Antispasmodic
Hyoscine butylbromide is an antispasmodic agent which relaxes the smooth muscle of the gastrointestinal, biliary and urinary tracts. It is believed to act predominantly at the parasympathetic ganglia in the walls of the viscera of these organs. Structurally, hyoscine exists as a quaternary ammonium compound and as a single positively charged cation throughout the entire pH range. In the rat, hyoscine butylbromide concentrates in the gastrointestinal tract, liver and kidney tissues. The high tissue affinity of the substance is further reflected in the extremely short distribution half-life (t1/2 a) in the plasma of approximately 2 to 3 minutes. Protein binding in the human plasma occurs at 8 to 13 % and in a 4.4% human serum albumin solution at 3 to 11%. Hyoscine butylbromide does not readily cross the blood brain barrier. A high portion of the absorbed hyoscine butylbromide (14C) undergoes elimination in an unchanged form within the first few hours of administration in man and animals. Later in elimination, the metabolized portion predominates. In man, following the intravenous administration of 14C-labelled substance, the elimination followed a 3-phase course: t1/2a=3.5 min, t1/2b=0.8 hours; t1/2=14.0 hours. Metabolites from rat urine detected in quantities ranging from 4 to 44% include 3 main metabolites (phenyl acetic acid-scopine ester- butochloride; 4-hydroxy tropic acid-scopine ester-butochloride; and scopine butobromide) and four minor metabolites (including AD 12 and Ba 790).
HYOSCINE BUTYLBROMIDE INJECTION is indicated for the relief of acute genitourinary or gastrointestinal spasm (e.g., renal or biliary colic), or to produce smooth muscle relaxation prior to radiological procedures such as pyelography or other diagnostic procedures where spasm may be a problem (e.g., gastroduodenal endoscopy).
Hypersensitivity to hyoscine butylbromide or atropinics (see WARNINGS) or to any of the product excipients. Parenteral administration of hyoscine butylbromide is contraindicated in patients with glaucoma, prostatic hypertrophy with urinary retention, stenotic lesions of the gastrointestinal tract, tachycardia, angina, cardiac failure and megacolon.
Therapy should be discontinued if the patient reports any unusual visual disturbances or pressure pain within the eye. Patients intolerant of one belladonna alkaloid or derivative may also be intolerant of other belladonna alkaloids or derivatives such as hyoscine butylbromide.
General: Hyoscine butylbromide should be used with caution in patients with prostatic enlargement. Hyoscine butylbromide may precipitate or aggravate urinary retention in patients with the following conditions: nonobstructive prostatic hypertrophy, urinary retention (or the predisposition to) or obstructive uropathy such as a bladder neck obstruction due to prostatic hypertrophy (see CONTRAINDICATIONS).
Occupational Hazards
: The parenteral administration of hyoscine butylbromide, particularly of higher doses, has been reported to cause transient disturbances of accommodation which recede spontaneously. Therefore, patients should be cautioned about driving or operating machinery after receiving hyoscine butylbromide injection.
As large doses of anticholinergics/systemic antispasmodics may cause an increase in heart rate, due care is necessary in patients with cardiac disease, especially cardiac arrhythmias, congestive heart failure, coronary artery disease and mitral stenosis. The increase in heart rate may also be undesirable in patients with unstable cardiovascular status in an acute hemorrhage situation. Exercise caution in patients with reflux esophagitis or gastrointestinal tract obstructive disease (i.e., achalasia and pyloroduodenal stenosis) due to the ability of anticholinergics/systemic antispasmodics to decrease smooth muscle motility and tone resulting in gastric retention. Anticholinergics may aggravate hiatal hernia associated with reflux esophagitis, myasthenia gravis or pyloric obstruction. In patients with ulcerative colitis, large anticholinergic doses may suppress intestinal motility, possibly causing paralytic ileus or resulting in obstruction; also, use may precipitate or aggravate toxic megacolon. The mydriatic effect of anticholinergics/systemic antispasmodics may result in increased intraocular pressure. In patients with angle-closure glaucoma or with this predisposition, anticholinergics/systemic antispasmodics may precipitate an acute angle-closure glaucoma attack (see CONTRAINDICATIONS).
Use in Geriatrics
: Geriatric patients are especially susceptible to the anticholinergic side effects of constipation, dryness of mouth and urinary retention (especially in males). If these side effects continue or persevere, discontinuation of medication should be considered.
Due care is necessary when anticholinergics are administered to geriatric patients due to the danger of precipitating undiagnosed glaucoma. Administration of anticholinergics/systemic antispasmodics to elderly patients with intestinal atony or in debilitated patients may result in obstruction.
Use in Pregnancy
: Safety during pregnancy has not yet been established. Limited preclinical data has not indicated a hazard; nevertheless, the usual precautions regarding the use of drugs during pregnancy, especially during the first trimester, should be observed.
Use During Lactation
: No specific studies have been conducted on the excretion of this drug in breast milk. The benefits of hyoscine butylbromide use during lactation should therefore be weighed against possible effects on the infant.
Use in Children
: Hyoscine butylbromide is not currently recommended for use in children.
Drug Interactions
: As hyoscine butylbromide can reduce the motility and secretory activity of the gastrointestinal system, the systemic absorption and pharmacologic effects of other oral medications may be delayed.
Tricyclic antidepressants, quinidine and amantadine can potentiate the anticholinergic effect of parenterally administered hyoscine butylbromide. Concurrent use with MAO inhibitors may result in intensified anticholinergic side effects of hyoscine butylbromide. Also, concurrent use of MAO inhibitors may block detoxification of anticholinergics, thus potentiating their action. Concurrent use with anticholinergics may intensify anticholinergic effects. Concurrent use with antacids or absorbent antidiarrheals may reduce the absorption of anticholinergics, resulting in decreased therapeutic effectiveness. Anticholinergics such as hyoscine butylbromide should be given at least 1 hour before these medications. The severity of potassium chloride induced gastrointestinal lesions may increase with concurrent anticholinergic therapy.
A slight increase in pulse rate may occur when hyoscine butylbromide is administered intravenously. In some cases hypersensitivity reactions, such as urticaria, angioedema and fixed drug eruptions have been described. Following parenteral administration, very rare cases of shock reactions have been observed. Parenteral administration, especially of large doses, may occasionally cause a transient disturbance of accommodation which recedes spontaneously. The following effects have been reported rarely:Body as a Whole: anaphylactic shock, anaphylactoid reaction; Heart Rate and Rhythm: tachycardia, pulse rate increased; Autonomic Nervous system: hypotension;
Gastrointestinal System Disorders
: diarrhea, nausea;
Skin and Appendages Disorders: urticaria, rash, angioedema, fixed drug eruptions; Vision Disorders: retinal pigmentation, abnormal accommodation, glaucoma.
Symptoms
Single oral doses of up to 590 mg and quantities of active drug up to 1,090 mg within 5 hours have produced dry mouth, tachycardia, slight drowsiness and transient visual disorders. Other symptoms which occurred in animals and which may be encountered in humans include: shock, Cheyne-Stokes respiration, respiratory paralysis, clonic spasms, paresis of the striated muscle, coma, paralytic ileus and cystoparalysis.
Treatment
In the case of an oral overdose, perform gastric lavage with activated charcoal followed by magnesium sulfate (15%). Hyoscine butylbromide overdose symptoms respond to parasympathomimetics. For patients with glaucoma, administer pilocarpine locally. Other overdosage symptoms should be treated with standard supportive therapy.
Individual response to hyoscine butylbromide may vary and doses should be adjusted accordingly.
One-half (10 mg/0.5 mL) to one vial (20 mg/1 mL) administered parenterally by intramuscular, subcutaneous or intravenous routes, at an injection rate of 1 mL/min. No dilution of the vial contents is necessary prior to administration. The maximum dose should not exceed 100 mg/day (5 vials). The rapid action of injected hyoscine butylbromide is advantageous in acutely ill patients and in those situations where prompt spasmolytic activity facilitates diagnostic procedures such as radiological examinations. Hyoscine butylbromide may also be used intramuscularly 10 to 15 minutes before radiological examinations of the stomach to slow peristaltic movements.
Drug Substance
Proper Name
: Hyoscine butylbromide
Chemical Name: (1S,3s,5R,6R,7S,8r)-6,7-epoxy-8-butyl-3-[(S)-tropoyloxy] tropanium bromide
Structural Formula:
Molecular Formula: C21H30BrNO4 Molecular Weight: 440.4 Description: A white or almost white, odourless or almost odourless, crystalline powder, soluble 1 to 1 in water, 1 in 50 of alcohol, and 1 in 5 of chloroform. A 10% solution in water has a pH of 5.5 to 6.5. The melting point is approximately 139-141degC.
Composition
Each mL contains: hyoscine butylbromide 20 mg, sodium chloride 6.6 mg, hydrochloric acid and/or sodium hydroxide to adjust pH, and water for injection.
Stability and Storage Recommendations
Store between 15 and 30degC. Protect from light.
HYOSCINE BUTYLBROMIDE INJECTION is available as a 20 mg/mL solution of hyoscine butylbromide in 1 mL preservative-free, single use, amber glass vials, boxes of 10. Discard any unused portion.
Hyoscine butylbromide is an anticholinergic and acts as a smooth muscle relaxant in the gastrointestinal tract. Due to its low lipid solubility, hyoscine butylbromide should not cross the blood-brain barrier, thus reducing the risk of central nervous system side effects. In five conscious beagle dogs provided with ileal or colonic fistulas, intravenous hyoscine butylbromide (10 to 100 mg/kg) depressed the phasic motility index and other motility parameters such as intestinal tonus and contraction frequency. This effect is attributed to blockage of muscarinic receptors in the gut. Application of hyoscine butylbromide directly into the fistula (300 to 3,000 mg/kg) caused a long-lasting potent inhibition of phasic motility index. Other systemic manifestations of muscarinic inhibition, such as increased heart rate, were evident with intravenous administration, but not with direct intraluminal application. Hyoscine butylbromide present in the intestine is poorly absorbed but depresses intestinal reflex by a local action on smooth muscle cells. In another study, intravenously administered hyoscine butylbromide produced no effect on the gastrointestinal motility of conscious dogs during the period of motor quiescence in the interdigestive state and suppressed the activity of the gastrointestinal tract during the digestive state. Hyoscine butylbromide is a synthetic parasympathicolytic agent which exerts an atropine-like action without affecting the central nervous system. It affects the smooth muscle of the bronchi as well as that of the digestive tract, but not that of the blood vessels. Hyoscine butylbromide also exerts action on the exocrine glands. In the eye, the ciliary muscle which has an exclusively parasympathetic innervation, is paralyzed to some extent.
Acute Toxicity:
| Species | Route | LD 50 (mg/kg) |
| mouse | oral | 1170 mg/kg |
| intravenous | 20 mg/kg | |
| intraperitoneal | 72.5 mg/kg | |
| subcutaneous | 310 mg/kg | |
| rat | oral | 1040 mg/kg |
| intravenous | 24.0 mg/kg | |
| intraduodenal | 180 mg/kg | |
| subcutaneous | 510 mg/kg | |
| guinea pig | subcutaneous | 155 mg/kg |
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