Dicyclomine Information
Dicyclomine ()
Dicyclomine () Description
Dicyclomine () hydrochloride is an antispasmodic and anticholinergic (antimuscarinic) agent available in the following form:
Each tablet, for oral administration, contains 20 mg of Dicyclomine () hydrochloride. They also contain the following inactive ingredients: Anhydrous Lactose, FD&C Blue No. 1 Lake, Lactose Monohydrate, Magnesium Stearate, and Microcrystalline Cellulose.
Chemically, Dicyclomine () hydrochloride is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethylester, hydrochloride with the structural formula:
Dicyclomine () hydrochloride occurs as a fine, white, crystalline, practically odorless powder with a bitter taste. It is soluble in water, freely soluble in alcohol and chloroform, and very slightly soluble in ether.
Dicyclomine () Clinical Pharmacology
Dicyclomine () relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism: (1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites with approximately 1/8 the milligram potency of atropine (, guinea pig ileum); and (2) a direct effect upon smooth muscle (musculotropic) as evidenced by Dicyclomine () 's antagonism of bradykinin- and histamine-induced spasms of the isolated guinea pig ileum. Atropine did not affect responses to these two agonists. studies in cats and dogs showed Dicyclomine () to be equally potent against acetylcholine (ACh)- or barium chloride (BaCl)-induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCl. Tests for mydriatic effects in mice showed that Dicyclomine () was approximately 1/500 as potent as atropine; antisialagogue tests in rabbits showed Dicyclomine () to be 1/300 as potent as atropine.
In man, Dicyclomine () is rapidly absorbed after oral administration, reaching peak values within 60-90 minutes. The principal route of elimination is via the urine (79.5% of the dose). Excretion also occurs in the feces, but to a lesser extent (8.4%). Mean half-life of plasma elimination in one study was determined to be approximately 1.8 hours when plasma concentrations were measured for 9 hours after a single dose. In subsequent studies, plasma concentrations were followed for up to 24 hours after a single dose, showing a secondary phase of elimination with a somewhat longer half-life. Mean volume of distribution for a 20 mg oral dose is approximately 3.65 L/kg suggesting extensive distribution in tissues.
In controlled clinical trials involving over 100 patients who received drug, 82% of patients treated for functional bowel/irritable bowel syndrome with Dicyclomine () hydrochloride at initial doses of 160 mg daily (40 mg q.i.d.) demonstrated a favorable clinical response compared with 55% treated with placebo. (P<.05 in these trials most of the side effects were typically anticholinergic nature table and reported by patients.>
Nine percent (9%) of patients were discontinued from the drug because of one or more of these side effects (compared with 2% in the placebo group). In 41% of the patients with side effects, side effects disappeared or were tolerated at the 160 mg daily dose without reduction. A dose reduction from 160 mg daily to an average daily dose of 90 mg was required in 46% of the patients with side effects who then continued to experience a favorable clinical response; their side effects either disappeared or were tolerated. (See .)
Dicyclomine () Indications And Usage
For the treatment of functional bowel/irritable bowel syndrome.
Dicyclomine () Warnings
In the presence of a high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). If symptoms occur, the drug should be discontinued and supportive measures instituted.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with this drug would be inappropriate and possibly harmful.
Dicyclomine () hydrochloride may produce drowsiness or blurred vision. The patient should be warned not to engage in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work while taking this drug.
Psychosis has been reported in sensitive individuals given anticholinergic drugs. CNS signs and symptoms include confusion, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, coma, euphoria, decreased anxiety, fatigue, insomnia, agitation and mannerisms, and inappropriate affect. These CNS signs and symptoms usually resolve within 12 to 24 hours after discontinuation of the drug.
Dicyclomine () IS CONTRAINDICATED IN INFANTS LESS THAN 6 MONTHS OF AGE AND IN NURSING MOTHERS. (See and and ).
Safety and efficacy of Dicyclomine () hydrochloride in children have not been established.
Dicyclomine () Precautions
General:
1. Autonomic neuropathy
2. Hepatic or renal disease
3. Ulcerative colitis - large doses may suppress intestinal motility to the point of producing a paralytic ileus and the use of this drug may precipitate or aggravate the serious complication of toxic megacolon (see )
4. Hyperthyroidism
5. Hypertension
6. Coronary heart disease
7. Congestive heart failure
8. Cardiac tachyarrhythmia
9. Hiatal hernia (see )
10. Known or suspected prostatic hypertrophy.
Investigate any tachycardia before administration of Dicyclomine () hydrochloride, since it may increase the heart rate.
With overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
Information for Patients:
Dicyclomine () hydrochloride is contraindicated in infants less than 6 months of age and in nursing mothers. (See and )
In the presence of a high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). If symptoms occur, the drug should be discontinued and a physician contacted.
Drug Interactions:
Anticholinergics antagonize the effects of antiglaucoma agents. Anticholinergic drugs in the presence of increased intraocular pressure may be hazardous when taken concurrently with agents such as corticosteroids. (See also )
Anticholinergic agents may affect gastrointestinal absorption of various drugs, such as slowly dissolving dosage forms of digoxin; increased serum digoxin concentrations may result. Anticholinergic drugs may antagonize the effects of drugs that alter gastrointestinal motility, such as metoclopramide. Because antacids may interfere with the absorption of anticholinergic agents, simultaneous use of these drugs should be avoided.
The inhibiting effects of anticholinergic drugs on gastric hydrochloric acid secretion are antagonized by agents used to treat achlorhydria and those used to test gastric secretion.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Long-term studies in animals to determine carcinogenic potential are not known to have been conducted.
In studies in rats at doses of up to 100 mg/kg/day, Dicyclomine () hydrochloride produced no deleterious effects on breeding, conception, or parturition.
Pregnancy: Teratogenic Effects:
Reproduction studies have been performed in rats and rabbits at doses up to 33 times the maximum recommended human dose based on 160 mg/day (3 mg/kg) and have revealed no evidence of impaired fertility or harm to the fetus due to Dicyclomine () . Epidemiologic studies in pregnant women with products containing Dicyclomine () hydrochloride (at doses up to 40 mg/day) have not shown that Dicyclomine () increases the risk of fetal abnormalities if administered during the first trimester of pregnancy. There are, however, no adequate and well-controlled studies in pregnant women at the recommended doses (80-160 mg/day). Because animal reproduction studies are not always predictive of human response, Dicyclomine () hydrochloride as indicated for functional bowel/irritable bowel syndrome should be used during pregnancy only if clearly needed.
Nursing Mothers:
Safety and effectiveness in pediatric patients have not been established.
Controlled clinical trials have provided frequency information for reported adverse effects of Dicyclomine () hydrochloride listed in a decreasing order of frequency. (See )
Not all of the following adverse reactions have been reported with Dicyclomine () hydrochloride. Adverse reactions are included here that have been reported for pharmacologically similar drugs with anticholinergic/antispasmodic action.
Gastrointestinal:
Central Nervous System:
Ophthalmologic:
Dermatologic/Allergic:
Genitourinary:
Cardiovascular:
The only oral dose clearly shown to be effective is 160 mg per day (in 4 equally divided doses). Since this dose is associated with a significant incidence of side effects, it is prudent to begin with 80 mg per day (in 4 equally divided doses). Depending upon the patient's response during the first week of therapy, the dose should be increased to 160 mg per day unless side effects limit dosage escalation.
If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued. Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.
Dicyclomine () How Supplied
Dicyclomine () Hydrochloride Tablets USP, 20 mg are supplied as blue, round, unscored tablets; embossed “WW 27” and are available in:
To prevent fading, avoid exposure to direct sunlight. Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Manufactured By: Eatontown, NJ 07724Revised March 200
Dicyclomine () Package Label Principal Display Panel
Dicyclomine () Hydrochloride Tabs,
USP 20mg
