Butorphanol

Pregnancy Category: C; D if used for prolonged periods or near term

Lactation: excreted in breast milk, but infant likely exposed to insignificant amounts (AAP Committee states compatible w/ nursing)

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Butorphanol is used in the treatment of:

• Pain

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Butorphanol is available in the following forms:

• Injectable Solution

Butorphanol tartrate is a synthetically derived opioid agonist-antagonist analgesic of the phenanthrene series. The chemical name is (-)-17-(cyclobutylmethyl) morphinan-3, 14-diol D-(-)- tartrate (1:1) (salt). The molecular formula is C21H29NO2 • C4H6O6, which corresponds to a molecular weight of 477.56 and the following structural formula:

Butorphanol tartrate is a white crystalline substance. The dose is expressed as the tartrate salt. One milligram of the salt is equivalent to 0.68 mg of the free base. The n-octanol/aqueous buffer partition coefficient of Butorphanol is 180:1 at pH 7.5.

Butorphanol tartrate injection is a sterile, nonpyrogenic parenteral aqueous solution of Butorphanol tartrate for intravenous or intramuscular administration.

Each milliliter (mL) contains Butorphanol tartrate 1 or 2 mg; sodium citrate, dihydrate, 6.4 mg; citric acid hydrous 3.3 mg; sodium chloride 6.4 mg. The pH is 4.5 (3.0 to 5.5).

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 Use

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

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].

InitialDosage

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].

Agonist of kappa opiate receptors and partial agonist of mu opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces analgesia, respiratory depression, and sedation similar to opioids

Absorption

Rapid and well absorbed

Distribution

Vd: 305 to 901 L

Metabolism

Hepatic to major metabolite, hydroxybutorphanol

Excretion

Primarily urine (70% to 80%; ~5% unchanged); feces (15%)

>10%:

Central nervous system: Drowsiness (43%), dizziness (19%), insomnia (nasal spray 11%)

Gastrointestinal: Nausea and vomiting (13%)

Respiratory: Nasal congestion (nasal spray 13%)

1% to 10%:

Cardiovascular: Palpitations, vasodilatation

Central nervous system: Anxiety, burning sensation, confusion, euphoria, floating feeling, headache, lethargy, nervousness, paresthesia

Dermatologic: Cold and clammy skin, diaphoresis, pruritus

Gastrointestinal: Anorexia, constipation, stomach pain, unpleasant taste, xerostomia

Neuromuscular & skeletal: Tremor, weakness

Ophthalmic: Blurred vision

Otic: Otalgia, tinnitus

Respiratory: Bronchitis, cough, dyspnea, epistaxis, nasal discomfort, pharyngitis, rhinitis, sinus congestion, sinusitis, upper respiratory tract infection

<1% (Limited to important or life-threatening): Apnea, chest pain, convulsions, delusions, depression, drug dependence (prolonged use), dysphoria, edema, hallucinations, hives, hostility, hypertension, hypogonadism (Brennan, 2013; Debono, 2011), hypotension, respiratory depression, seizure, shallow respiration, skin rash, speech disturbance (transient), syncope, tachycardia, withdrawal syndrome