Used in fixed combination with chlordiazepoxide as adjunctive therapy in the treatment of peptic ulcer disease; however, no conclusive data that antimuscarinics aid in the healing, decrease the rate of recurrence, or prevent complications of peptic ulcers.
With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.
GI Motility Disturbances
Used in fixed combination with chlordiazepoxide in the treatment of functional GI motility disturbances (e.g., irritable bowel syndrome).
Has limited efficacy in treatment of GI motility disturbance and should only be used if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit.
Acute Enterocolitis
Used in fixed combination with chlordiazepoxide in the treatment of acute enterocolitis. However, antimuscarinics should be used with extreme caution in patients with diarrhea or ulcerative colitis. (See Cautions.)
Dosage and Administration
Administration
Oral Administration
Administer orally 3 or 4 times daily before meals and at bedtime.
Dosage
Available as clidinium bromide; dosage expressed in terms of the salt.
As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect.
Clidinium bromide is commercially available in the US only in fixed combination with chlordiazepoxide hydrochloride. Fixed-ratio combination preparations do not permit individual titration of dosages.
Adults
GI Disorders
Oral
Usual maintenance clidinium bromide dosage is 2.5 or 5 mg (1 or 2 capsules of clidinium bromide in fixed combination with chlordiazepoxide hydrochloride) 3 or 4 times daily administered before meals and at bedtime.
Special Populations
Hepatic Impairment
No specific dosage recommendations. Use with caution.
Renal Impairment
No specific dosage recommendations. Use with caution.
Geriatric Patients
Initially, no more than 5 mg of clidinium bromide daily (2 capsules of clidinium bromide in fixed combination with chlordiazepoxide hydrochloride). Gradually increase dosage if needed and tolerated. Administer the smallest effective dosage. (See Geriatric Use under Cautions.)
Debilitated Patients
Initially, administer up to 5 mg of clidinium bromide daily (2 capsules of clidinium bromide in fixed combination with chlordiazepoxide hydrochloride); then adjust subsequent dosages based on patient tolerance and response. Administer the smallest effective dosage.
Known hypersensitivity to clidinium or any ingredient in the formulation.
Warnings/Precautions
Warnings
CNS Effects
Risk of drowsiness. Performance of activities requiring mental alertness and physical coordination (e.g., operating a vehicle or other machinery, performing hazardous work) may be impaired. (See Advice to Patients.)
Thermoregulatory Effects
Exposure to high environmental temperatures may result in heat prostration in patients receiving antimuscarinics. Increased risk of hyperthermia in patients with fever. Use with caution in patients who may be exposed to elevated environmental temperatures or in febrile patients.
Clidinium is commercially available in the US only in fixed combination with chlordiazepoxide hydrochloride. Consider cautions, precautions, and contraindications associated with chlordiazepoxide.
GI Effects
Caution in patients with ulcerative colitis; large doses may suppress intestinal motility, resulting in paralytic ileus and toxic megacolon.
Specific Populations
Pregnancy
Category C.
Lactation
Not known whether clidinium is distributed into milk.
Risk of lactation suppression.
Pediatric Use
Safety and efficacy of clidinium bromide in fixed combination with chlordiazepoxide hydrochloride not established in pediatric patients.
Geriatric Use
Use with caution in geriatric patients. Geriatric patients may be prone to adverse effects (e.g., drowsiness, ataxia, confusion) when receiving clidinium bromide in fixed combination with chlordiazepoxide hydrochloride. Such adverse effects may occur even at the lower end of dosage range. (See Geriatric Patients under Dosage and Administration.)
Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation). Advise of possibility of increased anticholinergic effects.
Orally Administered Drugs
Potential pharmacokinetic interaction (altered GI absorption of various drugs). Antimuscarinics may inhibit GI motility, delay gastric emptying, and prolong GI transit time.
Antimuscarinics may slow GI transit, increasing risk of potassium chloride GI mucosal toxicity
Administer concomitantly with caution (especially with wax matrix potassium chloride preparations)
Pharmacokinetics
Absorption
Bioavailability
Incompletely absorbed from the GI tract (apparently from the intestines) because completely ionized.
Onset
Following oral administration, antisecretory activity occurs within <1 hour.
Duration
Following oral administration, antisecretory activity persists for ≤hours.
Distribution
Extent
Does not readily penetrate the CNS or the eye.
Not known whether clidinium bromide crosses the placenta or is distributed into milk.
Elimination
Metabolism
Principally in the liver to its 3-hydroxy alcohol.
Elimination Route
Limited data; in 2 adults, approximately 36% of dose excreted in urine within 7 days of oral administration, with 90% of urinary excretion occurring within the first day; 20–46% eliminated in feces.
Half-life
Biphasic; in 2 adults, initial half-life was 2.4 hours and terminal half-life was 20 hours.
Stability
Storage
Oral
Capsules
Clidinium bromide-chlordiazepoxide hydrochloride fixed combination: Tight, light-resistant container at 25°C (may be exposed to 15–30°C).
Actions
Has pronounced antispasmodic and antisecretory effect on the GI tract.
Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic cholinergic nerves and, to a lesser extent, on smooth muscles that lack cholinergic innervation.
At usual doses, antimuscarinics principally antagonize cholinergic stimuli at muscarinic receptors and have little or no effect on cholinergic stimuli at nicotinic receptors.
Antimuscarinics also have been referred to as anticholinergics (cholinergic blocking agents), but this term is appropriate only when it describes the antagonism of cholinergic stimuli at any cholinergic receptor, whether muscarinic or nicotinic.
Antimuscarinics also have been referred to as parasympatholytics since the antagonized functions principally are under the parasympathetic division of the nervous system.
Advice to Patients
Potential for hyperthermia and heat prostration; avoid exposure to high environmental temperature and use with caution when febrile.
Risk of drowsiness or blurred vision; exercise caution when performing activities requiring mental alertness (e.g., driving a motor vehicle, operating machinery) or when performing other hazardous work.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
5 mg Chlordiazepoxide Hydrochloride and Clidinium Bromide 2.5 mg*
Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsules (with parabens)
Actavis
Librax® (with parabens)
Valeant
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
