Dicyclomine

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 0143-1227

Application: ANDA040161

Effective: 20211130

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

2 DOSAGE AND ADMINISTRATION Dosage must be adjusted to individual patient needs. Dosage for dicyclomine hydrochloride tablets 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.

4 CONTRAINDICATIONS Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age [see Use in Specific P opu l a ti on s (8.4) ] , nursing mothers [see Use in Specific Populations (8.3) ] and in patients with: • unstable cardiovascular status in acute hemorrhage • myasthenia gravis [see Warnings and Precautions (5.4) ] • glaucoma [see Adverse Reactions (6.3) and 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)

Not available.

6 ADVERSE REACTIONS The pattern of adverse effects seen with dicyclomine is mostly related to its pharmacological actions at muscarinic receptors [s ee Clinical Pharmacology (12) ] . They are a consequence of the inhibitory effect on muscarinic receptors within the autonomic nervous system. These effects are dose-related and are usually reversible when treatment is discontinued. The most serious adverse reactions reported with dicyclomine hydrochloride include cardiovascular and central nervous system symptoms [see Warnings and Precautions ( 5.2 , 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 Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.com 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 ( MedDRA 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 hydrochloride 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 hydrochloride. 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. C a r d i a c Disorders: palpitations, tachyarrhythmias E y e Disorders: cycloplegia, mydriasis, vision blurred G a s t r o i n t e s ti n a l Disorders: abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, nausea, vomiting G e n e r a l Disorders and Administration Site Conditions: fatigue, malaise I mm un e System Disorders: drug hypersensitivity including face edema, angioedema, anaphylactic shock N e r v o u s System Disorders: dizziness, headache, somnolence, syncope P s yc h i a t r i c Disorders: As with the other anticholinergic 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. R e p r od u c ti v e System and Breast Disorders: suppressed lactation R e s p i r a t o r y , Thoracic and Mediastinal Disorders: dyspnoea, nasal congestion S k i n and Subcutaneous Tissue Disorder: dermatitis allergic, erythema, rash 6.3 Adverse Reactions Reported with Similar Drugs with Anticholinergic/Antispasmodic Action G a s t r o i n t e s ti n a l : anorexia C e n t r a l Nervous System: tingling, numbness, dyskinesia, speech disturbance, insomnia P e r i p h e r a l Nervous System: With overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis) O p h t h a l m o l og i c : diplopia, increased ocular tension D e r m a t o l og i c / A ll e r g i c : urticaria, itching, and other dermal manifestations G e n it o u r i n a r y : urinary hesitancy, urinary retention in patients with prostatic hypertrophy C a r d i o v a s c u l a r : hypertension R e s p i r a t o r y : apnea O t h e r : decreased sweating, sneezing, throat congestion, impotence. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.com