Butorphanol tartrate is a synthetic parenteral opiate agonist-antagonist. Although it is structurally related to morphine, butorphanol is more similar in action to nalbuphine, another agonist-antagonist. Butorphanol is available parenterally for treating moderate to severe pain and as a nasal spray that has been used to treat migraine. Although studies suggest equianalgesic parenteral doses are as effective as morphine, clinical response may indicate otherwise, perhaps due to the development of tolerance. Butorphanol does not offer significant advantages over pure opiate-agonists in the treatment of acute pain or cancer pain. Butorphanol is also used to provide preoperative sedation and analgesia, and to supplement surgical anesthesia. Butorphanol injection was approved by the FDA in 1978; the nasal spray was approved in 1991. Although butorphanol was not a controlled substance in the United States when it was originally introduced, the DEA recommended in June 1997 that both the injection and the nasal spray be classified as a controlled substance.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-No dilution necessary.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Inject directly into a vein or into the tubing of a freely-flowing compatible IV infusion.
Intramuscular Administration
-Inject deeply into a large muscle mass.
Inhalation Administration
Intranasal Inhalation Administration
-Blow nose gently to clear both nostrils.
-Remove protective clip from neck of pump unit.
-Prime by pumping sprayer unit firmly and quickly until a fine spray appears (up to 7 or 8 strokes). If the unit is not used for 48 hours or longer, prime with 1 or 2 strokes.
-Insert spray tip approximately 1 centimeter into one nostril and point tip toward back of nose.
-Close other nostril with forefinger and tilt head forward.
-Pump spray unit firmly and quickly. Sniff gently with mouth closed.
-Remove pump unit from nose, tilt head backwards, and sniff gently for a few more seconds.
-If a 2 spray dose is needed, administer the second spray in the other nostril.
-Replace protective clip and clear cover after each dose.
-Storage: Keep butorphanol secured in a location not accessible by others.
-Disposal: Unscrew the cap, rinse the bottle, and place the parts in a waste container when the unit is no longer needed.
Because butorphanol is an antagonist at the mu-opiate receptor, it is less likely to produce respiratory depression than morphine. When it occurs, however, respiratory depression is serious, and patients should be carefully monitored. Shallow breathing was reported in less than 1% of patients during clinical trials, and apnea has been observed during postmarketing surveillance. Respiratory depression can be reversed with the use of naloxone. Routine use of opiate agonists by an expectant mother can lead to respiratory depression in the newborn. In patients using butorphanol by the intranasal route, bronchitis, cough, dyspnea, epistaxis, nasal irritation, pharyngitis, rhinitis, sinus congestion, sinusitis, and upper respiratory tract infection were reported by at least 1% of patients, with generalized nasal congestion reported by 13%.
Butorphanol frequently causes nausea and or vomiting, which were reported during clinical trials in 13% of patients. Gastrointestinal effects occurring in at least 1% of patients included anorexia, constipation, abdominal pain, dysgeusia, and xerostomia.
Vasodilation (peripheral vasodilation) and palpitations may occur with butorphanol use, and were documented in >= 1% of patients during clinical trials. This may lead to hypotension, or syncope, which were noted in < 1% of patients. Orthostatic hypotension may occur. Hypertension, sinus bradycardia, sinus tachycardia, and chest pain (unspecified) occurred in < 1% of patients. Severe hypertension has been reported with butorphanol therapy; if this effect occurs, discontinue butorphanol and provide appropriate treatment with antihypertensive drugs. In patients who are not opioid dependent, naloxone has also been reported to be effective.
Like most opiates, butorphanol can cause dermatologic reactions. Pruritus was reported in >= 1% of patients during pre-marketing clinical trials. Rash (unspecified) and urticaria occurred in less than 1% of patients.
Blurred vision, tinnitus, and ear pain (otalgia) occurred in at least 1% of patients during pre-marketing clinical trials of butorphanol.
For the body as a whole, diaphoresis, sensations of heat, asthenia, and lethargy were reported with an incidence of 1% or greater during pre-marketing clinical trials with butorphanol (n = 2446). Edema was noted in < 1% of patients.
Urinary retention was rarely reported with butorphanol (< 1% of 2446 patients) during clinical trial experience with the nasal spray and injectable formulations.
Physiological dependence will occur during chronic opiate agonist therapy as evidenced by a withdrawal syndrome occurring after abrupt discontinuation of the drug in these patients. Symptoms of withdrawal include nausea and diarrhea, coughing, lacrimation, yawning, sneezing, rhinorrhea, profuse sweating, twitching muscles, abdominal and muscle pain/cramps, hot and cold flashes, and piloerection. Elevations in body temperature, respiratory rate, heart rate, and blood pressure may also occur. In a chronic nonmalignant pain study, symptoms consistent with withdrawal were reported in 8 (2.6%) patients using butorphanol nasal spray compared to 0 patients using placebo; most patients abruptly discontinued the nasal spray after long-term use or administration of high doses. Without treatment most symptoms resolve within 5 to 14 days; however, there appears to be a secondary or chronic abstinence syndrome which may last 2 to 6 months, characterized by insomnia, irritability and muscle aches. The shorter the onset and duration of action of the opiate agonist, the greater the intensity and rapidity of onset of withdrawal symptoms. Routine use of opiate agonists by an expectant mother can lead to neonatal respiratory depression in the newborn and/or neonatal opioid withdrawal syndrome. Withdrawal symptoms in a newborn occur 1 to 4 days after birth and include generalized tremors, hypertonicity with any form of tactile stimuli, hyperalertness, sleeplessness, excessive crying, vomiting, diarrhea, yawning, and fever. It is important to differentiate physiological dependence, the onset of a withdrawal syndrome upon abrupt discontinuation of the drug from psychological dependence. Although the possibility of psychological dependence with butorphanol is less than pure opiate agonists due to the opiate antagonistic effects, opiate agonists-antagonists do have the potential to cause psychological dependence leading to drug abuse. Psychological dependence is a behavioral syndrome characterized by drug craving, overwhelming concern with acquisition of the drug and other drug-related behaviors such as drug selling and seeking the drug from multiple sources. During postmarketing surveillance, more cases of abuse with the nasal dosage form have been reported than with the injectable dosage form.
Pharmacologic tolerance to the analgesic affects of opiate agonists including butorphanol may occur in some patients. Tolerance is the need for increasing opioid doses to maintain initial pain relief. Typically, tolerance presents as a decrease in the duration of analgesia and is managed by increasing the opioid dose or frequency. When increasing doses of analgesia are required causes may be multi-factorial including tolerance, progression of disease or psychological distress. During a controlled clinical trial in patients with nonmalignant chronic pain, 9 patients (2.9%) treated with butorphanol nasal spray (n = 303) for up to 6 months reported overuse, which may suggest the development of tolerance.
There appears to be little difference in the incidence of adverse effects reported from either injectable or intranasal butorphanol. Drowsiness (somnolence) is the most frequently reported adverse effect that occurred in 43% of patients during premarketing clinical trials (n = 2,446). Dizziness was reported in 19% and insomnia in 11% of patients treated with butorphanol. Adverse effects also affecting the CNS with an incidence of at least 1% with probable drug causality include confusion, tremor, anxiety, nervousness, headache, euphoria and feelings of floating, and paresthesias. Advise patients that activity requiring mental alertness can be affected because of CNS depression with butorphanol. Effects considered to be probably related to butorphanol that occurred in less than 1% of patients include hallucinations, abnormal dreams, agitation, hostility, and dysphoria. Depression also occurred in less than 1% of patients. Increased intracranial pressure may also occur. Overuse of drugs for treating acute headaches, including butorphanol, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of butorphanol or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use.
Serotonin syndrome has been reported in patients taking opioids at recommended doses. Patients taking opioids concomitantly with a serotonergic medication should seek immediate medical attention if they develop symptoms such as agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea. Symptoms generally present within hours to days of taking an opioid with another serotonergic agent, but may also occur later, particularly after a dosage increase. If serotonin syndrome is suspected, either the opioid and/or the other agent should be discontinued.
Opioid agonists can interfere with the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH), and by stimulating secretion of prolactin, growth hormone (GH), insulin, and glucagon. Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression). Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence (erectile dysfunction), amenorrhea, or infertility. Other various medical, physical, lifestyle, and psychological stressors may influence gonadal hormone concentrations; these stressors have not been adequately controlled for in clinical studies with opioids. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation. Opioid agonists can inhibit the release of thyrotropin, leading to a decrease in thyroid hormone. Morphine and related compounds can stimulate the release of vasopressin (ADH). Hyponatremia can occur as a result of SIADH.
Opioids may interfere with the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH) and cortisol. Rarely, adrenocortical insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency.
Cases of opioid-induced hyperalgesia (OIH) have been reported, both with short-term and longer-term use of opioids. OIH occurs when an opioid paradoxically causes an increase in pain or an increase in sensitivity to pain. Symptoms of OIH include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Data suggests a strong biologic plausibility between opioids and OIH and allodynia. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching to a different opioid).
Hypoglycemia has been reported during opioid therapy. Most reports occurred in persons with at least 1 predisposing risk factor, such as diabetes.
Butorphanol is contraindicated in persons with butorphanol hypersensitivity or hypersensitivity to any of the formulation excipients, including benzethonium chloride hypersensitivity, which is a preservative in butorphanol nasal spray.
Opioid use requires an experienced clinician who is knowledgeable about the use of opioids and how to mitigate the associated risks. Opioids expose users to the risks of addiction, abuse, and misuse, which can occur at any dosage or duration. Although the risk of addiction in any individual is unknown, it can occur in persons appropriately prescribed an opioid. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each individual's risk for opioid addiction, abuse, or misuse before prescribing an opioid, and monitor for the development of these behaviors or conditions. Risks are increased in persons with a personal or family history of substance abuse (including alcoholism) or mental illness (e.g., major depression). The potential for these risks should not prevent the proper management of pain in any given individual. Persons at increased risk may be prescribed opioids but use in such persons necessitates intensive counseling about the risks and proper use of the opioid along with intensive monitoring for signs of addiction, abuse, and misuse. Abuse and addiction are separate and distinct from physical dependence and tolerance; persons with addiction may not exhibit tolerance and symptoms of physical dependence. Opioids are sought by drug abusers and persons with addiction disorders and are subject to criminal diversion. Abuse of opioids has the potential for overdose or poisoning and death. Consider these risks when prescribing or dispensing opioids. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. Keep opioids out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure or improper use may cause respiratory failure and a fatal overdose. Accidental exposure of even a single dose of an opioid, especially by younger persons, can result in a fatal overdose. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of an opioid for persons in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Do not use immediate-release opioids for an extended period unless the pain remains severe enough to require an opioid and for which alternative treatment options continue to be inadequate. Many acute pain conditions (e.g., pain occurring with surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid. Clinical guidelines on opioid prescribing for some acute pain conditions are available. Discuss the availability of naloxone with all patients and consider prescribing it in persons who are at increased risk of opioid overdose, such as those who are also using other CNS depressants, who have a history of opioid use disorder (OUD), who have experienced a previous opioid overdose, or who have household members or other close contacts at risk for accidental exposure or opioid overdose.
Butorphanol is contraindicated in persons with known or suspected GI obstruction, including paralytic ileus. Butorphanol may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor persons with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Butorphanol is contraindicated in persons with significant respiratory depression and those with acute or severe asthma in an unmonitored setting or in the absence of resuscitative equipment. Avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in persons for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective dosages and minimum treatment durations needed. Monitor closely for signs or symptoms of respiratory depression and sedation. Persons with chronic obstructive pulmonary disease (COPD), cor pulmonale, respiratory insufficiency, hypoxemia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive even at recommended doses. Persons with advanced age, cachexia, or debilitation are also at an increased risk for opioid-induced respiratory depression. Monitor such persons closely, particularly when initiating and titrating the opioid; consider the use of non-opioid analgesics. Opioids increase the risk of central sleep apnea (CSA) and sleep-related hypoxemia in a dose-dependent fashion. Consider decreasing the opioid dosage in persons with CSA. Respiratory depression, if left untreated, may cause respiratory arrest and death. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Management of respiratory depression may include observation, necessary supportive measures, and opioid antagonist use when indicated.
Avoid abrupt discontinuation of butorphanol in a physically-dependent patient. When a patient who has been taking opioids regularly and may be physically dependent no longer requires therapy with butorphanol, taper the dose gradually while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Consider tapering to reduced opioid dosage, or tapering and discontinuing long-term opioid therapy, when pain improves; the patient requests dosage reduction or discontinuation; pain and function are not meaningfully improved; the patient is receiving higher opioid doses without evidence of benefit from the higher dose; the patient has current evidence of opioid misuse; the patient experiences side effects that diminish quality of life or impair function; the patient experiences an overdose or other serious event (e.g., hospitalization, injury) or has warning signs for an impending event such as confusion, sedation, or slurred speech; the patient is receiving medications (e.g., benzodiazepines) or has medical conditions (e.g., lung disease, sleep apnea, liver disease, kidney disease, fall risk, advanced age) that increase risk for adverse outcomes; or the patient has been treated with opioids for a prolonged period and current benefit-harm balance is unclear. If the patient has a serious mental illness, is at high suicide risk, or has suicidal ideation, offer or arrange for consultation with a behavioral health provider before initiating a taper. In patients with opioid use disorder, offer or arrange for medication-assisted treatment. Individualize opioid tapering schedules. The longer the duration of previous opioid therapy, the longer the taper may take. Common tapers involve dose reduction of 5% to 20% every 4 weeks; a faster taper may be appropriate for some patients. Significant opioid withdrawal symptoms may indicate the need to pause or slow the taper. Opioids may be stopped, if appropriate, when taken less often than once daily. Advise patients that there is an increased risk for overdose on abrupt return to a previously prescribed higher dose; provide opioid overdose education, and consider offering naloxone. Monitor patients closely for anxiety, depression, suicidal ideation, and opioid use disorder, and offer support and referral as needed.
Avoid butorphanol use in persons with CNS depression, impaired consciousness, or coma; opioids may obscure the clinical course in a person with a head trauma injury. Monitor persons who may be susceptible to the intracranial effect of carbon dioxide retention (e.g., those with evidence of increased intracranial pressure, brain tumor, or intracranial mass) for signs of sedation and respiratory depression, particularly when initiating butorphanol therapy. Butorphanol may reduce respiratory drive and resultant carbon dioxide retention can further increase intracranial pressure.
Limit the use of butorphanol in persons with acute myocardial infarction, ventricular dysfunction, or coronary insufficiency to those situations where the benefits clearly outweigh the risk because butorphanol may increase the work of the heart, especially the pulmonary circuit.
Drug accumulation can occur in patients with renal impairment, renal failure, or hepatic disease, prolonging butorphanol's duration of action and increasing the risk of adverse reactions; lower initial doses are advised (see Dosage). Butorphanol and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to butorphanol may be greater in patients with impaired renal function.
Geriatric patients are more susceptible to the adverse reactions of butorphanol and should be carefully monitored; lower initial doses are advised (see Dosage). In clinical studies, elderly patients had an increased incidence of headache, dizziness, drowsiness, vertigo, constipation, nausea/vomiting, and nasal congestion as compared to younger patients.
Monitor persons with a history of seizure disorder for worsened seizure control during opioid therapy. Opioids may increase the frequency of seizures in persons with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.
Butorphanol readily crosses the placenta and the manufacturer recommends caution with use in pregnant women. It is classified as FDA pregnancy risk category C. Premature neonates are especially sensitive to respiratory depression and apnea. There have been rare reports of infant respiratory distress/apnea following the administration of butorphanol injection during labor. The reports of respiratory distress/apnea have been associated with administration of a dose within 2 hours of obstetric delivery, use of multiple doses, use with additional analgesic or sedative drugs, or use in preterm pregnancies. In a study of 119 patients, the administration of 1 mg of IV butorphanol during labor was associated with transient (10 to 90 minutes) sinusoidal fetal heart rate patterns, but was not associated with adverse neonatal outcomes. Further, prolonged maternal use of butorphanol during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.
Butorphanol has been detected in milk after intravenous administration to breast-feeding mothers. There is no clinical experience with use of the nasal spray; however, similar concentrations would be expected. The manufacturer states that 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). The American Academy of Pediatrics (AAP) suggests that butorphanol is usually compatible with breast-feeding. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Patients should be warned that butorphanol can impair the mental and physical abilities required for the performance of potentially dangerous tasks such as driving or operating machinery. These effects may persist for varying periods of time after dosing.
Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.
General dosing information:
-Individualize dosing for each patient; consider severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse. Use the lowest effective dose for the shortest duration consistent with individual treatment goals.
-There is substantial interpatient variability in the relative potency of different opioid drugs and products. For conversion between opioids, assessment of individual clinical response is necessary. When converting from another opioid agonist, it is preferable to underestimate the patient's daily dose requirements and give rescue medication than to overestimate and risk an adverse event. Refer to the Opioid Agonists Drug Class Overview for approximate equianalgesic doses.
-Monitor patients closely for respiratory depression, especially within the first 24 to 48 hours after initiation and dose escalation, and adjust the dosage accordingly. Continually reevaluate patients to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as to monitor for the development of addiction, abuse, or misuse. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the opioid dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
-When a patient who has been taking opioids regularly and may be physically dependent no longer requires therapy with butorphanol, taper the dose gradually while monitoring carefully for signs and symptoms of withdrawal.
For the treatment of severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate:
-for the treatment of severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate:
Intranasal dosage:
Adults: 1 mg into 1 nostril once; may repeat dose after 60 to 90 minutes after the first dose and may repeat the initial dose sequence after 3 to 4 hours after the second dose if adequate pain relief is not achieved. Alternately, 1 mg into each nostril once; may repeat dose after 3 to 4 hours after first dose.
Older Adults: 1 mg into 1 nostril once; may repeat dose after 90 to 120 minutes after the first dose and may repeat the initial dose sequence after at least 6 hours after the second dose if adequate pain relief is not achieved.
Intravenous dosage:
Adults: 0.5 to 2 mg IV every 3 to 4 hours as needed. Usual dose: 1 mg IV every 3 to 4 hours as needed.
Older Adults: 0.5 to 1 mg IV once, then 1 mg IV after 90 to 120 minutes after first dose as needed and may repeat the initial dose sequence after at least 6 hours as needed.
Intramuscluar dosage:
Adults: 1 to 4 mg IM every 3 to 4 hours as needed. Usual dose: 2 mg IM every 3 to 4 hours as needed.
Older Adults: 1 mg IM once, then 1 mg IM after 90 to 120 minutes after first dose as needed and may repeat the initial dose sequence after at least 6 hours as needed.
-for the treatment of severe obstetric pain in persons at full term in early labor when delivery is not expected to occur within 4 hours:
Intravenous or intramuscular dosage:
Adults: 1 to 2 mg IV or IM; may repeat dose after 4 hours. Use alternative analgesia for pain associated with delivery of if delivery is expected to occur within 4 hours.
For the acute treatment of migraine:
Intranasal dosage:
Adults: 1 mg into 1 nostril as a single dose; may repeat dose after 60 to 90 minutes after the first dose and may repeat the initial dose sequence after 3 to 4 hours after the second dose if adequate pain relief is not achieved. Alternately, 1 mg into each nostril as a single dose; may repeat dose after 3 to 4 hours after first dose. Guidelines classify intranasal butorphanol as having established efficacy for the treatment of acute migraine.
Older Adults: 1 mg into 1 nostril as a single dose; may repeat dose after 90 to 120 minutes after the first dose and may repeat the initial dose sequence after at least 6 hours after the second dose if adequate pain relief is not achieved. Guidelines classify intranasal butorphanol as having established efficacy for the treatment of acute migraine.
For preanesthesia:
Intramuscular dosage:
Adults: 2 mg IM once at 60 to 90 minutes before surgery.
Geriatric Adults: 1 mg IM once at 60 to 90 minutes before surgery.
For general anesthesia induction and general anesthesia maintenance as an adjunct to balanced anesthesia:
Intravenous dosage:
Adults: 2 mg IV shortly before induction and/or 0.5 to 4 mg IV as needed during anesthesia. Usual total dose: 4 to 12.5 mg.
Geriatric Adults: 1 mg IV shortly before induction and/or 0.5 to 1 mg IV as needed during anesthesia.
Maximum Dosage Limits:
-Adults
The maximum dosage is dependent on route of administration and indication for therapy.
-Elderly
The maximum dosage is dependent on route of administration and indication for therapy.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Intranasal dosage should not exceed 1 mg followed by 1 mg in 90-120 minutes. The initial IM or IV dose for pain relief should generally be half the recommended adult dose (0.5 mg IV or 1 mg IM). Repeat dosage interval for intranasal, IV, or IM administration should generally not be less than 6 hours.
Patients with Renal Impairment Dosing
Intranasal dosage should not exceed 1 mg followed by 1 mg in 90-120 minutes. The initial IM or IV dose for pain relief should generally be half the recommended adult dose (0.5 mg IV or 1 mg IM). Repeat dosage interval for intranasal, IV, or IM administration should generally not be less than 6 hours.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as dihydrocodeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce the analgesic effects of dihydrocodeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acetaminophen; Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acetaminophen; Diphenhydramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acetaminophen; Hydrocodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of hydrocodone. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Acetaminophen; Oxycodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as oxycodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Acetaminophen; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Acrivastine; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Alfentanil: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as alfentanil. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Alprazolam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Amitriptyline: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Amobarbital: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Amoxapine: (Major) Concomitant use of butorphanol with amoxapine may cause excessive sedation and somnolence. Limit the use of butorphanol with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use in necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Anticholinergics: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Aripiprazole: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as aripiprazole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Asenapine: (Moderate) Drugs that can cause CNS depression, if used concomitantly with asenapine, may increase adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when asenapine is given in combination with butorphanol.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with other CNS depressants, such as carisoprodol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Aspirin, ASA; Oxycodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as oxycodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Atropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Atropine; Difenoxin: (Moderate) Butorphanol is a synthetic parenteral opiate agonist-antagonist. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of butorphanol and antidiarrheals, such as diphenoxylate, can lead to severe constipation and possibly additive CNS depression. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including butorphanol.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including butorphanol.
Baclofen: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as baclofen, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Barbiturates: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Belladonna; Opium: (Major) Butorphanol may partially block the analgesic, respiratory depressant and CNS depressant effects of pure opiate agonists. Butorphanol may also be used concurrently with some opiate agonists and cause additive CNS, respiratory, and hypotensive effects. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benzhydrocodone; Acetaminophen: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as benzhydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Benztropine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Brexpiprazole: (Moderate) Due to the CNS effects of brexpiprazole, caution is advisable when brexpiprazole is given in combination with other centrally-acting medications including butorphanol.
Brompheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Brompheniramine; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Buprenorphine: (Major) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Bupropion; Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Buspirone: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as buspirone, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Butalbital; Acetaminophen: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Cannabidiol: (Moderate) Concomitant use of mixed opioid agonists/antagonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of mixed opioid agonists/antagonists with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opioid agonist/antagonist is initiated in a patient taking cannabidiol, reduce initial dosage and titrate to clinical response. If cannabidiol is initiated in a patient taking a mixed opioid agonist/antagonist, use a lower initial dose of cannabidiol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Capsaicin; Metaxalone: (Major) Concomitant use of butorphanol with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of butorphanol with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of butorphanol and metaxalone increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of opiate agonists-antagonists with other central nervous system (CNS) depressants, such as COMT inhibitors, can potentiate the effects of the opiate agonists-antagonist and may lead to additive CNS or respiratory depression. Prior to concurrent use of a mixed opiate agonist-antagonist in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension and CNS depression.
Carbinoxamine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution is advisable when cariprazine is given in combination with other centrally-acting medications including butorphanol.
Carisoprodol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as carisoprodol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Celecoxib; Tramadol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as tramadol. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. There is also a potential increased risk of seizures if tramadol is given with other opiates.
Cenobamate: (Moderate) Concomitant use of butorphanol with cenobamate may cause excessive sedation and somnolence. Limit the use of butorphanol with cenobamate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with butorphanol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with butorphanol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorcyclizine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlordiazepoxide: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlordiazepoxide; Clidinium: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Chlorpheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Hydrocodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of hydrocodone. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpheniramine; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Chlorpromazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Chlorzoxazone: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as chlorzoxazone, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Clemastine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Clobazam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Clomipramine: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Clonazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Clorazepate: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Clozapine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as clozapine, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Codeine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Codeine; Guaifenesin: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Codeine; Phenylephrine; Promethazine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Codeine; Promethazine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as codeine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of codeine. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
COMT inhibitors: (Major) Concomitant use of opiate agonists-antagonists with other central nervous system (CNS) depressants, such as COMT inhibitors, can potentiate the effects of the opiate agonists-antagonist and may lead to additive CNS or respiratory depression. Prior to concurrent use of a mixed opiate agonist-antagonist in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension and CNS depression.
Cyclobenzaprine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as cyclobenzaprine, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Cyproheptadine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dantrolene: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as dantrolene, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Daridorexant: (Moderate) Concomitant use of butorphanol with daridorexant may cause excessive sedation and somnolence. Limit the use of butorphanol with daridorexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Desipramine: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Deutetrabenazine: (Major) Concomitant use of mixed opiate agonists/antagonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking deutetrabenazine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If deutetrabenazine is prescribed for a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Dexbrompheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dexchlorpheniramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Diazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If parental diazepam is used with a mixed opiate agonist/antagonist, reduce the mixed opiate agonist/antagonist dosage by at least 1/3. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Dicyclomine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Diphenhydramine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Diphenhydramine; Ibuprofen: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Diphenhydramine; Naproxen: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Diphenoxylate; Atropine: (Moderate) Butorphanol is a synthetic parenteral opiate agonist-antagonist. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of butorphanol and antidiarrheals, such as diphenoxylate, can lead to severe constipation and possibly additive CNS depression. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Doxepin: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Doxylamine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Doxylamine; Pyridoxine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Dronabinol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as dronabinol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Droperidol: (Major) Mixed opiate agonists/antagonists have additive or potentiating effects with droperidol. Following administration of droperidol, lower doses of the other CNS depressant should be used.
Entacapone: (Major) Concomitant use of opiate agonists-antagonists with other central nervous system (CNS) depressants, such as COMT inhibitors, can potentiate the effects of the opiate agonists-antagonist and may lead to additive CNS or respiratory depression. Prior to concurrent use of a mixed opiate agonist-antagonist in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension and CNS depression.
Esketamine: (Major) Closely monitor patients receiving esketamine and butorphanol for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered CNS depressants should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Fenfluramine: (Moderate) Concomitant use of opioid agonists-antagonists with fenfluramine may cause excessive sedation and somnolence. Limit the use of opioid agonists with fenfluramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as fentanyl. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Flavoxate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as mixed opiate agonists/antagonists or their combinations (e.g., buprenorphine; naloxone), may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Fluphenazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Flurazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Concomitant use of butorphanol with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of butorphanol with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
General anesthetics: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Glycopyrrolate; Formoterol: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Guaifenesin; Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Haloperidol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Homatropine; Hydrocodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of hydrocodone. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hydrocodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of hydrocodone. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Hydrocodone; Ibuprofen: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydrocodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of hydrocodone. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Hydromorphone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as hydromorphone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Hydroxyzine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Hyoscyamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Ibuprofen; Oxycodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as oxycodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Iloperidone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when iloperidone is given in combination with other centrally-acting medications including butorphanol.
Imipramine: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Indacaterol; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Isocarboxazid: (Major) Avoid coadministration of butorphanol with monoamine oxidase inhibitors (MAOIs) due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Data are not available about the use of butorphanol concurrently with MAOIs. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Isoflurane: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Ketamine: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Lasmiditan: (Moderate) Concomitant use of butorphanol with lasmiditan may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of butorphanol with lasmiditan to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and serotonin syndrome.
Lemborexant: (Moderate) Concomitant use of opiate agonists-antagonists with lemborexant may cause excessive sedation and somnolence. Limit the use of the opiate agonists-antagonist with lemborexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with butorphanol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levorphanol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as levorphanol. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Linezolid: (Major) Avoid concomitant use of butorphanol with linezolid due to the risk of serotonin syndrome. If concomitant use is warranted, carefully monitor the patient, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and butorphanol. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and butorphanol. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications such as butorphanol.
Maprotiline: (Moderate) Pain medications such as buprenorphine; butorphanol; nalbuphine; pentazocine; should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension.
Meclizine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Meperidine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as meperidine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Meprobamate: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as meprobamate, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Metaxalone: (Major) Concomitant use of butorphanol with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of butorphanol with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of butorphanol and metaxalone increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary.
Methadone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as methadone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Methocarbamol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as methocarbamol, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Methohexital: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Methscopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Midazolam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as butorphanol. Caution should be exercised when using these agents concurrently.
Mirtazapine: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. Butorphanol should be used cautiously in any patient receiving these agents, which may include mirtazapine.
Molindone: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as molindone, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage of butorphanol and/or molindone may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Monoamine oxidase inhibitors: (Major) Avoid coadministration of butorphanol with monoamine oxidase inhibitors (MAOIs) due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Data are not available about the use of butorphanol concurrently with MAOIs. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Morphine: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as morphine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Morphine; Naltrexone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as morphine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Nabilone: (Major) The use of nabilone with opiate agonist/antagonists may lead to additive CNS or respiratory depression, profound sedation, or coma. If these agents are used together, a reduced dosage of either drug may be advisable. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Cross-tolerance may occur between these drugs over time. Consider the patient's use of alcohol or illicit drugs. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Nalbuphine: (Major) Concomitant use of nalbuphine with other CNS depressants can potentiate the effects of nalbuphine on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Nalbuphine should be used cautiously in any patient receiving these agents. If a CNS depressant needs to be used with nalbuphine, the dose of one or both drugs needs to be reduced.
Nalmefene: (Major) Naloxone, nalmefene, and naltrexone act as opiate antagonists at all opiate receptors. Administration of an opiate antagonist will override the actions of mixed opiate agonist/antagonists and precipitate opioid withdrawal effects. While opiate antagonism may be desirable in a patient with respiratory depression caused by the mixed opiate agonist/antagonist, severe pain can be unmasked and opiate withdrawal symptoms may occur in patients who have received chronic opiate agonist therapy.
Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Nefazodone: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as nefazodone, can potentiate the effects of the butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Neostigmine; Glycopyrrolate: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Nortriptyline: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Olanzapine: (Moderate) Other drugs that can cause CNS depression, such as butorphanol, if used concomitantly with olanzapine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Olanzapine; Fluoxetine: (Moderate) Other drugs that can cause CNS depression, such as butorphanol, if used concomitantly with olanzapine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Olanzapine; Samidorphan: (Contraindicated) Salmidorphan is contraindicated in patients who are using opiate agonists or undergoing acute opioid withdrawal. Salmidorphan increases the risk of precipitating acute opioid withdrawal in patients dependent on opioids. Before initiating salmidorphan, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations, if a salmidorphan-treated patient requires opiates for anesthesia or analgesia, discontinue salmidorphan. The opiate agonist should be administered by properly trained individual(s), and the patient properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations, if a salmidorphan-treated patient requires opiate agonist treatment (e.g., for analgesia) discontinue salmidorphan at least 5 days before opioid treatment. Salmidorphan, as an opioid antagonist, may cause opioid treatment to be less effective or ineffective shortly after salmidorphan discontinuation. (Moderate) Other drugs that can cause CNS depression, such as butorphanol, if used concomitantly with olanzapine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Oliceridine: (Major) Avoid concomitant use of oliceridine with opioid agonists-antagonists. Coadministration may reduce the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
Opicapone: (Major) Concomitant use of opiate agonists-antagonists with other central nervous system (CNS) depressants, such as COMT inhibitors, can potentiate the effects of the opiate agonists-antagonist and may lead to additive CNS or respiratory depression. Prior to concurrent use of a mixed opiate agonist-antagonist in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension and CNS depression.
Orphenadrine: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Oxazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Oxybutynin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Oxycodone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as oxycodone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Oxymetazoline: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as oxymetazoline. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Oxymorphone: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as oxymorphone. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Ozanimod: (Moderate) Coadministration of butorphanol, an opioid agonist/antagonist, with ozanimod is not recommended due to the potential for serotonergic effects. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for serotonin syndrome or increased blood pressure. If concomitant use of butorphanol is warranted in a patient taking an MAO inhibitor, carefully observe the patient and monitor blood pressure, particularly during treatment initiation and dose adjustment. Discontinue serotonergic agents if serotonin syndrome is suspected. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration.
Paliperidone: (Moderate) Drugs that can cause CNS depression, including butorphanol, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness when used with paliperidone, an antipsychotic with potential CNS depressant properties. Monitor for signs and symptoms of CNS depression and advise patients to avoid driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
Pentazocine; Naloxone: (Major) Concomitant use of butorphanol and pentazocine can potentiate respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. If these drugs need to be administered together, use the smallest effective dose and the longest dosing frequency of butorphanol.
Pentobarbital: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Perphenazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Perphenazine; Amitriptyline: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Phenelzine: (Major) Avoid coadministration of butorphanol with monoamine oxidase inhibitors (MAOIs) due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Data are not available about the use of butorphanol concurrently with MAOIs. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Phenobarbital: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Phenothiazines: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Phenylephrine: (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Pimozide: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as pimozide, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage butorphanol may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Pramipexole: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as pramipexole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Pregabalin: (Major) Concomitant use of butorphanol with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of butorphanol with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
Primidone: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Prochlorperazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Promethazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Promethazine; Phenylephrine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation. (Moderate) The rate of butorphanol absorption through the nasal mucosa is decreased when administered with sympathomimetic nasal decongestants such as phenylephrine. However, the extent of absorption is not decreased. A slower onset of action should be expected if butorphanol is administered concurrently with or immediately following a sympathomimetic nasal decongestant.
Propantheline: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Propofol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Protriptyline: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Pseudoephedrine; Triprolidine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Quazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Quetiapine: (Moderate) Concomitant use of butorphanol with quetiapine can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Rasagiline: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including butorphanol. Use these drugs cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them. In some cases, the dosages of the CNS depressants may need to be reduced.
Remifentanil: (Major) Concurrent use of butorphanol may reduce the analgesic effect of remifentanil and/or precipitate withdrawal symptoms. If coadministration is necessary, carefully observe the patient, especially during remifentanil initiation and dosage adjustment. Consider discontinuing remifentanil and instituting alternative analgesia if the patient is not responding appropriately. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Remimazolam: (Major) Concomitant use of opioid agonists-antagonists with remimazolam may cause respiratory depression, hypotension, profound sedation, and death. Titrate the dose of remimazolam to the desired clinical response and continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation.
Risperidone: (Moderate) Concomitant use of butorphanol with risperidone can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Ropinirole: (Moderate) Concomitant use of butorphanol with ropinirole can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Rotigotine: (Moderate) Concomitant use of rotigotine with other CNS depressants, such as opiate agonists-antagonists, can potentiate the sedation effects of rotigotine.
Safinamide: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids.
Scopolamine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Secobarbital: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as barbiturates, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Sedating H1-blockers: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Selegiline: (Major) Avoid coadministration of butorphanol with selegiline due to the risk for serotonin syndrome and additive CNS depression. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for CNS depression and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sevoflurane: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Solifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Stiripentol: (Major) Concomitant use of mixed opioid agonists/antagonists like butorphanol with stiripentol may cause excessive sedation and somnolence. Limit the use of butorphanol with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If butorphanol is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking butorphanol, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Sufentanil: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as sufentanil. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist.
Sumatriptan: (Moderate) The safety of using intranasal butorphanol and 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. Theoretically, the effect of intranasal butorphanol may be increased by intranasal sumatriptan. To reduce the likelihood of this interaction, allow 30 minutes between the administration of each drug. In healthy volunteers, the pharmacokinetics of butorphanol intranasal (1 mg) were not affected by the coadministration of a single dose of sumatriptan SC 6 mg. However, in another study, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in Cmax) when butorphanol intranasal (1 mg) was administered 1 minute after a 20-mg dose of sumatriptan nasal spray (in opposite nostrils); however, if patients wait 30 minutes between administrations any interaction effect should be minimal. Butorphanol intranasal administration does not affect the pharmacokinetics of sumatriptan when given intranasally.
Sumatriptan; Naproxen: (Moderate) The safety of using intranasal butorphanol and 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. Theoretically, the effect of intranasal butorphanol may be increased by intranasal sumatriptan. To reduce the likelihood of this interaction, allow 30 minutes between the administration of each drug. In healthy volunteers, the pharmacokinetics of butorphanol intranasal (1 mg) were not affected by the coadministration of a single dose of sumatriptan SC 6 mg. However, in another study, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in Cmax) when butorphanol intranasal (1 mg) was administered 1 minute after a 20-mg dose of sumatriptan nasal spray (in opposite nostrils); however, if patients wait 30 minutes between administrations any interaction effect should be minimal. Butorphanol intranasal administration does not affect the pharmacokinetics of sumatriptan when given intranasally.
Tapentadol: (Major) Avoid the concomitant use of tapentadol and opiate agonists/antagonists (e.g., buprenorphine, butorphanol, nalbuphine, or pentazocine). Opiate agonists/antagonists may partially block the analgesic, respiratory depressant, and CNS depressant effects of tapentadol. Due to their antagonistic properties, opiate agonists/antagonists may cause withdrawal symptoms in patients receiving chronic opiate agonists. These agents may also be used concurrently with some opiate agonists and cause additive CNS, respiratory, and hypotensive effects. Consider dose reduction of the opiate agonist in situations of concomitant prescription. The additive or antagonistic effects are dependent upon the dose of pure opiate agonist used; antagonistic effects are more common at low to moderate doses of the pure opiate agonist.
Temazepam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tetrabenazine: (Moderate) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression, like butorphanol. Concurrent use of tetrabenazine and butorphanol can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as butorphanol due to the potential for additive sedative effects.
Thioridazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as butorphanol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Tizanidine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as tizanidine, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Tolcapone: (Major) Concomitant use of opiate agonists-antagonists with other central nervous system (CNS) depressants, such as COMT inhibitors, can potentiate the effects of the opiate agonists-antagonist and may lead to additive CNS or respiratory depression. Prior to concurrent use of a mixed opiate agonist-antagonist in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, reduced dosages may be necessary. Carefully monitor the patient for hypotension and CNS depression.
Tolterodine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug, such as tolterodine. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Tramadol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as tramadol. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. There is also a potential increased risk of seizures if tramadol is given with other opiates.
Tramadol; Acetaminophen: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as tramadol. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. There is also a potential increased risk of seizures if tramadol is given with other opiates.
Tranylcypromine: (Major) Avoid coadministration of butorphanol with monoamine oxidase inhibitors (MAOIs) due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Data are not available about the use of butorphanol concurrently with MAOIs. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Trazodone: (Moderate) Because of the potential risk and severity of CNS depression, respiratory depression, and serotonin syndrome, caution should be observed when administering butorphanol with trazodone. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Triazolam: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of mixed opiate agonists/antagonists with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If a mixed opiate agonist/antagonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the mixed opiate agonist/antagonist and titrate to clinical response. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tricyclic antidepressants: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Trifluoperazine: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as phenothiazines, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Trihexyphenidyl: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, such as butorphanol, may potentiate the effects of either trimethobenzamide or the other medication.
Trimipramine: (Moderate) Pain medications such as mixed opiate agonists/antagonists should be combined cautiously with tricyclic antidepressants due to the possibility of additive CNS depression, respiratory depression, hypotension, or decreased intestinal motility. Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tricyclic antidepressants with other drugs that have serotonergic properties such as pentazocine. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If serotonin syndrome is suspected, tricyclic antidepressants and concurrent serotonergic agents should be discontinued. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Triprolidine: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Trospium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when butorphanol is used concomitantly with an anticholinergic drug, such as trospium. The concomitant use of butorphanol and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect.
Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with butorphanol.
Vilazodone: (Moderate) Because of the potential risk and severity of CNS depression, respiratory depression, and serotonin syndrome, caution should be observed when administering butorphanol with vilazodone. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering butorphanol with vortioxetine. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Zaleplon: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as zaleplon, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage of butorphanol and/or zaleplon may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Ziconotide: (Moderate) Concurrent use of ziconotide and opiate agonists-antagonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists.
Ziprasidone: (Moderate) Concomitant use of butorphanol with other central nervous system (CNS) depressants, such as ziprasidone, can potentiate the effects of butorphanol and may lead to additive CNS or respiratory depression. Prior to concurrent use of butorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. If these agents are used together, a reduced dosage of butorphanol and/or ziprasidone may be necessary. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
Zolpidem: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Butorphanol should be used cautiously in any patient receiving these agents, which may include zolpidem. A dosage reduction of the Intermezzo brand of sublingual zolpidem tablets to 1.75 mg/night is recommended in patients receiving concomitant CNS depressants. A reduction in dose of the CNS depressant may also be needed. Concurrent use Intermezzo with other sedative-hypnotics, including other zolpidem products, at bedtime or the middle of the night is not recommended.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Butorphanol is a mixed agonist-antagonist opioid analgesic. Specifically, butorphanol is a kappa-receptor agonist and a partial agonist or mixed agonist-antagonist with low intrinsic activity at mu-receptors. Opioids exert their effects by stimulating specific opioid receptors, designated as mu, kappa, and delta. Mu-receptors are considered the classic morphine-receptor type, and stimulation at this receptor produces supraspinal analgesia, respiratory depression, euphoria, and physical dependence. Stimulation of kappa-receptors produces spinal analgesia, miosis, and sedation. Because of limited stimulation at the mu-receptor, butorphanol is believed to produce less respiratory depression and to pose a lower risk of physical dependence than morphine.
Butorphanol is administered via oral, intravenous, intramuscular or intranasal route. Butorphanol and its metabolites are widely distributed. The volume of distribution is between 305-901 liters. The drug crosses the blood-brain barrier and the placenta and is distributed into breast milk. Protein binding is 80%. Hepatic metabolism is extensive, primarily producing an inactive metabolite, hydroxybutorphanol. N-dealkylation and conjugation also occur. The metabolites produced during first pass have no analgesic activity. Elimination of butorphanol is via the kidneys and feces. Sixty to 80% of a dose of butorphanol is excreted via the kidneys as inactive metabolites; approximately 5% is excreted as unchanged drug. Between 11% and 14% of a parenteral dose is excreted in the feces.
-Route-Specific Pharmacokinetics
Oral Route
Butorphanol is readily absorbed from the gut, but it undergoes significant first-pass metabolism, so that only 17% of unchanged drug reaches the systemic circulation after oral administration.
Intravenous Route
An IV injection produces analgesia within 1 minute and peaks within 4-5 minutes. The duration of action is 2-4 hours after IV administration.
Intramuscular Route
After an IM injection, analgesic effects begin within 15 minutes, peaking within 30-60 minutes. The duration of action is 3-4 hours after IM administration.
Other Route(s)
Intranasal Route
Onset of analgesia after intranasal administration occurs within 15 minutes, however, onset may be delayed if administered concurrently with or immediately following a nasal vasoconstrictor (e.g., oxymetazoline). The intranasal route has a more prolonged duration of analgesia (4-5 hours) than the intravenous or intramuscular routes. Peak blood levels occur within 30-60 minutes of a 1 mg dose, with an absolute bioavailability of 60-70%.
-Special Populations
Hepatic Impairment
After intravenous administration to patients with hepatic impairment, the half-life of butorphanol tripled as compared to healthy subjects (16.8 hours vs. 4.8 hours, respectively). The exposure of hepatically impaired patients to butorphanol was 2-fold greater than that in healthy subjects. Similar results were seen after nasal administration.
Renal Impairment
In patients with creatinine clearance < 30 mL/min, the elimination half-life doubled and the total body clearance was approximately half compared to healthy subjects (10.5 hours vs. 5.8 hours, respectively).