VA Class:AU350

AHFS Class:

• Antimuscarinics/Antispasmodics 12:08.08

Generic Name(s):

• Propantheline Bromide

Propantheline bromide is a synthetic quaternary ammonium antimuscarinic.

Propantheline bromide is used as an adjunct in the treatment of peptic ulcer disease. Propantheline has also been used in combination with phenobarbital as an adjunct in the treatment of peptic ulcer disease; however, there are no data that support the superiority of combination preparations over antimuscarinics alone. As with other antimuscarinics, there are no conclusive data from well-controlled studies which indicate that, in usually recommended dosage, propantheline aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. In addition, in patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis. With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition. 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.

Although propantheline has been used in combination with phenobarbital for the treatment of functional disturbances of GI motility such as irritable bowel syndrome, attempts to substantiate claims of efficacy for fixed combinations that include an antimuscarinic and phenobarbital have generally failed, and these combinations are generally considered as lacking substantial evidence of efficacy in the treatment of this condition.

Propantheline has been used in conjunction with a histamine H₂-receptor antagonist (i.e., cimetidine) in the treatment of Zollinger-Ellison syndrome†. (See Uses: Peptic Ulcer Disease and GI Hypersecretory States, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.)

Administration

Propantheline bromide is administered orally. The drug is preferably given 30 minutes before meals and at bedtime. Although propantheline bromide also has been administered IV or IM, a parenteral preparation of the drug is no longer commercially available in the US.

Dosage

The usual initial adult dosage of propantheline bromide is 15 mg 3 times daily before meals and 30 mg at bedtime (a total dosage of 75 mg daily). In adults with mild symptoms, in geriatric patients, or in patients of small stature, the initial dosage is 7.5 mg 3 times daily, although such a low dosage strength currently is not available in the US. While an exact dose (7.5 mg) cannot be obtained in these patients, one manufacturer (Roxane) states that the 15-mg film-coated tablets can be broken in half without substantially damaging the tablets.

As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.

Safety and efficacy of propantheline in children have not been established.

Pharmacokinetics

Absorption

Propantheline bromide, like other quaternary ammonium drugs, is incompletely absorbed from the GI tract since it is completely ionized. There is considerable interindividual variation in the extent of absorption following oral administration of the drug. Food appears to substantially decrease the extent of absorption of propantheline bromide. Propantheline bromide appears to undergo extensive metabolism in the upper small intestine prior to absorption. Peak plasma concentrations are reached about one hour after oral administration. In a study in healthy males, mean peak plasma propantheline concentrations of 20.6 and 53.1 ng/mL were achieved within about 2 hours following oral administration of a single 30- and 60-mg dose, respectively.

Distribution

Distribution of propantheline in the body has not been determined. Quaternary ammonium antimuscarinics are completely ionized and possess poor lipid solubility. Accordingly, they do not readily penetrate the CNS or eye.

Elimination

Following oral administration of single doses of propantheline bromide in healthy males in one study, plasma concentrations of the drug declined with a mean elimination half-life of about 1.6 hours.

Propantheline is thought to be extensively metabolized in the GI tract and/or liver, principally by hydrolysis to the inactive metabolites, xanthene-9-carboxylic acid and (2-hydroxyethyl) diisopropylmethylammonium bromide. Propantheline is excreted in urine as metabolites and as unchanged drug. Following oral administration, about 70% of the dose is excreted in urine, principally as metabolites; only about 3% of the dose is excreted unchanged.

Chemistry and Stability

Chemistry

Propantheline bromide is a synthetic quaternary ammonium antimuscarinic. Propantheline bromide is an aminoalcohol ester that differs structurally from methantheline (no longer commercially available in the US) by the replacement of 2 ethyl groups at the nitrogen with 2 isopropyl groups. The drug occurs as odorless, white or practically white crystals having a bitter taste, and is very soluble in water and in alcohol.

Stability

Commercially available propantheline bromide tablets should be stored in tight, light-resistant containers at a temperature of 20-25°C.

Additional Information

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