Butorphanol Tartrate 10 mg/mL Spray, Metered, 1 bottle — NDC 0054-3090-36 (Billing 00054-3090-36)
This is a package of 1 bottle of Butorphanol Tartrate 10 mg/mL Spray, Metered from Hikma Pharmaceuticals USA Inc., marketed since Mar 2002 and currently FDA-listed; retail pharmacies pay about $15.46 per mL (NADAC). It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 0054-3090-36 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 0054 labeler · 3090 product · 36 package
- Package marketed since
- Mar 12, 2002
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Barcode (UPC-A, from the NDC)
- 3 0054309036 1
- Medicaid fills, this package
- 1,464 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 016674
- GCN: 20351
- GPI-14 (Medi-Span): 65200020102050
- HICL (First Databank): 001777
- AHFS class code: 28:08.12.00
- RxCUI (RxNorm): 886634
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 6, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 8, 2026
RxNorm drug class
This medicine belongs to the Opioid Agonist/Antagonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It's for pain that's severe enough to need an opioid when other options, like non-opioid pain relievers, haven't worked or can't be used. It isn't meant for long-term use unless yo...
- You spray it into one or both nostrils as your prescriber directs, usually as needed with a few hours between doses. Use the lowest amount that controls your pain. Don't stop sudde...
- Sleepiness and dizziness are the most common, and nausea, headache, constipation, dry mouth and nasal congestion can happen too. Don't drive until you know how it affects you. Call...
- Avoid alcohol. Mixing it with sedatives like benzodiazepines, sleep aids, muscle relaxants, gabapentin or other opioids can dangerously slow your breathing. Also tell me about anti...
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 6, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $15.460 | $38.65 / 2.5 ml |
| Medicaid paysCMS SDUD · 12 mo | $14.93 | $37.31 / 2.5 ml |
| Medicare drug plans payPart D · Q2 2026 | $14.32 | $35.81 / 2.5 ml |
Where does this data come from?
- CMS NADAC weekly file · file of Oct 7, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 00054-3090-36 You're viewing this Main listing | 1 BOTTLE, SPRAY in 1 CONTAINER / 2.5 mL in 1 BOTTLE, SPRAY | 2002-03-12 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Butorphanol Tartrate 10 mg/mLthis 00054-3090-36 | Hikma | 1 bottle | $15.460 | AB | Availability likely | — |
| Butorphanol Tartrate 10 mg/mL 60505-0813-01 | Apotex | 1 bottle | $15.460 | AB | Availability likely | — |
| Butorphanol Tartrate 10 mg/mL 72162-2099-02 | Bryant | 1 bottle | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Oct 7, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Butorphanol Nasal Spray inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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UNII PH41D05744
A synthetic antimicrobial chemical compound used as a preservative in medicines and personal care products. It prevents bacterial and fungal growth to keep the product safe during storage and use.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 6, 2026
- FDA openFDA NDC Directory · synced Oct 8, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Hikma Pharmaceuticals USA Inc. labeler code 00054
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- Diphenoxylate Hydrochloride and Atropine Sulfate 2.5 mg/5mL; .025 mg/5mL Solution NDC 0054-3194-46
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
Addiction, Abuse, and Misuse Because the use of Butorphanol Tartrate Nasal Spray exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Butorphanol Tartrate Nasal Spray, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of Butorphanol Tartrate Nasal Spray are essential [see WARNINGS ] . Accidental Exposure Accidental exposure of even one dose of Butorphanol Tartrate Nasal Spray, especially in children, can result in a fatal overdose of butorphanol [see WARNINGS ]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of Butorphanol Tartrate Nasal Spray and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see WARNINGS , PRECAUTIONS; Drug Interactions ] . Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see WARNINGS ].
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see WARNINGS ] . Cytochrome P450 3A4 Interaction The concomitant use of Butorphanol Tartrate Nasal Spray with all cytochrome P450 3A4 inhibitors may result in an increase in butorphanol plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in butorphanol plasma concentration. Monitor patients receiving Butorphanol Tartrate Nasal Spray and any CYP3A4 inhibitor or inducer [see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS; Drug Interactions ] .
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Butorphanol Tartrate Nasal Spray is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see WARNINGS ] , reserve opioid analgesics, including Butorphanol Tartrate Nasal Spray, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Butorphanol Tartrate Nasal Spray should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Butorphanol Tartrate Nasal Spray for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors.
Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Butorphanol Tartrate Nasal Spray. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ] .
Patients Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.
The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS ; Addiction, Abuse, and Misuse ; Life-Threatening Respiratory Depression ; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ] . Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics.
Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Initial Dosage Use of Butorphanol Tartrate Nasal Spray as the First Opioid Analgesic 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 [see PRECAUTIONS and CLINICAL PHARMACOLOGY: Individualization of Dosage ] .
The following doses are for patients who do not have impaired hepatic or renal function and who are not on CNS active agents. Use for Pain: Initiate treatment with Butorphanol Tartrate Nasal Spray in a dosing range of 1 mg (1 spray in one nostril) to 2 mg (1 spray in each nostril) every 3 to 4 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Butorphanol Tartrate Nasal Spray.
The usual recommended dose for initial nasal administration of Butorphanol Tartrate Nasal Spray is 1 mg (1 spra… [Excerpted — this section continues on DailyMed.]
⛔ Contraindications ▾
CONTRAINDICATIONS Butorphanol Tartrate Nasal Spray is contraindicated in: • Patients with significant respiratory depression [see WARNINGS ] . • Patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] . • Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] . • Patients with hypersensitivity to butorphanol tartrate, the preservative benzethonium chloride, or any of the formulation excipients (e.g., anaphylaxis) [see WARNINGS ] .
⚠️ Warnings ▾
WARNINGS Addiction, Abuse, and Misuse Butorphanol Tartrate Nasal Spray contains butorphanol, a Schedule IV controlled substance. As an opioid, Butorphanol Tartrate Nasal Spray exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE ] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Butorphanol Tartrate Nasal Spray.
Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see ADVERSE REACTIONS ].
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Butorphanol Tartrate Nasal Spray, and reassess all patients receiving Butorphanol Tartrate Nasal Spray for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient.
Patients at increased risk may be prescribed opioids such as Butorphanol Tartrate Nasal Spray but use in such patients necessitates intensive counseling about the risks and proper use of Butorphanol Tartrate Nasal Spray along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS , Life-Threatening Respiratory Depression ; DOSAGE AND ADMINISTRATION , Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose ] .
Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing Butorphanol Tartrate Nasal Spray. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug.
Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.
Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient’s clinical status [see OVERDOSAGE ] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Butorphanol Tartrate Nasal Spray, the risk is greatest during the initiation of therapy or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of Butorphanol Tartrate Nasal Spray are essential [see DOSAGE AND ADMINISTRATION ] . Overestimating the Butorphanol Tartrate Nasal Spray dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental exposure to even one dose of Butorphanol Tartrate Nasal Spray, especially by children, can result in respiratory depression and death due to an overdose of butorphanol.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [s… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
ADVERSE REACTIONS Clinical Trial Experience A total of 788 patients were studied in premarketing clinical trials of Butorphanol Tartrate Nasal Spray. In nearly all cases the type and incidence of side effects with butorphanol 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 intranasal butorphanol, except acute studies in normal subjects.
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 with Butorphanol Tartrate Nasal Spray were somnolence (49%), dizziness (23%), nausea and/or vomiting (8%). In long-term trials with Butorphanol Tartrate Nasal Spray 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, pain Cardiovascular: Hypertension, hypotension Digestive: Anorexia, constipation, dry mouth, nausea and/or vomiting, diarrhea Nervous: Anxiety, confusion, dizziness, euphoria, floating feeling, insomnia, nervousness, paresthesia, somnolence, tremor Respiratory: Epistaxis, nasal congestion, nasal irritation, rhinitis, sinus congestion, sinusitis, nose pain Skin and Appendages: Sweating, 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 The following infrequent additional adverse experiences were reported in a frequency of less than 1% of the patients studied in short-term Butorphanol Tartrate Nasal Spray trials or trials of butorphanol tartrate injection and under circumstances where the association between these events and butorphanol administration is unknown.
They are being listed as alerting information for the physician due to their clinical significance. Body as a Whole: Edema Cardiovascular: Chest pain, hypertension, tachycardia Nervous: Depression Respiratory: Shallow breathing Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Postmarketing Experience The following adverse reactions have been identified during post approval use of Butorphanol Tartrate Nasal Spray. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Serotonin Syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. • Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. • Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Butorphanol Tartrate Nasal Spray. • Androgen Deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY ] . • Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ] .
Opioid-induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
Drug Interactions Sumatriptan In healthy volunteers, the pharmacokinetics of a 1 mg dose of butorphanol administered as Butorphanol Tartrate Nasal Spray were not affected by the coadministration 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% decreases in C max ) when a 1 mg dose of Butorphanol Tartrate Nasal Spray was administered 1 minute after a 20 mg dose of sumatriptan nasal spray.
(The two drugs were administered in opposite nostrils.) When the Butorphanol Tartrate Nasal Spray was administered 30 minutes after the sumatriptan nasal spray, the AUC of butorphanol increased 11% and C max decreased 18%. In neither case were the pharmacokinetics of sumatriptan affected by coadministration with Butorphanol Tartrate Nasal Spray. These results suggest that the analgesic effect of Butorphanol Tartrate Nasal Spray may be diminished when it is administered shortly after sumatriptan nasal spray, but by 30 minutes any such reduction in effect should be minimal.
The safety of using Butorphanol Tartrate Nasal Spray and IMITREX ®1 (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. Cimetidine The pharmacokinetics of a 1 mg dose of butorphanol administered as Butorphanol Tartrate Nasal Spray were not affected by the coadministration of cimetidine (300 mg QID).
Conversely, the administration of Butorphanol Tartrate Nasal Spray (1 mg butorphanol QID) did not alter the pharmacokinetics of a 300 mg dose of cimetidine. Oxymetazoline The fraction of Butorphanol Tartrate Nasal Spray 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 Spray is administered concomitantly with, or immediately following, a nasal vasoconstrictor.
Drug Interactions Benzodiazepine and Other Central Nervous System (CNS) Depressants Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, such as benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS ; DOSAGE AND ADMINISTRATION ] .
Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information for Patients ] .
If concomitant use is warranted, frequently evaluate the pa… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
Pregnancy 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/m 2 ) had a higher frequency of stillbirths than controls. Butorphanol at 30 mg/kg/oral (360 mg/m 2 ) and 60 mg/kg/oral (720 mg/m 2 ) also showed higher incidences of postimplantation loss in rabbits.
There are no adequate and well-controlled studies of Butorphanol Tartrate Nasal Spray in pregnant women before 37 weeks of gestation. Butorphanol Tartrate Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the infant. Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS ] .
🧒 Pediatric Use ▾
Pediatric Use Butorphanol Tartrate Nasal Spray is not recommended for use in patients below 18 years of age because safety and efficacy have not been established in this population.
🧓 Geriatric Use ▾
Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to Butorphanol Tartrate Nasal Spray. Of the approximately 1700 patients treated with Butorphanol Tartrate Nasal Spray 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 [see CLINICAL PHARMACOLOGY: Pharmacokinetics ].
Elderly patients may be more sensitive to the side effects of butorphanol. In clinical studies of Butorphanol Tartrate Nasal Spray, 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 Spray should be generally 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 ]. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy [see DOSAGE AND ADMINISTRATION ].
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were coadministered with other agents that depress respiration. Titrate the dosage of Butorphanol Tartrate Nasal Spray slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS ]. This drug is known to be substantially excreted by the kidney, and the risk of adverse 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, and it may be useful to regularly evaluate renal function.
🆘 Overdosage ▾
OVERDOSAGE Clinical Presentation Acute overdose with Butorphanol Tartrate Nasal Spray can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see CLINICAL PHARMACOLOGY ] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.
Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.
For clinically significant respiratory or circulatory depression secondary to butorphanol tartrate overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. As butorphanol is a mixed opioid agonist/antagonist, larger doses of naloxone may be needed to reverse the effects of an overdose. Because the duration of opioid reversal is expected to be less than the duration of action of butorphanol in Butorphanol Tartrate Nasal Spray, carefully monitor the patient until spontaneous respiration is reliably re-established.
If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered.
If a decision is made to treat serious respiratory depression in the physically-dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Mechanism of Action Butorphanol is a partial opioid agonist at the mu opioid receptor and a full agonist at the kappa opioid receptor. The principal therapeutic action of butorphanol is analgesia. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Pharmacodynamics The analgesic effect of butorphanol is influenced by the route of administration.
Onset of analgesia is within 15 minutes for the nasal administration doses. Peak analgesic activity occurs within 1 to 2 hours following nasal spray administration. The duration of analgesia varies depending on the pain model as well as the route of administration.
Compared to the injectable form and other drugs in this class, Butorphanol Tartrate Nasal Spray has a longer duration of action (4 to 5 hours) [see CLINICAL PHARMACOLOGY ; Clinical Trials ] . Effects on the Central Nervous System Butorphanol produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
In human studies involving individuals without significant respiratory dysfunction, 2 mg of butorphanol IV and 10 mg of morphine sulfate IV depressed respiration to a comparable degree. At higher doses, the magnitude of respiratory depression with butorphanol is not appreciably increased; however, the duration of respiratory depression is longer. Respiratory depression noted after administration of butorphanol to humans by any route is reversed by treatment with naloxone, a specific opioid antagonist [see OVERDOSAGE ] .
Butorphanol, like other mixed agonist-antagonists with a high affinity for the κ-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. In human studies of butorphanol [see CLINICAL PHARMACOLOGY ; 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 causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings).
Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on the Gastrointestinal Tract and Other Smooth Muscle Butorphanol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased.
Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Hemodynamic changes noted during cardiac catheterization in patients receiving single 0.025 mg/kg intravenous doses of butorphanol have included increases in pulmonary artery pressure, wedge pressure and vascular resistance, increases in left ventricular end diastolic pressure, and in systemic arterial pressure.
Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ] . They als… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
Mechanism of Action Butorphanol is a partial opioid agonist at the mu opioid receptor and a full agonist at the kappa opioid receptor. The principal therapeutic action of butorphanol is analgesia. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Butorphanol Tartrate Nasal Spray, USP is supplied in a child-resistant vial containing a 2.5 mL bottle of nasal spray solution (10 mg/mL) and a metered-dose spray pump with protective clip and dust cover, a bottle of nasal spray solution, and a patient instruction leaflet and medication guide. On average, one bottle will deliver 14 to 15 doses if no repriming is necessary. Butorphanol Tartrate Nasal Spray, USP, 10 mg/mL NDC 0054-3090-36: 2.5 mL Bottle.
Storage Conditions Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. 1 IMITREX ® is a registered trademark of Glaxo-Wellcome, Inc. Store Butorphanol Tartrate Nasal Spray securely and dispose of properly [see PRECAUTIONS: Information for Patients ] .
📋 Description ▾
DESCRIPTION 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-dihydroxybutanedioate (1:1) (salt). The molecular formula is C 21 H 29 NO 2 •C 4 H 6 O 6 , which corresponds to a molecular weight of 477.55 g/mol and the following structural formula: Butorphanol tartrate, USP is a white crystalline substance.
The dose is expressed as the tartrate salt. One milligram of the salt is equivalent to 0.68 mg of the free base. The n-octanol/aqueous buffer partition coefficient of butorphanol is 180:1 at pH 7.5.
Butorphanol Tartrate Nasal Spray, USP is an aqueous solution of butorphanol tartrate for administration as a metered spray to the nasal mucosa. Each bottle of Butorphanol Tartrate Nasal Spray, USP contains 2.5 mL of a 10 mg/mL solution of butorphanol tartrate with sodium chloride, citric acid, and benzethonium chloride in purified water with sodium hydroxide and/or hydrochloric acid added to adjust the pH to 5.0. The pump reservoir must be fully primed [see PATIENT INSTRUCTIONS ] prior to initial use.
After initial priming each metered spray delivers an average of 1.0 mg of butorphanol tartrate and the 2.5 mL bottle will deliver an average of 14 to 15 doses of Butorphanol Tartrate Nasal Spray, USP. If not used for 48 hours or longer, the unit must be reprimed [see PATIENT INSTRUCTIONS ]. With intermittent use requiring repriming before each dose, the 2.5 mL bottle will deliver an average of 8 to 10 doses of Butorphanol Tartrate Nasal Spray, USP depending on how much repriming is necessary. chem.jpg
💬 Information for Patients ▾
Information for Patients/Caregivers Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store Butorphanol Tartrate Nasal Spray securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving Butorphanol Tartrate Nasal Spray unsecured can pose a deadly risk to others in the home [see WARNINGS , DRUG ABUSE AND DEPENDENCE ] .
Addiction, Abuse, and Misuse Inform patients that the use of Butorphanol Tartrate Nasal Spray, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ]. Instruct patients not to share Butorphanol Tartrate Nasal Spray with others and to take steps to protect Butorphanol Tartrate Nasal Spray from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Butorphanol Tartrate Nasal Spray or when the dosage is increased, and that it can occur even at recommended dosages.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS, Life Threatening Respiratory Depression ] . Accidental Exposure Inform patients that accidental exposure, especially by children, may result in respiratory depression or death [see WARNINGS ]. Instruct patients to take steps to store Butorphanol Tartrate Nasal Spray securely and to dispose of unused Butorphanol Tartrate Nasal Spray by unscrewing the cap, rinsing the bottle, and placing the parts in the waste container.
Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if Butorphanol Tartrate Nasal Spray is used with benzodiazepines or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a healthcare provider [see WARNINGS , PRECAUTIONS; Drug Interactions ].
Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.
Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see WARNINGS ; DOSAGE AND ADMINISTRATION ] . Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if an opioid overdose reversal agent is administered [see OVERDOSAGE ] .
Advise patients and caregivers: • how to treat with the overdose reversal agent in the event of an opioid overdose. • to tell family and friends about their opioid overdose reversal agent, and to keep it in a place where family and friends can access it in an emergency. • to read the Patient Information (or other educational material) that will come… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Butorphanol Tartrate Nasal Spray, USP CIV (bue tor’ fa nol tar’ trate) Rx only Butorphanol Tartrate Nasal Spray is: • A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. • An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.
Important information about Butorphanol Tartrate Nasal Spray: • Get emergency help or call 911 right away if you take too much Butorphanol Tartrate Nasal Spray (overdose). When you first start taking Butorphanol Tartrate Nasal Spray, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. • Taking Butorphanol Tartrate Nasal Spray with other opioid medicines, benzodiazepines, gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma and death. • Never give anyone else your Butorphanol Tartrate Nasal Spray.
They could die from taking it. Selling or giving away Butorphanol Tartrate Nasal Spray is against the law. • Store Butorphanol Tartrate Nasal Spray securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not take Butorphanol Tartrate Nasal Spray if you have: • Severe asthma, trouble breathing, or other lung problems. • A bowel blockage or have narrowing of the stomach or intestines. • Previously had an allergic reaction to butorphanol or the preservative benzethonium chloride.
Before taking Butorphanol Tartrate Nasal Spray, tell your healthcare provider if you have a history of: • Head injury, seizures • Liver, kidney, thyroid problems • Problems urinating • Pancreas or gallbladder problems • Abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems Tell your healthcare provider if you are: • Noticing your pain getting worse. If your pain gets worse after you take Butorphanol Tartrate Nasal Spray, do not take more of Butorphanol Tartrate Nasal Spray without first talking to your healthcare provider.
Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking Butorphanol Tartrate Nasal Spray. • Pregnant or planning to become pregnant. Use of Butorphanol Tartrate Nasal Spray for an extended period of time during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. • Breastfeeding. Butorphanol passes into breast milk and may harm your baby.
Carefully observe infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Seek immediate medical care if you notice these signs. • Living in a household where there are small children or someone who has abused street or prescription drugs. • Taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking Butorphanol Tartrate Nasal Spray with certain other medicines can cause serious side effects that could lead to death.
When taking Butorphanol Tartrate Nasal Spray: • Do not change your dose. Take Butorphanol Tartrate Nasal Spray exactly as prescribed by your healthcare provider. See the detailed Patient Instructions for information about how to take Butorphanol Tartrate Nasal Spray.
Use the lowest dose possible for the shortest time needed. • For acute (short-term) pain, you may only need to take Butorphanol Tartrate Nasal Spray for a few days. You may have some B… [Excerpted — this section continues on DailyMed.]
⚠️ Precautions ▾
PRECAUTIONS General Hypotension associated with syncope during the first hour of dosing with Butorphanol Tartrate Nasal Spray has been reported rarely, particularly in patients with past history of similar reactions to opioid analgesics. Therefore, patients should be advised to avoid activities with potential risks. Risks of Driving and Operating Machinery Butorphanol Tartrate Nasal Spray may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Butorphanol Tartrate Nasal Spray and know how they will react to the medication [see PRECAUTIONS ; Information for Patients ] . Disorders of Respiratory Function or Control Butorphanol may produce respiratory depression, especially in patients receiving other CNS active agents, or patients suffering from CNS diseases or respiratory impairment. Hepatic and Renal Disease In patients with hepatic or renal impairment, the initial dose sequence of Butorphanol Tartrate Nasal Spray should be limited to 1 mg followed, if needed, by 1 mg in 90 to 120 minutes.
The repeat dose sequence in these patients should be determined by the patient’s response rather than at fixed times but will generally be at intervals of no less than at 6 hours [see CLINICAL PHARMACOLOGY : Pharmacokinetics and Individualization of Dosage ] . Information for Patients/Caregivers Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store Butorphanol Tartrate Nasal Spray securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.
Inform patients that leaving Butorphanol Tartrate Nasal Spray unsecured can pose a deadly risk to others in the home [see WARNINGS , DRUG ABUSE AND DEPENDENCE ] . Addiction, Abuse, and Misuse Inform patients that the use of Butorphanol Tartrate Nasal Spray, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ]. Instruct patients not to share Butorphanol Tartrate Nasal Spray with others and to take steps to protect Butorphanol Tartrate Nasal Spray from theft or misuse.
Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Butorphanol Tartrate Nasal Spray or when the dosage is increased, and that it can occur even at recommended dosages. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS, Life Threatening Respiratory Depression ] .
Accidental Exposure Inform patients that accidental exposure, especially by children, may result in respiratory depression or death [see WARNINGS ]. Instruct patients to take steps to store Butorphanol Tartrate Nasal Spray securely and to dispose of unused Butorphanol Tartrate Nasal Spray by unscrewing the cap, rinsing the bottle, and placing the parts in the waste container. Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if Butorphanol Tartrate Nasal Spray is used with benzodiazepines or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a healthcare provider [see WARNINGS , PRECAUTIONS; Drug Interactions ].
Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Ove… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
Nursing Mothers Although there is no clinical experience with the use of Butorphanol Tartrate Nasal Spray in nursing mothers, butorphanol has been detected in milk following administration of butorphanol tartrate injection to nursing mothers. The amount an infant would receive is probably clinically insignificant (estimated 4 mcg/L of milk in a mother receiving 2 mg IM four times a day). It should be assumed that butorphanol will appear in the milk in similar amounts following the nasal route of administration.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Butorphanol Tartrate Nasal Spray and any potential adverse effects on the breastfed infant from butorphanol or from the underlying maternal condition. Infants exposed to Butorphanol Tartrate Nasal Spray through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
🧬 Pharmacokinetics ▾
Pharmacokinetics 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 Spray 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 ). Figure 1: Butorphanol Plasma Levels after IV, IM and Nasal Spray Administration of 2 mg Dose 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/hr (see Table 1 ). Table 1: Mean Pharmacokinetic Parameters of Butorphanol in Young and Elderly Subjects Young subjects (n=24) are from 20 to 40 years old and elderly (n=24) are greater than 65 years of age. Intravenous Nasal Parameters Young Elderly Young Elderly T max Time to peak plasma concentration.
(hr) 0.62 (0.32) Mean (1 S.D.) (0.15 to 1.50) (range of observed values) 1.03 (0.74) (0.25 to 3.00) C max Peak plasma concentration normalized to 1 mg dose. (ng/mL) 1.04 (0.40) (0.35 to 1.97) 0.90 (0.57) (0.10 to 2.68) AUC (inf) Area under the plasma concentration-time curve after a 1 mg dose. (hr·ng/mL) 7.24 (1.57) (4.40 to 9.77) 8.71 (2.02) (4.76 to 13.03) 4.93 (1.24) (2.16 to 7.27) 5.24 (2.27) (0.30 to 10.34) Half-life (hr) 4.56 (1.67) (2.06 to 8.70) 5.61 (1.36) (3.25 to 8.79) 4.74 (1.57) (2.89 to 8.79) 6.56 (1.51) (3.75 to 9.17) Absolute Bioavailability (%) 69 (16) (44 to 113) 61 (25) (3 to 121) Volume of Distribution Derived from IV data.
(L) 487 (155) (305 to 901) 552 (124) (305 to 737) Total Body Clearance (L/hr) 99 (23) (70 to 154) 82 (21) (52 to 143) Dose proportionality for Butorphanol Tartrate Nasal Spray 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 [see PRECAUTIONS : Labor and Delivery and Nursing Mothers ] . 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 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 Spray in elderly women (48%) was less than that in elderly men (75%), young men (68%), or yo… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
Pharmacodynamics The analgesic effect of butorphanol is influenced by the route of administration. Onset of analgesia is within 15 minutes for the nasal administration doses. Peak analgesic activity occurs within 1 to 2 hours following nasal spray administration.
The duration of analgesia varies depending on the pain model as well as the route of administration. Compared to the injectable form and other drugs in this class, Butorphanol Tartrate Nasal Spray has a longer duration of action (4 to 5 hours) [see CLINICAL PHARMACOLOGY ; Clinical Trials ] . Effects on the Central Nervous System Butorphanol produces respiratory depression by direct action on brain stem respiratory centers.
The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. In human studies involving individuals without significant respiratory dysfunction, 2 mg of butorphanol IV and 10 mg of morphine sulfate IV depressed respiration to a comparable degree. At higher doses, the magnitude of respiratory depression with butorphanol is not appreciably increased; however, the duration of respiratory depression is longer.
Respiratory depression noted after administration of butorphanol to humans by any route is reversed by treatment with naloxone, a specific opioid antagonist [see OVERDOSAGE ] . Butorphanol, like other mixed agonist-antagonists with a high affinity for the κ-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.
In human studies of butorphanol [see CLINICAL PHARMACOLOGY ; 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 causes miosis, even in total darkness.
Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on the Gastrointestinal Tract and Other Smooth Muscle Butorphanol causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum.
Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).
Effects on the Cardiovascular System Hemodynamic changes noted during cardiac catheterization in patients receiving single 0.025 mg/kg intravenous doses of butorphanol have included increases in pulmonary artery pressure, wedge pressure and vascular resistance, increases in left ventricular end diastolic pressure, and in systemic arterial pressure. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ] .
They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS ] .
Effects on the… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
DRUG ABUSE AND DEPENDENCE Controlled Substance Butorphanol Tartrate Nasal Spray contains butorphanol, a Schedule IV controlled substance. Abuse Butorphanol Tartrate Nasal Spray contains butorphanol, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see WARNINGS ] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.
Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of Butorphanol Tartrate Nasal Spray increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death.
The risk is increased with concurrent abuse of Butorphanol Tartrate Nasal Spray with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.
All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Butorphanol Tartrate Nasal Spray abuse include those with a history of prolonged use of any opioid, including products containing butorphanol, those with a history of drug or alcohol abuse, or those who use Butorphanol Tartrate Nasal Spray in combination with other abused drugs. “Drug-seeking” behavior is very common in persons with substance use disorders.
Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.
Butorphanol Tartrate Nasal Spray, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of Butorphanol Tartrate Nasal Spray Abuse of Butorphanol Tartrate Nasal Spray poses a risk of overdose and death. The risk is increased with concurrent use of Butorphanol Tartrate Nasal Spray with alcohol and/or other CNS depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Dependence Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptati… [Excerpted — this section continues on DailyMed.]
🔒 Controlled Substance ▾
Controlled Substance Butorphanol Tartrate Nasal Spray contains butorphanol, a Schedule IV controlled substance.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Two-year carcinogenicity studies were conducted in mice and rats given butorphanol tartrate in the diet up to 60 mg/kg/day (24 and 48 times the human daily dose of 12 mg/day based on a body surface area comparison, respectively). There was no evidence of carcinogenicity in either species in these studies. Mutagenesis Butorphanol was not genotoxic in the in vitro bacterial reverse mutation assay (Ames) or in an in vitro unscheduled DNA synthesis and repair assay conducted in cultured human fibroblast cells.
Impairment of Fertility In a study where male rats were treated subcutaneously with 0.5 or 2.5 mg/kg butorphanol for 75 days prior to mating to female rats treated subcutaneously with 0.5 or 2.5 mg/kg butorphanol for 14 days prior to mating and throughout gestation and lactation, no adverse effects on fertility were noted (0.4- and 2 times the human daily dose of 12 mg based on body surface area). In a study where male rats were treated orally with 10, 40, or 160 mg/kg for 63 days prior to mating to female rats treated orally with the same doses of butorphanol for 14 days prior to mating, reduced pregnancy rates were reported in the high dose group (130-times the human daily dose of 12 mg based on body surface area).
📄 Package Label / Principal Display Panel ▾
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0054- 3090 -36 2.5 mL Butorphanol Tartrate Nasal Spray, USP CIV 10 mg per mL For Nasal Use Only. Rx only bottle label image