URECHOLINE* (Bethanechol Chloride), a cholinergic agent, is a synthetic ester which is structurally and pharmacologically related to acetylcholine.
It is designated chemically as 2-[(aminocarbonyl)oxy]- N, N, N- trimethyl-1-propanaminium chloride. Its empirical formula is C 7 H 17 ClN 2 O 2 and its structural formula is:
It is a white, hygroscopic crystalline compound having a slight amine-like odor, freely soluble in water, and has a molecular weight of 196.68.
URECHOLINE is supplied as 5 mg, 10 mg, 25 mg, and 50 mg tablets for oral use. Inactive ingredients in the tablets are calcium phosphate, lactose, magnesium stearate, and starch. Tablets URECHOLINE 10 mg also contain FD&C Red 3 and FD&C Red 40. Tablets URECHOLINE 25 mg and 50 mg also contain D&C Yellow 10 and FD&C Yellow 6.
URECHOLINE is also supplied as a sterile solution for subcutaneous use only. The sterile solution is essentially neutral. Each milliliter contains bethanechol chloride, 5.15 mg, and Water for Injection, q.s., 1 mL. It may be autoclaved at 120° C for 20 minutes without discoloration or loss of potency.
* Registered trademark of MERCK & CO., INC.
Bethanechol chloride acts principally by producing the effects of stimulation of the parasympathetic nervous system. It increases the tone of the detrusor urinae muscle, usually producing a contraction sufficiently strong to initiate micturition and empty the bladder. It stimulates gastric motility, increases gastric tone, and often restores impaired rhythmic peristalsis.
Stimulation of the parasympathetic nervous system releases acetylcholine at the nerve endings. When spontaneous stimulation is reduced and therapeutic intervention is required, acetylcholine can be given, but it is rapidly hydrolyzed by cholinesterase, and its effects are transient. Bethanechol chloride is not destroyed by cholinesterase and its effects are more prolonged than those of acetylcholine.
Effects on the GI and urinary tracts sometimes appear within 30 minutes after oral administration of bethanechol chloride, but more often 60-90 minutes are required to reach maximum effectiveness. Following oral administration, the usual duration of action of bethanechol is one hour, although large doses (300-400 mg) have been reported to produce effects for up to six hours. Subcutaneous injection produces a more intense action on bladder muscle than does oral administration of the drug.
Because of the selective action of bethanechol, nicotinic symptoms of cholinergic stimulation are usually absent or minimal when orally or subcutaneously administered in therapeutic doses, while muscarinic effects are prominent. Muscarinic effects usually occur within 5-15 minutes after subcutaneous injection, reach a maximum in 15-30 minutes, and disappear within two hours. Doses that stimulate micturition and defecation and increase peristalsis do not ordinarily stimulate ganglia or voluntary muscles. Therapeutic test doses in normal human subjects have little effect on heart rate, blood pressure, or peripheral circulation.
Bethanechol chloride does not cross the blood-brain barrier because of its charged quaternary amine moiety. The metabolic fate and mode of excretion of the drug have not been elucidated.
A clinical study** was conducted on the relative effectiveness of oral and subcutaneous doses of bethanechol chloride on the stretch response of bladder muscle in patients with urinary retention. Results showed that 5 mg of the drug given subcutaneously stimulated a response that was more rapid in onset and of larger magnitude than an oral dose of 50 mg, 100 mg, or 200 mg. All the oral doses, however, had a longer duration of effect than the subcutaneous dose. Although the 50 mg oral dose caused little change in intravesical pressure in this study, this dose has been found in other studies to be clinically effective in the rehabilitation of patients with decompensated bladders.
**Diokno, A. C.; Lapides, J., Urol. 10: 23-24, July 1977.
For the treatment of acute postoperative and postpartum nonobstructive (functional) urinary retention and for neurogenic atony of the urinary bladder with retention.
Hypersensitivity to URECHOLINE tablets or to any component of URECHOLINE injection, hyperthyroidism, peptic ulcer, latent or active bronchial asthma, pronounced bradycardia or hypotension, vasomotor instability, coronary artery disease, epilepsy, and parkinsonism.
URECHOLINE should not be employed when the strength or integrity of the gastrointestinal or bladder wall is in question, or in the presence of mechanical obstruction; when increased muscular activity of the gastrointestinal tract or urinary bladder might prove harmful, as following recent urinary bladder surgery, gastrointestinal resection and anastomosis, or when there is possible gastrointestinal obstruction; in bladder neck obstruction, spastic gastrointestinal disturbances, acute inflammatory lesions of the gastrointestinal tract, or peritonitis; or in marked vagotonia.
The sterile solution is for subcutaneous use only. It should never be given intramuscularly or intravenously. Violent symptoms of cholinergic over-stimulation, such as circulatory collapse, fall in blood pressure, abdominal cramps, bloody diarrhea, shock, or sudden cardiac arrest are likely to occur if the drug is given by either of these routes. Although rare, these same symptoms have occurred after subcutaneous injection, and may occur in cases of hypersensitivity or overdosage.
In urinary retention, if the sphincter fails to relax as URECHOLINE contracts the bladder, urine may be forced up the ureter into the kidney pelvis. If there is bacteriuria, this may cause reflux infection.
Information for Patients
URECHOLINE tablets should preferably be taken one hour before or two hours after meals to avoid nausea or vomiting. Dizziness, lightheadedness or fainting may occur, especially when getting up from a lying or sitting position.
Special care is required if this drug is given to patients receiving ganglion blocking compounds because a critical fall in blood pressure may occur. Usually, severe abdominal symptoms appear before there is such a fall in the blood pressure.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the effects upon fertility, mutagenic or carcinogenic potential of URECHOLINE.
Pregnancy Category C. Animal reproduction studies have not been conducted with URECHOLINE. It is also not known whether URECHOLINE can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. URECHOLINE should be given to a pregnant woman only if clearly needed.
It is not known whether this drug is secreted in human milk. Because many drugs are secreted in human milk and because of the potential for serious adverse reactions from URECHOLINE in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Adverse reactions are rare following oral administration of bethanechol, but are more common following subcutaneous injection. Adverse reactions are more likely to occur when dosage is increased.
The following adverse reactions have been observed: Body as a Whole: malaise Digestive: abdominal cramps or discomfort, colicky pain, nausea and belching, diarrhea, borborygmi, salivation; Renal: urinary urgency; Nervous System: headache; Cardiovascular a fall in blood pressure with reflex tachycardia, vasomotor response; Skin: flushing producing a feeling of warmth, sensation of heat about the face, sweating; Respiratory: bronchial constriction, asthmatic attacks; Special Senses: lacrimation, miosis.
Causal Relationship Unknown: The following adverse reactions have been reported, and a causal relationship to therapy with URECHOLINE has not been established: Body as a Whole: hypothermia Nervous System: seizures.
Early signs of overdosage are abdominal discomfort, salivation, flushing of the skin ("hot feeling"), sweating, nausea and vomiting.
Atropine is a specific antidote. The recommended dose for adults is 0.6 mg (1/100 grain). Repeat doses can be given every two hours, according to clinical response. The recommended dosage in infants and children up to 12 years of age is 0.01 mg/kg (to a maximum single dose of 0.4 mg) repeated every two hours as needed until the desired effect is obtained, or adverse effects of atropine preclude further usage. Subcutaneous injection of atropine is preferred except in emergencies when the intravenous route may be employed.
When URECHOLINE is administered subcutaneously, a syringe containing a dose of atropine sulfate should always be available to treat symptoms of toxicity.
The oral LD 50 of bethanechol chloride is 1510 mg/kg in the mouse.
Dosage and route of administration must be individualized, depending on the type and severity of the condition to be treated.
Preferably give the drug when the stomach is empty. If taken soon after eating, nausea and vomiting may occur.
Oral --The usual adult dosage is 10 to 50 mg three or four times a day. The minimum effective dose is determined by giving 5 or 10 mg initially and repeating the same amount at hourly intervals until satisfactory response occurs or until a maximum of 50 mg has been given. The effects of the drug sometimes appear within 30 minutes and usually within 60 to 90 minutes. They persist for about an hour.
Subcutaneous --The usual dose is 1 mL (5.15 mg), although some patients respond satisfactorily to as little as 0.5 mL (2.575 mg). The minimum effective dose is determined by injecting 0.5 mL (2.575 mg) initially and repeating the same amount at 15 to 30 minute intervals to a maximum of four doses until satisfactory response is obtained, unless disturbing reactions appear. The minimum effective dose may be repeated thereafter three or four times a day as required.
Rarely, single doses up to 2 mL (10.30 mg) may be required. Such large doses may cause severe reactions and should be used only after adequate trial of single doses of 0.5 to 1 mL (2.575 to 5.15 mg) has established that smaller doses are not sufficient.
URECHOLINE is usually effective in 5 to 15 minutes after subcutaneous injection.
If necessary, the effects of the drug can be abolished promptly by atropine (see OVERDOSAGE ).
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Tablets URECHOLINE are round, compressed tablets, scored on one side. They are supplied as follows:
No. 7785--5 mg, white in color, coded MSD 403 on one side and URECHOLINE on the other.
NDC 0006-0403-68 in bottles of 100.
No. 7787--10 mg, pink in color, coded MSD 412 on one side and URECHOLINE on the other.
NDC 0006-0412-68 in bottles of 100
(6505-00-616-7856 10 mg 100's).
No. 7788--25 mg, yellow in color, coded MSD 457 on one side and URECHOLINE on the other.
NDC 0006-0457-68 in bottles of 100
(6505-00-912-7440 25 mg, 100's).
No. 7790 -- 50 mg, yellow in color, coded MSD 460 on one side and URECHOLINE on the other.
NDC 0006-0460-68 in bottles of 100.
No. 7786--Injection URECHOLINE, 5.15 mg per mL, is a clear, colorless solution, and is supplied as follows:
NDC 0006-7786-29 in box of 6 × 1 mL vials
(6505-00-616-8947 in box of 6 × 1 mL vials).
Store Tablets URECHOLINE in a tightly-closed container. Avoid storage at temperatures above 40°C (104°F).
Avoid storage of Injection URECHOLINE at temperatures below -20°C (-4°F) and above 40°C (104°F).
7875834 Issued August 1997
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