Usual Adult Dose for Anesthesia

Preoperative Medication:
Initial dose: 2 mg IM 60 to 90 minutes before surgery

Balanced Anesthesia:
Initial dose: 2 mg IV shortly before induction and/or 0.5 mg to 1 mg IV in increments during anesthesia
Minimum doses: Total dose is seldom less than 4 mg (0.06 mg/kg)
Maximum doses: Total dose is seldom more than 12.5 mg (0.18 mg/kg)

Comments:

• The above doses are provided as guidance, doses should be individualized; age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia, and surgical procedure should be considered when determining dose.
• Because butorphanol nasal spray has not been studied for use in induction or maintenance anesthesia, use of the nasal spray for anesthesia is not recommended.

Uses: As a preoperative or pre-anesthetic medication; as a supplement to balanced anesthesia.

Usual Adult Dose for Labor Pain

Full term early labor:
Initial dose: 1 or 2 mg IV or IM; may repeat dose in 4 hours if necessary

Comments:

• Alternative analgesia should be used for pain associated with delivery or if delivery is expected to occur within 4 hours.
• Because butorphanol nasal spray has not been studied for use in labor, use of the nasal spray for labor is not recommended.

Use: For the relief of pain during early labor.

Usual Adult Dose for Pain

Parenteral (IM or IV):

• Initial dose: 1 mg IV every 3 to 4 hours; effective dose range: 0.5 to 2 mg every 3 to 4 hours
• Initial dose: 2 mg IM every 3 to 4 hours; effective dose range: 1 to 4 mg every 3 to 4 hours

Maximum IM dose: 4 mg

Nasal Spray:

• Initial dose sequence: 1 mg (1 spray) into 1 nostril; an additional 1 mg may be given in 60 to 90 minutes if adequate pain relief is not achieved, then every 3 to 4 hours (after the second dose of the sequence) as needed
• SEVERE PAIN: 2 mg intranasally (1 spray in each nostril); additional doses may be give every 3 to 4 hours as needed

Comments:

• Doses should be adjusted according to the severity of the pain, age, weight, physical status, and use of concomitant medications.
• For patients receiving the nasal spray, the incidence of adverse events is higher with the initial 2-mg dose; these patients should be recumbent with the first dose in the event drowsiness or dizziness occurs.
• Monitor closely for respiratory depression especially on initiation and with each dose increase.
• Because of the risks of addiction, abuse, and misuse, even at recommended doses, this drug should be reserved for use in patients for whom alternative treatment options have not or are not expected to be tolerated or have not or are not expected to provide adequate analgesia.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Renal Dose Adjustments

Parenteral:

• Initial dose should be limited to 1 mg (e.g. 0.5 mg IV and 1 mg IM), may repeat dose in 90 to 120 minutes as needed; repeat doses should be determined by response, but generally no more frequently than every 6 hours

Nasal spray:

• Initial dose should be limited to 1 mg; if additional pain relief is needed, a second 1 mg dose may be given in 90 to 120 minutes; repeat doses should be determined by response, but generally no more frequently than every 6 hours

Liver Dose Adjustments

Parenteral:

• Initial dose should be limited to 1 mg (e.g. 0.5 mg IV and 1 mg IM), may repeat dose in 90 to 120 minutes as needed; repeat doses should be determined by response, but generally no more frequently than every 6 hours

Nasal spray:

• Initial dose should be limited to 1 mg; if additional pain relief is needed, a second 1 mg dose may be given in 90 to 120 minutes; repeat doses should be determined by response, but generally no more frequently than every 6 hours

Dose Adjustments

Elderly:

• Parenteral: Initial dose should be limited to 1 mg (e.g. 0.5 mg IV and 1 mg IM), may repeat dose in 90 to 120 minutes as needed; repeat doses should be determined by response, but generally no more frequently than every 6 hours

• Nasal spray: Initial dose should be limited to 1 mg; if additional pain relief is needed, a second 1 mg dose may be given in 90 to 120 minutes; repeat doses should be determined by response, but generally no more frequently than every 6 hours

CYP450 3A4 Interactions:

• Consult drug interactions for patients receiving any CYP450 3A4 inhibitor or inducer

Discontinuation in Physically Dependent Patients:

• Taper dose gradually by 25% to 50% every 2 to 4 days
• If signs and symptoms of withdrawal appear, may raise the dose to the previous level and taper more slowly (either by increasing the interval between doses, decreasing the dose, or both)
• Do not abruptly discontinue in the physically-dependent patient

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:

• ADDICTION, ABUSE, AND MISUSE: This drug 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 this drug and monitor all patients regularly for the development of these behaviors or conditions.

RISK EVALUATION AND MITIGATION STRATEGY (REMS): To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.

• LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur with use. Monitor for respiratory depression, especially during initiation of therapy or following a dose increase.
• ACCIDENTAL INGESTION of even one dose, especially by children, can result in a fatal overdose of butorphanol.
• NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use 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 withdrawal syndrome and ensure that appropriate treatment will be available.
• CYP450 3A4 INTERACTION: Concomitant use with CYP450 3A4 inhibitors may result in increased butorphanol plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may result in increased butorphanol plasma concentration. Monitor patients receiving any CYP450 3A4 inhibitor or inducer
• RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: 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. Reserve concomitant use for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required, and follow patients for signs and symptoms of respiratory depression.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule IV

Dialysis

Data not available

Other Comments

Administration advice:
Nasal Spray:

• Must be fully primed prior to initial use; re-prime if not used for 48 hours or longer
• Instruct patients on proper administration (blow nose gently to clear nostrils; insert spray tip approximately 1 cm into 1 nostril pointing tip toward back of nose; close off other nostril; pump 1 spray and sniff gently with mouth closed; after spraying, tilt head back and sniff gently)

Storage requirements:

• Store at controlled room temperature (20C to 25C [68F to 77F]0
• Protect from light

Reconstitution/preparation techniques:
Nasal Spray:

• In the priming process, a certain amount of butorphanol may be aerosolized increasing risk of exposure to those nearby (e.g. other people or animals); when priming, ensure the pump sprayer is aimed away from people or pets.
• The nasal spray should be assembled by the pharmacist prior to dispensing.
• Prior to use, prime the bottle by pressing firmly and quickly until a fine spray appears (usually up to 7 or 8 pumps)
• Once primed, each metered spray delivers 1 mg of butorphanol; a 2.5 mL bottle provides an average of 14 to 15 doses; if intermittent use requires re-priming, the number of doses will decrease

General:

• Due to the risk of addiction, abuse, and misuse with opioids, even at recommended doses, this drug is reserved for use in patients for whom alternative treatment options (non-opioid analgesics) are ineffective, not tolerated, or would be otherwise be inadequate to provide sufficient pain management; the lowest effective dose should be used for the shortest duration consistent with individual patient treatment goals.
• Proper dosing and titration of this drug are essential to reduce the risk of respiratory depression, for patients receiving other opioid analgesics and switching to this drug, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.

Monitoring:

• Cardiovascular: Monitor for signs of hypotension upon initiating therapy and following dose increases, especially those whose blood pressure is compromised
• Respiratory: Monitor for respiratory depression, especially within the first 24 to 72 hours of initiation and with dose increases.
• Gastrointestinal: Monitor for constipation and decreased bowel motility in post-operative patients.
• General: Monitor routinely for maintenance of pain control and incidence of adverse reactions.
• Psychiatric: Patients should be monitored for the development of addiction, abuse, or misuse.

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Patients should understand that this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest; patients should be advised to avoid alcoholic beverages, or respiratory depressant medications while on treatment.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery during therapy.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.