DICYCLOMINE HYDROCHLORIDE- dicyclomine hydrochloride_tablet

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 ( 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. Atropine did not affect responses to these two agonists. In vivo 2 2 Dicyclomine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate and depress motor function. Absorption and Distribution: Elimination:.

Dicyclomine hydrochloride is indicated for the treatment of patients with functional bowel/ irritable bowel syndrome. Dicyclomine is an antispasmodic and anticholinergic (antimuscarinic) agent indicated for the treatment of functional bowel/irritable bowel syndrome ( 1.

Dosage must be adjusted to individual patient needs. Dosage for dicyclomine 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 4 times a day. After a week treatment with the starting dose, the dose may be escalated to 40 mg 4 times a day, unless side effects limit dosage escalation Discontinue dicyclomine if efficacy not achieved or side effects require doses less than 80 mg per day after 2 weeks of treatment The recommended initial dose is 20 mg 4 times a day. After one week treatment with the initial dose, the dose may be increased to 40 mg 4 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.

The pattern of adverse effects seen with dicylomine is mostly related to its pharmacological actions at muscarinic receptors [see Clinical Pharmacology (12) The most serious adverse reactions reported with dicyclomine hydrochloride include cardiovascular and central nervous system symptoms [see Warnings and Precautions (5. 3) The most serious adverse reactions include cardiovascular and central nervous system symptoms. The most common adverse reactions (> 5% of patients) are dizziness, dry mouth, vision blurred, nausea, somnolence, asthenia and nervousness ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure in controlled clinical trials involving over 100 patients treated for functional bowel/irritable bowel syndrome with dicyclomine hydrochloride at initial doses of 160 mg daily (40 mg 4 times a day). In these trials most of the side effects were typically anticholinergic in nature and were reported by 61% of the patients. Table 1 presents adverse reactions ( MedDRA 13. 0 Table 1: Adverse reactions experienced in controlled clinical trials with decreasing order of frequency MedDRA Preferred Term Dicyclomine Hydrochloride (40 mg four times a day) % Placebo % Dry Mouth 33 5 Dizziness 40 5 Vision Blurred 27 2 Nausea 14 6 Somnolence 9 1 Asthenia 7 1 Nervousness 6 2 Nine percent (9%) of patients were discontinued from dicyclomine because of one or more of these side effects (compared with 2% in the placebo group). In 41% of the patients with side effects, side effects disappeared or were tolerated at the 160 mg daily dose without reduction. A dose reduction from 160 mg daily to an average daily dose of 90 mg was required in 46% of the patients with side effects who then continued to experience a favorable clinical response; their side effects either disappeared or were tolerated. The following adverse reactions, presented by system organ class in alphabetical order, have been identified during post approval use of dicyclomine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: Eye Disorders: Gastrointestinal Disorders: General Disorders and Administration Site Conditions: Immune System Disorders: Nervous System Disorders: Psychiatric Disorders: Reproductive System and Breast Disorders: Respiratory, Thoracic and Mediastinal Disorders: Skin and Subcutaneous Tissue Disorder: Gastrointestinal: Central Nervous System: Peripheral Nervous System: Ophthalmologic: Dermatologic/Allergic: Genitourinary: Cardiovascular: Respiratory: Other:.

Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age [see Use in Specific Populations (8. 4) [see Use in Specific Populations (8. 3) unstable cardiovascular status in acute hemorrhage myasthenia gravis [see Warnings and Precautions (5. 4) glaucoma [see Adverse Reactions (6. 3) Drug Interactions (7. 1) obstructive uropathy [see Warnings and Precautions (5. 8) obstructive disease of the gastrointestinal tract [see Warnings and Precautions (5. 5) severe ulcerative colitis [see Warnings and Precautions (5. 7) reflux esophagitis Infants less than 6 months of age ( 4 Nursing mothers ( 4 Unstable cardiovascular status in acute hemorrhage ( 4 Myasthenia gravis ( 4 Glaucoma ( 4 Obstructive uropathy ( 4 Obstructive disease of the gastrointestinal tract ( 4 Severe ulcerative colitis ( 4 Reflux esophagitis ( 4.

Pregnancy: use only if clearly needed ( 8. 1 Pediatric Use: Safety and effectiveness not established ( 8. 4 Hepatic and renal impairment: caution must be taken with patients with significantly impaired hepatic and renal function ( 8. 6 Pregnancy Category B: Dicyclomine is contraindicated in women who are breastfeeding. Dicyclomine hydrochloride is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed infants from dicyclomine, 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) Safety and effectiveness in pediatric patients have not been established. Dicyclomine is contraindicated in infants less than 6 months of age [see Contraindications (4) Clinical studies of dicyclomine 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 in adults, 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. Effects of renal impairment on PK, safety and efficacy of dicyclomine have not been studied. Dicyclomine drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Dicyclomine should be administered with caution in patients with renal impairment. Dicyclomine should be administered with caution in patients with hepatic impairment.

Antiglaucoma agents 7 Anticholinergic agents 7 Antacids 7 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 in patients with glaucoma is not recommended [see Contraindications (4) The following agents may increase certain actions or side effects of anticholinergic drugs including dicyclomine: amantadine, antiarrhythmic agents of Class I (e. , quinidine), antihistamines, antipsychotic agents (e. , phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e. , meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants and other drugs having anticholinergic activity. Interaction with other gastrointestinal motility drugs may antagonize the effects of drugs that alter gastrointestinal motility, such as metoclopramide. Because antacids may interfere with the absorption of anticholinergic agents including dicyclomine, simultaneous use of these drugs should be avoided. Anticholinergic agents may affect gastrointestinal absorption of various drugs by affecting on gastrointestinal motility, such as slowly dissolving dosage forms of digoxin; increased serum digoxin concentration may result. 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
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 4 times daily). These events resolved after discontinuing the dicyclomine. The acute oral LD 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 [see Warnings and Precautions (5.1) It is not known if dicyclomine 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.
NONCLINICAL TOXICOLOGY
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of dicyclomine. In studies in rats at doses of up to 100 mg/kg/day, dicyclomine produced no deleterious effects on breeding, conception or parturition.
CLINICAL STUDIES
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 4 times daily) demonstrated a favorable clinical response compared with 55% treated with placebo (p < 0.05).

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