VA Class:AU350

AHFS Class:

• Antimuscarinics/Antispasmodics 12:08.08

Generic Name(s):

• Clidinium Bromide

• Chlordiazepoxide Hydrochloride and Clidinium Bromide

Clidinium bromide is a synthetic quaternary ammonium antimuscarinic.

Clidinium bromide, as the fixed-combination with chlordiazepoxide hydrochloride, has been used as an adjunct in the treatment of peptic ulcer disease. However, current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers, and the American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, see Uses: Helicobacter pylori Infection, in Clarithromycin 8:12.12.92.

Clidinium bromide is used in combination with chlordiazepoxide hydrochloride in the treatment of functional disturbances of GI motility such as irritable bowel syndrome. Therapeutic benefits achieved with the combination preparation may be attributed to the anxiolytic and/or sedative properties of chlordiazepoxide. As with other antimuscarinics, clidinium 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.

Clidinium bromide, as a fixed-combination preparation containing chlordiazepoxide hydrochloride, is administered orally. The drug is usually administered 3 or 4 times daily before meals and at bedtime.

Dosage

Chlordiazepoxide Hydrochloride and Clidinium Bromide

When clidinium bromide is used in fixed combination with chlordiazepoxide hydrochloride, the usual adult maintenance dosage of clidinium bromide is 2.5 or 5 mg 3 or 4 times daily. If the fixed combination is used, the precautions and contraindications associated with chlordiazepoxide must be considered.

Safety and efficacy of the fixed-combination preparation containing clidinium bromide and chlordiazepoxide hydrochloride in pediatric patients have not been established.

When clidinium bromide is used in fixed combination with chlordiazepoxide hydrochloride (e.g., Librax^®), the initial dosage of clidinium bromide in geriatric or debilitated patients should not exceed 5 mg daily, which may be gradually increased according to the patient's tolerance and response. Geriatric patients may be especially prone to adverse effects such as drowsiness, ataxia, and confusion when receiving clidinium bromide in fixed combination with chlordiazepoxide hydrochloride. These adverse effects usually can be prevented by proper dosage adjustment. Therefore, it is recommended that the initial dosage of this preparation in geriatric patients be selected carefully and gradually increased if needed and tolerated. However, these adverse effects occasionally have been observed in geriatric patients receiving the lower range of the usual dosage of this preparation.

Pharmacokinetics

Little information is available on the pharmacokinetics of clidinium bromide, since a suitable assay for determining plasma concentrations of the drug does not exist.

Absorption

Clidinium bromide, like other quaternary ammonium drugs, is incompletely absorbed from the GI tract since it is completely ionized. The drug is apparently absorbed from the intestine. Following oral administration, the antisecretory activity of clidinium bromide is seen within 1 hour and persists for up to 3 hours.

Distribution

Quaternary ammonium antimuscarinics are completely ionized and possess poor lipid solubility. Accordingly, they do not readily penetrate the CNS, placenta, or the eye. It is not known whether clidinium bromide is distributed into milk.

Elimination

Clidinium bromide is metabolized mainly in the liver to its corresponding 3-hydroxy alcohol. Following oral administration in 2 adults of a single 0.3-mg/kg dose, urinary elimination of 3-hydroxy-1-methylquinuclidinium bromide (the alcohol metabolite of clidinium bromide) was biphasic with an initial half-life of 2.4 hours and a terminal half-life of 20 hours. Approximately 36% of an oral dose of the drug was excreted in urine within 7 days, with 90% of urinary excretion occurring within the first day. About 20-46% of a dose was eliminated in feces.

Chemistry and Stability

Chemistry

Clidinium bromide is a synthetic quaternary ammonium antimuscarinic. Clidinium bromide is an aminoalcohol ester which differs structurally from mepenzolate (no longer commercially available in the US) by substitution of a two-carbon bridge for a methyl group at the nitrogen. The drug occurs as a white or nearly white, crystalline powder and is soluble in water and in alcohol. Clidinium bromide is commercially available in the US only as the fixed-combination preparation containing chlordiazepoxide hydrochloride.

Stability

Clidinium bromide is stable in aqueous solution at pH 2-8. In more alkaline solutions, the drug undergoes rapid decomposition.

Additional Information

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