Dicycloverine Other names: Dicyclomine

Adequate and well-controlled studies have not been conducted with dicycloverine 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.

Dicycloverine 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 dicycloverine, 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.

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.

The pattern of adverse effects seen with dicylomine is mostly related to its pharmacological actions at muscarinic receptors. 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.

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. The table below presents adverse reactions (MedDRA 13.0 preferred terms) by decreasing order of frequency in a side-by-side comparison with placebo.

Adverse reactions experienced in controlled clinical trials with decreasing order of frequency:

Nine percent (9%) of patients were discontinued from dicycloverine 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.

Postmarketing Experience

The following adverse reactions, presented by system organ class in alphabetical order, have been identified during post approval use of dicycloverine. 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: dyspnoea, 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 dicycloverine.

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 dicycloverine.