Bethanechol (Systemic)


VA CLASSIFICATION
Primary: AU300

Commonly used brand name(s): Duvoid; Urabeth; Urecholine.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Cholinergic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Urinary retention (treatment)—Although it generally has been replaced by more effective agents, {14} bethanechol is indicated for the treatment of acute postoperative nonobstructive urinary retention and for neurogenic atony of the urinary bladder with retention. {03} {05} {08}

[Atony, postoperative, gastric (treatment)]1{02}{11}{12} or
[Megacolon, congenital (treatment)]1{12}{15}—Bethanechol is used in certain cases of gastric atony or stasis, and is also used in selected cases of congenital megacolon.

[Reflux, gastroesophageal (treatment)]—Oral bethanechol is used for treatment of gastroesophageal reflux associated with decreased pressure of the lower esophageal sphincter. {03} {04} {05} {06} {07}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    196.68

Mechanism of action/Effect:

Bethanechol is a muscarinic cholinomimetic, which acts at cholinergic receptors in the smooth muscle of the urinary bladder and gastrointestinal tract. {11} It increases the tone of the detrusor urinae muscle, {02} producing an increase in the intravesical pressure. {08} It may initiate micturition and empty the bladder; however, its clinical effectiveness in such conditions as voiding dysfunction has not been fully established. {10} It also stimulates gastric and intestinal motility, and increases lower esophageal sphincter pressure. {07} {11}


Other actions/effects:

Following oral or subcutaneous administration, cardiovascular effects and nicotinic activity are minimal. {02}

Onset of action:
{08}
Oral–Within 30 to 90 minutes.

Subcutaneous–Within 5 to 15 minutes.

Time to peak effect {08}

Oral–About 1 hour.

Subcutaneous–Within 15 to 30 minutes.

Duration of action:
{08}
Oral—Up to 6 hours, depending on dose.

Subcutaneous—About 2 hours.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

Studies have not been done in animals.

FDA Pregnancy Category C. {08}

Breast-feeding

It is not known whether bethanechol is distributed into breast milk. {08}

Pediatrics

Appropriate studies on the relationship of age to the effects of bethanechol have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Appropriate studies on the relationship of age to the effects of bethanechol have not been performed in the geriatric population. However, geriatric-specific problems that would limit the usefulness of this medication in the elderly are not expected.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Cholinergics, other, especially cholinesterase inhibitors    (concurrent use may increase the effects of either these medications or bethanechol and increase the potential for toxicity {01})


Ganglionic blocking agents, such as mecamylamine, pentolinium, and trimethaphan    (concurrent use with bethanechol may produce a critical fall in blood pressure, which is usually preceded by severe abdominal symptoms {01} {03} {08})


Procainamide or{01}{09}
Quinidine{01}{09}{13}    (concurrent use may antagonize the cholinergic effects of bethanechol)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Amylase, serum, and
Lipase, serum    (concentrations may be increased because bethanechol stimulates pancreatic secretion and constricts the sphincter of Oddi {03})


Aspartate aminotransferase, serum (AST [SGOT])    (concentrations may be increased because bethanechol impairs excretion by causing contractions in the sphincter of Oddi {03})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Asthma, bronchial, active or latent    (bethanechol may cause bronchospasm and may precipitate asthmatic attack {03} {08})


Atrioventricular conduction defects    (bethanechol may aggravate this condition by decreasing the rate of conduction {11})


» Bradycardia, pronounced{08}    (bethanechol slows heart rate and may exacerbate the condition {16})


» Hypotension    (bethanechol may reduce blood pressure {03})


» Conditions in which increased muscular activity of the gastrointestinal tract or urinary bladder might be harmful, such as:{01}{08}
Anastomosis{01}
Bladder surgery, recent{01}
Gastrointestinal resection{01}
» Conditions in which strength or integrity of gastrointestinal or bladder wall is questionable or{01}{08}
» Gastrointestinal obstruction or{03}
Urinary tract obstruction{03}    (increased muscular activity of the gastrointestinal tract or urinary bladder may be harmful {08})


» Coronary artery disease, especially occlusion{08}    (bethanechol may decrease coronary blood flow {17})


Epilepsy{08}    (although no causal relationship has been established, seizures have been reported in patients receiving bethanechol {20})


Hypertension    (bethanechol may cause sudden fall in blood pressure {08})


» Hyperthyroidism    (risk of atrial fibrillation may be increased {11})


» Peptic ulcer    (bethanechol may aggravate symptoms probably by increasing acid secretion and/or by increasing gastric motility {08} {25})


Parkinsonism{08} or
Vagotonia, marked{08}    (bethanechol may exacerbate these conditions)


» Peritonitis{01}    (bethanechol may increase cramping and exacerbate the condition and increase patient discomfort {22})


Sensitivity to bethanechol


Side/Adverse Effects

Note: In addition to those side/adverse effects needing medical attention listed below, other severe symptoms of cholinergic overstimulation such as circulatory collapse, hypotension, bloody diarrhea, shock, or sudden cardiac arrest are likely to occur in cases of hypersensitivity or overdosage, and may occur rarely after subcutaneous administration. {05}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
—more frequent with subcutaneous injection{08}    
Shortness of breath, wheezing, or tightness in chest, especially in patients with predisposition to bronchoconstriction



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
—more frequent with subcutaneous injection{08}    
Belching
    
blurred vision or change in near or distance vision
    
diarrhea
    
frequent urge to urinate

With high doses
    
CNS stimulation{23}{24} (sleeplessness, nervousness, or jitters)
    
orthostatic hypotension {08}(dizziness or lightheadedness; feeling faint)
    
parasympathetic stimulation {03}{08}(headache; increased salivation or sweating; nausea or vomiting; redness or flushing of skin or feeling of warmth; stomach discomfort or pain)
    
seizures{24}





Overdose
For specific information on the agents used in the management of bethanechol overdose, see:
   • Atropine in Anticholinergics/Antispasmodics monograph .
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Contol Center Listing ).

Treatment of overdose


Specific treatment:
Treatment consists of subcutaneous administration of atropine in doses of 500 mcg (0.5 mg) to 1 mg for adults and 10 mcg (0.01 mg) per kg of body weight for infants and children, repeated as needed every 2 hours. {08} In emergencies, intravenous injection of atropine may be used to counteract severe toxic cardiovascular or bronchoconstrictor effects of bethanechol {21}.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Bethanechol (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to bethanechol
Other medical problems, especially anastomosis, recent bladder surgery or gastrointestinal resection; asthma; pronounced bradycardia or hypotension; coronary artery disease; hyperthyroidism; peptic ulcer; peritonitis; or conditions in which the strength or integrity of the gastrointestinal or bladder wall is in question or in the presence of mechanical obstruction; or marked vagotonia

Proper use of this medication
» Taking medication on an empty stomach to minimize the possibility of nausea and vomiting, unless otherwise directed by physician

» Importance of not taking more medication than the amount prescribed

» Proper dosing
Missed dose: Taking if remembered within an hour or so; not taking if remembered after 2 or more hours; not doubling doses

» Proper storage

Precautions while using this medication
Caution when getting up suddenly from a lying or sitting position


Side/adverse effects
Signs of potential side effects, especially shortness of breath, wheezing, or tightness in chest


General Dosing Information

For oral dosage forms only
Preferably, bethanechol should be taken on an empty stomach to minimize the possibility of nausea and vomiting. {05} {08}

For parenteral dosage forms only
Bethanechol injection is for subcutaneous use only. It should not be given intravenously or intramuscularly because severe symptoms of cholinergic overstimulation may occur, and the selectivity of bethanechol's action may be decreased. {08}

After administration of bethanechol, the patient should be observed for 30 minutes to 1 hour for possible severe reactions, and a syringe containing a dose of atropine should be immediately available during this period. {08}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

BETHANECHOL CHLORIDE TABLETS USP

Usual adult and adolescent dose
Cholinergic
Oral, 25 to 50 mg three or four times a day. {26} {28}


Note: The minimum effective dose may be determined by administering 5 or 10 mg initially and repeating the same dose at one- to two-hour intervals until a satisfactory response is obtained or up to a maximum of 50 mg; {08} or by administering 10 mg initially, and repeating with 25 mg and then 50 mg at six-hour intervals until the desired response is obtained. {27}

[Treatment of gastroesophageal reflux]
Oral, 10 to 25 mg four times a day, after meals and at bedtime. {03}


Usual pediatric dose
Cholinergic
Oral, 0.6 mg per kg of body weight a day in 3 or 4 divided doses. {29} {30}

[Treatment of gastroesophageal reflux]
Oral, 0.4 mg per kg of body weight a day in 4 divided doses or 3 mg per square meter of body surface every eight hours. {29} {30}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


5 mg (Rx) [Urabeth] [Urecholine][Generic] (may be scored)


10 mg (Rx) [Duvoid (scored)] [Urabeth] [Urecholine (scored)][Generic] (may be scored)


25 mg (Rx) [Duvoid (scored)] [Urabeth] [Urecholine (scored)][Generic] (may be scored)


50 mg (Rx) [Duvoid (scored)] [Urabeth] [Urecholine (scored)][Generic] (may be scored)

Canada—


10 mg (Rx) [Duvoid (scored)] [Urecholine (scored)]


25 mg (Rx) [Duvoid (scored)] [Urecholine (scored)]


50 mg (Rx) [Duvoid (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.



Parenteral Dosage Forms

BETHANECHOL CHLORIDE INJECTION USP

Usual adult and adolescent dose
Cholinergic
Subcutaneous, 5 mg three or four times a day as needed. {08}


Note: The minimum effective dose may be determined by administering 2.5 mg initially and repeating the same dose at 15- to 30-minute intervals up to a maximum of four doses until a satisfactory response is obtained. {08}
Single doses of 10 mg may be required. However, such a large dose may cause severe side effects and should be used only after single doses of 2.5 to 5 mg have proven to be ineffective. {01}


Usual pediatric dose
Cholinergic
Subcutaneous, 0.2 mg per kg of body weight a day in 3 or 4 divided doses. {18} {19}


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


5 mg per mL (Rx) [Urecholine]

Canada—


5 mg per mL (Rx) [Urecholine]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Note: For subcutaneous use only. Discard unused portion.




Revised: 06/27/1994



References
  1. Duvoid product information, Roberts, 1992 CPS.
  1. Am Society of Hospital Pharmacists. AHFS. 1992 ed.
  1. AMA-DE, 1992 Annual Edition.
  1. Sondheimer J, Mintz H, Michaels M. Bethanechol treatment of gastroesophageal reflux in infants: effect on continuous esophageal pH records. J Pediatr 1984; 104(1): 128-31.
  1. Urecholine product information (Fross–Canada), Rec 1/91, Rev 12/80.
  1. Levin G, Fisher R. Gastroesophageal reflux disease: an update. Clin Ther 1983; 6(1): 4-16.
  1. Strickland A, Chang J. Results of treatment of gastroesophageal reflux with bethanechol. J Pediatr 1983; 103(2): 311-5.
  1. Urecholine package insert (MSD–US), Rev 5/86.
  1. Hansten P, Horn J. Drug Interactions. 6th ed. Philadelphia: Lea & Febiger, 1989.
  1. Finkbeiner A. Is bethanechol chloride clinically effective in promoting bladder emptying? A literature review. J of Urology 1985; 134: 443-9
  1. Goodman & Gilman's the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press, 1990.
  1. Panel consensus, 1983.
  1. Quinidine product information (Danbury Pharmacal–US), Rec 1/89, Rev 3/86.
  1. Panel consensus, 1992 revision.
  1. Panel consensus, 1992 revision.
  1. Panelists comments, 1992 revision.
  1. Panelists comments, 1992 revision.
  1. Rowe P, editor. The Harriet Lane Handbook. 11th ed. Chicago: Year Book Medical Publishers, 1987: 137.
  1. Panelist comment, 1992 revision.
  1. Bethanechol Urecholine product information (MSD–US), Rev 5/92, Rec 11/92.
  1. Panel consensus, 1992.
  1. Panelists comments, 1992.
  1. Penn R, Martin E, Wilson R, et al. Intraventricular bethanechol infusion for Alzheimer's disease: results of double-blind and escalating-dose trials. Neurology 1988; 38: 219-22.
  1. Read S, Frazee J, Shapira J, et al. Intracerebroventricular bethanechol for Alzheimer's disease. Arch Neurol 1990; 47: 1025-30.
  1. Panelists' comments, 1993.
  1. Panelists' comments, 1993.
  1. Panelist comment, 1993.
  1. Wein A. Lower urinary tract function and pharmacologic management of lower urinary tract dysfunction. Urol Clinics of N Am 1987; 14(2): 289.
  1. Panelist comment, 1993.
  1. Greene M, editor. The Harriet Lane Handbook. 12th ed. Chicago: Mosby Year Book, 1991: 158.
Hide
(web1)