Dicyclomine Hydrochloride (Page 2 of 4)

6.1 Clinical Trials Experience

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 four 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 (Med-DRA 13.0 preferred terms) by decreasing order of frequency in a side-by-side comparison with placebo.

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.

6.2 Postmarketing Experience

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: palpitations, tachyarrhythmias
• Eye disorders: cycloplegia, mydriasis, vision blurred
• Gastrointestinal disorders: abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, nausea, vomiting
• General disorders and administration site conditions: fatigue, malaise
• Immune system disorders: drug hypersensitivity including face edema, angioedema, anaphylactic shock
• Nervous system disorders: dizziness, headache, somnolence, syncope
• Psychiatric disorders: As with the other anti-cholinergic drugs, cases of delirium or symptoms of delirium such as amnesia (or transient global amnesia), agitation, confusional state, delusion, disorientation, hallucination (including visual hallucination) as well as mania, mood altered and pseudodementia, have been reported with the use of dicyclomine. Nervousness and insomnia have also been reported.
• Reproductive system and breast disorders: suppressed lactation
• Respiratory, thoracic and mediastinal disorders: dyspnea, nasal congestion
• Skin and subcutaneous tissue disorder: dermatitis allergic, erythema, rash

Cases of thrombosis, thrombophlebitis and injection site reactions such as local pain, edema, skin color change and even reflex sympathetic dystrophy syndrome have been reported following inadvertent IV injection of dicyclomine.

6.3 Adverse Reactions Reported with Similar Drugs with Anticholinergic/Antispasmodic Action

Gastrointestinal: anorexia

Central Nervous System: tingling, numbness, dyskinesia, speech disturbance, insomnia

Peripheral Nervous System: With overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).

Ophthalmologic: diplopia, increased ocular tension

Dermatologic/Allergic: urticaria, itching, and other dermal manifestations

Genitourinary: urinary hesitancy, urinary retention in patients with prostatic hypertrophy

Cardiovascular: hypertension

Respiratory: apnea

Other: decreased sweating, sneezing, throat congestion, impotence. With the injectable form, there may be temporary sensation of light-headedness. Some local irritation and focal coagulation necrosis may occur following the intramuscular injection of dicyclomine.

7 DRUG INTERACTIONS

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 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: 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, simultaneous use of these drugs should be avoided.

7.5 Effect on Absorption of Other Drugs

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.

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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B Adequate and well-controlled studies have not been conducted with dicyclomine 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 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.