BETHANECHOL 50 MG TABLET (Generic Urecholine)

Uses Advice to Patients Dosage and Administration Cautions Drug Interactions Pharmacokinetics

Uses

Urinary Retention

Bethanechol is used in the treatment of acute postoperative and postpartum nonobstructive urinary retention and neurogenic atony of the bladder with retention. Bethanechol is preferred to other parasympathomimetic drugs for these indications because of its relatively localized effect on the urinary tract and lack of adverse cardiovascular effects.

Other Uses

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.

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.

Dosage and Administration

Administration

Bethanechol chloride is administered orally. 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.

Bethanechol chloride also has been administered by subcutaneous injection. However, a parenteral dosage form no longer is commercially available in the US. The drug should not be given IV or IM. (See Cautions: Precautions and Contraindications and see Acute Toxicity.)

Dosage

Dosage of bethanechol chloride must be individualized according to the type and severity of the condition being treated.

Urinary Retention

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. 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.

Other Uses

Chronic gastroesophageal reflux (heartburn) has been treated with 25 mg of bethanechol chloride 4 times daily.

Cautions

Adverse Effects

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. (See Acute Toxicity: Treatment.)

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.

Pediatric Precautions

Safety and efficacy of bethanechol in pediatric patients have not been established.

Mutagenicity and Carcinogenicity

Long-term studies to determine the carcinogenic and mutagenic potentials of bethanechol chloride have not been performed to date.

Pregnancy, Fertility, and Lactation

Pregnancy

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.

Fertility

Animal reproduction studies have not been performed with bethanechol chloride, and it is not known whether the drug can affect reproductive capacity.

Lactation

It is not known whether bethanechol is distributed into milk. 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.

Drug Interactions

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.

Pharmacokinetics

Absorption

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.