Clidinium Bromide

Class: Antimuscarinics/Antispasmodics
VA Class: AU350
Chemical Name: 3-hydroxy-1-methylquinuclidinium bromide benzilate
CAS Number: 3485-62-9
Brands: Librax

Introduction

Antimuscarinic; synthetic quaternary ammonium.a c

Uses for Clidinium Bromide

Peptic Ulcer Disease

Used in fixed combination with chlordiazepoxide as adjunctive therapy in the treatment of peptic ulcer disease;a b however, no conclusive data that antimuscarinics aid in the healing, decrease the rate of recurrence, or prevent complications of peptic ulcers.c

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With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.c

GI Motility Disturbances

Used in fixed combination with chlordiazepoxide in the treatment of functional GI motility disturbances (e.g., irritable bowel syndrome).a b e

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.a

Acute Enterocolitis

Used in fixed combination with chlordiazepoxide in the treatment of acute enterocolitis.b e However, antimuscarinics should be used with extreme caution in patients with diarrhea or ulcerative colitis.c (See Cautions.)

Clidinium Bromide Dosage and Administration

Administration

Oral Administration

Administer orally 3 or 4 times daily before meals and at bedtime.a b c e

Dosage

Available as clidinium bromide; dosage expressed in terms of the salt.b e

As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect.c

Clidinium bromide is commercially available in the US only in fixed combination with chlordiazepoxide hydrochloride.a e Fixed-ratio combination preparations do not permit individual titration of dosages.c

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.a b e

Special Populations

Hepatic Impairment

No specific dosage recommendations.a b Use with caution.b c e

Renal Impairment

No specific dosage recommendations.a b Use with caution.b c e

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.a b e Administer the smallest effective dosage.b e (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.b e Administer the smallest effective dosage.b e

Cautions for Clidinium Bromide

Contraindications

  • Glaucoma (to avoid mydriasis).b c e

  • Prostatic hypertrophy or benign bladder neck obstruction.b c e

  • Known hypersensitivity to clidinium or any ingredient in the formulation.b c e

Warnings/Precautions

Warnings

CNS Effects

Risk of drowsiness.b c e Performance of activities requiring mental alertness and physical coordination (e.g., operating a vehicle or other machinery, performing hazardous work) may be impaired.b c e (See Advice to Patients.)

Thermoregulatory Effects

Exposure to high environmental temperatures may result in heat prostration in patients receiving antimuscarinics.c Increased risk of hyperthermia in patients with fever.c Use with caution in patients who may be exposed to elevated environmental temperatures or in febrile patients.c

Diarrhea

Diarrhea may be an early sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy; use with extreme caution.c

General Precautions

Use of Fixed Combinations

Clidinium is commercially available in the US only in fixed combination with chlordiazepoxide hydrochloride.a b e Consider cautions, precautions, and contraindications associated with chlordiazepoxide.a b e

GI Effects

Caution in patients with ulcerative colitis; large doses may suppress intestinal motility, resulting in paralytic ileus and toxic megacolon.c

Specific Populations

Pregnancy

Category C.d

Lactation

Not known whether clidinium is distributed into milk.a d

Risk of lactation suppression.b e

Pediatric Use

Safety and efficacy of clidinium bromide in fixed combination with chlordiazepoxide hydrochloride not established in pediatric patients.a b c e

Geriatric Use

Use with caution in geriatric patients.c Geriatric patients may be prone to adverse effects (e.g., drowsiness, ataxia, confusion) when receiving clidinium bromide in fixed combination with chlordiazepoxide hydrochloride.a Such adverse effects may occur even at the lower end of dosage range. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with hepatic disease.b c e

Renal Impairment

Use with caution in patients with renal disease.b c e

Common Adverse Effects

Xerostomia,b c blurred vision,b c constipation,b c urinary hesitancy.b c

Interactions for Clidinium Bromide

Drugs with Anticholinergic Effects

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation).c Advise of possibility of increased anticholinergic effects.c

Orally Administered Drugs

Potential pharmacokinetic interaction (altered GI absorption of various drugs).c Antimuscarinics may inhibit GI motility, delay gastric emptying, and prolong GI transit time.c

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

Decrease rate but not extent of acetaminophen absorption; may delay onset of acetaminophen therapeutic effectsc

Amantadine

Possible additive adverse anticholinergic effectsc

Inform patient of possibilityc

Antacids

Possible decreased absorption of antimuscarinicc

Administer antimuscarinic at least 1 hour before antacidsc

Antiarrhythmic agents, type I (e.g., disopyramide, procainamide, quinidine)

Possible additive adverse anticholinergic effectsc

Inform patient of possibilityc

Antidepressants, tricyclic

Possible additive adverse anticholinergic effectsc

Inform patient of possibilityc

Antihistamines

Possible additive adverse anticholinergic effectsb c

Inform patient of possibilityc

Antiparkinsonian agents

Possible additive adverse anticholinergic effectsc

Inform patient of possibilityc

Corticosteroids

Possible increased IOPc

Digoxin (slow dissolving)

Increased serum digoxin concentration with another anticholinergic drug and slowly-dissolving digoxin tabletsc

Use digoxin oral solution or rapidly-dissolving tablets; observe for signs of digoxin toxicityc

Ketoconazole

Possible decreased ketoconazole absorptionc

Administer antimuscarinic ≥2 hours after ketoconazolec

Levodopa

Possible increased gastric levodopa metabolism, resulting in decreased levodopa absorptionc

Possible levodopa toxicity if antimuscarinic is discontinued without a concomitant reduction in levodopa dosagec

Meperidine

Possible additive adverse anticholinergic effectsc

Inform patient of possibilityc

Phenothiazines

Possible additive adverse anticholinergic effectsb c

Inform patient of possibilityc

Potassium chloride

Antimuscarinics may slow GI transit, increasing risk of potassium chloride GI mucosal toxicityc

Administer concomitantly with caution (especially with wax matrix potassium chloride preparations)c

Clidinium Bromide Pharmacokinetics

Absorption

Bioavailability

Incompletely absorbed from the GI tract (apparently from the intestines) because completely ionized.a

Onset

Following oral administration, antisecretory activity occurs within <1 hour.a

Duration

Following oral administration, antisecretory activity persists for ≤hours.a

Distribution

Extent

Does not readily penetrate the CNS or the eye.a

Not known whether clidinium bromide crosses the placenta or is distributed into milk.a c d

Elimination

Metabolism

Principally in the liver to its 3-hydroxy alcohol.a

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.a

Half-life

Biphasic; in 2 adults, initial half-life was 2.4 hours and terminal half-life was 20 hours.a

Stability

Storage

Oral

Capsules

Clidinium bromide-chlordiazepoxide hydrochloride fixed combination: Tight, light-resistant container at 25°C (may be exposed to 15–30°C).b

Actions

  • Has pronounced antispasmodic and antisecretory effect on the GI tract.b e

  • 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.c

  • At usual doses, antimuscarinics principally antagonize cholinergic stimuli at muscarinic receptors and have little or no effect on cholinergic stimuli at nicotinic receptors. c

  • 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.c

  • Antimuscarinics also have been referred to as parasympatholytics since the antagonized functions principally are under the parasympathetic division of the nervous system.c

Advice to Patients

  • Potential for hyperthermia and heat prostration; avoid exposure to high environmental temperature and use with caution when febrile.c

  • 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.b c e

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b e

  • Importance of informing patients of other precautionary information. (See Cautions.)a

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chlordiazepoxide Hydrochloride and Clidinium Bromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

5 mg Chlordiazepoxide Hydrochloride and Clidinium Bromide 2.5 mg*

Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsules (with parabens)

Actavis

Librax (with parabens)

Valeant

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Clidinium-Chlordiazepoxide 2.5-5MG Capsules (OCEANSIDE PHARMACEUTICALS): 30/$35.99 or 90/$75.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS Drug Information 2008. McEvoy GK, ed. Clidinium. Bethesda, MD: American Society of Health-System Pharmacists; 2008:1307.

b. Actavis Totowa LLC. Chlordiazepoxide hydrochloride and clidinium bromide capsules prescribing information. Totowa, NJ; 2006 June.

c. AHFS Drug Information 2008. McEvoy GK, ed. Antimuscarinics/Antispasmodics General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008:1293–1300.

d. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:342.

e. ICN Pharmaceuticals. Librax (clidinium bromide and chlordiazepoxide hydrochloride) capsules prescribing information. Costa Mesa, CA; 1999 Apr.

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