Data from FDA - Curated by EPG Health - Last updated 04 March 2018


INDICATIONS AND USAGE Butorphanol tartrate injection is indicated as a preoperative or preanesthetic medication, as a supplement to balanced anesthesia, for the relief of pain during labor, and for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of U se Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see WARNINGS]. reserve butorphanol tartrate for use in patients for whom alternative treatment options [e.g. non-opioid analgesics or opioid combination products] Have not been tolerated, or are not expected to be tolerated Have not provided adequate analgesia, or are not expected to provide adequate analgesia

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Advisory information

CONTRAINDICATIONS Butorphanol tartrate injection is contraindicated in patients hypersensitive to butorphanol tartrate.
Special warnings and precautions
PRECAUTIONS 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. Hepatic and Renal Disease In patients with hepatic or renal impairment, the initial dose of butorphanol tartrate injection should generally be half the recommended adult dose (0.5 mg IV and 1 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 apart (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Individualization of Dosage sections). 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 (see CLINICAL PHARMACOLOGY) 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. Use in Ambulatory Patients 1. 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. Effects such as drowsiness or dizziness can appear, usually within the first hour after dosing. These effects may persist for varying periods of time after dosing. Patients who have taken butorphanol should not drive or operate dangerous machinery for at least 1 hour and.until the effects of the drug are no longer present. 2. Alcohol should not be consumed while using butorphanol. Concurrent use of butorphanol with drugs that affect the central nervous system (e.g., alcohol, barbiturates, tranquilizers, and antihistamines) may result in increased central nervous system depressant effects such as drowsiness, dizziness and impaired mental function. 3. Butorphanol is one of a class of drugs known to be abused and thus should be handled accordingly (see DRUG ABUSE AND DEPENDENCE section). Information for Patients Addiction, Abuse, and Misuse Inform patients that the use of butorphanol tartrate, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS] . Instruct patients not to share butorphanol tartrate with others and to take steps to protect butorphanol tartrate from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting butorphanol tartrate or when the dosage is increased, and that it can occur even at recommended dosages [see WARNINGS ] . Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Interactions with CNS Depressants Inform patients that potentially serious additive effects may occur if butorphanol tartrate is used with CNS depressants and to seek medical attention if they experience increased sedation or difficulty breathing [see WARNINGS, PRECAUTIONS; Drug Interactions]. Serotonin Syndrome Inform patients that butorphanol tartrate could cause a rare but potentially life­ threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications. [see PRECAUTIONS ; Drug Interactions] Pregnancy Neonatal Opioid Withdrawal Syndrome Inform patients that prolonged use of butorphanol tartrate during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS, PRECAUTIONS; Pregnancy] Embryo-Fetal Toxicity Inform female patients of reproductive potential that butorphanol tartrate can cause fetal harm and to inform the prescriber of a known or suspected pregnancy [see PRECAUTIONS; Pregnancy]. Lactation Advise nursing mothers to monitor infants for increased sleepiness (more than usual). breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see PRECAUTIONS ; Nursing Mothers]. Drug Interactions It is not known if the effects of butorphanol are altered by other concomitant medications that affect hepatic metabolism of drugs (erythromycin,theophylline, etc.). but physicians should be alert to the possibility that a smaller initial dose and longer intervals between doses may be needed. Central Nervous System Depressants Due to additive pharmacologic effect, the concomitant use of CNS depressants such as alcohol, benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Consider dose reduction of one or both drugs. Monitor patients for signs of respiratory depression, sedation, and hypotension [see WARNINGS ] . Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors ISSRis). serotonin and norepinephrine reuptake inhibitors ISNRis), tricyclic antidepressants ITCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone,tramadol), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). has resulted in serotonin syndrome. [see PRECAUTIONS ; INFORMATION FOR PATIENTS] If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue butorphanol tartrate if serotonin syndrome is suspected. Carcinogenesis, Mutagenesis, Impairment of Fertility lnfertilitv Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see ADVERSE REACTIONS] . Pregnancy Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho­ physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Butorphanol tartrate is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including butorphanol tartrate, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Nursing Mothers The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for butorphanol tartrate and any potential adverse effects on the breastfed infant from butorphanol tartrate or from the underlying maternal condition. Infants exposed to butorphanol tartrate through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Pediatric Use Butorphanol is not recommended for use in patients below 18 years of age because safety and efficacy have not been established in this population. Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to butorphanol tartrate. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of butorphanol tartrate slowly in geriatric patients [see WARNINGS ] .
Adverse reactions
ADVERSE REACTIONS Clinical Trial Experience A total of 2446 patients were studied in premarketing clinical trials of butorphanol. Approximately half received butorphanol tartrate injection with the remainder receiving butorphanol tartrate nasal spray. In nearly all cases the type and incidence of side effects with butorphanol by any route were those commonly observed with opioid analgesics. The adverse experiences described below are based on data from short- and long-term clinical trials in patients receiving butorphanol by any route. There has been no attempt to correct for placebo effect or to subtract the frequencies reported by placebo treated patients in controlled trials. The most frequently reported adverse experiences across all clinical trials with butorphanol tartrate injection and nasal spray were somnolence (43%), dizziness (19%). nausea and/or vomiting (13%). In long-term trials with nasal butorphanol only, nasal congestion (13%) and insomnia (11%) were frequently reported. The following adverse experiences were reported at a frequency of 1% or greater in clinical trials and were considered to be probably related to the use of butorphanol: Body as a Whole: Asthenia/Lethargy, Headache, Sensation of Heat Cardiovascular: Vasodilation, Palpitations Digestive : Anorexia, Constipation, Dry Mouth, Nausea and/or Vomiting, Stomach Pain Nervous: Anxiety, Confusion, Dizziness, Euphoria,Floating Feeling, Insomnia, Nervousness, Paresthesia, Somnolence, Tremor Respiratory : Bronchitis, Cough, Dyspnea, Epistaxis, Nasal Congestion, Nasal Irritation, Pharyngitis, Rhinitis, Sinus Congestion, Sinusitis, Upper Respiratory Infection Skin and Appendages : Sweating/Clammy, Pruritus Special Senses: Blurred Vision, Ear Pain, Tinnitus, Unpleasant Taste The following adverse experiences were reported with a frequency of less than 1% in clinical trials and were considered to be probably related to the use of butorphanol: Cardiovascular: Hypotension, Syncope Nervous: Abnormal Dreams, Agitation, Dysphoria, Hallucinations, Hostility, Withdrawal Symptoms Skin and Appendages: Rash/Hives Urogenital: Impaired Urination The following infrequent additional adverse experiences were reported in a frequency of less than 1% of the patients studied in short-term butorphanol tartrate nasal sprays trials and under circumstances where the association between these events and butorphanol administration is unknown. They are being listed as alerting information for the physician: Body as a Whol e : Edema Cardiovascular: Chest Pain, Hypertension, Tachycardia Nervous: Depression Respiratory: Shallow Breathing Postmarketing Experience Postmarketing experience with butorphanol tartrate injection has shown an adverse event profile similar to that seen during the premarketing evaluation of butorphanol by all routes of administration. Adverse experiences that were associated with the use of butorphanol tartrate injection and that are not listed above have been chosen for inclusion below because of their seriousness, frequency of reporting, or probable relationship to butorphanol. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse experiences include apnea, convulsion, delusion, drug dependence, excessive drug effect associated with transient difficulty speaking and/or executing purposeful movements, overdose and vertigo. Reports of butorphanol overdose with a fatal outcome have usually but not always been associated with ingestion of multiple drugs. serotonin syndrome adrenal insufficiency Androgen deficiency Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as symptoms of hypogonadism, such as impotence, erectile dysfunction, or amenorrhea. The causal role of opioids in the syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled tor in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation. DRUG ABUSE AND DEPENDENCE Butorphanol tartrate injection is a Schedule IV Controlled Substance. Abuse Butorphanol tartrate is a substance with a high potential for abuse similar to other opioids including. Butorphanol tartrate injection can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS] . All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, tor its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. "Drug-seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated "loss" of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating health care provider(s). "Doctor shopping" (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction. Butorphanol tartrate, like other opioids, can be diverted tor non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia lin the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates tor different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmetene). mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine). or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. Butorphanol tartrate should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If butorphanol tartrate is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS ; Pregnancy].

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with butorphanol tartrate and adjust the dosage accordingly [see WARNINGS] . Initial Dosage Factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and surgical procedure involved. Use in the elderly, patients with hepatic or renal disease, or in labor requires extra caution (see PRECAUTIONS section and CLINICAL PHARMACOLOGY: Individualization of Dosage section). The following doses are tor 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 three to tour hours as necessary. The effective dosage range, depending on the severity of pain, is 0.5 to 2 mg repeated every three to tour 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 three to tour hours, as necessary. The effective dosage range depending on the severity of pain is 1 to 4 mg repeated every three to tour hours. There are insufficient clinical data to recommend single doses above 4 mg. Use as Preoperative/Preanesthetic Medication The preoperative medication dosage of butorphanol tartrate injection should be individualized (see CLINICAL PHARMACOLOGY : Individualization of Dosage section). The usual adult dose is 2 mg IM, administered 60 to 90 minutes before surgery. This is approximately equivalent in sedative effect to 10 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 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 injection will vary; however, patients seldom require less than 4 mg or more than 12.5 mg (approximately 0.06 to 0.18 mg/kg). Labor In patients at full term in early labor a 1 to 2 mg dose of butorphanol tartrate IV or IM may be administered and repeated after 4 hours. Alternative analgesia should be used for pain associated with delivery or if delivery is expected to occur within 4 hours. If concomitant use of butorphanol with drugs that may potentiate its effects is deemed necessary (see PRECAUTIONS: Drug Interactions section) the lowest effective dose should be employed. Safety and Handling Butorphanol tartrate injection is supplied in sealed delivery systems that have a low risk of accidental exposure to health care workers. Ordinary care should be taken to avoid aerosol generation while preparing a syringe for use. Following skin contact, rinsing with cool water is recommended. The disposal of Schedule IV controlled substances must be consistent with State and Federal Regulations. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Titration and Maintenance of Therapy Individually titrate butorphanol tartrate to a dose that provides adequate analgesia end minimizes adverse reactions. Continually reevaluate patients receiving butorphanol tartrate to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS] . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the [established name] 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. Discontinuation of Butorphanol Tartrate When a patient who has been taking butorphanol tartrate regularly and may be physically dependent no longer requires therapy with butorphanol tartrate, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. Do not stop butorphanol tartrate abruptly [see WARNINGS, DRUG ABUSE AND DEPENDENCE ] .

More information

Category Value
Authorisation number ANDA074626
Agency product number 2L7I72RUHN
Orphan designation No
Product NDC 52584-626
Date Last Revised 23-02-2018
RXCUI 1728351
Marketing authorisation holder General Injectables & Vaccines, Inc
Warnings WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE THREATENING RESPIRATORY DEPRESSION; and NEONATAL OPIOID WITHDRAWL SYNDROME Addiction, Abuse, and Misuse Butorphanol tartrate injection exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing butorphanol tartrate injection, and monitor all patients regularly for the development of these behaviors or conditions [see WARNINGS]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of butorphanol tartrate injection. Monitor for respiratory depression, especially during initiation of butorphanol tartrate injection or following a dose increase [see WARNINGS]. Neonata l Opioid Withdrawa l Syndrome Prolonged use of butorphanol tartrate injection during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawalsyndrome and ensure that appropriate treatment will be available [see WARNINGS].