FDA

Butorphanol Tartrate

Approved 12 Mar 2002NasalSpray, metered

The FDA lists this product in 12 strengths and forms.

Indications

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.

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 and precautions

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.

At a glance

Brand name: Butorphanol Tartrate
Route: Nasal
Dosage form: Spray, metered
Applicant: Hikma
Status: Prescription
FDA approval: 12 Mar 2002
Application: ANDA075824-001

Indications

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 and precautions

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 patient, particularly during treatment initiation and dose adjustment. Discontinue Butorphanol Tartrate Nasal Spray if serotonin syndrome is suspected. Cytochrome P450 (CYP 450) Interactions It is not known if the effects of Butorphanol Tartrate Nasal Spray are altered by concomitant medications that affect hepatic metabolism of drugs (CYP 450 inhibitors or inducers) (e.g., erythromycin, theophylline, etc.), but physicians should be alert to the possibility that a smaller initial dose and longer intervals between doses may be needed.

Monoamine Oxidase Inhibitors (MAOIs) No information is available about the use of butorphanol concurrently with MAO inhibitors. Advise patient to avoid concomitant use of these drugs.

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 longer term [see WARNINGS ] . Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90 day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months. Over 12 months:
approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to-severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and
approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in DRUG ABUSE AND DEPENDENCE ] , respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days’ supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates. The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.

Butorphanol Tartrate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Butorphanol Tartrate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information