Butorphanol Tartrate

Pronunciation

Pronunciation: bue-TOR-fa-nol TAR-trate
Class: Opioid agonist-antagonist analgesic

Trade Names

Butorphanol Tartrate
- Injection, solution 1 mg/mL
- Injection, solution 2 mg/mL
- Solution, intranasal 10 mg/mL

Apo-Butorphanol (Canada)
PMS-Butorphanol (Canada)

Pharmacology

Potent analgesic that stimulates and inhibits opiate receptors in CNS. Antagonist effects decrease (but do not eliminate) abuse potential and may cause withdrawal symptoms in patients with opiate dependence.

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Pharmacokinetics

Absorption

IM

Rapidly absorbed; T max is 20 to 40 min.

Nasal

T max is 30 to 60 min and C max is 0.9 to 1.04 ng/mL. Absolute bioavailability is 60% to 70%. Steady state is reached within 2 days.

Distribution

Approximately 80% protein bound. Vd varies from 305 to 901 L. Butorphanol crosses the blood-brain barrier and placenta and is excreted into human milk.

Metabolism

Extensively metabolized in liver to major metabolite hydroxybutorphanol; norbutorphanol is produced in small amounts.

Elimination

70% to 80% excreted in urine (5% as unchanged drug); 15% excreted in feces. The half-life is 2.1 to 8.8 h (IV) and 2.9 to 9.2 h (nasal). Cl is 52 to 154 L/h.

Onset

IM

Within 15 min.

IV

Few min.

Nasal

Within 15 min.

Peak

IM/IV

30 to 60 min.

Nasal

1 to 2 h.

Duration

IM/IV

3 to 4 h.

Nasal

4 to 5 h.

Special Populations

Renal Function Impairment

For those with CrCl less than 30 mL/min, the elimination half-life is approximately doubled and the total body Cl is approximately one-half.

Hepatic Function Impairment

The half-life may be tripled and total body Cl is approximately one-half.

Elderly

Elderly half-life is increased 25%. Absolute bioavailability of nasal spray is less in elderly women (48%) than in elderly men (75%). Elimination half-life is increased.

Indications and Usage

Management of pain when use of an opioid analgesic is appropriate; preoperative or preanesthetic medication, as a supplement to balanced anesthesia, and for the relief of pain during labor (IM/IV only).

Contraindications

Hypersensitivity to butorphanol or the preservative benzethonium chloride.

Dosage and Administration

Labor
Adults IM / IV

1 to 2 mg in patients at full term in early labor; may repeat after 4 h.

Pain
Adults IM

2 mg every 3 to 4 h in patients who will be able to remain recumbent. The effective dose range is 1 to 4 mg every 3 to 4 h (max, 4 mg per single dose).

IV

1 mg every 3 to 4 h as needed. The effective dosage range, depending on the severity of pain, is 0.5 to 2 mg every 3 to 4 h.

Nasal

1 mg (1 spray in 1 nostril) initially. Wait 60 to 90 min before giving second 1 mg dose. Repeat dose sequence in 3 to 4 h after second dose of sequence if needed. For severe pain, in patients able to remain recumbent, initial dose 2 mg (1 spray in each nostril) every 3 to 4 h.

Preoperative/Preanesthetic
Adults IM

2 mg 60 to 90 min before surgery.

IV

2 mg shortly before induction and/or 0.5 to 1 mg in increments during anesthesia. The increment may be higher, up to 0.06 mg/kg depending on previous sedative, analgesic, and hypnotic drugs administered.

Renal or Hepatic Function Impairment/Elderly
Adults IM / IV

Administer one-half the normal dose initially. Repeat doses should be determined by the patient's response, but generally no less often than 6-h intervals.

Nasal

1 mg (1 spray in 1 nostril) initially. Wait 90 to 120 min before giving second 1 mg dose. Repeat dose sequence based on patient response, but generally no less often than 6-h intervals.

General Advice

  • Nasal
  • For intranasal use only.
  • Pump reservoir must be fully primed prior to initial use; pump sprayer firmly and quickly until a fine spray appears (up to 7 to 8 strokes).
  • Pump reservoir must be reprimed (1 or 2 strokes) if not used for 48 h or longer.
  • Butorphanol may be aerosolized during priming process; aim pump sprayer away from the patient, other people, and animals.
  • One bottle will deliver 14 to 15 doses if no repriming is needed. With intermittent use requiring repriming before each dose, 1 bottle may deliver only 8 to 10 doses.
  • Follow institutional or organizational policies and procedures to dispose of used pump units. Dispose of used units by unscrewing the cap, rinsing the bottle, and placing parts in waste container.
  • Injection
  • For IV or IM use only.
  • When administering IM, inject slowly and deeply.
  • Do not administer if solution is discolored, cloudy, or contains particulate matter.
  • Following skin contact, rinsing with cool water is recommended.

Storage/Stability

Store between 59° and 86°F. Protect vials from light.

Drug Interactions

CNS depressants (eg, alcohol, antihistamines, barbiturates, sedatives, tranquilizers)

Additive CNS depression. Avoid alcohol.

Nasal vasoconstrictor (eg, oxymetazoline)

A slower onset of butorphanol nasal spray can be anticipated if administered with or immediately following a nasal vasoconstrictor.

Sumatriptan

The analgesic effect of butorphanol may be diminished when it is administered shortly after sumatriptan, but by 30 min any such reduction in effect should be minimal.

Adverse Reactions

Cardiovascular

Palpitations, vasodilation (at least 1%).

CNS

Somnolence (43%); dizziness (19%); insomnia (11%); anxiety, asthenia, confusion, euphoria, floating feeling, headache, lethargy, nervousness, paresthesia, tremor (at least 1%); convulsions, delusions, difficulty executing purposeful movements, difficulty speaking, drug dependence, vertigo (postmarketing).

Dermatologic

Pruritus, sweating/clamminess (at least 1%).

EENT

Nasal congestion (13%); blurred vision, ear pain, pharyngitis, rhinitis, tinnitus, unpleasant taste (at least 1%).

GI

Nausea, vomiting (13%); anorexia, constipation, dry mouth, stomach pain (at least 1%).

Respiratory

Bronchitis, cough, dyspnea, epistaxis, nasal congestion, nasal irritation, sinus congestion, sinusitis, upper respiratory tract infection (at least 1%).

Miscellaneous

Sensation of heat (at least 1%); apnea (postmarketing).

Precautions

Pregnancy

Category C . Nasal spray is not recommended for use during labor or delivery.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established; not recommended for use.

Elderly

More sensitive to adverse effects.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Hazardous Tasks

May cause drowsiness, dizziness, or hypotension during first hour of dosing.

Cardiovascular effects

Because butorphanol may increase the work of the heart, especially the pulmonary circuit, use in patients with acute MI, ventricular dysfunction, or coronary insufficiency should be limited to when the benefits clearly outweigh the risks. Severe hypertension has been reported rarely.

Drug dependency

Abuse may occur. Tolerance and psychological and physical dependence may occur with long-term use. Not recommended for use in patients dependent on narcotics.

Head injury and increased intracranial pressure

May cause CO 2 retention and secondary elevation of CSF pressure, drug-induced miosis, and alterations in mental status that could obscure interpretation of clinical course of patients with head injuries.

Hypotension

Hypotension associated with syncope during the first hour of nasal spray dosing has been reported rarely.

Respiratory depression

May occur, especially in patients on other CNS drugs or in patients with CNS disease or respiratory impairment.

Withdrawal

Abrupt cessation of use by patients with physical dependence may result in symptoms of withdrawal.

Overdosage

Symptoms

Cardiovascular insufficiency, coma, death, hypoventilation.

Patient Information

  • Advise patient to review the Medication Guide carefully before starting therapy and to read and check for new information each time the medication is refilled.
  • Advise patient that medication may be habit forming and to take exactly as prescribed and not increase the dose or frequency of use unless advised by health care provider. Instruct patient to notify health care provider if prescribed dose does not adequately control pain.
  • Ensure patient understands how to use nasal spray: prime pump prior to initial use (7 to 8 strokes or until fine mist appears) or reprime (1 or 2 strokes) if unit has not been used for 48 h or longer); insert spray tip into 1 nostril, pointing tip toward back of the nose, close other nostril with finger, and pump spray unit firmly and quickly while gently sniffing with mouth closed; remove pump unit from nose, tilt head backwards, and continue sniffing gently for a few more seconds.
  • Caution patient that butorphanol may be aerosolized during priming process and to aim pump sprayer away from themselves, other people, and animals.
  • Advise patient that 1 bottle of nasal spray will deliver 14 to 15 doses if no repriming needed, but with intermittent use requiring repriming before each dose, 1 bottle may deliver only 8 to 10 doses.
  • Instruct patient regarding proper disposal of used spray units: unscrew cap, rinse bottle, and place parts in waste container.
  • Caution patient that medication may cause drowsiness or dizziness and to use caution while performing potentially hazardous tasks (eg, driving, operating machinery) until tolerance is determined.
  • Caution patient to avoid alcohol and other depressants (eg, sleep medications, tranquilizers) because dangerous additive effects may occur.

Copyright © 2009 Wolters Kluwer Health.

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