Opiate Partial Agonist (Systemic Drug)
- Partial opiate agonist/antagonist used in a variety of species as an analgesic, premedication, antitussive, or antiemetic.
- Reasonably good analgesic for horses; however, there are better choices available for moderate to severe pain in small animals.
- Contraindicated or use with caution in patients with liver disease, hypothyroidism, renal insufficiency, Addison’s, head trauma, increased CSF pressure, or other CNS dysfunction (eg, coma) & in geriatric or severely debilitated patients.
- Reduce dose in dogs with MDR1 mutation.
- Potential adverse effects in dogs/cats may include sedation, ataxia, anorexia, or diarrhea (rarely).
- In horses (at usual doses), potential adverse effects may include transient ataxia, reduced gut sounds, & sedation, but CNS excitement is possible.
- Controlled substance (C-IV).1
The FDA-approved indication for butorphanol in horses is “…for the relief of pain associated with colic in adult horses and yearlings.” In horses, it appears that combining butorphanol with an alpha agonist (eg, detomidine, xylazine), enhances analgesia and sedation.
FDA-approved indication for butorphanol in dogs is “…for the relief of chronic non-productive cough associated with tracheobronchitis, tracheitis, tonsillitis, laryngitis and pharyngitis originating from inflammatory conditions of the upper respiratory tract.”
Butorphanol is also used in both dogs and cats as an adjunctive preanesthetic medication and analgesic and as an antiemetic before cisplatin treatment (although it is not very effective in cats for this indication). Compared with other opiate analgesics, butorphanol is not very useful in small animals (particularly dogs) for treating pain and has to be dosed frequently. Butorphanol can be a useful reversal agent for the CNS and respiratory depressant effects of mu-opioid agonists (eg, morphine, hydromorphone). Because of its kappa effects, butorphanol can reverse CNS and respiratory depression caused by mu-opioid agonists without completely reversing the analgesic effects.
Butorphanol has also been used in cattle, camelids, small ruminants, small mammals, and several wildlife species. Butorphanol use in reptiles is somewhat controversial, but most studies show it has minimal analgesic or anesthetic-sparing efficacy in many of these species.1
Commonly used to treat horses and dogs. Extra-label use in some other species.
On a weight basis, butorphanol is considered to be 4 to 7 times more potent an analgesic than morphine, 15 to 30 times more potent than pentazocine, and 30 to 50 times more potent than meperidine; however, a ceiling effect is reached at higher dosages, where analgesia is no longer enhanced and may be reduced. Its agonist activity is thought to occur primarily at the kappa and sigma opioid receptors as well as in the analgesic receptors in the limbic system (subcortical level and spinal levels). Its use as an analgesic in small animals has been disappointing, primarily because of its very short duration of action and ability to alleviate only mild to moderate pain.
The antagonist potency of butorphanol is considered to be approximately 30 times that of pentazocine and 1/40th that of naloxone, and it will antagonize the effect of true opioid agonists (eg, morphine, meperidine, oxymorphone).
Besides the analgesic qualities of butorphanol, it possesses significant antitussive activity. In dogs, butorphanol has been shown to elevate the CNS respiratory center threshold to CO2 but, unlike pure mu opiate agonists, it does not depress respiratory center sensitivity. Butorphanol, unlike morphine, apparently does not cause histamine release in dogs. CNS depression may occur in dogs receiving butorphanol, while CNS excitation has been noted (usually at high dosages) in horses and dogs.1
Although possessing less cardiovascular effects than the classical opiate agonists, butorphanol can cause a decrease in cardiac rate secondary to increased parasympathetic tone and mild decreases in arterial blood pressures. However, increased heart rates have been noted in horses after IV injection.2
The risk for causing physical dependence seems to be minimal when butorphanol is used in veterinary patients.1
In general, butorphanol is absorbed completely in the gut when administered orally but, because of a high first-pass effect, only about one-sixth of the administered dose reaches systemic circulation. The drug has also been shown to be completely absorbed following IM administration.
Butorphanol is well distributed, with highest levels (of the parent compound and metabolites) found in the liver, kidneys, and intestine. Concentrations in the lungs, endocrine tissues, spleen, heart, adipose tissue, and blood cells are also higher than those found in plasma. Approximately 80% of the drug is bound to plasma proteins (human data). Butorphanol will cross the placenta, and neonatal plasma levels have been roughly equivalent to maternal levels. The drug is also distributed into maternal milk.
Butorphanol is metabolized in the liver, primarily by hydroxylation. Other methods of metabolism include N-dealkylation and conjugation. The metabolites of butorphanol do not exhibit any analgesic activity. These metabolites—and the parent compound—are mainly excreted into the urine (only 5% is excreted unchanged), but 11% to 14% of a dose is excreted into the bile and eliminated with the feces. Terminal half-lives reported in various species include approximately 5 to 6 hours (IM/transmucosal) in cats; 2.6 hours (IM/SC) in dogs; and 1.87 hours (IV) and 2.75 hours (IM) in goats.1
In adult horses, the onset of action after IV administration is approximately 3 minutes, with a peak analgesic effect at 15 to 30 minutes. The duration of action in horses may be up to 4 hours after a single dose. After a single 0.1 mg/kg IV dose, volume of distribution is approximately 1.4 L/kg, clearance is approximately 12 mL/min/kg, and elimination half-life is 6 hours. In plasma, concentrations below the level of detection (0.1 ng/mL) occurred in 48 hours. In urine (as the conjugate), 7 of 10 horses had butorphanol urine levels below the level of detection (0.05 ng/mL) at 120 hours post dose.2 Butorphanol 0.1 mg/kg SC is absorbed rapidly with high bioavailability (87%) with plasma concentration and analgesic effects comparable to IV administration; half-life is about 5.3 hours.3 After IV administration of 0.1 mg/kg, horses may show signs of restlessness and excitation. Another study suggested that the half-life in conscious horses is approximately 44 minutes with a clearance of 21 mL/kg/min after a single 0.1 – 0.13 mg/kg IV dose.4 Bioavailability after IM injections in adult horses is relatively low (≈37%).5 In neonatal foals, IM bioavailability is approximately 67%, and peak levels occurred about 6 minutes after dosing. Terminal half-life was about 2 hours after an IV dose.6
The half-life of butorphanol in dairy cattle has been reported to be 82 minutes.7
Contraindications / Precautions:
Butorphanol is contraindicated in patients that are hypersensitive to it. All opiates should be used with caution in patients with hypothyroidism, severe renal insufficiency, adrenocortical insufficiency (Addison’s), and in geriatric or severely debilitated patients.
Like other opiates, butorphanol must be used with extreme caution in patients with head trauma, increased CSF pressure, or other CNS dysfunction (eg, coma).
Dogs with MDR1 mutations (‘white feet,’ many collies, Australian shepherd dogs) may develop a more pronounced sedation that persists longer than normal. The Washington State University Veterinary Clinical Pharmacology Lab (vcpl.vetmed.wsu.edu) recommends reducing the dosage by 25% in dogs heterozygous for the MDR1 mutation and by 30% to 50% in dogs homozygous (mutant/mutant) for the mutation.
The manufacturer states that butorphanol “should not be used in dogs with a history of liver disease” and, because of its cough suppression effects, “it should not be used in conditions of the lower respiratory tract associated with copious mucous production” (Package insert; Torbutrol®—Zoetis US). The drug should be used cautiously in dogs with heartworm disease, as safety for butorphanol has not been established in these cases.
Butorphanol may not be a very good analgesic and may cause respiratory depression in turtles or tortoises.8
As butorphanol injection is available in different concentrations, be certain which concentration is being used when drawing up dosages. Do not order doses in mL.
Butorphanol is commonly administered with other medications in the same syringe. Because of the negative pressure in the vial, it may become contaminated with other medications. Although one study showed the contamination to be below clinically important levels,9 50-mL vials may reach significant levels during their use. Caution should be used in critically ill patients when drawing from a previously used vial if the practice of drawing up multiple medications in the same syringe is employed.
Adverse effects reported in dogs and cats include sedation, excitement, respiratory depression, ataxia, anorexia, or diarrhea (rarely). Adverse effects may be less severe than those seen with pure agonists.
Adverse effects seen in horses (at usual doses) may include transient ataxia and sedation, but excitement has also been noted (see below). Although reported to have minimal effects on the GI tract, butorphanol has the potential to decrease intestinal motility, and ileus is possible. Horses may exhibit increased heart rates and CNS excitement (eg, tossing and jerking of head, increased ambulation, augmented avoidance response to auditory stimuli), particularly if given high doses (0.2 mg/kg) IV rapidly. Very high doses IV (1 – 2 mg/kg) may lead to the development of nystagmus, salivation, seizures, hyperthermia, and decreased GI motility. It has been suggested that when used for analgesia, butorphanol administered as a continuous rate IV infusion can minimize adverse effects and maximize analgesia.1
The following drug interactions have either been reported or are theoretical in humans or animals receiving butorphanol and may be of significance in veterinary patients.
- ANTICHOLINERGICS (eg, atropine, glycopyrrolate): Concurrent use may increase risk for CNS depression, urinary retention, constipation, and ileus.
- ANTIDIARRHEALS: Concurrent use can lead to severe constipation and ileus.
- ANTIHYPERTENSIVES: Concurrent use may increase risk for hypotension and orthostasis.
- APOMORPHINE: Concurrent use may increase risk for CNS depression.
- BROMOCRIPTINE: Concurrent use may increase CNS depression and respiratory depression.
- CIMETIDINE: May decrease metabolism of butorphanol, increasing risk for respiratory depression and apnea.
- CNS DEPRESSANT AGENTS (eg, anesthetic agents, antihistamines, anticonvulsants, benzodiazepines, phenothiazines, barbiturates, muscle relaxants, tranquilizers, opioids): May cause increased CNS or respiratory depression when used with butorphanol; dosage may need to be decreased.
- DESMOPRESSIN: Concurrent use may increase levels and pharmacologic activity of desmopressin, increasing risk for hyponatremia and water intoxication.
- DIURETICS (eg, bumetanide, furosemide): Concurrent use may increase risk for hypotension and orthostasis.
- ERYTHROMYCIN: Could potentially decrease metabolism of butorphanol.
- FENOLDOPAM: Concurrent use may increase risk for hypotension and orthostasis.
- FENTANYL (and other pure opioid agonists): Butorphanol may potentially antagonize some analgesic effects (Note: This is controversial.) but may also reverse some of the sedative and respiratory depressant effects of pure agonists.
- FURAZOLIDONE: Concurrent use may increase risk for anxiety, confusion, respiratory depression, hypotension, cyanosis, and coma by an unknown mechanism. A 14-day washout should be observed between discontinuation of furazolidone and initiation of butorphanol.
- IFOSFAMIDE: Concurrent use may increase risk for neurotoxic effects of ifosfamide, including sleepiness, confusion, hallucinations, extrapyramidal symptoms, seizures, psychotic behavior, and coma.
- IOHEXOL: Concurrent use of intrathecal iohexol may increase risk for seizures. Withhold butorphanol 48 hours before and 24 hours after intrathecal iohexol, if possible.
- LITHIUM: Concurrent use may increase risk for CNS and respiratory depression.
- METHYLENE BLUE: Concurrent use may increase risk for anxiety, confusion, respiratory depression, hypotension, cyanosis, and coma by an unknown mechanism. May also increase risk for constipation and urinary retention.
- METOCLOPRAMIDE: The prokinetic effects of metoclopramide may be decreased and risk for CNS depression may be increased.
- PANCURONIUM: May cause increased conjunctival changes if used with butorphanol.
- PHENOXYBENZAMINE: Concurrent use may result in additive hypotension and orthostasis.
- POLYETHYLENE GLYCOL: Concurrent use may increase risk for seizures associated with the use of bowel cleansing preparations.
- PROCARBAZINE: Concurrent use may increase risk for anxiety, confusion, respiratory depression, hypotension, cyanosis, and coma by an unknown mechanism.
- SSRIs (eg, fluoxetine): Concurrent use may increase risk for CNS, respiratory depression, and serotonin syndrome.
- TAMSULOSIN: Concurrent use may increase risk for hypotension and orthostasis.
- THEOPHYLLINE: Could potentially decrease metabolism of butorphanol.
- TRAMADOL: Concurrent use may increase risk for seizures, CNS depression, and respiratory depression.
- TRICYCLIC ANTIDEPRESSANTS (eg, amitriptyline): Concurrent use may increase risk for CNS and respiratory depression, constipation, and urinary retention.
- VASODILATORS (eg, nitroglycerin, nitroprusside): Concurrent use may result in additive hypotension and orthostasis.1
Note: Butorphanol is a class IV controlled substance. The veterinary products (Torbutrol®, Torbugesic®) strengths are listed as base activity while the human product (Stadol®) strength is labeled as the tartrate salt; these 2 strengths are not equal.
Butorphanol Tartrate Injection: 0.5 mg/mL (activity as base) in 10-mL vials; Torbutrol®; (Rx, C-IV). FDA-approved for use in dogs. NADA 102-990.
Butorphanol Tartrate Injection: 2 mg/mL (activity as base) in 10-mL vials. Torbugesic®-SA, generic; (Rx, C-IV). FDA-approved for use in cats. NADA 141-047.
Butorphanol Tartrate Injection: 10 mg/mL (activity as base) in 10-mL & 50-mL vials; Torbugesic® , Dolorex®, Butorphic®, generic; (Rx, C-IV). FDA-approved for use in horses not intended for food.
Butorphanol Tartrate Tablets: 1, 5, & 10 mg (activity as base) tablets; bottles of 100; Torbutrol®; (Rx, C-IV). FDA-approved for use in dogs. NADA 103-390.
The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance.
In case of accidental exposure, call your doctor for medical advice about side effects.
Note: All doses are expressed in mg/kg of the base activity. If using the human product (Stadol®), 1 mg of tartrate salt = 0.68 mg base.
Dogs - Antitussive (labeled dosage; FDA-approved indication):
Injection: 0.055 mg/kg SC every 6-12 hours; may be increased to 0.11 mg/kg SC every 6-12 hours. Treatment should not normally be required for longer than 7 days.
Oral: 0.55 mg/kg PO every 6-12 hours; may increase dose to 1.1 mg/kg PO every 6-12 hours (These oral doses correspond to one 5-mg tablet per 20 lb and 10 lb of body weight, respectively); treatment should not normally be required for longer than 7 days (Package insert; Torbutrol®— Zoetis).
Analgesic (all are extra-label):
a) 0.1 – 0.5 mg/kg IV, IM, SC. Commonly 0.2 mg/kg is chosen. Butorphanol provides only mild to moderate analgesia (good visceral analgesia); duration of sedative action is 2-4 hours, but analgesic action may be less than 1 hour.
b) As a CRI: 0.1 – 0.4 mg/kg/h, following a loading dose of 0.2 mg/kg IV.
c) As an epidural analgesic: 0.25 mg/kg diluted with preservative-free saline (0.2 mL) or local anesthetic epidurally. Onset of action is less than 30 minutes and duration is 2-4 hours. This method of delivery has predominantly supraspinal effects.11
In combination as an anesthetic adjunct and immobilizing agent (all are extra-label): Note: There are many potential combinations that have been suggested; the following are examples and not inclusive. For additional information refer to other anesthesia-specific references such as Handbook of Veterinary Anesthesia, 5th ed, Muir & Hubbell, Elsevier 2012; Essentials of Small Animal Anesthesia & Analgesia, 2nd ed, Grimm, Wiley-Blackwell 2011; or the Veterinary Anesthesia & Analgesia Support Group website (vasg.org).
a) Uncooperative dogs and short procedures (eg, nail trims, radiographs): Butorphanol 0.2 mg/kg with medetomidine 0.001 – 0.01 mg/kg and midazolam 0.05 – 0.2 mg/kg; combined and given IM.
b) Dogs requiring more sedation: Butorphanol 0.2 mg/kg with medetomidine 0.01 – 0.02 mg/kg and midazolam 0.05 – 0.2 mg/kg; combined and given IM. Consider adding tiletamine with zolazepam (Telazol®) 1 – 2 mg/kg if insufficient sedation from above drug combination. For painful procedures, consider adding buprenorphine at 0.02 – 0.04 mg/kg or substituting butorphanol or buprenorphine with either morphine 0.5 – 1 mg/kg or hydromorphone 0.1 – 0.2 mg/kg. More information is available from vasg.org.12
c) Butorphanol 0.4 mg/kg with acepromazine 0.02 mg/kg mixed in same syringe and given IM. Study was done in dogs undergoing ovariohysterectomy (OHE). Approximately 30 minutes postdose, propofol IV was used as induction agent, and isoflurane was used for maintenance anesthesia. Meloxicam was used for rescue analgesia postoperatively, if needed. Authors concluded that acepromazine with butorphanol (or meperidine [pethidine]) produced satisfactory sedation, decreased the amount of anesthetic necessary to induce and maintain anesthesia, and produced similar postoperative analgesia in dogs.13
d) Butorphanol 0.4 mg/kg IM has been combined with dexmedetomidine at 5 – 10 micrograms/kg IM for heart echocardiography. This combination results in sedation but with decreased heart rate, cardiac output, and the development of valvular regurgitation. Caution should be used when giving this drug combination to dogs with cardiovascular disease.14
e) Butorphanol 0.1 mg/kg has been combined with medetomidine 10 micrograms/kg and alfaxalone 1.5 mg/kg IM to induce anesthesia/analgesia. Substantial cardiorespiratory depression was noted.15
f) Butorphanol 0.2 mg/kg IV followed by midazolam 0.2 mg/kg IV then administration of alfaxalone 2.0 mg/kg IV over 1 minute provides excellent quality of induction and good to excellent recovery with minimal cardiopulmonary effects in healthy dogs. Time from induction to extubation was 29 ± 6 minutes and to standing was 36 ± 8 minutes.16
g) Butorphanol 0.4 mg/kg IM can be combined with medetomidine 2.5 micrograms/kg IM to provide moderate to deep sedation for 20 to 30 minutes, there will be a decrease in heart rate.17
Reversal agent for the sedative and respiratory depressant effects of mu-opioid agonists (extra-label): 0.05 – 0.1 mg/kg IV; the benefit of using butorphanol over naloxone is that it does not completely reverse analgesic effects.18
Antiemetic prior to cisplatin treatment (extra-label): 0.4 mg/kg IM 30 minutes before cisplatin infusion; can be repeated in 4-6 hours.19
Cats - Analgesic:
Labeled dosage (FDA-approved): 0.4 mg/kg SC. The dose may be repeated up to 4 times per day for up to 2 days (Adapted from label; Torbugesic SA®—Zoetis).
The following are extra-label dosages:
a) 0.1 – 0.5 mg/kg IV, IM, SC; provides only mild to moderate analgesia (good visceral analgesia); duration of sedative action 2-4 hours, but analgesic action may be 1 hour or less.20
b) Postoperative CRI (usually in combination with ketamine) for mild to moderate pain: Loading dose of butorphanol 0.1 – 0.2 mg/kg IV, followed by a butorphanol CRI of 0.1 – 0.2 mg/kg/h. Ketamine may be added in for complementary analgesia with a loading dose of 0.1 mg/kg IV followed by a ketamine CRI of 0.4 mg/kg/h. Opioid and ketamine CRI combinations may allow reduction in dosage of both drugs.21
c) Epidural analgesic: 0.25 mg/kg, diluted with preservative-free saline (0.2 mL) or local anesthetic and given epidurally. Onset of action is less than 30 minutes with a duration of 2-4 hours. This drug delivery combination has predominantly supraspinal effects.11
In combination as a preoperative or immobilizing agent (all are extra-label): Note: There are many potential combinations that have been suggested; the following are examples and are not inclusive. For additional information, refer to other anesthesia-specific references such as Handbook of Veterinary Anesthesia, 5th ed, Muir & Hubbell, Elsevier 2012; Essentials of Small Animal Anesthesia & Analgesia, 2nd ed, Grimm, Wiley-Blackwell 2011; or the Veterinary Anesthesia & Analgesia Support Group website (vasg.org).
a) Combining butorphanol, ketamine, midazolam, and medetomidine: In the study (assessing analgesia after OHE), the following protocol was used: 10 minutes before surgery, ketamine 60 mg/m2 (≈3 mg/kg), midazolam 3 mg/m2 (≈0.2 mg/kg), medetomidine 600 micrograms/m2 (≈30 micrograms/kg), and butorphanol 6 mg/m2 (≈0.3 mg/kg) were combined and given as a single IM injection in quadriceps muscles. Additionally, either carprofen (4 mg/kg) or meloxicam (0.3 mg/kg) were given SC. All protocols in the study provided adequate analgesia.22
b) Combining butorphanol and dexmedetomidine: In the study comparing dexmedetomidine (20 micrograms/kg IM) alone, or dexmedetomidine 10 micrograms/kg with either butorphanol 0.4 mg/kg or meperidine (pethidine) 2.5 mg/kg combined in same syringe and given IM, the results were similar for quality of sedation, analgesia, muscle relaxation, and possibility of performing some clinical procedures; all were deemed suitable.23
c) Combining butorphanol and midazolam with ketamine or dexmedetomidine: In a small (n = 6) healthy cat crossover study, the authors concluded that the combination of butorphanol 0.4 mg/kg, midazolam 0.4 mg/kg and ketamine 3 mg/kg combined and given IM provided acceptable sedation and minimal cardiovascular changes. Substituting dexmedetomidine 5 micrograms/kg for the ketamine produced excellent sedation and recovery, but caused more cardiovascular depression and hematologic changes.24
d) Combining butorphanol and alfaxalone (SC dosing) for sedation during short procedures: Study was done in hyperthyroid cats. Alfaxalone 3 mg/kg with butorphanol 0.2 mg/kg drawn up in the same syringe and administered SC as a single SC injection in the region dorsal to the right hip. Maximum sedation occurs 45 minutes post injection. Blood pressure, heart rate, and respiratory rate all were significantly decreased. Monitoring BP is recommended. Further studies are required to determine whether the sedative, respiratory, and cardiovascular effects are similar in euthyroid cats.25
e) Combining butorphanol, dexmedetomidine, and ketamine: The study evaluated efficacy and cardiorespiratory effects of a combination of dexmedetomidine 25 micrograms/kg with ketamine 3 mg/kg and either butorphanol 0.2 mg/kg, hydromorphone 0.05 mg/kg, or buprenorphine 30 micrograms/kg as a single IM injection (with or without reversal by atipamezole), in cats undergoing castration. Cats also received meloxicam 0.2 mg/kg SC immediately before the conclusion of surgery. Supplemental isoflurane was used when anesthesia was considered inadequate during surgery. Authors concluded that combinations including butorphanol or hydromorphone were suitable injectable anesthetic protocols for castration in cats commencing at 10 minutes after injection. Postoperative atipamezole shortened recovery times.26
f) Short-term restraint: Dexmedetomidine 5 micrograms/kg with butorphanol 0.3 mg/kg IM mixed in the same syringe or dexmedetomidine 5 micrograms/kg, butorphanol 0.3 mg/kg, and ketamine 3 mg/kg IM mixed in the same syringe. Duration of sedation is longer when ketamine is added.27
g) Rapid, deep, short duration sedation can be achieved with butorphanol 0.2 mg/kg IM and alfaxalone 2 mg/kg IM; recumbency attained within 36 ± 4.4 minutes. Cats had smooth recovery with no adverse effects.28
h) Prevent dexmedetomidine induced emesis: Butorphanol 0.1 – 0.2 mg/kg IM when given concurrently with dexmedetomidine.29
i) Injectable anesthesia can be achieved with butorphanol 0.2 mg/kg, medetomidine 20 micrograms/kg, and alfaxalone 5 mg/kg IM mixed in the same syringe. Adverse effects included bradycardia and vomiting. Analgesia lasted approximately 1 hour and recovery took 2 hours.30
Reversal agent for sedative and respiratory depressant effects of mu-opioid agonists (extra-label): 0.05 – 0.1 mg/kg IV. The benefit of using butorphanol over naloxone is that it does not completely reverse analgesic effects.17 However, one study showed that butorphanol administration decreased the duration of hydromorphone effects in cats.31
Ferrets - Analgesic (extra-label): Because butorphanol appears to have shorter duration of action, buprenorphine is more commonly recommended for use as an analgesic in ferrets, but a butorphanol CRI of 0.1 – 0.2 mg/kg can be useful. Recommended analgesic dosages generally range from 0.1 – 0.4 mg/kg IM, IV, or SC every 2-6 hours.
Anesthetic adjunct (extra-label):
a) Butorphanol 0.1 mg/kg, ketamine 5 mg/kg, medetomidine 80 micrograms/kg. Combine in one syringe and give IM. May need to supplement with isoflurane 0.5-1.5% for abdominal surgery.32
b) Butorphanol 0.2 mg/kg with xylazine 2 mg/kg IM.33
c) Butorphanol 0.2 mg/kg with Telazol® 1.5 mg/kg and xylazine 1.5 mg/kg IM; may reverse xylazine with yohimbine 0.05 mg/kg IM.33
Rabbits, Rodents, & Small Mammals - Analgesic (extra-label):
a) Rabbits: Dosage recommendations generally range from 0.1 – 0.5 mg/kg SC, IM, or IV every 2-4 hours. An IV CRI dosage of 0.1 – 0.2 mg/kg/h has also been recommended.34
b) Rabbits: Transnasal dexmedetomidine 0.1 mg/kg with midazolam 2 mg/kg and butorphanol 0.4 mg/kg produces profound sedation and analgesia lasting 45 minutes, with moderate sedation lasting another 25 minutes. Residual central nervous system impairment lasted up to 100 minutes. Blood pressure and respiratory rates decrease; oxygen supplementation and careful monitoring are required. Use cautiously in compromised rabbits.35
c) Rodents and guinea pigs: 1 – 2 mg/kg SC every 4 hours. Chinchillas: 0.2 – 2 mg/kg SC every 2-4 hours.36
Birds - Analgesic (extra-label):
a) 1 – 4 mg/kg IM has been suggested in birds, but dosing frequencies range from every 2-24 hours. Limited pharmacokinetic studies in birds suggests that frequent dosing may be necessary in birds, which raises issues of the practicality of using this drug.37
b) Psittacid species: Butorphanol 1 mg/kg IM with midazolam 0.5 mg/kg IM in the pectoral muscle provided good anesthetic premedication before isoflurane. The combination improved quality and time of induction without adverse effects on cardiorespiratory parameters.38
Cattle - Note: FARAD recommends a 5 day meat withdrawal and 3 day milk withdrawal with butorphanol use.39
Analgesic (extra-label): When used alone in cattle, butorphanol has been recommended anecdotally at dosages such as 0.02 – 0.04 mg/kg IV or SC every 4 hours.
Analgesia, sedation/restraint, and disassociation from a noxious procedure in combination as “ketamine stun” (extra-label): A combination of xylazine 0.02 to 0.05 mg/kg, ketamine 0.04 to 0.1 mg/kg with butorphanol 0.01 – 0.04 mg/kg IV or IM has been recommended. See the ketamine monograph for further details.
CRI in calves: Butorphanol has been used as a CRI in isoflurane anesthetized calves at a dose of 0.1 mg/kg IV followed by a CRI of 20 micrograms/kg/min IV. Hemodynamic variables were unaffected and recovery was uneventful.40
Goats - Premedication (extra-label): A combination of midazolam 0.3 mg/kg and butorphanol 0.1 mg/kg IM has been used to decrease the amount of IV alfaxalone needed for induction of general anesthesia. Cardiorespiratory parameters were within clinically accepted limits.41
Horses (Note: ARCI UCGFS Class 3 Drug) - Analgesic:
a) Labeled dosage; FDA-approved: 0.1 mg/kg IV every 3-4 hours; not to exceed 48 hours (Package insert; Torbugesic®—Zoetis).
The following are extra-label:
b) SC administration: One study showed that 0.1 mg/kg SC reached and maintained target plasma concentrations greater than 10 ng/mL for approximately 2 hours. This route of administration provided less marked physiologic and behavioral effects compared to the same dose given IV.3
c) CRI (extra-label): There is evidence that giving butorphanol via a CRI may provide better analgesia and reduce the potential for adverse effects. One study that administered butorphanol at 13 micrograms/kg/h as a CRI (begun at the time surgery ended and continued for 24 hours, along with flunixin at 1.1 mg/kg IV every 12 hours) in horses following celiotomy, showed that butorphanol-treated horses had delayed passage of feces following surgery, but pain scores were significantly decreased, less weight was lost, and horses had improved recovery scores.42 On average, treated horses were discharged 3 days sooner than those treated with flunixin alone; cost savings were considerable. Another study suggested that a loading dose of 17.8 micrograms/kg followed by a CRI of 23.7 micrograms/kg/h may be useful for sedation. However, adding a butorphanol loading dose and CRI to horses sedated with xylazine increased the degree of ataxia and instances of falling down.3 Another study evaluated a loading dose of butorphanol 18 micrograms/kg IV followed by butorphanol 25 micrograms/kg/h CRI and a romifidine 80 micrograms/kg loading dose IV followed by 29 micrograms/kg/h CRI and found the combination effective for dental procedures.43
d) Foals: Most recommend dosages around 0.1 mg/kg IV or IM. One study in pony foals (both neonatal and older) found that 0.1 mg/kg IV, but not 0.05 mg/kg IV, significantly raised thermal nociceptive threshold.44 However, a pharmacokinetic study done in neonatal foals found that dosages of 0.05 mg/kg IV significantly changed behaviors (eg, increased nursing, sedation). Because elimination half-life in foals is longer than in adults, consider giving repeat doses every 4-6 hours when needed.
Sedative and analgesic in combination with other agents (extra-label): Several protocols have been described using butorphanol in conjunction with an alpha agonist (eg, xylazine, romifidine, detomidine); often butorphanol is used at a lower dosage than labeled (eg, 0.02 – 0.05 mg/kg). One such protocol for field anesthesia follows: Premedicate with xylazine 1 mg/kg IV OR 2 mg/kg IM 5-10 minutes (longer for IM route) before induction of anesthesia with ketamine 2 mg/kg IV. Horse must be adequately sedated (head to the knees) before giving the ketamine, as ketamine alone can cause muscle rigidity and seizures. If adequate sedation does not occur, either 1) Re-dose xylazine using up to half the original dose. 2) Add butorphanol 0.02 – 0.04 mg/kg IV. Butorphanol can be given with the original xylazine premedication if you suspect that the horse will be difficult to tranquilize (eg, high-strung thoroughbreds) or added before the ketamine induction. This drug combination improves induction, increases analgesia, and increases recumbency time by about 5-10 minutes. 3) Give diazepam 0.03 mg/kg IV. Mix the diazepam with the ketamine. This combination will improve induction when sedation is marginal, improve muscle relaxation during anesthesia, and prolong anesthesia by about 5-10 minutes. 4) Guaifenesin 5% solution administered IV to effect can also be added to increase sedation and muscle relaxation.45
Donkeys: As an analgesic and sedative (extra-label): One study recommended a combination of butorphanol 0.05 mg/kg and either detomidine 0.04 mg/kg OR romifidine 0.08 mg/kg IV. These combinations provided safe and effective sedation with complete analgesia in standing donkeys.46 Another study recommended xylazine 0.5 mg/kg and butorphanol 0.04 mg/kg IV.47
Camelids - Analgesic and sedative (extra-label): Most butorphanol dosage recommendations fall into the 0.05 – 0.1 mg/kg range either IM or IV and are administered every 4-6 hours. Several dosing protocols have been suggested for combining butorphanol with other sedative and/or anesthetic agents:
a) Anesthetic: Butorphanol 0.07 – 0.1 mg/kg with ketamine 0.2 – 0.3 mg/kg and xylazine 0.2 – 0.3 mg/kg combined and given IV OR butorphanol 0.05 – 0.1 mg/kg with ketamine 0.2 – 0.5 mg/kg and xylazine 0.2 – 0.5 mg/kg combined and given IM.48
b) Procedural pain relief (eg, castrations) when recumbency (up to 30 minutes) is desired: Alpacas: Butorphanol 0.046 mg/kg with xylazine 0.46 mg/kg and ketamine 4.6 mg/kg combined and given IM. Llamas: Butorphanol 0.037 mg/kg with xylazine 0.37 mg/kg and ketamine 3.7 mg/kg combined and given IM. May administer 50% of original dose of ketamine and xylazine during anesthesia to prolong effect up to 15 minutes. If doing castrations on 3 or more animals sequentially, it is acceptable to make up bottle of the drug mixture: Add butorphanol 10 mg (1 mL) and xylazine 100 mg (1 mL) to ketamine 1 g (10 mL vial). This mixture is dosed at 1 mL/40 lb (18 kg) for alpacas, and 1 mL per 50 lb (22 kg) for llamas. Handle quietly and allow plenty of time before starting procedure. Expect 20 minutes of surgical time; patient should stand 45 minutes to 1 hour after injection.49
c) Alpacas: Ketamine 4 mg/kg with xylazine 0.4 mg/kg and butorphanol 0.04 mg/kg combined and given IM resulted in approximately 30 minutes of anesthesia time for castrations. Additional anesthesia (one-third the induction dose) was given at the discretion of the anesthetist.50
Zoo, Exotic, Wildlife Species - For use of butorphanol in zoo, exotic, and wildlife medicine, refer to specific references, including:
a) Zoo Animal and Wildlife Immobilization and Anesthesia. 2nd ed. West G, Heard D, Caulkett N, eds. Blackwell Publishing; 2014.
b) Handbook of Wildlife Chemical Immobilization. 3rd ed. Kreeger TJ, Arnemo JM. 2007.
c) Fowler’s Zoo and Wild Animal Medicine Current Therapy. Vol 7. Miller RE, Fowler ME, Saunders; 2011.
d) Exotic Animal Formulary. 4th ed. Carpenter JW. Saunders; 2012.
e) The 2009 American Association of Zoo Veterinarian Proceedings by D. K. Fontenot also has several dosages listed for restraint, anesthesia, and analgesia for a variety of drugs for carnivores and primates. VIN members can access them here or here.
1Plumb's Veterinary Drugs.
2Knych HK, Casbeer HC, McKemie DS, Arthur RM. Pharmacokinetics and pharmacodynamics of butorphanol following intravenous administration to the horse. J Vet Pharmacol Ther. 2013;36(1):21-30.
3Chiavaccini L, Claude AK, Lee JH, Ross MK, Meyer RE, Langston VC. Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses. J Vet Pharmacol Ther. 2015;38(4):365-374.
4Valverde A. Balanced anesthesia and constant-rate infusions in horses. Vet Clin North Am Equine Pract. 2013;29(1):89-+.
5Sellon DC, Papich MG, Palmer L, Remund B. Pharmacokinetics of butorphanol in horses after intramuscular injection. J Vet Pharmacol Ther. 2009;32(1):62-65.
6Arguedas MG, Hines MT, Papich MG, Farnsworth KD, Sellon DC. Pharmacokinetics of butorphanol and evaluation of physiologic and behavioral effects after intravenous and intramuscular administration to neonatal foals. J Vet Intern Med. 2008;22(6):1417-1426.
7Coetzee JF. A review of analgesic compounds used in food animals in the United States. Vet Clin North Am Food Anim Pract. 2013;29(1):11-+.
8Sladky KK, Miletic V, Paul-Murphy J, Kinney ME, Dallwig RK, Johnson SM. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. J Am Vet Med Assoc. 2007;230(9):1356-1362.
9Bell A, Yamaoka TT, Akil L, Watson D, Devine C. Contamination of multidose butorphanol vials in small animal general practices. J Small Anim Pract. 2015;56(11):637-640.
10Papich M. Effects of drugs on pregnancy. In: Kirk R, ed. Current Veterinary Therapy X: Small Animal Practice. Philadelphia, PA: Saunders; 1989:1291-1299.
11Valverde A. Epidural analgesia and anesthesia in dogs and cats. Vet Clin North Am Small Anim Pract. 2008;38(6):1205-1230.
12Moffat K. Addressing canine and feline aggression in the veterinary clinic. Vet Clin North Am Small Anim Pract. 2008;38(5):983-1003.
13Vettorato E, Bacco S. A comparison of the sedative and analgesic properties of pethidine (meperidine) and butorphanol in dogs. J Small Anim Pract. 2011;52(8):426-432.
14Kellihan HB, Stepien RL, Hassen KM, Smith LJ. Sedative and echocardiographic effects of dexmedetomidine combined with butorphanol in healthy dogs. J Vet Cardiol. 2015;17(4):282-292.
15Lee J, Suh S, Choi R, Hyun C. Cardiorespiratory and anesthetic effects produced by the combination of butorphanol, medetomidine and alfaxalone administered intramuscularly in beagle dogs. J Vet Med Sci. 2015;77(12):1677-1680.
16Seo JI, Han SH, Choi R, Han J, Lee L, Hyun C. Cardiopulmonary and anesthetic effects of the combination of butorphanol, midazolam and alfaxalone in beagle dogs. Vet Anaesth Analg. 2015;42(3):304-308.
17Puighibet Z, Costa-Farre C, Santos L, Canfran S, de Segura IAG. The sedative effects of intramuscular low-dose medetomidine in combination with butorphanol or methadone in dogs. Vet Anaesth Analg. 2015;42(6):590-596.
18Quandt J. Sedation and analgesia for the critically ill patient: comprehensive review. In: 27th ACVIM Forum Proceedings. Montreal, QC: American College of Veterinary Internal Medicine; 2009.
19Klausner JS, Bell FW. Personal communication. 1988.
20Perkowski S. Practicing pain management in the acute setting. In: 24th ACVIM Forum Proceedings. Minneapolis, MN: American College of Veterinary Internal Medicine; 2006.
21Lichtenberger, M. Pain management protocols for the ICU patient. In: 78th Annual Western Veterinary Conference Notes. Las Vegas, NV: Western Veterinary Conference; 2006.
22Polson S, Taylor PM, Yates D. Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenorphine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial. J Feline Med Surg. 2012;14(8):553-559.
23Nagore L, Soler C, Gil L, Serra I, Soler G, Redondo JI. Sedative effects of dexmedetomidine, dexmedetomidine/pethidine and dexmedetomidine/butorphanol in cats. J Vet Pharmacol Ther. 2013;36(3):222-228.
24Biermann K, Hungerbuhler S, Mischke R, Kastner SBR. Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats. Vet Anaesth Analg. 2012;39(2):137-150.
25Ramoo S, Bradbury LA, Anderson GA, Abraham LA. Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol. Aust Vet J. 2013;91(4):131-136.
26Ko JC, Austin BR, Barletta M, Weil AB, Krimins RA, Payton ME. Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats. J Am Vet Med Assoc. 2011;239(11):1453-1462.
27Volpato J, Mattoso CRS, Beier SL, et al. Sedative, hematologic and hemostatic effects of dexmedetomidine-butorphanol alone or in combination with ketamine in cats. J Feline Med Surg. 2015;17(6):500-506.
28Ribas T, Bublot I, Junot S, et al. Effects of intramuscular sedation with alfaxalone and butorphanol on echocardiographic measurements in healthy cats. J Feline Med Surg. 2015;17(6):530-536.
29Papastefanou AK, Galatos AD, Pappa E, Lymperis AG, Kostoulas P. The effect of butorphanol on the incidence of dexmedetomidine-induced emesis in cats. Vet Anaesth Analg. 2015;42(6):608-613.
30Kim YW, Suh SI, Choi R, Hyun C. Evaluation of quality of anesthesia and analgesia and of vital signs after intramuscular administration of a combination of butorphanol, medetomidine and alfaxalone in cats. J Vet Med Sci. 2016;78(3):431-433.
31Simon BT, Steagall PV, Monteiro BP, Troncy E, Lizarraga I. Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats. Am J Vet Res. 2016;77(3):245-251.
32Finkler, M. Anesthesia in ferrets. In: 2009 CVC in Kansas City Proceedings. Kansas City, MO: Central Veterinary Conference; 1999.
33Williams, B. Therapeutics in ferrets. Vet Clin North Am Exotic Anim Pract. 2000;3(1):131-153.
34Lichtenberger, M. Anesthesia protocols and pain management for exotic animal patients. In: 78th Annual Western Veterinary Conference Notes. Las Vegas, Nevada: Western Veterinary Conference; 2006.
35Santangelo B, Micieli F, Mozzillo T, et al. Transnasal administration of a combination of dexmedetomidine, midazolam and butorphanol produces deep sedation in New Zealand white rabbits. Vet Anaesth Analg. 2016;43(2):209-214.
36Miller, AL, Richardson, C. Rodent analgesia. Vet Clin North Am Exotic Anim Pract. 2011;14(1):81-92.
37Hawkins MG, Paul-Murphy J. Avian analgesia. Vet Clin North Am Exotic Anim Pract. 2011;14(1):61-80.
38Kubiak, M, Roach, L, Eatwell, K. The influence of a combined butorphanol and midazolam premedication on anesthesia in psittacid species. J Avian Med Surg. 2016;30(4):317-323.
39Smith G. Extralabel use of anesthetic and analgesic compounds in cattle. Vet Clin North Am Food Anim Pract. 2013;29(1):29-+.
40Araujo, MA, Dias, BP, Bovino, F, et al. Cardiovascular effects of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane. Vet Anaesth Analg. 2014;41(2):145-152.
41Dzikiti TB, Zeiler GE, Dzikiti LN, Garcia ER. The effects of midazolam and butorphanol, administered alone or combined, on the dose and quality of anaesthetic induction with alfaxalone in goats. J S Afr Vet Assoc. 2014;85(1):1047.
42Sellon, DC, Roberts, MC, Blikslager, AT, Ulibarri, C, Papich, MG. Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy. J Vet Intern Med. 2004;18(4):555-563.
43Marly C, Bettschart-Wolfensberger R, Nussbaumer P, Moine S, Ringer SK. Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses. Vet Anaesth Analg. 2014;41(5):491-497.
44McGowan KT, Elfenbein JR, Robertson SA, Sanchez LC. Effect of butorphanol on thermal nociceptive threshold in healthy pony foals. Equine Vet J. 2013;45(4):503-506.
45Mathews, N. Anesthesia in large animals—injectable (field) anesthesia: how to make it better. In: 2009 CVC in Kansas City Proceedings. Kansas City, MO: Central Veterinary Conference; 1999.
46El-Kammar, MH, Gad, SB. Evaluation of the sedative, analgesic, clinicophysiological and haematological effects of intravenous detomidine, detomidine-butorphanol, romifidine and romifidine-butorphanol in standing donkeys. Equine Vet Ed. 2014;26(4):202-207.
47Lizarraga, I, Castillo-Alcala, F. Sedative and mechanical hypoalgesic effects of butorphanol in xylazine-premedicated donkeys. Equine Vet J. 2015;47(3):308-312.
48Wolff, P. Camelid medicine. In: Collected Annual Conference Proceedings 1968-2009. Tulsa, OK: American Association of Zoo Veterinarians; 2009.
49Miesner, M. Field anesthesia techniques in camelids. In: Conference Notes 2009: Notes from Selected Sessions Presented at the 81st Annual Western Veterinary Conference. Las Vegas, NV: Western Veterinary Conference; 2009.
50Nickell J, Barter LS, Dechant JE. Effects of intratesticular and incisional local anesthetic administration for castration of alpacas anesthetized with intramuscular ketamine-xylazine-butorphanol. Vet Surg. 2015;44(2):168-173.