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Clinical Trial Experience

A total of 2446 patients were studied in premarketing clinical trials of butorphanol. Approximately half received STADOL (butorphanol tartrate) Injection with the remainder receiving STADOL (butorphanol tartrate) NS. In nearly all cases the type and incidence of side effects with butorphanol by any route 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 butorphanol by any route. 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 STADOL (butorphanol tartrate) Injection and STADOL (butorphanol tartrate) NS were somnolence (43%), dizziness (19%), nausea and/or vomiting (13%). In long-term trials with STADOL (butorphanol tartrate) NS 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.

Cardiovascular: vasodilation, palpitations.

Digestive: anorexia, constipation, dry mouth, nausea and/or vomiting, stomach pain.

Nervous: anxiety, confusion, dizziness, euphoria, floating feeling, insomnia, nervousness, paresthesia, somnolence, tremor.

Respiratory: bronchitis, cough, dyspnea, epistaxis, nasal congestion, nasal irritation, pharyngitis, rhinitis, sinus congestion, sinusitis, upper respiratory infection.

Skin and Appendages: sweating/clammy, 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 STADOL (butorphanol tartrate) NS trials and under circumstances where the association between these events and butorphanol administration is unknown. They are being listed as alerting information for the physician.

Body as a Whole: edema.

Cardiovascular: chest pain, hypertension, tachycardia.

Nervous: depression.

Respiratory: shallow breathing.

Postmarketing Experience

Postmarketing experience with STADOL (butorphanol tartrate) NS and STADOL (butorphanol tartrate) Injection has shown an adverse event profile similar to that seen during the premarketing evaluation of butorphanol by all routes of administration. Adverse experiences that were associated with the use of STADOL (butorphanol tartrate) NS or STADOL (butorphanol tartrate) Injection and that are not listed above have been chosen for inclusion below because of their seriousness, frequency of reporting, or probable relationship to butorphanol. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These adverse experiences include apnea, convulsion, delusion, drug dependence, excessive drug effect associated with transient difficulty speaking and/or executing purposeful movements, overdose, and vertigo. Reports of butorphanol overdose with a fatal outcome have usually but not always been associated with ingestion of multiple drugs.

Drug Abuse And Dependence

STADOL (butorphanol tartrate) Injection and STADOL NS (butorphanol tartrate) Nasal Spray are listed in Schedule IV of the Controlled Substances Act (CSA).

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 with butorphanol tartrate. Special care should be exercised in administering butorphanol to patients with a history of drug abuse or to patients receiving the drug on a continuous basis for an extended period.

Clinical Trial Experience

In all clinical trials, less than 1% of patients using STADOL (butorphanol tartrate) NS had experiences that suggested the development of physical dependence or tolerance. Much of this information is based on experience with patients who did not have prolonged continuous exposure to STADOL (butorphanol tartrate) NS. However, in one controlled clinical trial where patients with chronic pain from nonmalignant disease were treated with STADOL (butorphanol tartrate) NS (n=303) or placebo (n=99) for up to 6 months, overuse (which may suggest the development of tolerance) was reported in nine (2.9%) patients receiving STADOL (butorphanol tartrate) NS and no patients receiving placebo. Probable withdrawal symptoms were reported in eight (2.6%) patients using STADOL (butorphanol tartrate) NS and no patients receiving placebo in the chronic nonmalignant pain study. Most of these patients abruptly discontinued STADOL (butorphanol tartrate) NS after extended use or high doses. Symptoms suggestive of withdrawal included anxiety, agitation, tremulousness, diarrhea, chills, sweats, insomnia, confusion, incoordination, and hallucinations.

Postmarketing Experience

Butorphanol tartrate has been associated with episodes of abuse and dependence. Of the cases received, there were more reports of abuse with the nasal spray formulation than with the injectable formulation.