The FDA has information on side effects and uses of Stadol.

The Stadol brand name has been discontinued in the US.Generic equivalents may be available if the product has been approved by the FDA.

Butorphanol is a synthetically derived opiate.The chemical name is dihydroxybutanedioate.The structure of the formula is C21H29NO2,C4H6O6, which corresponds to a weight of 477.55.

Butorphanol is a white substance.The salt is expressed as a dose.The free base is equivalent to 0.68 grams of salt.Butorphanol has a n-octanol/aqueous buffer partition coefficients of 180:1

Stadol is a sterile, parenteral solution of butorphanol.Each mL of solution contains more than 1 or 2 grams of butorphanol, as well as a number of other ingredients.

Stadol NS is a metered spray that can be used to administer butorphanol tartrate.The solution of butorphanol tartrate with sodium chloride, citric acid, and benzethonium chloride is added to the water to adjust the pH to 5.0.The pump must be primed before use.The metered spray and bottle deliver an average of 1.0 and 2.5 grams of butorphanol, respectively.The unit must be reprimed if it isn't used for 48 hours or more.Depending on how much repriming is needed, the bottle will deliver an average of 8–10 doses of Stadol NS.

Butorphanol has low activity at the -opioid type.It is an opiate.

Most of its pharmacologic effects, including analgesia, can be attributed to its interactions with the central nervous system.

Depression of respiratory activity and cough, stimulation of the emetic center, and sedation are included in the central nervous system's effects.Alterations in cardiovascular resistance and capacitance, bronchomotor tone, and gastrointestinal secretory may be caused by non-CNS mechanisms.

In an animal model, the amount of butorphanol needed to antagonize morphine analgesia by 50% was the same as for nalorphine and more than that for naloxone.

In animal studies, butorphanol metabolites have shown some analgesic activity.

In human studies of butorphanol, sedation is often noted at doses of more than a few hundredths of a gram.The butorphanol is administered over a period of 10–15 minutes.

Butorphanol, like other mixed agonist-antagonists with a high affinity for the -receptor, can cause unpleasant psychotomimetic effects in some individuals.

In human studies with individuals without respiratory problems, butorphanol IV and morphine sulfate IV depressed respiration to a comparable degree.The duration of respiratory depression with butorphanol is longer at higher doses.After administration of butorphanol to humans by any route, respiratory depression can be reversed by treatment with naloxone, a specific opioid antagonist.

The antitussive effects of butorphanol tartrate are less than those required for analgesia.

Patients receiving a single 0.025 dose of butorphanol have seen a variety of hemodynamic changes during cardiac catheterization.

The route of administration affects the effect of butorphanol.Within a few minutes, analgesia can be given in the form of IV administration, injection, and spray.

Within 60 minutes after the administration of the IV and the nasal spray, peak analgesic activity occurs.

The duration of analgesia varies depending on the pain model as well as the route of administration, but is generally 3–4 hours with IV andIM doses as defined by the time 50% of patients required remedication.The duration of analgesia with IV orIM butorphanol was similar to morphine, meperidine, and pentazocine when administered in the same fashion.Stadol NS has a longer duration of action than the other drugs in this class.

peak levels are reached in 20–40 minutes after the injection.

Mean peak blood levels are 30–60 minutes after a 1 dose.There is no change in the absolute bioavailability of Stadol NS in patients with allergic rhinitis.The fraction of the dose absorbed was not changed, but the rate of absorption was slowed.The peak concentrations were less than those achieved without the vasoconstrictor.

The single dose pharmacokinetics of butorphanol by the different routes of administration are similar after its initial absorption/distribution phase.

There is a bound fraction of 80% that is independent of concentration over the range achieved in clinical practice.

The total body clearance varies from 52 to 154 liters/hour.

At steady state, the doses have been determined at 6 hour intervals.Within 2 days, steady state is achieved.The peak concentration following a single dose was 1.8-fold.

The drug enters the human milk through the blood brain and placental barriers.

Butorphanol is in the bloodstream.Metabolism is qualitatively and quantitatively the same as it was before.The oral metabolism of butorphanol is extensive.

Small amounts of norbutorphanol are produced in the major metabolite.Norbutorphanol is present at trace levels at most time points.When butorphanol is dosed to steady state, the half-life of the drug is about 18 hours.

The elimination is done by urine and fecal excretion.When 3H labelled butorphanol is administered to normal subjects, most of the dose is recovered in the urine and the rest in feces.

Butorphanol is recovered in about 5% of the dose.Forty-nine percent of the urine is eliminated as hydroxybutorphanol.Norbutorphanol is less than 5% in the urine.

The elderly have different butorphanol pharmacokinetics than younger patients.In elderly women, the mean absolute bioavailability was less than it was in elderly men, young men or young women.The elimination half-life is increased in the elderly.

The elimination half-life was doubled and the total body clearance was halved in patients with creatinine clearances greater than 30 mL/min.There was no effect on Cmax or Tmax after a single dose.

The elimination half-life of butorphanol was tripled and the total body clearance was less than healthy subjects.The exposure of hepatically impaired patients to butorphanol was more than that in healthy subjects.The results were the same after nasal administration.There was no effect on Cmax or Tmax after a single dose.

It is recommended that you refer to the PRECAUTIONS: Hepatic and Renal Disease, Drug Interactions, and Geriatric Use as well as the CLINICAL PHARMACOLOGY: Individualization of Dosage.

Different pain syndromes have different levels of effectiveness.As a supplement to balanced anesthesia, studies with Stadol Injection have been performed in abdominal and orthopedic pain, as well as in labor and delivery.

Studies with Stadol NS have been performed in a number of pain areas.

The efficacy of Stadol Injection was investigated in several studies.The following doses were found to have the same effect.

By the time of first observation (30 minutes), the peak effect of Stadol Injection had occurred.The peak effect occurred between 30 minutes and 1 hour after the injection.The time needed for pain intensity to return to pretreatment level or the time to retreatment was defined by the duration of action of Stadol Injection.

Approximately 35 patients per treatment group were evaluated in a general and orthopedic surgery trial.The single doses of Stadol NS and meperidine were compared.The analgesia provided by 1 and 2 doses of Stadol NS was similar to 75 and 37.5 meperidine and had a peak effect within an hour.The average duration of pain relief was 3.5 hours with either dose of meperidine or Stadol NS.

In a postcesarean section trial, 35 patients were given Stadol NS as two 1-mg doses 60 minutes apart, compared with a single 2-mg dose or single IV dose.The analgesia was within 15 minutes.The peak effects of Stadol Injection were similar in magnitude.The duration of pain relief provided by Stadol Injection was less than 2.5 hours.

The efficacy of two 1-mg doses 1 hour apart of Stadol NS was compared with a single dose of 10.Within 15 minutes, significant analgesia occurred for both Stadol NS and IM methadone.The peak effect on Stadol was 2 hours and 1.5 hours.When half of the patients remedicated, the median duration of pain relief was 6 hours.

In two other trials in patients with headaches, the initial dose of Stadol NS followed by an additional dose 1 hour later was compared with placebo.Onset, peak activity, and duration were similar with both active treatments; however, the incidence of adverse experiences (nausea, vomiting, dizziness) was higher in these two trials with the 2-mg initial dose of Stadol NS.

Stadol Injection and meperidine were studied for use in hospitalized surgical patients.90 minutes prior to anesthesia, patients received a single dose of either Stadol Injection or meperidine.The anesthesia regimen included barbiturate induction, followed by nitrous oxide and oxygen with halothane or enflurane, or without a muscle relaxant.

All 42 Stadol Injection patients had anesthetic preparation that was satisfactory.

In 50 Class 1 and 2 patients, Stadol Injection was compared to IV morphine sulfate as premedication, followed by balanced anesthesia.Stadol Injection and morphine were averaged for each patient.

Regardless of the type of surgery performed, anesthetic maintenance was generally rated as satisfactory.Emergence from anesthesia was the same as that of both agents.

During labor, the efficacy of Stadol Injection was studied.The relief of pain in labor with no effect on the duration or progress of labor was achieved by Stadol Injection in a total of 146 patients.Both drugs entered fetal circulation.The condition of the infants in these studies was determined by Apgar scores at 1 and 5 minutes and time to sustained respiration.

Babies exposed to Stadol Injection at a mean of 18.6 hours after delivery showed no significant differences between treatment groups.

Extra caution is required when using butorphanol in geriatric patients, patients withrenal impairment, and during labor.

The recommended initial dose of Stadol Injection is 1 gIV or 2 gIM with repeated doses every 3 to 4 hours for pain relief.The majority of patients will likely benefit from this regimen.Observations of the beneficial and adverse effects of Stadol Injection should be used to make dosage adjustments.The initial dose in the elderly should be half of the adult dose.In these patients, repeat doses should be determined by the patient's response rather than at fixed intervals but will be no longer than 6 hours.

The usual pre- surgery dose is 2 to 3 times the normal dose.This is equivalent to 10 or 80 meperidines.This single preoperative dose should be individualized based on age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.

Incremental dose of Stadol Injection is used during maintenance in balanced anesthesia.Depending on previous drugs, the incremental dose may be higher.The total dose of Stadol Injection will vary depending on the patient's requirement.

Stadol Injection may not provide adequate analgesia in every patient or under all conditions.Increased sympathetic tone is a result of a failure to achieve successful analgesia during balanced anesthesia.If blood pressure or heart rate continues to rise, consideration should be given to adding a potent volatile liquid inhalation anesthetic or another IV medication.

In labor, the recommended initial dose of Stadol Injection is 1 or 2 IU or IV in mothers without signs of fetal distress.Dosage adjustments of Stadol Injection in labor should be based on the initial response and the expected delivery time.The dose should not be repeated in less than 4 hours prior to the delivery.

One spray in one nostril is recommended for initial nasal administration.An additional dose may be given if adequate pain relief is not achieved within 90 minutes.

After the second dose of the sequence, the initial dose sequence may be repeated in 3–4 hours.

For the management of severe pain, an initial dose of 2mg (1 spray in each nostril) may be used in patients who will be able to remain upright.Extra doses should not be given for more than 3 hours.The incidence of adverse events is higher with an initial dose.

If needed, the initial dose sequence in elderly patients and patients with hepatic impairment should be limited to 1 dose in 90 to 120 minutes.The repeat dose sequence in these patients should be determined by the patient's response rather than at fixed times but will generally be no less than 6 hours.

The use of an opiate analgesic is appropriate for the management of pain.

Stadol Injection can be used as a supplement to balanced anesthesia, as well as for the relief of pain during labor.

Patients who are hypersensitive to butorphanol tartrate or the preservative benzethonium chloride are not good candidates for Stadol Injection.

Butorphanol is not recommended for use in patients dependent on narcotics.Prior to beginning butorphanol therapy, patients should have an adequate period of withdrawal from opiate drugs.Butorphanol can cause withdrawal symptoms in patients taking chronic pain killers.

Caution should be used in the administration of butorphanol to patients who have recently received a lot of narcotic pain medication because of the difficulty in assessing tolerance.

Drug Abuse, by all routes of administration, has been associated with Butorphanol.There were more reports of abuse with the spray than the injection.

A decrease in response to a given dose may be the result of physical dependence or tolerance.Symptoms of withdrawal may result from abrupt cessation of use by patients with physical dependence.

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.Drug abuse and dependency can be seen.

Hypotension associated with syncope in patients with a history of similar reactions to opiate drugs is rare.Patients should be advised to avoid certain activities.

The use of butorphanol in patients with head injuries may be associated with alterations in mental state that would obscure the interpretation of the clinical course.If the benefits of use outweigh the risks, butorphanol should only be used.

Butorphanol can cause respiratory depression in patients who are receiving other CNS active agents.

The initial dose of Stadol Injection should be half of the adult dose.In these patients, repeat doses should be determined by the patient's response rather than at fixed intervals but will generally be no more than 6 hours apart.If needed, the initial dose sequence of Stadol NS should be 1 dose followed by another in 90– 120 minutes.The repeat dose sequence in these patients should be determined by the patient's response rather than at fixed times but will generally be at intervals of no less than 6 hours.

The use of butorphanol in patients with acute myocardial infarction, ventricular insufficiency, or coronary insufficiency should be limited to those situations where the benefits clearly outweigh the risk.

Severe hypertension is rare during butorphanol therapy.In such cases, butorphanol should be stopped and the hypertension treated with antihypertensive drugs.Naloxone has been reported to be effective in patients who are not dependent on drugs.

Increased central nervous system depressant effects may be a result of concurrent use of butorphanol.The dose of butorphanol should be the smallest effective one when used with drugs that potentiate the action of opioids.

The coadministration of a single 6-mg dose of sumatriptan did not affect the pharmacokinetics of butorphanol in healthy volunteers.In a study of healthy volunteers, butorphanol's AUC and Cmax were altered when a single dose of Stadol NS was given 1 minute after a 20-mg dose.The drugs were administered in different ways.After the sumatriptan nasal spray, the AUC of butorphanol increased and the Cmax decreased.The sumatriptan's pharmacokinetics were unaffected by coadministration with Stadol NS.The results suggest that the analgesic effect of Stadol NS may be diminished when it is administered shortly after sumatriptan nasal spray, but by 30 minutes any such reduction in effect should be minimal.

The safety of using Stadol NS and IMITREX® during the same episode of migraines has not been established.Transient increases in blood pressure can be produced by both products.

The coadministration of cimetidine did not affect the pharmacokinetics of a 1-mg dose of butorphanol.The administration of butorphanol QID did not change the pharmacokinetics of cimetidine.

It is not known if the effects of butorphanol are altered by other drugs.Doctors should be aware of the possibility of a smaller initial dose and longer intervals between doses.

The rate of absorption is decreased because of the administration of a nasal vasoconstrictor.If Stadol NS is administered immediately following a nasal vasoconstrictor, a slower onset can be anticipated.

Two-year carcinogenicity studies were conducted in mice and rats that were given butorphanol tartrate in the diet.There was no evidence of cancer in either species.

In cultured human fibroblast cells, butorphanol was not genotoxic.

There was a reduced pregnancy rate when rats were treated with a large amount of water.A similar effect was not observed with a 2.5 dose.

There was no evidence of a teratogenic potential to butorphanol in the studies of mice, rats, and rabbits.The rats that were treated with butorphanol had a higher incidence of stillbirths.There were higher incidences of post-implantation loss in rabbits with butorphanol at 30 and 60.

There are no studies of Stadol in pregnant women.Stadol should only be used if the benefit outweighs the risk to the baby.

There have been few reports of infant respiratory distress/apnea after the administration of Stadol Injection.The reports of respiratory distress/apnea have been associated with administration of a dose within 2 hours of delivery, multiple doses, use with additional analgesic or sedative drugs, or use in preterm pregnancies.

Transient (10–90 minutes) sinusoidal fetal heart rate patterns were not associated with adverse neonatal outcomes in a study of 118 patients.Stadol Injection should be used with caution if the fetal heart rate pattern is abnormal.

There is no clinical experience with using Stadol during labor or delivery.

Milk has been found to have butorphanol in it.The amount of milk an infant would receive is not clinically significant.

Although there is no clinical experience with the use of Stadol NS in nursing mothers, it should be assumed that butorphanol will appear in the milk in similar amounts.

Butorphanol is not recommended for use in patients below 18 years of age because safety and efficacy have not been established.

Of the approximately 1500 patients treated with Stadol Injection in clinical studies, 15% were 61 years of age or older.Of the 1700 patients treated with Stadol NS in clinical studies, 8% were 65 years of age or older.

The mean half-life of butorphanol is increased by 25% in patients over the age of 65 years.Elderly patients may be more sensitive to the side effects of butorphanol.Older patients had an increased incidence of headaches, dizziness, nausea, and vomiting, compared with younger patients, in clinical studies of Stadol NS.There is not enough data to determine if patients respond differently from younger patients.

For elderly patients, the initial dose of Stadol Injection should be half the adult dose.Repeated doses should be determined by the patient's response rather than at fixed intervals, but will generally be no less than 6 hours apart.

Initially a 1-mg dose of Stadol NS should be used in geriatric patients and 90– 120 minutes should elapse before administering a second dose, if needed.

The risk of toxic reactions to butorphanol is higher in patients with impaired renal function.Elderly patients are more likely to have a decreased renal function, so care should be taken in dose selection.

There were 2446 patients studied in the premarketing trials of butorphanol.Stadol Injection was received by half of the people.The type and incidence of side effects with butorphanol by any route were common with opioid analgesics.

Data from short- and long-term clinical trials in patients receiving butorphanol are used to describe the adverse experiences.There was no attempt to correct for placebo effect or to subtract frequencies reported by placebo-treated patients in controlled trials.

Somnolence, dizziness, nausea and/or vomiting were the most common adverse experiences reported in all clinical trials.Insomnia and nasal congestion were frequently reported in long-term trials with Stadol NS only.

The use of butorphanol was thought to be a factor in the reported adverse experiences.

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

Respiratory diseases include bronchitis, cough, dyspnea, epistaxis, nasal congestion, pharyngitis, rhinitis, and upper respiratory infections.

The use of butorphanol was thought to be related to the following adverse experiences.

The association between these events and butorphanol administration is unknown, but the following infrequent additional adverse experiences were reported in less than 1% of the patients studied in short-term Stadol NS trials.They are listed as an alert for the doctor.

During the premarketing evaluation of butorphanol, there was an adverse event profile similar to that seen with Stadol Injection.Adverse experiences that were associated with the use of Stadol Injection and that are not listed above have been chosen for inclusion because of their seriousness, frequency of reporting, or probable relationship to butorphanol.Estimates of Frequency can't be made because they are voluntary.Drug dependence, excessive drug effect, and dizziness are some of the adverse experiences.Reports of butorphanol overdose with a fatal outcome are usually associated with ingestion of multiple drugs.

There are two drugs listed in Schedule IV of theCSA.

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.Special care should be given to patients with a history of drug abuse who are receiving butorphanol on a continuous basis.

Less than 1% of patients in all clinical trials had experiences that suggested physical dependence or tolerance.Some of the information is based on experience with patients who did not have long-term exposure to Stadol.In one controlled clinical trial where patients with chronic pain from nonmalignant disease were treated with Stadol NS for up to 6 months, there were nine cases of overuse, which may suggest the development of tolerance.In the chronic nonmalignant pain study, withdrawal symptoms were reported in eight patients, but no patients received placebo.After extended use or high doses, most of these patients stopped using Stadol.There are a number of symptoms suggestive of withdrawal.

Abuse and dependence have been associated with butorphanol.There were more reports of abuse with the spray than the injection.

Opioid drugs in general have clinical manifestations of butorphanol overdose.The amount of butorphanol taken and the individual response to the effects of opiates have consequences.Hypoventilation, cardiovascular insufficiency, coma, and death are the most serious symptoms.Butorphanol overdose can be linked to ingestion of multiple drugs.

Accidental or intentional misuse of butorphanol can lead to overdose in young children who may gain access to the drug in the home.

The management of suspected butorphanol overdosage includes the maintenance of adequate ventilation, peripheral perfusion, normal body temperature, and protection of the airway.Patients should be monitored continuously with adequate measures of mental state, responsiveness, and vital signs.Continuous monitoring by pulse oximetry should be used for oxygen and ventilatory assistance.In the event of a coma, an artificial airway may be required.An adequate portal is needed to facilitate treatment of hypotension.

The use of a specific drug should be considered.If the duration of butorphanol action exceeds that of naloxone, a repeat dose of the drug may be required.

In cases of suspected butorphanol overdoses, the possibility of multiple drug ingestion should always be considered.

Factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other drugs, and surgical procedure involved.Caution is required when using in the elderly, in patients with hepatic orrenal disease, or in labor.The following doses are given to patients who are not on active agents.

The usual recommended single dose for IV administration is 1mg repeated every 3 to 4 hours.The dosage range is dependent on the severity of the pain.

In patients who will be able to remain upright in the event of dizziness or drowsiness, the recommended single dose is 2 grams.This can be done every 3 to 4 hours.Depending on the severity of the pain, the effective dosage range is 1 to 4% repeated every 3 to 4 hours.There is not enough clinical data to recommend a higher dose.

One spray in one nostril is recommended for initial nasal administration.The incidence of dizziness and drowsiness can be reduced by adhering to this dose.An additional dose may be given if adequate pain relief is not achieved within 90 minutes.

After the second dose of the sequence, the initial dose sequence may be repeated in 3–4 hours.

Depending on the severity of the pain, an initial dose of 1 spray in each nostril may be used in patients who will be able to remain upright.Patients should not be given additional doses for more than 3 hours.

CLINICAL PHARMACOLOGY: Individualization of Dosage states that the preoperative medication dosage of Stadol Injection should be individualized.60–90 minutes before surgery is when the usual adult dose is given.This is equivalent to 10 or 80 meperidines.

During anesthesia, the usual dose of Stadol Injection is between 2 and 1.0 IV.The increment may be higher if previous drugs are used.The total dose of Stadol Injection will vary depending on the patient's requirement.

The use of Stadol is not recommended because it has not been studied.

Stadol Injection IV can be given to patients at full term in early labor.If delivery is expected to occur within 4 hours, alternative analgesia should be used.

If Stadol is used with drugs that may potentiate its effects, the lowest effective dose should be used.

Stadol 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.It is recommended to rinse with cool water after skin contact.

The pump sprayer should be aimed away from the patient or other people if a certain amount of butorphanol is aerosolized.

The disposal of Schedule IV controlled substances must be in line with state and federal regulations.You can dispose of the unit by removing the cap, rinsing the bottle, and putting the parts in a waste container.

A metered-dose spray pump with protective clip and dust cover, a bottle of nasal spray solution, and a patient instruction leaflet are included in a child-resistant prescription.If no repriming is necessary, one bottle will deliver 14–15 doses.

The patient will be given Stadol NS by the pharmacist.

The room temperature is controlled at 25 C.You can see the USP.When solution and container permit, parenteral drug products should be inspected for particulate matter and discoloration.

Dayton, NJ 08810 USA 565001DIL-8 1117206A2 was revised in April 2002.

Related Posts:

  1. Doctor answers on healthcaremagicprotonix oral: uses, side effects, interactions and pictures...
  2. Neulasta: Side effects, uses, and more.
  3. Budesonide is an overview of a product.
  4. FDA prescribe information, side effects, and uses of cefprozil.