The dose is expressed as the tartrate salt. One milligram of the salt is equivalent to 0. 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.
After initial priming each metered spray delivers an average of 1. With intermittent use requiring repriming before each dose, the 2. 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.
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. 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.
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. Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. 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, and transient elevations in serum amylase. Hemodynamic changes noted during cardiac catheterization in patients receiving single 0. They also stimulate prolactin, growth hormone GH secretion, and pancreatic secretion of insulin and glucagon.
Chronic use of opioids 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 ].
Opioids have been shown to have a variety of effects on components of the immune system. The clinical significance of these findings is unknown.
Overall, the effects of opioids appear to be modestly immunosuppressive. The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. There is a relationship between increasing butorphanol plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression.
After nasal administration, mean peak blood levels of 0. 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. 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. Butorphanol is extensively metabolized in the liver. Metabolism is qualitatively and quantitatively similar following intravenous, intramuscular, or nasal administration. 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. Elimination occurs by urine and fecal excretion.
Forty-nine percent is eliminated in the urine as hydroxybutorphanol. Butorphanol pharmacokinetics in the elderly differ from younger patients see Table 1. Elimination half-life is increased in the elderly 6. No effect on C max or T max 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 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 C max or T max was observed after a single intranasal dose. 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.
The two drugs were administered in opposite nostrils. 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. 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 spray were not affected by the coadministration of cimetidine mg QID. Conversely, the administration of butorphanol tartrate nasal spray 1 mg butorphanol QID did not alter the pharmacokinetics of a mg dose of cimetidine. 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. The effectiveness of opioid analgesics varies in different pain syndromes. Studies with butorphanol tartrate nasal spray have been performed in postoperative general, orthopedic, oral, cesarean section pain, in postepisiotomy pain, in pain of musculoskeletal origin, and in migraine headache pain see below.
Postoperative Pain: The analgesic efficacy of butorphanol tartrate nasal spray was evaluated approximately 35 patients per treatment group in a general and orthopedic surgery trial. Single doses of butorphanol tartrate nasal spray 1 or 2 mg and IM meperidine Analgesia provided by 1 and 2 mg doses of butorphanol tartrate nasal spray was similar to The median duration of pain relief was 2.
In a postcesarean section trial, butorphanol tartrate nasal spray administered to 35 patients as two 1 mg doses 60 minutes apart was compared with a single 2 mg dose of butorphanol tartrate nasal spray or a single 2 mg IV dose of butorphanol tartrate injection 37 patients each. Onset of analgesia was within 15 minutes for all butorphanol tartrate regimens. Peak analgesic effects of 2 mg intravenous butorphanol tartrate injection and butorphanol tartrate nasal spray were similar in magnitude.
The duration of pain relief provided by both 2 mg butorphanol tartrate nasal spray regimens was approximately 4. Migraine Headache Pain: The analgesic efficacy of two 1 mg doses 1 hour apart of butorphanol tartrate nasal spray in migraine headache pain was compared with a single dose of 10 mg IM methadone 31 and 32 patients, respectively. Significant onset of analgesia occurred within 15 minutes for both butorphanol tartrate nasal spray and IM methadone.
Peak analgesic effect occurred at 2 hours for butorphanol tartrate nasal spray and 1. The median duration of pain relief was 6 hours with butorphanol tartrate nasal spray and 4 hours with methadone as judged by the time when approximately half of the patients remedicated.
In two other trials in patients with migraine headache pain, a 2 mg initial dose of butorphanol tartrate nasal spray followed by an additional 1 mg dose 1 hour later 76 patients was compared with either 75 mg IM meperidine 24 patients or placebo 72 patients. Onset, peak activity and duration were similar with both active treatments; however, the incidence of adverse experiences nausea, vomiting, dizziness was higher in these two trials with the 2 mg initial dose of butorphanol tartrate nasal spray than in the trial with the 1 mg initial dose.
The usual recommended dose for initial nasal administration is 1 mg 1 spray in one nostril. 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. For the management of severe 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 additional doses should not be given for 3 to 4 hours. The incidence of adverse events is higher with an initial 2-mg dose see Clinical Trials.
The initial dose sequence in elderly patients and patients with renal or hepatic impairment should be limited to 1 mg followed, if needed, by 1 mg in 90 to minutes. 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, and misuse, with opioids, even at recommended doses [see WARNINGS ], reserve butorphanol tartrate nasal spray for use in patients for whom alternative treatment options [e.
Butorphanol tartrate nasal spray contains butorphanol, a Schedule IV controlled substance. 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. 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.
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 intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing butorphanol tartrate nasal spray. 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. Healthcare providers are strongly encouraged to do all of the following:. 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. Carbon dioxide CO2 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.
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of butorphanol. 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. Opioids can cause sleep-related breathing disorders including central sleep apnea CSA and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion.
Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with butorphanol tartrate nasal spray. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines e.
The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members including children or other close contacts at risk for accidental ingestion or overdose.
Prolonged use of butorphanol tartrate nasal spray during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Concomitant use of butorphanol tartrate nasal spray with a CYP3A4 inhibitor, such as macrolide antibiotics e.
Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in butorphanol tartrate nasal spray -treated patients may increase butorphanol plasma concentrations and prolong opioid adverse reactions. Concomitant use of butorphanol tartrate nasal spray with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease butorphanol plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to butorphanol.
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of butorphanol tartrate nasal spray with benzodiazepines or other CNS depressants e. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use.
In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.
Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when butorphanol tartrate nasal spray is used with benzodiazepines or other CNS depressants including alcohol and illicit drugs.
Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. The use of butorphanol tartrate nasal spray in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease Butorphanol tartrate nasal spray -treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of butorphanol tartrate nasal spray [see WARNINGS ]. Elderly, Cachetic, or Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see WARNINGS ].
Monitor such patients closely, particularly when initiating and titrating butorphanol tartrate nasal spray and when butorphanol tartrate nasal spray is given concomitantly with other drugs that depress respiration [see WARNINGS ]. Alternatively, consider the use of non-opioid analgesics in these patients. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 month of use.
Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. In patients who may be susceptible to the intracranial effects of CO2 retention e. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with butorphanol tartrate nasal spray.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of butorphanol tartrate nasal spray in patients with impaired consciousness or coma. Butorphanol tartrate nasal spray is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.
Butorphanol in butorphanol tartrate nasal spray may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. The butorphanol in butorphanol tartrate nasal spray may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occuring in other clinical settings associated with seizures.
Monitor patients with a history of seizure disorders for worsened seizure control during butorphanol tartrate nasal spray. Do not abruptly discontinue butorphanol tartrate nasal spray in a patient physically dependent on opioids. When discontinuing butorphanol tartrate nasal spray in a physically dependent patient, gradually taper the dosage. Rapid tapering of butorphanol tartrate nasal spray in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration , Drug Abuse and Dependence ].
Avoid concomitant use of butorphanol tartrate nasal spray with a full opioid agonist analgesic. Severe hypertension has been reported rarely during butorphanol tartrate nasal spray therapy. In such cases, butorphanol tartrate nasal spray should be discontinued and the hypertension treated with antihypertensive drugs. In patients who are not opioid dependent, naloxone has also been reported to be effective.
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. 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.
Butorphanol may produce respiratory depression, especially in patients receiving other CNS active agents, or patients suffering from CNS diseases or respiratory impairment.
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 minutes. Inform patients that leaving butorphanol tartrate nasal spray unsecured can pose a deadly risk to others in the home. 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 protectbutorphanol 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 or getting emergency medical help right away in the event of a known or suspected overdose see WARNINGS , Life Threatening Respiratory Depression. Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with butorphanol tartrate nasal spray.
If naloxone is prescribed, also advise patients and caregivers: 1. 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.
Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Adrenal Insufficiency Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition.
Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in butorphanol tartrate nasal spray. Lactation Advise nursing mothers to monitor infants for increased sleepiness more than usual , breathing difficulties, or limpness. Infertility Inform patients that chronic use of opioids may cause reduced fertility.
Disposal of Unused Butorphanol Tartrate Advise patients to dispose of butorphanol tartrate by unscrewing the cap, rinsing the bottle, and placing the parts in a waste container. Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, such as alcohol, other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, 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.
Follow patients closely for signs of respiratory depression and sedation. 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. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
Discontinue butorphanol tartrate nasal spray if serotonin syndrome is suspected. It is not known if the effects of butorphanol tartrate nasal spray are altered by concomitant medications that affect hepatic metabolism of drugs CYP inhibitors or inducers e.
There was no evidence of carcinogenicity in either species in these studies. 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. In a study where male rats were treated subcutaneously with 0. Pregnancy Category C: Reproduction studies in mice, rats, and rabbits during organogenesis did not reveal any teratogenic potential to butorphanol.
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. Prolonged use of opioid analgesics 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.
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Butorphanol tartrate nasal spray is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including butorphanol tartrate nasal spray, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.
Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Butorphanol tartrate nasal spray is not recommended during labor or delivery because there is no clinical experience with its use in this setting. 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. It should be assumed that butorphanol will appear in the milk in similar amounts following the nasal route of administration.
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. 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.
Elderly patients aged 65 years or older may have increased sensitivity to butorphanol tartrate nasal spray. Elderly patients may be more sensitive to the side effects of butorphanol.
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 co-administered with other agents that depress respiration.
Titrate the dosage of butorphanol tartrate nasal spray slowly in geriatric patients and monitor closely 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 monitor renal function.
A total of 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. Nervous: Anxiety, confusion, dizziness, euphoria, floating feeling, insomnia, nervousness, paresthesia, somnolence, tremor. Respiratory: Epistaxis, nasal congestion, nasal irritation, rhinitis, sinus congestion, sinusitis, nose pain.
Nervous: Abnormal dreams, agitation, dysphoria, hallucinations, hostility, withdrawal symptoms. They are being listed as alerting information for the physician due to their clinical significance. 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.
Butorphanol tartrate nasal spray contains butorphanol, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
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 health care provider s.
Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. Butorphanol tartrate nasal spray, like other opioids, can be diverted for non-medical 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. Manufacturer Bristol-Myers Squibb vehemently disagrees. Darlene Jody, contended.
The FDA has received reports of 41 deaths and addiction-associated side effects possibly involving Stadol. The injectable version, sold since , accounted for some. The spray was approved for marketing only in Every week, Dr. Instead, the problem is unique to migraines: The more painkillers some sufferers take, the more headaches they actually get. Within 15 minutes your pain is starting to be relieved.
Stadol was especially developed to be less addictive than such narcotics as morphine. But seven states already have made Stadol a controlled substance. The DEA curbs will limit how often doctors prescribe Stadol and how many refills patients get.
The FDA also is considering whether to warn doctors officially of the addiction potential. The danger may not be sufficient to warrant such an expensive, intrusive move, FDA addictive drugs chief Dr.
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