Butorphanol

INDICATIONS AND USAGE Butorphanol tartrate nasal spray is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use : Because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration [see WARNINGS ] reserve butorphanol tartrate nasal spray for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia, or are not expected to provide adequate analgesia Butorphanol tartrate nasal spray should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Butorphanol tartrate nasal spray should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of butorphanol tartrate nasal spray for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with butorphanol tartrate nasal spray. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ]. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with butorphanol tartrate nasal spray (see WARNINGS , Life-Threatening Respiratory Depression ; PRECAUTIONS , Information for Patients ). Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing regulations (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient (see WARNINGS , Addiction, Abuse, and Misuse , Life-Threatening Respiratory Depression , Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ). Consider prescribing naloxone when the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. Initial Dosage Use of Butorphanol Tartrate Nasal Spray as the first Opioid Analgesic 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 and in patients with hepatic or renal disease requires extra caution ( see PRECAUTIONS and CLINICAL PHARMACOLOGY: Individualization of Dosage ). 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: Initiate treatment with butorphanol tartrate nasal spray in a dosing range of 1 mg (1 spray in one nostril) to 2 mg (1 spray in each nostril) every 3 to 4 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of butorphanol tartrate nasal spray. The usual recommended dose for initial nasal administration of butorphanol tartrate nasal spray is 1 mg (1 spray in one nostril). Adherence to this dose reduces the incidence of drowsiness and dizziness. If adequate pain relief is not achieved within 60 to 90 minutes, an additional 1 mg dose may be given. The initial dose sequence outlined above may be repeated in 3 to 4 hours as required after the second dose of the sequence. Depending on the severity of the pain, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent in the event drowsiness or dizziness occurs. In such patients single additional 2 mg doses should not be given for 3 to 4 hours. Use in Balanced Anesthesia: The use of butorphanol tartrate nasal spray is not recommended because it has not been studied in induction or maintenance of anesthesia. Labor: The use of butorphanol tartrate nasal spray is not recommended as it has not been studied in labor. Conversion from Other Opioids to Butorphanol Tartrate Nasal Spray There is inter-patient variability in the potency of opioid drugs and opioid

ADVERSE REACTIONS Clinical Trial Experience A total of 788 patients were studied in premarketing clinical trials of butorphanol tartrate nasal spray. In nearly all cases the type and incidence of side effects with butorphanol were those commonly observed with opioid analgesics. The adverse experiences described below are based on data from short-term and long-term clinical trials in patients receiving intranasal butorphanol, except acute studies in normal subjects. There has been no attempt to correct for placebo effect or to subtract the frequencies reported by placebo-treated patients in controlled trials. The most frequently reported adverse experiences across all clinical trials with Butorphanol Tartrate Nasal Spray were somnolence (49%), dizziness (23%), nausea and/or vomiting (8%). In long-term trials with butorphanol tartrate nasal spray 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, pain. Cardiovascular: Hypertension, hypotension Digestive: Anorexia, constipation, dry mouth, nausea and/or vomiting, diarrhea. Nervous: Anxiety, confusion, dizziness, euphoria, floating feeling, insomnia, nervousness, paresthesia, somnolence, tremor Respiratory: Epistaxis, nasal congestion, nasal irritation, rhinitis, sinus congestion, sinusitis, nose pain. Skin and Appendages: Sweating, 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 spray trials or trials of butorphanol tartrate injection and under circumstances where the association between these events and butorphanol administration is unknown. They are being listed as alerting information for the physician due to their clinical significance. Body as a Whole: edema. Cardiovascular: chest pain, hypertension, tachycardia. Nervous: depression. Respiratory: shallow breathing. Postmarketing Experience The following adverse reactions have been identified during post approval use of butorphanol tartrate nasal spray. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with ingredients contained in butorphanol tartrate nasal spray. Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY ]. Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ].