Dicyclomine Hydrochloride 20 MG Oral Tablet
DRUG INTERACTIONS
7 : anticholinergics antagonize antiglaucoma agents and may increase intraoccular pressure Antiglaucoma agents (7) : may affect the gastrointestinal absorption of various drugs; may also increase certain actions or side effects of other anticholinergic drugs Anticholinergic agents (7) : interfere with the absorption of anticholinergic agents Antacids (7) 7.1 Antiglaucoma Agents Anticholinergics antagonize the effects of antiglaucoma agents.
Anticholinergic drugs in the presence of increased intraocular pressure may be hazardous when taken concurrently with agents such as corticosteroids.
Use of dicyclomine hydrochloride in patients with glaucoma is not recommended .
[see Contraindications (4)] 7.2 Other Drugs with Anticholinergic Activity The following agents may increase certain actions or side effects of anticholinergic drugs including dicyclomine hydrochloride: amantadine, antiarrhythmic agents of Class I (e.g., quinidine), antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity.
7.3 Other Gastrointestinal Motility Drugs Interaction with other gastrointestinal motility drugs may antagonize the effects of drugs that alter gastrointestinal motility, such as metoclopramide.
7.4 Effect of Antacids Because antacids may interfere with the absorption of anticholinergic agents including dicyclomine hydrochloride, simultaneous use of these drugs should be avoided.
7.5 Effect on Absorption of Other Drugs Anticholinergic agents may affect the gastrointestinal absorption of various drugs by affecting the gastrointestinal motility, such as slowly dissolving dosage forms of digoxin; increased serum digoxin concentration may result.
7.6 Effect on Gastric Acid Secretion The inhibiting effects of anticholinergic drugs on gastric hydrochloric acid secretion are antagonized by agents used to treat achlorhydria and those used to test gastric secretion.
OVERDOSAGE
10 In case of an overdose, patients should contact a physician, poison control center (1-800-222-1222), or emergency room.
The signs and symptoms of overdosage include: headache; nausea; vomiting; blurred vision; dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation including convulsion.
A curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
One reported event included a 37-year-old who reported numbness on the left side, cold fingertips, blurred vision, abdominal and flank pain, decreased appetite, dry mouth, and nervousness following ingestion of 320 mg daily (four 20 mg tablets four times daily.) These events resolved after discontinuing the dicyclomine.
The acute oral LD of the drug is 625 mg/kg in mice.
50 The amount of drug in a single dose that is ordinarily associated with symptoms of overdosage or that is likely to be life-threatening, has not been defined.
The maximum human oral dose recorded was 600 mg by mouth in a 10-month-old child and approximately 1500 mg in an adult, each of whom survived.
In three of the infants who died following administration of dicyclomine hydrochloride , the blood concentrations of drug were 200, 220, and 505 ng/mL.
[see Warnings and Precautions (5.1)] It is not known if dicyclomine hydrochloride is dialyzable.
Treatment should consist of gastric lavage, emetics, and activated charcoal.
Sedatives (e.g., short-acting barbiturates, benzodiazepines) may be used for management of overt signs of excitement.
If indicated, an appropriate parenteral cholinergic agent may be used as an antidote.
DESCRIPTION
11 Molecular weight: 345.95 Dicyclomine hydrochloride occurs as a fine, white, crystalline, practically odorless powder with a bitter taste.
It is soluble in water, freely soluble in alcohol and chloroform, and very slightly soluble in ether.
Dicyclomine hydrochloride is an antispasmodic and anticholinergic (antimuscarinic) agent available in the following dosage forms: Dicyclomine Hydrochloride Capsules, USP for oral use contain 10 mg dicyclomine hydrochloride, USP.
Dicyclomine hydrochloride 10 mg capsules also contain inactive ingredients: Corn Starch, Lactose Monohydrate, Magnesium Stearate, and Microcrystalline Cellulose.
Capsule shells contain FD&C Blue No.
1, FD&C Red No.
4, and Gelatin.
The imprinting ink contains Titanium Dioxide.
Dicyclomine Hydrochloride Tablets, USP for oral use contain 20 mg dicyclomine hydrochloride, USP.
Dicyclomine hydrochloride 20 mg tablets also contain inactive ingredients: Anhydrous Lactose, FD&C Blue No.
1, Lactose Monohydrate, Magnesium Stearate, and Microcrystalline Cellulose.
Dicyclomine hydrochloride is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethyl ester, hydrochloride, with a molecular formula of C H NO •HCl and the following structural formula: 19 35 2 BENTYL Structure
CLINICAL STUDIES
14 In controlled clinical trials involving over 100 patients who received drug, 82% of patients treated for functional bowel/irritable bowel syndrome with dicyclomine hydrochloride at initial doses of 160 mg daily (40 mg four times daily) demonstrated a favorable clinical response compared with 55% treated with placebo (p<0.05).
HOW SUPPLIED
16 /STORAGE AND HANDLING NDC:54569-0419-0 in a BOTTLE, PLASTIC of 30 TABLETS NDC:54569-0419-2 in a BOTTLE, PLASTIC of 20 TABLETS
GERIATRIC USE
8.5 Geriatric Use Clinical studies of dicyclomine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
DOSAGE FORMS AND STRENGTHS
3 Dicyclomine Hydrochloride 10 mg capsules: dark blue capsules printed “West-ward 3126” Dicyclomine Hydrochloride 20 mg tablets: Blue, Round Tablets; Embossed “WW27” Dicyclomine hydrochloride capsules 10 mg (3) Dicyclomine hydrochloride tablets 20 mg (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Atropine did not affect responses to these two agonists.
studies in cats and dogs showed dicyclomine to be equally potent against acetylcholine (ACh)- or barium chloride (BaCl )-induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCl .
Tests for mydriatic effects in mice showed that dicyclomine was approximately 1/500 as potent as atropine; antisialagogue tests in rabbits showed dicyclomine to be 1/300 as potent as atropine.
Dicyclomine relieves smooth muscle spasm of the gastrointestinal tract.
Animal studies indicate that this action is achieved via a dual mechanism: A specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor sites with approximately 1/8 the milligram potency of atropine ( , guinea pig ileum); and in vitro A direct effect upon smooth muscle (musculotropic) as evidenced by dicyclomine’s antagonism of bradykinin- and histamine-induced spasms of the isolated guinea pig ileum.
In vivo 2 2
INDICATIONS AND USAGE
1 Dicyclomine hydrochloride is indicated for the treatment of patients with functional bowel/irritable bowel syndrome.
Dicyclomine hydrochloride is an antispasmodic and anticholinergic (antimuscarinic) agent indicated for the treatment of functional bowel/irritable bowel syndrome (1)
PEDIATRIC USE
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age.
There are published cases reporting that the administration of dicyclomine hydrochloride syrup to infants has been followed by serious respiratory symptoms (dyspnea, shortness of breath, breathlessness, respiratory collapse, apnea and asphyxia), seizures, syncope, pulse rate fluctuations, muscular hypotonia, and coma, and death, however; no causal relationship has been established.
[see Contraindications (4)]
PREGNANCY
8.1 Pregnancy Pregnancy Category B Adequate and well-controlled studies have not been conducted with dicyclomine hydrochloride in pregnant women at the recommended doses of 80 to 160 mg/day.
However, epidemiologic studies did not show an increased risk of structural malformations among babies born to women who took products containing dicyclomine hydrochloride at doses up to 40 mg/day during the first trimester of pregnancy.
Reproduction studies have been performed in rats and rabbits at doses of up to 33 times the maximum recommended human dose based on 160 mg/day (3 mg/kg) and have revealed no evidence of harm to the fetus due to dicyclomine.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
NUSRING MOTHERS
8.3 Nursing Mothers Dicyclomine hydrochloride is contraindicated in women who are human milk feeding.
Dicyclomine hydrochloride is excreted in human milk.
Because of the potential for serious adverse reactions in human milk-fed infants from dicyclomine hydrochloride, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
[see Use in Specific Populations (8.4)].
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS : worsening of conditions Cardiovascular conditions (5.2) : heat prostration can occur with drug use (fever and heat stroke due to decreased sweating); drug should be discontinued and supportive measures instituted Peripheral and central nervous system (5.3) : signs and symptoms resolve within 12 to 24 hours after discontinuation of dicyclomine hydrochloride Psychosis in patients sensitive to anticholinergic drugs (5.3) : overdose may lead to muscular weakness and paralysis.
Dicyclomine hydrochloride should be given to patients with myasthenia gravis only to reduce adverse muscarinic effects of an anticholinesterase Myasthenia Gravis (5.4) : diarrhea may be an early symptom especially in patients with ileostomy or colostomy.
Treatment with dicyclomine hydrochloride would be inappropriate and possibly fatal Incomplete intestinal obstruction (5.5) : due to risk of toxic megacolon Salmonella dysenteric patients (5.6) : dicyclomine hydrochloride should be used with caution in these patients; large doses may suppress intestinal motility or aggravate the serious complications of toxic megacolon Ulcerative colitis (5.7) : dicyclomine hydrochloride should be used with caution in these patients; may lead to urinary retention Prostatic hypertrophy (5.8) : should be used with caution Hepatic and renal disease (5.9) : use with caution in elderly who may be more susceptible to dicyclomine hydrochloride’s adverse events Geriatric (5.10) 5.2 Cardiovascular Conditions Dicyclomine hydrochloride needs to be used with caution in conditions characterized by tachyarrhythmia such as thyrotoxicosis, congestive heart failure and in cardiac surgery, where they may further accelerate the heart rate.
Investigate any tachycardia before administration of dicyclomine hydrochloride.
Care is required in patients with coronary heart disease, as ischemia and infarction may be worsened, and in patients with hypertension .
[see Adverse Reactions (6.3)] 5.3 Peripheral and Central Nervous System The peripheral effects of dicyclomine hydrochloride are a consequence of their inhibitory effect on muscarinic receptors of the autonomic nervous system.
They include dryness of the mouth with difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of pupils (mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, with palpitations and arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation .
[see Adverse Reactions (6)] In the presence of a high environmental temperature heat prostration can occur with drug use (fever and heat stroke due to decreased sweating).
It should also be used cautiously in patients with fever.
If symptoms occur, the drug should be discontinued and supportive measures instituted.
Because of the inhibitory effect on muscarinic receptors within the autonomic nervous system, caution should be taken in patients with autonomic neuropathy.
Central nervous system (CNS) signs and symptoms include confusion, disorientation, short-term amnesia, hallucinations, dysarthria, ataxia, coma, euphoria, fatigue, insomnia, agitation and mannerisms, and inappropriate affect.
Psychosis has been reported in sensitive individuals given anticholinergic drugs.
These CNS signs and symptoms usually resolve within 12 to 24 hours after discontinuation of the drug Dicyclomine hydrochloride may produce drowsiness, dizziness or blurred vision.
The patient should be warned not to engage in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work while taking dicyclomine hydrochloride.
5.4 Myasthenia Gravis With overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).
It should not be given to patients with myasthenia gravis except to reduce adverse muscarinic effects of an anticholinesterase [see Contraindications (4)] 5.5 Intestinal Obstruction Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy.
In this instance, treatment with this drug would be inappropriate and possibly harmful .
[see Contraindications (4)] Rarely development of Ogilvie’s syndrome (colonic pseudo-obstruction) has been reported.
Ogilvie’s syndrome is a clinical disorder with signs, symptoms, and radiographic appearance of an acute large bowel obstruction but with no evidence of distal colonic obstruction.
5.6 Toxic Dilatation of Intestinemegacolon Toxic dilatation of intestine and intestinal perforation is possible when anticholinergic agents are administered in patients with Salmonella dysentery.
5.7 Ulcerative Colitis Caution should be taken in patients with ulcerative colitis.
Large doses may suppress intestinal motility to the point of producing a paralytic ileus and the use of this drug may precipitate or aggravate the serious complication of toxic megacolon .
Dicyclomine hydrochloride is contraindicated in patients with severe ulcerative colitis .
[see Adverse Reactions (6.3)] [see Contraindications (4)] 5.8 Prostatic Hypertrophy Dicyclomine hydrochloride should be used with caution in patients with known or suspected prostatic enlargement, in whom prostatic enlargement may lead to urinary retention [see Adverse Reactions (6.3)] 5.9 Hepatic and Renal Disease Dicyclomine hydrochloride should be used with caution in patients with known hepatic and renal impairment.
5.10 Geriatic Population Dicyclomine hydrochloride should be used with caution in elderly who may be more susceptible to its adverse effects.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION 17.2 Use in Infants Inform parents and caregivers not to administer dicyclomine hydrochloride in infants less than 6 months of age .
[see Use in Specific Populations (8.4)] 17.3 Use in Nursing Mothers Advise lactating women that dicyclomine hydrochloride should not be used while human milk feeding their infants .
[see Use in Specific Populations (8.3, 8.4)] 17.4 Peripheral and Central Nervous System In the presence of a high environmental temperature, heat prostration can occur with dicyclomine hydrochloride use (fever and heat stroke due to decreased sweating).
If symptoms occur, the drug should be discontinued and a physician contacted.
Dicyclomine hydrochloride may produce drowsiness or blurred vision.
The patients should be warned not to engage in activities requiring mental alertness, such as operating a motor vehicle or other machinery or to perform hazardous work while taking dicyclomine hydrochloride.
.
[see Warnings and Precautions (5.3)] Manufactured By: Eatontown, NJ 07724 USA West-ward Pharmaceutical Corp.
Revised September 2011
DOSAGE AND ADMINISTRATION
2 Dosage must be adjusted to individual patient needs.
Dosage for dicyclomine hydrochloride must be adjusted to individual patient needs .
(2) If a dose is missed, patients should continue the normal dosing schedule ).
(2 Oral in adults (2.1): Starting dose: 20 mg four times a day.
After a week treatment with the starting dose, the dose may be escalated to 40 mg four times a day, unless side effects limit dosage escalation Discontinue dicyclomine hydrochloride if efficacy not achieved or side effects require doses less than 80 mg per day after two weeks of treatment 2.1 Oral Dosage and Administration in Adults The recommended initial dose is 20 mg four times a day.
After one week treatment with the initial dose, the dose may be increased to 40 mg four times a day unless side effects limit dosage escalation.
If efficacy is not achieved within 2 weeks or side effects require doses below 80 mg per day, the drug should be discontinued.
Documented safety data are not available for doses above 80 mg daily for periods longer than 2 weeks.