Bentyl (Dicyclomine Hydrochloride) - Description and Clinical Pharmacology

DESCRIPTION

BENTYL is an antispasmodic and anticholinergic (antimuscarinic) agent available in the following forms:

1. BENTYL capsules for oral use contain 10 mg dicyclomine hydrochloride USP. BENTYL 10 mg capsules also contain inactive ingredients: calcium sulfate, corn starch, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lactose, magnesium stearate, pregelatinized corn starch, and titanium dioxide.
2. BENTYL tablets for oral use contain 20 mg dicyclomine hydrochloride USP. BENTYL 20 mg tablets also contain inactive ingredients: acacia, dibasic calcium phosphate, corn starch, FD&C Blue No. 1, lactose, magnesium stearate, pregelatinized corn starch, and sucrose.
3. BENTYL syrup for oral use contains 10 mg dicyclomine hydrochloride USP in each 5 mL (1 teaspoonful). BENTYL syrup also contains inactive ingredients: citric acid, D&C Red No. 33, FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, flavors, glucose, methylparaben, propylene glycol, propylparaben, saccharin sodium, and water.
4. BENTYL injection is a sterile, pyrogen-free, aqueous solution for intramuscular injection (NOT FOR INTRAVENOUS USE).

Ampule. 20 mg/2 mL (10 mg/mL) - Each mL contains 10 mg dicyclomine hydrochloride USP in sterile water for injection, made isotonic with sodium chloride.
Chemically, BENTYL (dicyclomine hydrochloride) is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethyl ester, hydrochloride with the following chemical structure:

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.

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 (in vitro, 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. In vivo studies in cats and dogs showed dicyclomine to be equally potent against acetylcholine (ACh)- or barium chloride (BaCI₂)-induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCI₂. 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 concentration 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 in nature (see table) and were reported by 61% of the patients.

Side Effect	Dicyclomine Hydrochloride (40 mg q.i.d.) %	Placebo %
Dry Mouth	33	5
Dizziness	29	2
Blurred Vision	27	2
Nausea	14	6
Light-Headedness	11	3
Drowsiness	9	1
Weakness	7	1
Nervousness	6	2

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 ADVERSE REACTIONS.)