VA Class:AU350

AHFS Class:

• Antimuscarinics/Antispasmodics 12:08.08

Generic Name(s):

• Dicyclomine Hydrochloride

Dicyclomine hydrochloride is a synthetic tertiary amine antispasmodic.

Dicyclomine hydrochloride is used in the treatment of functional disturbances of GI motility such as irritable bowel syndrome. As with other antispasmodics, dicyclomine has limited efficacy in the treatment of these disorders and should be used only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit. Although dicyclomine has also been used in combination with phenobarbital in the treatment of irritable bowel syndrome, attempts to substantiate claims of efficacy for fixed combinations that include an antispasmodic and phenobarbital have generally failed and these combinations are generally considered as lacking substantial evidence of efficacy in the treatment of this condition.

Dicyclomine has been used alone and in combination with phenobarbital in the treatment of infant colic† and acute enterocolitis†, but the drug alone and the combination are generally considered as lacking substantial evidence of efficacy in the treatment of these conditions. Infant colic is considered a benign, self-limiting condition that tends to resolve spontaneously and not require medical treatment.

Administration

Dicyclomine hydrochloride is usually administered orally. When oral therapy is not feasible, the drug may be administered by IM injection. IM injection of the drug may produce local irritation and/or transient sensation of lightheadedness. Oral therapy should replace IM therapy as soon as possible, and IM therapy should not be used for longer than 1 or 2 days. Dicyclomine should not be administered by IV or subcutaneous injection. The oral solutions should be diluted with an equal volume of water just prior to administration.

Dosage

Oral Dosage

The only oral dosage of dicyclomine hydrochloride clearly shown to be effective in adults is 40 mg 4 times daily. Because this dosage is associated with a substantial incidence of adverse effects, the usual initial dosage should be 20 mg 4 times daily. Depending on the patient's response, dosage should be increased during the first week of therapy to 40 mg 4 times daily unless adverse effects limit upward titration. If an adequate response is not obtained within 2 weeks or adverse effects limit dosage to less than 80 mg daily, the drug should be discontinued.

The safety of dosages of 80-160 mg daily for longer than 2 weeks has not been established. Abuse and/or dependence on dicyclomine for its anticholinergic effects has been reported rarely.

Parenteral Dosage

The recommended IM dosage of dicyclomine hydrochloride for adults is 20 mg 4 times daily.

Pharmacokinetics

The pharmacokinetics of dicyclomine hydrochloride have not been fully determined.

Absorption

Dicyclomine hydrochloride is absorbed rapidly from the GI tract, achieving peak plasma concentrations within 1-1.5 hours after oral administration of the drug (about 1, 1.1, and 1.5 hours for the solution, capsules, and tablets, respectively). Comparison of the areas under the plasma concentration-time curves (AUCs) for single, 40-mg doses of dicyclomine hydrochloride oral solution and IM injection indicates that the relative oral bioavailability of the drug is about 67% of that following IM injection. The drug is absorbed slightly faster following IM injection than after oral administration. The bioavailabilities (as determined by AUC) of dicyclomine hydrochloride oral solution, capsules, and tablets are equivalent.

Distribution

The apparent volume of distribution of dicyclomine is reportedly 3.65 L/kg.

Elimination

Plasma concentrations of dicyclomine hydrochloride appear to decline in a biphasic manner. The half-life of the drug in the initial distribution phase (t_½α) is about 1.8 hours and the half-life in the terminal elimination phase (t_½β) is about 9-10 hours. Although the metabolic fate of dicyclomine has not been determined, about 80% of a dose is eliminated in urine and about 10% in feces.

Chemistry and Stability

Chemistry

Dicyclomine hydrochloride is a synthetic tertiary amine antispasmodic. Dicyclomine hydrochloride is an aminoalcohol ester. The drug occurs as a fine, white, practically odorless, crystalline powder and has a very bitter taste. Dicyclomine hydrochloride has solubilities of approximately 77 mg/mL in water and 200 mg/mL in alcohol at 25°C. The drug has a pK_a of 9.

Commercially available dicyclomine hydrochloride injections are colorless, sterile solutions of the drug in water for injection which are made isotonic by the addition of sodium chloride. Dicyclomine hydrochloride injections are unbuffered and have a pH of 3-6. Dicyclomine hydrochloride solutions have a pH of 3-5.

Stability

Dicyclomine hydrochloride is unstable in alkaline media and is readily converted to the free base in such media when moisture is present. Dicyclomine hydrochloride injections are unstable at pH greater than 7; at these alkaline pHs, precipitation of the free base may occur. The manufacturer of Bentyl^® states that the injections are stable at pH 2-6.5. Dicyclomine hydrochloride preparations should be stored in containers protecting them from excessive heat, light, and moisture. Dicyclomine hydrochloride capsules and tablets should be stored in well-closed containers at room temperature, preferably less than 30°C. Dicyclomine hydrochloride solutions and injections should be stored at room temperature, preferably less than 30°C; exposure of the solutions to excessive heat and freezing of the injections should be avoided.

Additional Information

For further information on the chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, and dosage and administration of dicyclomine hydrochloride, see the Antimuscarinics/Antispasmodics General Statement 12:08.08.