Voltaren Acti may be available in the countries listed below.
Diclofenac potassium salt (a derivative of Diclofenac) is reported as an ingredient of Voltaren Acti in the following countries:
International Drug Name Search
In the US, Dihydrotachysterol (dihydrotachysterol systemic) is a member of the drug class vitamins and is used to treat Hypocalcemia, Hypoparathyroidism, Hypophosphatemia, Osteoporosis, Renal Osteodystrophy and Rickets.
US matches:
Rec.INN
A11CC02
0000067-96-9
C28-H46-O
398
Vitamin D analogue
9,10-Secoergosta-5,7,22-trien-3-ol, (3ß,5E,7E,10α,22E)-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Iodina may be available in the countries listed below.
Povidone-Iodine is reported as an ingredient of Iodina in the following countries:
International Drug Name Search
Pantoprazol beta may be available in the countries listed below.
Pantoprazole sodium (a derivative of Pantoprazole) is reported as an ingredient of Pantoprazol beta in the following countries:
International Drug Name Search
Bio Tarbun may be available in the countries listed below.
Norfloxacin is reported as an ingredient of Bio Tarbun in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
In the US, Acetylcysteine (acetylcysteine systemic) is a member of the following drug classes: antidotes, mucolytics and is used to treat Acetaminophen Overdose, Diagnostic Bronchograms and Expectoration.
US matches:
Rec.INN
R05CB01,S01XA08,V03AB23
0000616-91-1
C5-H9-N-O3-S
163
Antidote
Mucolytic agent
L-Cysteine, N-acetyl-
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Dot may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Dinitolmide is reported as an ingredient of Dot in the following countries:
Drotaverine is reported as an ingredient of Dot in the following countries:
International Drug Name Search
Butorphanol tartrate is a synthetically derived opioid agonist-antagonist analgesic of the phenanthrene series. The chemical name is (-)-17-(cyclobutylmethyl) morphinan-3, 14-diol [S-(R*,R*)] –2,3 – dihydroxybutanedioate (1:1) (salt). The molecular formula is C21H29NO2 • C4H6O6, which corresponds to a molecular weight of 477.55 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 Nasal Solution, USP is an aqueous solution of butorphanol tartrate for administration as a metered spray to the nasal mucosa. Each mL contains 10 mg of butorphanol tartrate, 6.5 mg sodium chloride, 1 mg citric acid, 1.2 mg sodium hydroxide, 0.2 mg benzethonium chloride in purified water; pH adjusted to 5.0 with sodium hydroxide and/or hydrochloric acid, if necessary. The pump reservoir must be fully primed (see PATIENT INSTRUCTIONS) prior to initial use. After initial priming each metered spray delivers an average of 1 mg of butorphanol tartrate and the 2.5 mL bottle will deliver an average of 14 to 15 doses of Butorphanol Tartrate Nasal Solution. If not used for 48 hours or longer, the unit must be reprimed (see PATIENT INSTRUCTIONS). With intermittent use requiring repriming before each dose, the 2.5 mL bottle will deliver an average of 8 to 10 doses of Butorphanol Tartrate Nasal Solution depending on how much repriming is necessary.
Butorphanol is a mixed agonist-antagonist with low intrinsic activity at receptors of the µ-opioid type (morphine-like). It is also an agonist at κ-opioid receptors.
Its interactions with these receptors in the central nervous system apparently mediate most of its pharmacologic effects, including analgesia.
In addition to analgesia, CNS effects include depression of spontaneous respiratory activity and cough, stimulation of the emetic center, miosis, and sedation. Effects possibly mediated by non-CNS mechanisms include alteration in cardiovascular resistance and capacitance, bronchomotor tone, gastrointestinal secretory and motor activity, and bladder sphincter activity.
In an animal model, the dose of butorphanol tartrate required to antagonize morphine analgesia by 50% was similar to that for nalorphine, less than that for pentazocine and more than that for naloxone.
The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity.
In human studies of butorphanol (see Clinical Trials), sedation is commonly noted at doses of 0.5 mg or more. Narcosis is produced by 10 to 12 mg doses of butorphanol administered over 10 to 15 minutes intravenously.
Butorphanol, like other mixed agonist-antagonists with a high affinity for the κ-receptor, may produce unpleasant psychotomimetic effects in some individuals.
Nausea and/or vomiting may be produced by doses of 1 mg or more administered by any route.
In human studies involving individuals without significant respiratory dysfunction,2 mg of butorphanol IV and 10 mg of morphine sulfate IV depressed respiration to a comparable degree. At higher doses, the magnitude of respiratory depression with butorphanol is not appreciably increased; however, the duration of respiratory depression is longer. Respiratory depression noted after administration of butorphanol to humans by any route is reversed by treatment with naloxone, a specific opioid antagonist (see OVERDOSAGE: Treatment).
Butorphanol tartrate demonstrates antitussive effects in animals at doses less than those required for analgesia.
Hemodynamic changes noted during cardiac catheterization in patients receiving single 0.025 mg/kg intravenous doses of butorphanol have included increases in pulmonary artery pressure, wedge pressure and vascular resistance, increases in left ventricular end diastolic pressure, and in systemic arterial pressure.
The analgesic effect of butorphanol is influenced by the route of administration. Onset of analgesia is within a few minutes for intravenous administration, within 15 minutes for intramuscular injection, and within 15 minutes for the nasal solution doses.
Peak analgesic activity occurs within 30 to 60 minutes following intravenous and intramuscular administration and within 1 to 2 hours following the nasal spray administration.
The duration of analgesia varies depending on the pain model as well as the route of administration, but is generally 3 to 4 hours with IM and IV doses as defined by the time 50% of patients required remedication. In postoperative studies, the duration of analgesia with IV or IM butorphanol was similar to morphine, meperidine, and pentazocine when administered in the same fashion at equipotent doses (see Clinical Trials). Compared to the injectable form and other drugs in this class, butorphanol tartrate nasal solution has a longer duration of action (4 to 5 hours) (see Clinical Trials).
After nasal administration, mean peak blood levels of 0.9 to 1.04 ng/mL occur at 30 to 60 minutes after a 1 mg dose (see Table 1). The absolute bioavailability of butorphanol tartrate nasal solution is 60% to 70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline), the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. The peak plasma concentrations were approximately half those achieved in the absence of the vasoconstrictor.
Following its initial absorption/distribution phase, the single dose pharmacokinetics of butorphanol by the intravenous, intramuscular, and nasal routes of administration are similar (see Figure 1).
Figure 1 Butorphanol Plasma Levels After IV, IM, and Nasal Solution Administration of 2 mg Dose
Serum protein binding is independent of concentration over the range achieved in clinical practice (up to 7 ng/mL) with a bound fraction of approximately 80%.
The volume of distribution of butorphanol varies from 305 to 901 liters and total body clearance from 52 to 154 liters/hour (see Table 1).
| ||||
| Intravenous | Nasal | |||
| Parameters | Young | Elderly | Young | Elderly |
| Tmax† (h) | 0.62 (0.32)‡ (0.15 to 1.50)§ | 1.03 (0.74) (0.25 to 3.00) | ||
| Cmax¶ (ng/mL) | 1.04 (0.40) (0.35 to 1.97) | 0.90 (0.57) (0.10 to 2.68) | ||
| AUC (inf)# (hr•ng/mL) | 7.24 (1.57) (4.40 to 9.77) | 8.71 (2.02) (4.76 to 13.03) | 4.93 (1.24) (2.16 to 7.27) | 5.24 (2.27) (0.30 to 10.34) |
| Half-life (h) | 4.56 (1.67) (2.06 to 8.70) | 5.61 (1.36) (3.25 to 8.79) | 4.74 (1.57) (2.89 to 8.79) | 6.56 (1.51) (3.75 to 9.17) |
| Absolute Bioavailability (%) | 69 (16) (44 to 113) | 61 (25) (3 to 121) | ||
| Volume of DistributionÞ (L) | 487 (155) (305 to 901) | 552 (124) (305 to 737) | ||
| Total Body Clearance (L/h) | 99 (23) (70 to 154) | 82 (21) (52 to 143) | ||
Dose proportionality for butorphanol tartrate nasal solution has been determined at steady state in doses up to 4 mg at 6 hour intervals. Steady state is achieved within 2 days. The mean peak plasma concentration at steady state was 1.8-fold (maximal 3-fold) following a single dose.
The drug is transported across the blood brain and placental barriers and into human milk (see PRECAUTIONS: Nursing Mothers).
Butorphanol is extensively metabolized in the liver. Metabolism is qualitatively and quantitatively similar following intravenous, intramuscular, or nasal administration. Oral bioavailability is only 5 to 17% because of extensive first pass metabolism of butorphanol.
The major metabolite of butorphanol is hydroxybutorphanol, while norbutorphanol is produced in small amounts. Both have been detected in plasma following administration of butorphanol, with norbutorphanol present at trace levels at most time points. The elimination half-life of hydroxybutorphanol is about 18 hours and, as a consequence, considerable accumulation (~5-fold) occurs when butorphanol is dosed to steady state (1 mg transnasally q6h for 5 days).
Elimination occurs by urine and fecal excretion. When 3H-labelled butorphanol is administered to normal subjects, most (70 to 80%) of the dose is recovered in the urine, while approximately 15% is recovered in the feces.
About 5% of the dose is recovered in the urine as butorphanol. Forty-nine percent is eliminated in the urine as hydroxybutorphanol. Less than 5% is excreted in the urine as norbutorphanol.
Butorphanol pharmacokinetics in the elderly differ from younger patients (see Table 1). The mean absolute bioavailability of butorphanol tartrate nasal solution in elderly women (48%) was less than that in elderly men (75%), young men (68%), or young women (70%). Elimination half-life is increased in the elderly (6.6 hours as opposed to 4.7 hours in younger subjects).
In renally impaired patients with creatinine clearances < 30 mL/min, the elimination half-life was approximately doubled and the total body clearance was approximately one half (10.5 hours [clearance 150 L/h] compared to 5.8 hours [clearance 260 L/h] in healthy subjects). No effect on Cmax or Tmax was observed after a single dose.
After intravenous administration to patients with hepatic impairment, the elimination half-life of butorphanol was approximately tripled and total body clearance was approximately one half (half-life 16.8 hours, clearance 92 L/h) compared to healthy subjects (half-life 4.8 hours, clearance 175 L/h). The exposure of hepatically impaired patients to butorphanol was significantly greater (about 2-fold) than that in healthy subjects. Similar results were seen after nasal administration. No effect on Cmax or Tmax was observed after a single intranasal dose.
For further recommendations refer to PRECAUTIONS: Hepatic and Renal Disease, Drug Interactions, and CLINICAL PHARMACOLOGY: Individualization of Dosage.
The effectiveness of opioid analgesics varies in different pain syndromes.
Studies with butorphanol tartrate nasal solution have been performed in postoperative (general, orthopedic, oral, cesarean section) pain, in postepisiotomy pain, in pain of musculoskeletal origin, and in migraine headache pain (see below).
The analgesic efficacy of butorphanol tartrate nasal solution was evaluated (approximately 35 patients per treatment group) in a general and orthopedic surgery trial. Single doses of butorphanol tartrate nasal solution (1 or 2 mg) and IM meperidine (37.5 or 75 mg) were compared. Analgesia provided by 1 and 2 mg doses of butorphanol tartrate nasal solution was similar to 37.5 and 75 mg meperidine, respectively, with onset of analgesia within 15 minutes and peak analgesic effect within 1 hour. The median duration of pain relief was 2.5 hours with 1 mg butorphanol tartrate nasal solution, 3.5 hours with 2 mg butorphanol tartrate nasal solution and 3.3 hours with either dose of meperidine.
In a postcesarean section trial, butorphanol tartrate nasal solution administered to 35 patients as two 1 mg doses 60 minutes apart was compared with a single 2 mg dose of butorphanol tartrate nasal solution or a single 2 mg IV dose of butorphanol tartrate injection (37 patients each). Onset of analgesia was within 15 minutes for all butorphanol tartrate regimens. Peak analgesic effects of 2 mg intravenous butorphanol tartrate injection and nasal solution were similar in magnitude. The duration of pain relief provided by both 2 mg butorphanol tartrate nasal solution regimens was approximately 4.5 hours and was greater than intravenous butorphanol tartrate injection (2.6 hours).
The analgesic efficacy of two 1 mg doses 1 hour apart of butorphanol tartrate nasal solution in migraine headache pain was compared with a single dose of 10 mg IM methadone (31 and 32 patients, respectively). Significant onset of analgesia occurred within 15 minutes for both butorphanol tartrate nasal solution and IM methadone. Peak analgesic effect occurred at 2 hours for butorphanol tartrate nasal solution and 1.5 hours for methadone. The median duration of pain relief was 6 hours with butorphanol tartrate nasal solution and 4 hours with methadone as judged by the time when approximately half of the patients remedicated.
In two other trials in patients with migraine headache pain, a 2 mg initial dose of butorphanol tartrate nasal solution followed by an additional 1 mg dose 1 hour later (76 patients) was compared with either 75 mg IM meperidine (24 patients) or placebo (72 patients). 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 butorphanol tartrate nasal solution than in the trial with the 1 mg initial dose.
Use of butorphanol tartrate nasal solution in geriatric patients, patients with renal impairment, and patients with hepatic impairment requires extra caution (see below and PRECAUTIONS).
The usual recommended dose for initial nasal administration is 1 mg (1 spray in one nostril). If adequate pain relief is not achieved within 60 to 90 minutes, an additional 1 mg dose may be given.
The initial dose sequence outlined above may be repeated in 3 to 4 hours as required after the second dose of the sequence.
For the management of severe pain, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent in the event drowsiness or dizziness occurs. In such patients additional doses should not be given for 3 to 4 hours. The incidence of adverse events is higher with an initial 2 mg dose (see Clinical Trials).
The initial dose sequence in elderly patients and patients with renal or hepatic impairment should be limited to 1 mg followed, if needed, by 1 mg 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 at 6 hour intervals (see PRECAUTIONS).
Butorphanol tartrate nasal solution is indicated for the management of pain when the use of an opioid analgesic is appropriate.
Butorphanol tartrate nasal solution is contraindicated in patients hypersensitive to butorphanol tartrate or the preservative benzethonium chloride.
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.
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 solution formulation than with the injectable formulation.
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.)
Hypotension associated with syncope during the first hour of dosing with butorphanol tartrate nasal solution has been reported rarely, particularly in patients with past history of similar reactions to opioid analgesics. Therefore, patients should be advised to avoid activities with potential risks.
As with other opioids, the use of butorphanol in patients with head injury may be associated with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, drug-induced miosis, and alterations in mental state that would obscure the interpretation of the clinical course of patients with head injuries. In such patients, butorphanol should be used only if the benefits of use outweigh the potential risks.
Butorphanol may produce respiratory depression, especially in patients receiving other CNS active agents, or patients suffering from CNS diseases or respiratory impairment.
In patients with hepatic or renal impairment, the initial dose sequence of butorphanol tartrate nasal solution should be limited to 1 mg followed, if needed, by 1 mg 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 at intervals of no less than 6 hours (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Individualization of Dosage).
Because butorphanol may increase the work of the heart, especially the pulmonary circuit, the use of butorphanol in patients with acute myocardial infarction, ventricular dysfunction, or coronary insufficiency should be limited to those situations where the benefits clearly outweigh the risk (see CLINICAL PHARMACOLOGY).
Severe hypertension has been reported rarely during butorphanol therapy. In such cases, butorphanol should be discontinued and the hypertension treated with antihypertensive drugs. In patients who are not opioid dependent, naloxone has also been reported to be effective.
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.
In healthy volunteers, the pharmacokinetics of a 1 mg dose of butorphanol administered as butorphanol tartrate nasal solution were not affected by the coadministration of a single 6 mg subcutaneous dose of sumatriptan. However, in another study in healthy volunteers, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in Cmax) when a 1 mg dose of butorphanol tartrate nasal solution was administered 1 minute after a 20 mg dose of sumatriptan nasal solution. (The two drugs were administered in opposite nostrils.) When butorphanol tartrate nasal solution was administered 30 minutes after the sumatriptan nasal solution, the AUC of butorphanol increased 11% and Cmax decreased 18%. In neither case were the pharmacokinetics of sumatriptan affected by coadministration with butorphanol tartrate nasal solution. These results suggest that the analgesic effect of butorphanol tartrate nasal solution may be diminished when it is administered shortly after sumatriptan nasal solution, but by 30 minutes any such reduction in effect should be minimal.
The safety of using butorphanol tartrate nasal solution and IMITREX® (sumatriptan) Nasal Spray during the same episode of migraine has not been established. However, it should be noted that both products are capable of producing transient increases in blood pressure.
The pharmacokinetics of a 1 mg dose of butorphanol administered as butorphanol tartrate nasal solution were not affected by the coadministration of cimetidine (300 mg QID). Conversely, the administration of butorphanol tartrate nasal solution (1 mg butorphanol QID) did not alter the pharmacokinetics of a 300 mg dose of cimetidine.
It is not known if the effects of butorphanol are altered by other 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.
The fraction of butorphanol tartrate nasal solution absorbed is unaffected by the concomitant administration of a nasal vasoconstrictor (oxymetazoline), but the rate of absorption is decreased. Therefore, a slower onset can be anticipated if butorphanol tartrate nasal solution is administered concomitantly with, or immediately following, a nasal vasoconstrictor.
No information is available about the use of butorphanol concurrently with MAO inhibitors.
(see PRECAUTIONS: Use in Ambulatory Patients, and PATIENT INSTRUCTIONS LEAFLET and MEDICATION GUIDE FOR PATIENTS).
Two-year carcinogenicity studies were conducted in mice and rats given butorphanol tartrate in the diet up to 60 mg/kg/day (180 mg/m2 for mice and 354 mg/m2 for rats). There was no evidence of carcinogenicity in either species in these studies.
Butorphanol was not genotoxic in S. typhimurium or E. coli assays or in unscheduled DNA synthesis and repair assays conducted in cultured human fibroblast cells.
Rats treated orally with 160 mg/kg/day (944 mg/m2) had a reduced pregnancy rate. However, a similar effect was not observed with a 2.5 mg/kg/day (14.75 mg/m2) subcutaneous dose.
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/m2) had a higher frequency of stillbirths than controls. Butorphanol at 30 mg/kg/oral (360 mg/m2) and 60 mg/kg/oral (720 mg/m2) also showed higher incidences of post-implantation loss in rabbits.
There are no adequate and well-controlled studies of butorphanol in pregnant women before 37 weeks of gestation. Butorphanol should be used during pregnancy only if the potential benefit justifies the potential risk to the infant.
Butorphanol tartrate nasal solution is not recommended during labor or delivery because there is no clinical experience with its use in this setting.
Although there is no clinical experience with the use of butorphanol tartrate nasal solution in nursing mothers, it should be assumed that butorphanol will appear in the milk in similar amounts following the nasal route of administration.
Butorphanol is not recommended for use in patients below 18 years of age because safety and efficacy have not been established in this population.
Of the approximately 1700 patients treated with butorphanol tartrate nasal solution in clinical studies, 8% were 65 years of age or older and 2% were 75 years or older.
Due to changes in clearance, the mean half-life of butorphanol is increased by 25% (to over 6 hours) in patients over the age of 65 years (see CLINICAL PHARMACOLOGY: Pharmacokinetics). Elderly patients may be more sensitive to the side effects of butorphanol. In clinical studies of butorphanol tartrate nasal solution, elderly patients had an increased frequency of headache, dizziness, drowsiness, vertigo, constipation, nausea and/or vomiting, and nasal congestion compared with younger patients. There are insufficient efficacy data for patients ≥ 65 years to determine whether they respond differently from younger patients.
Initially a 1 mg dose of butorphanol tartrate nasal solution should generally be used in geriatric patients and 90 to 120 minutes should elapse before administering a second 1 mg dose, if needed (see CLINICAL PHARMACOLOGY: Individualization of Dosage).
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 function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection.
A total of 2446 patients were studied in premarketing clinical trials of butorphanol. Approximately half received butorphanol tartrate injection with the remainder receiving butorphanol tartrate nasal solution. 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 were somnolence (43%), dizziness (19%), nausea and/or vomiting (13%). In long-term trials with butorphanol tartrate nasal solution 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 butorphanol tartrate nasal solution 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 with butorphanol tartrate nasal solution 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 butorphanol tartrate nasal solution 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.
Butorphanol tartrate nasal solution is 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.
In all clinical trials, less than 1% of patients using butorphanol tartrate nasal solution 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 butorphanol tartrate nasal solution. However, in one controlled clinical trial where patients with chronic pain from nonmalignant disease were treated with butorphanol tartrate nasal solution (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 butorphanol tartrate nasal solution and no patients receiving placebo. Probable withdrawal symptoms were reported in eight (2.6%) patients using butorphanol tartrate nasal solution and no patients receiving placebo in the chronic nonmalignant pain study. Most of these patients abruptly discontinued butorphanol tartrate nasal solution after extended use or high doses. Symptoms suggestive of withdrawal included anxiety, agitation, tremulousness, diarrhea, chills, sweats, insomnia, confusion, incoordination, and hallucinations.
Butorphanol tartrate has been associated with episodes of abuse and dependence. Of the cases received, there were more reports of abuse with the nasal solution formulation than with the injectable formulation.
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).
Overdose can occur due to accidental or intentional misuse of butorphanol, especially in young children who may gain access to the drug in the home.
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.
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 and in patients with hepatic or renal disease requires extra caution (see PRECAUTIONS and CLINICAL PHARMACOLOGY: Individualization of Dosage). The following doses are for patients who do not have impaired hepatic or renal function and who are not on CNS active agents.
The usual recommended dose for initial nasal administration of butorphanol tartrate nasal solution is 1 mg (1 spray in one nostril). Adherence to this dose reduces the incidence of drowsiness and dizziness. If adequate pain relief is not achieved within 60 to 90 minutes, an additional 1 mg dose may be given.
The initial dose sequence outlined above may be repeated in 3 to 4 hours as required after the second dose of the sequence.
Depending on the severity of the pain, an initial dose of 2 mg (1 spray in each nostril) may be used in patients who will be able to remain recumbent in the event drowsiness or dizziness occurs. In such patients, single additional 2 mg doses should not be given for 3 to 4 hours.
The use of butorphanol tartrate nasal solution is not recommended because it has not been studied in induction or maintenance of anesthesia.
The use of butorphanol tartrate nasal solution is not recommended as it has not been studied in labor.
Butorphanol tartrate nasal solution is an open delivery system with increased risk of exposure to health care workers.
In the priming process, a certain amount of butorphanol may be aerosolized; therefore, the pump sprayer should be aimed away from the patient or other people or animals.
The disposal of Schedule IV controlled substances must be consistent with State and Federal Regulations. The unit should be disposed of by unscrewing the cap, rinsing the bottle, and placing the parts in a waste container.
Butorphanol Tartrate Nasal Solution, USP is supplied in a child-resistant vial containing a 2.5 mL bottle of nasal spray solution (10 mg/mL) and a metered dose spray pump with protective clip and dust cover (NDC 0378-9639-43; individual unit). A Patient Instructions Leaflet and Medication Guide for patients are enclosed. On average, one bottle will deliver 14 to 15 doses if no repriming is necessary.
STORE AT CONTROLLED ROOM TEMPERATURE 15° TO 30°C (59° TO 86°F) [See USP].
Dispense in a tight, light-resistant container as defined in the USP using a child resistant closure.
PHARMACIST ASSEMBLY INSTRUCTIONS FOR BUTORPHANOL TARTRATE NASAL SOLUTION , USP: The pharmacist will assemble Butorphanol Tartrate Nasal Solution, USP prior to dispensing to the patient, according to the following instructions:
1. Open the child-resistant plastic container and remove the spray pump and solution bottle.
2. Assemble Butorphanol Tartrate Nasal Solution, USP by first unscrewing the white cap from the solution bottle and screwing the pump unit tightly onto the bottle. Make sure the clear dust cover is on the pump unit.
3. Return the Butorphanol Tartrate Nasal Solution, USP bottle to the child-resistant plastic container for dispensing to the patient with the patient instructions leaflet and medication guide for patients.
IMITREX® is the registered trademark of GlaxoSmithKline
REVISED September 2009
1172.1
BTNS:R3pm
Butorphanol Tartrate Nasal Solution, USP
CAUTION: Federal law prohibits the transfer of this drug to any person other than the patient for whom it was prescribed.
What is the most important information I should know about butorphanol tartrate
nasal solution?
What is butorphanol tartrate nasal solution?
Butorphanol tartrate nasal solution is an opioid narcotic pain reliever that is used for the relief of pain when the use of an opioid pain medication is appropriate. Butorphanol tartrate comes in the form of a nasal spray. One spray of butorphanol tartrate nasal solution is quickly absorbed in the nasal passages.
What do I need to know about using a strong opioid narcotic pain reliever such as butorphanol tartrate nasal solution?
Butorphanol tartrate nasal solution has been reported to be abused. Do not use butorphanol tartrate nasal solution more often or in larger doses than instructed by your doctor. Follow your doctor’s instructions exactly and have regular checkups with your doctor when using butorphanol tartrate nasal solution to ensure you are using butorphanol tartrate nasal solution properly.
Who should not take butorphanol tartrate nasal solution?
Butorphanol tartrate nasal solution should not be used if you have ever had an allergic reaction to the active ingredient, butorphanol, or if you are allergic to benzethonium chloride, a preservative in butorphanol tartrate nasal solution. Butorphanol tartrate nasal solution should not be used by patients less than 18 years old. Butorphanol has been found in the breast milk of women who are using butorphanol tartrate nasal solution. Therefore, butorphanol tartrate nasal solution should not be used by patients who are breastfeeding. Patients over the age of 65 years may need less butorphanol tartrate nasal solution than younger patients.
You should not use butorphanol tartrate nasal solution if you are dep
Rec.INN
J01FG02
0112362-50-2
C34-H50-N4-O9-S
690
Streptogramin antibacterial
(-)-(3R,4R,5E,10E,12E,14S,26R,26aS)-26-[2-(Diethylamino)ethylsulfonyl]-8,9,14,15,24,25,26,26a-octahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3H-21,18-nitrilo-1H,22H-pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone (JAN)
(26R,27S)-26-[[2-(Diethylamino)ethyl]sulfonyl]-26,27-dihydrovirginiamycin M₁
(3R,4R,5E,10E,12E,14S,26R,26aS)-26-[[2-(diethylamino)ethyl]sulfonyl]-8,9,14,15,24,25,26,26a-octahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3H-21,18-nitrilo-1H,22H-pyrrolo[2.1c][1,8,4,19]dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone (WHO)
(5E,10E,12E)-(3R$E,4$IR$E,14$IS,26R,26aS)-26-{[2-(Diethylamino)ethyl]sulfonyl}-8,9,14,15,24,25,26,26a-octahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3H-21,18-azeno-1H,22H-pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosene-1,7,16,22(4H,17H)-tetrone (BAN)
26-(2-diethylaminoethyl)sulfonylpristinamycin IIB
Virginiamycin M₁, 26-[[2-(diethylamino)ethyl]sulfonyl]-26,27-dihydro-, (26R,27S)- (USAN)
International Drug Name Search
Glossary
| BAN | British Approved Name |
| BANM | British Approved Name (Modified) |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
| WHO | World Health Organization |
Pediaprofen may be available in the countries listed below.
Ibuprofen is reported as an ingredient of Pediaprofen in the following countries:
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Dafalgan plus C may be available in the countries listed below.
Ascorbic Acid is reported as an ingredient of Dafalgan plus C in the following countries:
Paracetamol is reported as an ingredient of Dafalgan plus C in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
Chlortetracycline is reported as an ingredient of Cattlyst in the following countries:
Laidlomycin propionate potassium (a derivative of Laidlomycin) is reported as an ingredient of Cattlyst in the following countries:
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Doparalmin may be available in the countries listed below.
Dopamine hydrochloride (a derivative of Dopamine) is reported as an ingredient of Doparalmin in the following countries:
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