butorphanol tartrate 1 MG in 1 ML Injection
WARNINGS
Patients Dependent on Narcotics Because of its opioid antagonist properties, butorphanol is not recommended for use in patients dependent on narcotics.
Such patients should have an adequate period of withdrawal from opioid drugs prior to beginning butorphanol therapy.
In patients taking opioid analgesics chronically, butorphanol has precipitated withdrawal symptoms such as anxiety, agitation, mood changes, hallucinations, dysphoria, weakness and diarrhea.
Because of the difficulty in assessing opioid tolerance in patients who have recently received repeated doses of narcotic analgesic medication, caution should be used in the administration of butorphanol to such patients.
Drug Abuse and Dependence Drug Abuse Butorphanol tartrate, by all routes of administration, has been associated with episodes of abuse.
Of the cases received, there were more reports of abuse with the nasal spray formulation than with the injectable formulation.
Physical Dependence, Tolerance and Withdrawal Prolonged, continuous use of butorphanol tartrate may result in physical dependence or tolerance (a decrease in response to a given dose).
Abrupt cessation of use by patients with physical dependence may result in symptoms of withdrawal.
Note —Proper patient selection, dose and prescribing limitations, appropriate directions for use, and frequent monitoring are important to minimize the risk of abuse and physical dependence.
(See DRUG ABUSE AND DEPENDENCE section below.)
DRUG INTERACTIONS
Drug Interactions Concurrent use of butorphanol with central nervous system depressants (e.g., alcohol, barbiturates, tranquilizers, and antihistamines) may result in increased central nervous system depressant effects.
When used concurrently with such drugs, the dose of butorphanol should be the smallest effective dose and the frequency of dosing reduced as much as possible when administered concomitantly with drugs that potentiate the action of opioids.
It is not known if the effects of butorphanol are altered by 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.
No information is available about the use of butorphanol concurrently with MAO inhibitors.
OVERDOSAGE
Clinical Manifestations The clinical manifestations of butorphanol overdose are those of opioid drugs in general.
Consequences of overdose vary with the amount of butorphanol ingested and individual response to the effects of opiates.
The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma and death.
Butorphanol overdose may be associated with ingestion of multiple drugs (see ADVERSE REACTIONS : Postmarketing Experience section).
Overdosage can occur due to accidental or intentional misuse of butorphanol, especially in young children who may gain access to the drug in the home.
Treatment The management of suspected butorphanol overdosage includes maintenance of adequate ventilation, peripheral perfusion, normal body temperature, and protection of the airway.
Patients should be under continuous observation with adequate serial measures of mental state, responsiveness and vital signs.
Oxygen and ventilatory assistance should be available with continual monitoring by pulse oximetry if indicated.
In the presence of coma, placement of an artificial airway may be required.
An adequate intravenous portal should be maintained to facilitate treatment of hypotension associated with vasodilation.
The use of a specific opioid antagonist such as naloxone should be considered.
As the duration of butorphanol action usually exceeds the duration of action of naloxone, repeated dosing with naloxone may be required.
In managing cases of suspected butorphanol overdosage, the possibility of multiple drug ingestion should always be considered.
DESCRIPTION
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 C 21 H 29 NO 2 •C 4 H 6 O 6 , 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 USP is a sterile, parenteral, aqueous solution of butorphanol tartrate for intravenous or intramuscular administration.
In addition to 1 or 2 mg of butorphanol tartrate, each mL of solution contains 3.3 mg of citric acid, 7.29 mg sodium citrate, and 6.4 mg sodium chloride, and 0.1 mg benzethonium chloride (in multiple dose vial only) as a preservative.
The pH range is 3.5 to 5.0.
structural formula
CLINICAL STUDIES
Clinical Trials The effectiveness of opioid analgesics varies in different pain syndromes.
Studies with butorphanol tatrate injection have been performed in postoperative (primarily abdominal and orthopedic) pain and pain during labor and delivery, as preoperative and preanesthetic medication, and as a supplement to balanced anesthesia (see below).
HOW SUPPLIED
Butorphanol Tartrate Injection USP for IM or IV use is available as follows: NDC 55390-183-01 – 1 mg/mL, 1 mL vial, carton of 10.
NDC 55390-184-01 – 2 mg/mL, 1 mL vial, carton of 10.
NDC 55390-184-02 – 4 mg/2 mL, 2 mL vial, carton of 10.
NDC 55390-185-10 – 2 mg/mL, 10 mL multiple dose vial, individually boxed.
Store at room temperature, 15° to 30°C (59° to 86°F).
See USP.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Protect from light.
GERIATRIC USE
Geriatric Use Of the approximately 1500 patients treated with butorphanol tartrate injection in clinical studies, 15% were 61 years of age or older and 1% were 76 years or older.
Due to changes in clearance, the mean half-life of butorphanol is increased by 25% in patients over the age of 65 years (see CLINICAL PHARMACOLOGY , Pharmacokinetics section).
Elderly patients may be more sensitive to the side effects of butorphanol.
There are insufficient efficacy data for patients ≥65 years to determine whether they respond differently from younger patients.
The initial dose of butorphanol tartrate injection recommended for elderly patients should generally be half the recommended adult dose (0.5 mg IV and 1 mg IM).
Repeat dose 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 , Individualization of Dosage section).
Butorphanol and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal functions.
Because elderly patients are more likely to have decreased renal function, care should be taken in dosage selection.
INDICATIONS AND USAGE
Butorphanol tartrate injection is indicated for the management of pain when the use of an opioid analgesic is appropriate.
Butorphanol tartrate injection is also indicated as preoperative or preanesthetic medication, as a supplement to balanced anesthesia, and for the relief of pain during labor.
PEDIATRIC USE
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.
PREGNANCY
Pregnancy Teratogenic Effects: Pregnancy Category C Reproduction studies in mice, rats and rabbits during organogenesis did not reveal any teratogenic potential to butorphanol.
However, pregnant rats treated subcutaneously with butorphanol at 1 mg/kg (5.9 mg/m 2 ) had a higher frequency of stillbirths than controls.
Butorphanol at 30 mg/kg/oral (360 mg/m 2 ) and 60 mg/kg/oral(720 mg/m 2 ) also showed higher incidences of post-implantation loss in rabbits.
There are no adequate and well-controlled studies of butorphanol tartrate in pregnant women before 37 weeks of gestation.
Butorphanol tartrate injection should be used during pregnancy only if the potential benefit justifies the potential risk to the infant.
NUSRING MOTHERS
Nursing Mothers Butorphanol has been detected in milk following administration of butorphanol tartrate injection to nursing mothers.
The amount an infant would receive is probably clinically insignificant (estimated 4 mcg/L of milk in a mother receiving 2 mg IM four times a day).
INFORMATION FOR PATIENTS
Information for Patients (see PRECAUTIONS : Use in Ambulatory Patients ).
DOSAGE AND ADMINISTRATION
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 for 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 four hours, as necessary.
The effective dosage range, depending on the severity of pain, is 0.5 mg to 2 mg repeated every 3 to 4 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 3 to 4 hours as necessary.
The effective dosage range depending on the severity of pain is 1 mg to 4 mg repeated every 3 to 4 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 mg 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 tartrate 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 tartrate 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.