both have been detected in plasma following administration of butorphanol, with norbutorphanol present at trace levels at most time points. The elimination half-life of hydroxybutorphanol is about 18 hours and, as a consequence, considerable accumulation (≈ 5-fold) occurs when butorphanol is dosed to steady state (1 mg transnasally q6h for 5 days).

Elimination

Elimination occurs by urine and fecal excretion. When 3H labelled butorphanol is administered to normal subjects, most (70 to 80%) of the dose is recovered in the urine, while approximately 15% is recovered in the feces. About 5% of the dose is recovered in the urine as butorphanol. Forty-nine percent is eliminated in the urine as hydroxybutorphanol. Less than 5% is excreted in the urine as norbutorphanol.

Butorphanol pharmacokinetics in the elderly differ from younger patients (see Table 1). The mean absolute bioavailability of butorphanol tartrate nasal solution in elderly women (48%) was less than that in elderly men (75%), young men (68%) or young women (70%). Elimination half-life is increased in the elderly (6.6 hours as opposed to 4.7 hours in younger subjects).

In renally impaired patients with creatinine clearances <30 mL/min, the elimination half-life was approximately doubled and the total body clearance was approximately one half (10.5 hours [clearance 150 L/h] compared to 5.8 hours [clearance 260 L/h] in healthy subjects). No effect on Cmax or Tmax was observed after a single dose.

After intravenous administration to patients with hepatic impairment, the elimination half-life of butorphanol was approximately tripled and total body clearance was approximately one half (half-life 16.8 hours, clearance 92 L/h) compared to healthy subjects (half-life 4.8 hours, clearance 175 L/h). The exposure of hepatically impaired patients to butorphanol was significantly greater (about 2-fold) than that in healthy subjects. Similar results were seen after nasal administration. No effect on Cmax or Tmax was observed after a single intranasal dose.

Nonclinical Toxicology

There is limited information regarding Butorphanol (injection) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Butorphanol (injection) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Butorphanol (injection) How Supplied in the drug label.

Storage

There is limited information regarding Butorphanol (injection) Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Butorphanol (injection) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Butorphanol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Butorphanol (injection) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Butorphanol (injection) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Butorphanol
BUTORPHANOL TARTRATE spray® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages
Butorphanol tartrate (butorphanol tartrate) injection, solution® FDA Package Insert
Indications and Usage
Dosage and Administration
Dosage Forms and Strengths
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
Clinical Studies
How Supplied/Storage and Handling
Patient Counseling Information
Labels and Packages
Clinical Trials on Butorphanol
ClinicalTrials.gov

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [4]

For patient information about Butorphanol, click here.

Synonyms / Brand Names: BUTORPHANOL TARTRATE(butorphanol tartrate )solution [Apotex Corp.]^®,Butorphanol tartrate (butorphanol tartrate injection, solution [Apotex Inc.]^®, BUTORPHANOL TARTRATE injection, solution [West-ward Pharmaceutical Corp]^®

Overview

Butorphanol (injection)

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Clinical data
Pregnancy category	C/D (U.S.)
Routes of administration	IV, intranasal
ATC code	N02AX02 (WHO)
Legal status
Legal status	US: Schedule IV
Pharmacokinetic data
Bioavailability	Nasal: 60-70%
Metabolism	Hepatic hydroxylated & glucuronidated
Elimination half-life	4-7 hours
Excretion	Renal, 75% Biliary, 11-14% Fecal, 15%
Identifiers
IUPAC name 17-cyclobutylmethyl- morphinan-3,14-diol
CAS Number	42408-82-2
PubChem CID	5361092
DrugBank	APRD00835
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C21H29NO2
Molar mass	327.473

Butorphanol (INN) is a morphinan-type synthetic opioid analgesic marketed in the U.S. under the trade name Stadol. It is most closely structurally related to dextromethorphan. Butorphanol is available only as butorphanol tartrate in injectable and intranasal spray formulations.

BUTORPHANOL TARTRATE spray

| Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Butorphanol tartrate (butorphanol tartrate) injection, solution

Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Mechanism of Action

Butorphanol exhibits partial agonist and antagonist activity at the μ opioid receptor and agonist activity at the κ opioid receptor. Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways. Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.

Place in therapy

The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor. Butorphanol is more effective in reducing pain in women than in men.

Adverse effects

As with other opioid analgesics, central nervous system effects (such as sedation, confusion, and dizziness) are considerations with butorphanol. Nausea and vomiting are common. Less common are the gastrointestinal effects of other opioids (mostly constipation).

Proprietary preparations

Butorphanol is available in the U.S. as a generic drug; it is available in various nations under one of any number of trade names, including Moradol, Beforal, Stadol, and Stadol NS; veterinary trade names include Butorphic, Dolorex, Morphasol, Torbugesic, and Torbutrol.

Use in horses

Butorphanol is a commonly used narcotic for pain relief in horses. It is administered either IM or IV, with its analgestic properties beginning to take effect about 15 minutes after injection and lasting 4 hours. It is also commonly paired with sedatives, such as xylazine and detomidine, to make the horse easier to handle during veterinary proceedures.

Side effects, overdose, and precautions

Side effects specific to horses include sedation, CNS excitement (displayed by head pressing or tossing). Overdosing may result in seizures, falling, salivation, constipation, and muscle twitching. If an overdose occurs, a narcotic antagonist, such as naloxone, may be given. Caution should be used if Butorphanol is administered in addition to other narcotics, sedatives, depressants, or antihistamines as it will cause an additive effect.

Butorphanol can cross the placenta, and it will be present in the milk of lactating mares who are given the drug. Normal 0 false false false EN-US X-NONE X-NONE Normal 0 false false false EN-US X-NONE X-NONE

References

• Katzung, Bertam G. (Ed.) (2001) Basic & Clinical Pharmacology (8th ed.). New York: McGraw-Hill. ISBN 0-8385-0598-8.
• DiPiro, Joseph T. et al. (2005) Pharmacotherapy: A Pathophysiologic Approach (6th ed.). New York: McGraw-Hill. ISBN 0-07-141613-7.
• Stadol NS - monograph
• Forney, Barbara C, MS, VMD. Equine Medications, Revised Edition.' Blood Horse Publications. Lexington, KY. Copyright 2007.
• The Merck Manual of Vetrinary Medicine, 2004 edition (English)
• The Merck Manual, 2004 Edition (German)
• Mosby's Drug Guide 2004
• Various Usenet (alt.drugs.hard, alt.drugs.valium and rec.pets.cats) discussions about surgery on cats and a cat who was injured by being hit by am automobile.
• Surgery-related episode from c.a. June 2004 of "The Crocodile Hunter" television programme, section on doing surgery on a crocodile and shortly thereafter a Fierce Snake -- specifically commentary by Steve Irwin on the dangers that most or all general anaesthetics pose to reptiles and amphibians.

Antimigraine preparations