Bethanechol is a cholinergic drug that is related to acetylcholine.101
Bethanechol is used in the treatment of acute postoperative and postpartum nonobstructive urinary retention and neurogenic atony of the bladder with retention.101
Bethanechol has been used to prevent and treat phenothiazine-induced bladder dysfunction† and to antagonize the bladder and salivary gland inhibition caused by tricyclic antidepressants (e.g., amitriptyline, imipramine, protriptyline)†. Bethanechol should be used with extreme caution, if at all, to antagonize the effects of ganglionic blocking agents on the GI and urinary tracts because severe hypotension may result. (See Drug Interactions.)
Bethanechol has been recommended in the past for treatment of selected cases of postoperative GI atony† and gastric retention†; adynamic ileus† resulting from trauma†, infection†, toxic states†, or psychic causes†; postoperative abdominal distention†; and congenital megacolon†. However, the effectiveness of the drug for these indications has not been established.
Bethanechol has been shown to produce symptomatic improvement and decrease antacid use in some patients with chronic refractory heartburn† and gastroesophageal reflux disease (GERD), including vagotomized and antrectomized patients. However, use of the drug has decreased because of adverse CNS effects, and acid suppression therapy with other agents (e.g., proton-pump inhibitors, histamine H2-receptor antagonists) is principally used.105
Bethanechol has been shown to increase eye moisture, reduce gastric distention and vomiting, and improve esophageal motility and bladder control in a limited number of children with familial dysautonomia†. The long-term effects of the drug on children are unknown.
Bethanechol has been used as a diagnostic test for cystic infantile fibrosis† (although pilocarpine generally is considered to be the drug of choice) and for neurogenic bladder†. The drug has been used in diagnosing flaccid or atonic neurogenic bladder disease and in restoring bladder function in some of these patients.
Bethanechol chloride is administered orally.101 Bethanechol chloride should be administered on an empty stomach (e.g., 1 hour before or 2 hours after a meal) to minimize nausea and vomiting.101
Bethanechol chloride also has been administered by subcutaneous injection. However, a parenteral dosage form no longer is commercially available in the US.
Bethanechol chloride tablets should be stored in tight, light-resistant containers at a temperature of 20-25°C (excursions permitted between 15-30°C).101
Extemporaneously Compounded Oral Liquid
An extemporaneously compounded oral liquid formulation of bethanechol chloride 5 mg/mL has been prepared using the commercially available tablets and various commercially available vehicles.106
Standardized concentrations for an extemporaneously prepared oral liquid formulation of bethanechol have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 252Multidisciplinary expert panels were convened to determine recommended standard concentrations. 252Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 252 For additional information on S4S (including updates that may be available), see[Web]252 .
Concentration Standards |
|---|
5 mg/mL |
Dosage of bethanechol chloride must be individualized according to the type and severity of the condition being treated.101
For the treatment of acute postoperative or postpartum nonobstructive urinary retention or neurogenic atony of the bladder with retention, the manufacturer recommends an adult oral dosage of 10-50 mg of bethanechol chloride 3-4 times daily.101 The minimum effective oral dose can be determined by giving 5 or 10 mg initially and repeating the initial dose at hourly intervals until a satisfactory response occurs or a maximum of 50 mg has been given.101
Chronic gastroesophageal reflux† (heartburn) has been treated with 25 mg of bethanechol chloride 4 times daily.
Adverse effects are rare following oral administration of bethanechol, but have been more common following subcutaneous injection (a parenteral dosage form no longer is commercially available in the US). Adverse effects are most likely to occur when dosage is increased and may consist of abdominal cramps or discomfort, colicky pain, flushing of the skin producing a feeling of warmth or sensation of heat about the face, sweating, lacrimation, salivation, malaise, headache, diarrhea, nausea and vomiting, bronchial constriction, asthmatic attacks, belching, borborygmi, urinary urgency, or miosis. In patients with urinary retention, urine may be forced up the ureter into the renal pelvis if the sphincter fails to relax as bethanechol contracts the bladder. If there is bacteriuria, this may cause reflux infection. Miliaria crystallina occurred in a diabetic patient after several doses of bethanechol were administered subcutaneously.
Bethanechol may produce a slight, transient decrease in diastolic blood pressure with mild reflex tachycardia. Patients with hypertension may react to the drug with a precipitous fall in blood pressure. Short periods of atrial fibrillation have occurred in hyperthyroid patients following administration of cholinergic drugs. Although a causal relationship to bethanechol has not been established, hypothermia and seizures have been reported during therapy with the drug.
Precautions and Contraindications
A severe cholinergic reaction is likely to occur if bethanechol injection is given IV or IM; for this reason, the drug is contraindicated for IM or IV use (a parenteral dosage form no longer is commercially available in the US). Severe cholinergic reactions also have occurred rarely after subcutaneous injection and in cases of hypersensitivity or overdosage. Atropine sulfate should be readily available to counteract toxic reactions which may occur during treatment with bethanechol.
Bethanechol is contraindicated in patients with hyperthyroidism, peptic ulcer, or latent or active bronchial asthma. The drug also is contraindicated in patients with coronary artery disease, mechanical obstruction of the GI tract or bladder neck, marked vagotonia, epilepsy, parkinsonism, spastic GI disturbances, peritonitis or acute inflammatory conditions of the GI tract, pronounced bradycardia or hypotension, or vasomotor instability. Bethanechol should not be used when the strength or integrity of the GI or bladder wall is in question, or when increased muscular activity of the GI or urinary tract might prove harmful, as in recent urinary bladder surgery or GI resection or anastomosis. Bethanechol also is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.
Safety and efficacy of bethanechol in pediatric patients have not been established.101
Pregnancy, Fertility, and Lactation
Animal reproduction studies have not been performed with bethanechol chloride, and it is not known whether the drug can cause fetal harm when administered to pregnant women. Bethanechol should be used during pregnancy only when clearly needed.101
It is not known whether bethanechol is distributed into milk.101 Because many drugs are distributed into milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or bethanechol, taking into account the importance of the drug to the woman.101
Bethanechol should not be used concomitantly with other cholinergic drugs or anticholinesterase agents (e.g., neostigmine), because of the possibility of additive effects and increased toxicity. In combination with ganglionic blocking agents, bethanechol may produce a critical fall in blood pressure, usually preceded by severe abdominal symptoms.
Atropine antagonizes the effects of bethanechol and this interaction is used to therapeutic advantage to counteract the symptoms of bethanechol toxicity. Epinephrine and other sympathomimetic amines antagonize the effects of bethanechol at sites where adrenergic and cholinergic stimulation produce opposing effects. Quinidine and procainamide also may antagonize the effects of bethanechol.
Bethanechol is a cholinergic drug that acts primarily by directly stimulating cholinergic receptors, although the drug also stimulates ganglia to a lesser extent. Bethanechol is more stable to hydrolysis by cholinesterase than is acetylcholine and, therefore, has a more prolonged duration of action than does acetylcholine. The effects of therapeutic doses of orally or subcutaneously administered bethanechol are almost exclusively muscarinic; the drug has little, if any, nicotinic activity and its cardiovascular effects are negligible when given by these routes.
The most prominent pharmacologic effects of the drug are increased tone and peristaltic activity in the stomach and intestines, increased esophageal peristalsis and an increase in the resting pressure of the lower esophageal sphincter, increased pancreatic and GI secretion, contraction of the detrusor muscle of the urinary bladder, decreased bladder capacity, and an increase in the frequency of ureteral peristaltic waves. Bethanechol produces much more vigorous contractions in denervated smooth muscle than in normally innervated muscle, and this response was the basis of a diagnostic test for neurogenic bladder using subcutaneous administration of injectable bethanechol (no longer commercially available in the US). Some generalized cholinergic effects such as bronchial constriction, miosis, increased salivation and sweating, lacrimation, and increased bronchial secretion may occur with high doses or following IM or IV administration, but bethanechol acts primarily on the GI and urinary tracts following oral or subcutaneous administration. Bethanechol does not exert CNS effects in usual dosage.
Bethanechol chloride is poorly absorbed from the GI tract. In one patient, an oral dose of 200 mg of bethanechol chloride was required to produce the same response on bladder musculature as that which occurred after 10 mg was given subcutaneously. Effects on the GI and urinary tracts sometimes appear within 30 minutes after oral administration of the drug, but more often 60-90 minutes are required to reach maximum effectiveness. Following oral administration, the usual duration of action of bethanechol is 1 hour, although large (300-400 mg) doses have been reported to produce effects for up to 6 hours. Subcutaneous injection produces a more intense action on bladder muscle than does oral administration of the drug. However, an injectable dosage form no longer is commercially available in the US. Muscarinic effects occur within 5-15 minutes after subcutaneous injection, reach a maximum in 15-30 minutes, and disappear within 2 hours.
Bethanechol does not cross the blood-brain barrier in usual doses, but its distribution into other body fluids is largely unknown.
The metabolic fate and mode of excretion of the drug have not been elucidated.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 5 mg* | Bethanechol Chloride Tablets | |
10 mg* | Bethanechol Chloride Tablets | |||
25 mg* | Bethanechol Chloride Tablets | |||
50 mg* | Bethanechol Chloride Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
100. Guerra MF, Ives TJ. Bethanechol and hypothermia. Ann Intern Med . 1983; 99:279-80. [PubMed 6136246]
101. Amneal Pharmaceuticals. Bethanechol chloride tablets prescribing information. Bridgewater, NJ; 2023 Dec.
103. Merck, West Point, PA: Personal communication.
105. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol . 2005; 100:190-200. [PubMed 15654800]
106. Allen LV Jr, Erickson MA. Stability of bethanechol chloride, pyrazinamide, quinidine sulfate, rifampin, and tetracycline hydrochloride in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1998 Sep 1;55(17):1804-9. doi: 10.1093/ajhp/55.17.1804. PMID: 9775343.
252. ASHP. Standardize 4 Safety: compounded oral liquid standards. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]