Each mL contains Butorphanol Tartrate (USP) 2.0 mg.
Excipients/Inactive Ingredients: Sodium citrate hydrate, Citric acid hydrate, Sodium chloride, Water for injection.
Pharmacology: Pharmacodynamics: The analgesic effect of butorphanol is influenced by the route of administration. Onset of analgesia is within a few minutes for intravenous administration and within 15 minutes for intramuscular injection. Peak analgesic activity occurs within 30 to 60 minutes following intravenous and intramuscular administration. The duration of analgesia varies depending on the pain model as well as the route of administration, but is generally 3 to 4 hours with IM and IV doses as defined by the time 50% of patients required remedication. In postoperative studies, the duration of analgesia with IV or IM butorphanol was similar to morphine, meperidine. and pentazocine when administered in the same fashion at equipotent doses.
Pharmacokinetics: Butorphanol Tartrate Injection is rapidly absorbed after IM injection and peak plasma levels are reached in 20 to 40 minutes.
Butorphanol tartrate injection is indicated for the management of pain when the use of an opioid analgesic is appropriate.
Butorphanol tartrate injection is also indicated as preoperative or preanesthetic medication, as a supplement to balanced anesthesia, and for the relief of pain during labor.
This single preoperative dose should be individualized based on age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used and the surgical procedure involved. Use of butorphanol in geriatric patients, patients with renal impairment, patients with hepatic impairment, and during labor requires extra caution.
The following doses are for patients who do not have impaired hepatic or renal function and who are not on CNS active agents.
Use for Pain: Intravenous: The usual recommended single dose for IV administration is 1 mg repeated every 3 to 4 hours as necessary. The effective dosage range, depending on the severity of pain, is 0.5 to 2 mg repeated every 3 to 4 hours.
Intramuscular: The usual recommended single dose for IM administration is 2 mg in patients who will be able to remain recumbent, in the event drowsiness or dizziness occurs. This may be repeated every 3 to 4 hours, as necessary. The effective dosage range depending on the severity of pain is 1 to 4 mg repeated every 3 to 4 hours. There are insufficient clinical data to recommend single doses above 4 mg.
Dosage adjustments of butorphanol injection should be based on observations of its beneficial and adverse effects. The initial dose in the elderly and in patients with renal or hepatic impairment should generally be half the recommended adult dose (0.5 mg IV and 1.0 mg IM). Repeat doses in these patients should be determined by the patient's response rather than at fixed intervals but will generally be no less than 6 hours.
Use as Preoperative, Preanesthetic Medication: The preoperative medication dosage of Butorphanol Tartrate Injection should be individualized.
The usual adult dose is 2 mg IM, administered 60 to 90 minutes before surgery. This is approximately equivalent in sedative effect to 1 O mg morphine or 80 mg meperidine.
Use in Balanced Anesthesia: The usual dose of Butorphanol Tartrate Injection is 2 mg IV shortly before induction and/or 0.5 mg to 1 mg IV in increments during anesthesia. The increment may be higher, up to 0.06 mg/kg (4 mg/70 kg), depending on previous sedative, analgesic, and hypnotic drugs administered. The total dose of Butorphanol Tartrate Injection will vary; however, patients seldom require less than 4 mg or more than 12.5 mg (approximately 0.06 mg/kg to 0.18 mg/kg). As with other opioids of this class, butorphanol tartrate injection may not provide adequate intraoperative analgesia in every patient or under all conditions.
A failure to achieve successful analgesia during balanced anesthesia is commonly reflected by increases in general sympathetic tone. Consequently if blood pressure or heart rate continue to rise, consideration should be given to adding a potent volatile liquid inhalation anesthetic or another intravenous medication.
Labor and Delivery: In labor, the recommended initial dose of butorphanol tartrate is 1 or 2 mg IM or IV in mothers with fetuses of 37 weeks gestation or beyond and without signs of fetal distress. A dose should not be repeated in less than 4 hours nor administered less than 4 hours prior to the anticipated delivery. Dosage adjustments of butorphanol in labor should be based on initial response with consideration given to concomitant analgesic or sedative drugs and the expected time of delivery. If concomitant use of Butorphanol Tartrate Injection with drugs that may potentiate its effects is deemed necessary, the lowest effective dose should be employed.
The clinical manifestations of butorphanol overdose are those of opioid drugs in general.
The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death.
The management of suspected butorphanol overdosage includes maintenance of adequate ventilation, peripheral perfusion, normal body temperature, and protection of the airway.
Patients should be under continuous observation with adequate serial measures of mental state, responsiveness, and vital signs. Oxygen and ventilatory assistance should be available with continual monitoring by pulse oximetry if indicated. In the presence of coma, placement of an artificial airway may be required. An adequate intravenous portal should be maintained to facilitate treatment of hypotension associated with vasodilation. The use of a specific opioid antagonist such as naloxone should be considered. As the duration of butorphanol action usually exceeds the duration of action of naloxone, repeated dosing with naloxone may be required. In managing cases of suspected butorphanol overdosage, the possibility of multiple drug ingestion should always be considered.
Patients with hypersensitivity to butorphanol tartrate, or any of the formulation excipient.
Because of its opioid antagonist properties, butorphanol is not recommended for use in patients dependent on narcotics. Such patients should have an adequate period of withdrawal from opioid drugs prior to beginning butorphanol therapy. In patients taking opioid analgesics chronically, butorphanol has precipitated withdrawal symptoms such as anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, and diarrhea.
When ampoules are cut, glass particles can be mixed with drug solution. Caution should be taken to prevent from mixing. In particular, caution should be taken when it is used by elderly or children.
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. Follow patients closely for signs and symptoms of respiratory depression and sedation.
Because of the difficulty in assessing opioid tolerance in patients who have recently received repeated doses of narcotic analgesic medication, caution should be used in the administration of butorphanol to such patients.
Head Injury and Increased Intracranial Pressure: As with other opioids, the use of butorphanol in patients with head injury may be associated with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, drug-induced miosis, and alterations in mental state that would obscure the interpretation of the clinical course of patients with head injuries. In such patients, butorphanol should be used only if the benefits of use outweigh the potential risks.
Disorders of Respiratory Function or Control: Butorphanol may produce respiratory depression, especially in patients receiving other CNS active agents, or patients suffering from CNS diseases or respiratory impairment.
Cardiovascular effects: Because butorphanol may increase the work of the heart, especially the pulmonary circuit, the use of butorphanol in patients with acute myocardial infarction, ventricular dysfunction, or coronary insufficiency should be limited to those situations where the benefits clearly outweigh the risk.
Severe hypertension has been reported rarely during butorphanol therapy. In such cases, butorphanol should be discontinued and the hypertension treated with antihypertensive drugs. In patients who are not opioid dependent, naloxone has also been reported to be effective.
Carcinogenesis, Mutagenesis, Impairment of Fertility: There was no evidence of carcinogenicity in studies. Butorphanol was not genotoxic in S. typhimurium or E. coli assays or in unscheduled DNA synthesis and repair assays conducted in cultured human fibroblast cells.
Rats treated orally with 160 mg/kg/day (944 mg/m2) had a reduced pregnancy rate. However, a similar effect was not observed with a 2.5 mg/kg/day (14.75 mg/m2) subcutaneous dose.
General Caution: Opioid analgesics, including butorphanol, impair the mental and physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery.
Alcohol should not be consumed while using butorphanol.
Drugs having antagonistic action and effect of opioid, less frequent than morphine but can be abused. Due to prolonged use of this drug, light withdrawal symptoms, excessive use and addition have been reported. Special care should be exercised in administering butorphanol to patients with a history of drug abuse or to patients receiving the drug on a continuous basis for an extended period.
Use for outpatients: Drowsiness and dizziness may occur. Caution should be taken until individual characteristic response to this drug is obtained.
Use in Children: Butorphanol is not recommended for use in patients below 18 years of age because safety and efficacy have not been established in this population.
Use in Elderly: Due to changes in clearance, the mean half-life of butorphanol is increased by 25% (to over 6 hours)in patients over the age of 65 years. Elderly patients may be more sensitive to the side effects of butorphanol.
Pregnancy: Reproduction studies in mice, rats, and rabbits during organogenesis did not reveal any teratogenic potential to butorphanol. However. pregnant rats treated subcutaneously with butorphanol at 1 mg/kg (5.9 mg/m2) had a higher frequency of stillbirths than controls.
Butorphanol at 30 mg/kg/oral (5.1 mg/m2) and 60 mg/kg/oral (10.2 mg/m2) also showed higher incidences of post-implantation loss in rabbits. There are no adequate and well-controlled studies of Butorphanol Tartrate Injection in pregnant women before 37 weeks of gestation. Butorphanol Tartrate Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the infant.
There have been rare reports of infant respiratory distress/apnea following the administration of Butorphanol Tartrate Injection during labor. The reports of respiratory distress/apnea have been associated with administration of a dose within 2 hours of 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 Tartrate Injection during labor was associated with transient sinusoidal fetal heart rate patterns, but it was not associated with adverse neonatal outcomes. In the presence of an abnormal fetal heart rate pattern, Butorphanol Tartrate Injection should be used with caution.
Nursing Mothers: Butorphanol has been detected in milk following administration of Butorphanol Tartrate Injection to nursing mothers. The amount an infant would receive is probably clinically insignificant (estimated 4 mcg/L of milk in a mother receiving 2 mg IM four times a day).
The most frequently reported adverse experiences across all clinical trials with Butorphanol Tartrate Injection was somnolence (43%), dizziness (19%), nausea and/or vomiting (13%).
The following adverse experiences were reported at a frequency of 1% or greater in clinical trials and were considered to be probably related to the use of butorphanol: Body as a Whole:
Asthenia/lethargy, headache, sensation of heat.
Anorexia, constipation, dry mouth, nausea and/or vomiting, stomach pain.
Anxiety, confusion, dizziness, euphoria, floating feeling, insomnia, nervousness, paresthesia, somnolence, tremor.
Skin and Appendages:
The following adverse experiences were reported with a frequency of less than 1% in clinical trials and were considered to be probably related to the use of butorphanol: Cardiovascular:
abnormal dreams, agitation, dysphoria, hallucinations, hostility, withdrawal symptoms.
Skin and Appendages:
Concurrent use of butorphanol with drugs that affect the central nervous system (eg, alcohol, barbiturates, tranquilizers, and antihistamines) may result in increased central nervous system depressant effects such as drowsiness, dizziness, and impaired mental function. When used concurrently with such drugs, the dose of butorphanol should be the smallest effective dose and the frequency of dosing reduced as much as possible when administered concomitantly with drugs that potentiate the action of opioids.
It is not known if the effects of Butorphanol Tartrate Injection are altered by concomitant medications that affect hepatic metabolism of drugs (e.g., cimetidine, erythromycin, theophylline. etc.), but physicians should be alert to the possibility that a smaller initial dose and longer intervals between doses may be needed.
No information is available about the use of butorphanol concurrently with MAO inhibitors.
Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants such as alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, an1ipsychotics, and other opioids, can increases the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.
Store at temperatures not exceeding 30°C.
N02AF01 - butorphanol ; Belongs to the class of morphinan derivative opioids. Used to relieve pain.
Soln for inj (amp) 2 mg/mL (colorless & transparent) x 1 mL x 10's.