Dicyclomine

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Dicyclomine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

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Overview

Dicyclomine is an antispasmodic and anticholinergic agent that is FDA approved for the treatment of functional bowel disorder or irritable bowel syndrome. Common adverse reactions include dizziness, dry mouth, blurred vision, nausea, somnolence, asthenia, and nervousness.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Irritable Bowel Syndrome
  • Dosing Information
  • 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.
  • Intramuscular Dosage and Administration in Adults
  • BENTYL Intramuscular Injection must be administered via intramuscular route only. Do not administer by an other route. The recommended intramuscular dose is 10 mg to 20 mg four times a day.
  • The intramuscular injection is to be used only for 1 or 2 days when the patient cannot take oral medication.
  • Intramuscular injection is about twice as bioavailable as oral dosage forms.
  • Preparation for Intramuscular Administration
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  • Aspirate the syringe before injecting to avoid intravascular injection, since thrombosis may occur if the drug is inadvertently injected intravascularly.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Dicyclomine in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Dicyclomine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Dicyclomine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Dicyclomine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Dicyclomine in pediatric patients.

Contraindications

  • BENTYL is contraindicated in infants less than 6 months of age, nursing mothers], and in patients with:

Warnings

Precautions

  • Inadvertent Intravenous Administration
  • Cardiovascular Conditions
  • Peripheral and Central Nervous System
  • 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.
  • Intestinal Obstruction
  • Toxic Dilatation of Intestine megacolon
  • Ulcerative Colitis
  • Prostatic Hypertrophy
  • Hepatic and Renal Disease
  • BENTYL should be used with caution in patients with known hepatic and renal impairment.
  • Geriatric Population
  • Dicyclomine hydrochloride should be used with caution in elderly who may be more susceptible to its adverse effects.

Adverse Reactions

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.
This image is provided by the National Library of Medicine.
  • Nine percent (9%) of patients were discontinued from BENTYL 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 BENTYL. 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.
  • 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 inadverent IV injection of BENTYL.
Body as a Whole

Fatigue, malaise

Cardiovascular

Palpitations, tachyarrhythmias

Digestive

Abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, nausea, vomiting

Endocrine

Suppressed lactation

Psychiatric

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.

Neurologic

Dizziness, headache, somnolence, syncope

Respiratory

Dyspnoea, nasal congestion

Skin and Hypersensitivy Reactions

Drug hypersensitivity including face edema, angioedema, anaphylactic shock, dermatitis allergic, erythema, rash

Special Senses

Cycloplegia, mydriasis, blurred vision

Drug Interactions

  • Antiglaucoma Agents
  • Other Drugs with Anticholinergic Activity
  • Other Gastrointestinal Motility Drugs
  • Interaction with other gastrointestinal motility drugs may antagonize the effects of drugs that alter gastrointestinal motility, such as metoclopramide.
  • Effect of Antacids
  • Effect on Absorption of Other Drugs
  • 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.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category B
  • Adequate and well-controlled studies have not been conducted with BENTYL 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 amoung 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.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dicyclomine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Dicyclomine during labor and delivery.

Nursing Mothers

  • BENTYL 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 BENTYL, a decision should be made whether to discontine nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

  • Safety and effectiveness in pediatric patients have not been established.
  • BENTYL is contraindicated in infants less than 6 months of age. There are published cases reporting that the administration of dicyclomine hydrochloride 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.

Geriatic Use

  • Clinical studies of BENTYL 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.

Gender

There is no FDA guidance on the use of Dicyclomine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Dicyclomine with respect to specific racial populations.

Renal Impairment

  • Effects of renal impairment on PK, safety and efficacy of BENTYL have not been studied. BENTYL 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. BENTYL should be administered with caution in patients with renal impairment.

Hepatic Impairment

  • Effects of renal impairment on PK, safety and efficacy of BENTYL have not been studied. BENTYL should be administered with caution in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Dicyclomine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Dicyclomine in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intramuscular

Monitoring

There is limited information regarding Monitoring of Dicyclomine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Dicyclomine in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • In case of an overdose, patients should contact a physician, poison control centre (1-800-222-1222), or emergency room.
  • 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 LD50 of the drug is 625 mg/kg in mice.
  • 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.

Management

  • 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.

Chronic Overdose

There is limited information regarding Chronic Overdose of Dicyclomine in the drug label.

Pharmacology

Dicyclomine.png
Dicyclomine
Systematic (IUPAC) name
2-(diethylamino)ethyl 1-cyclohexylcyclohexane-1-carboxylate
Identifiers
CAS number 77-19-0
ATC code A03AA07
PubChem 3042
DrugBank DB00804
Chemical data
Formula C19H35NO2 
Mol. mass 309.487 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Protein binding >99%
Metabolism ?
Half life 5 h
Excretion ?
Therapeutic considerations
Pregnancy cat.

B1(AU) B(US)

Legal status

Prescription Only (S4)(AU) ?(CA) POM(UK) -only(US)

Routes ?

Mechanism of Action

  • Dicyclomine relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this action is achieved via a dual mechanism:
  • Atropine did not affect responses to these two agonists. In vivo studies in cats and dogs showed dicyclomine to be equally potent against acetylcholine (ACh)- or barium chloride (BaCl2)-induced intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCl2. 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.

Structure

  • BENTYL is an antispasmodic and anticholinergic (antimuscarinic) agent available in the following dosage forms:
  • BENTYL capsules for oral use contain 10 mg dicyclomine hydrochloride USP. BENTYL 10 mg capsules also contain inactive ingredients: calcium sulfate, corn starch, FD&C Blue No. 1, FD&C Red No. 40, gelatin, lactose, magnesium stearate, pregelatinized corn starch, and titanium dioxide.
  • BENTYL tablets for oral use contain 20 mg dicyclomine hydrochloride USP. BENTYL 20 mg tablets also contain inactive ingredients: acacia, dibasic calcium phosphate, corn starch, FD&C Blue No. 1, lactose, magnesium stearate, pregelatinized corn starch, and sucrose.
  • BENTYL injection is a sterile, pyrogen-free, aqueous solution for intramuscular injection (NOT FOR INTRAVENOUS USE) supplied as an ampoule containing 20 mg/2 mL (10 mg/mL). Each mL contains 10 mg dicyclomine hydrochloride USP in sterile water for injection, made isotonic with sodium chloride.
  • BENTYL (dicyclomine hydrochloride) is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethyl ester, hydrochloride, with a molecular formula of C19H35NO2•HCl and the following structural formula:
This image is provided by the National Library of Medicine.
  • 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.

Pharmacodynamics

(BENTYL 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.

Pharmacokinetics

  • Absorption and Distribution
  • In man, dicyclomine is rapidly absorbed after oral administration, reaching peak values within 60-90 minutes. Mean volume of distribution for a 20 mg oral dose is approximately 3.65 L/kg suggesting exentsive distribution in tissues.
  • Elimination
  • The metabolism of dicyclomine was not studied. The principal route of excretion is via the urine (79.5% of the dose). Excretion also occurs in the feces, but to a lesser extent (8.4%). Mean half-life of plasma elimination in one study was determined to be approximately 1.8 hours when plasma concentrations were measured for 9 hours after a single dose. In subsequent studies, plasma concentrations were followed for up to 24 hours after a single dose, showing a secondary phase of elimination with a somewhat longer half-life.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 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 four times daily) demonstrated a favorable clinical response compared with 55% treated with placebo (p<0.05).

How Supplied

  • BENTYL Capsules
  • 10 mg blue capsules, imprinted BENTYL 10, supplied in bottles of 100. Store at room temperature, preferably below 86°F (30°C).
  • NDC number: 58914-012-10.


  • BENTYL Tablets
  • 20 mg compressed, light blue, round tablets, debossed BENTYL 20, supplied in bottles of 100. To prevent fading, avoid exposure to direct sunlight. Store at room temperature, preferably below 86°F (30°C).
  • NDC 58914-013-10.
  • BENTYL Injection
  • 20 mg/2 mL (10 mg/mL) injection supplied in boxes of five 20 mg/2 mL ampules (10 mg/mL). Store at room temperature, preferably below 86°F (30°C). Protect from freezing.
  • NDC 58914-080-52.

Storage

There is limited information regarding Dicyclomine Storage in the drug label.

Images

Drug Images

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Drug Label Author:

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Package and Label Display Panel

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Patient Counseling Information

  • Inadvertent Intravenous Administration
  • Use in Infants
  • Inform parents and caregivers not to administer BENTYL in infants less than 6 months of age.
  • Use in Nursing Mothers
  • Advise lactating women that BENTYL should not be used while breastfeeding their infants .
  • Peripheral and Central Nervous System
  • In the presence of a high environmental temperature, heat prostration can occur with BENTYL use (fever and heat stroke due to decreased sweating). If symptoms occur, the drug should be discontinued and a physician contacted. BENTYL may produce drowsiness 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 to perform hazardous work while taking BENTYL.

Precautions with Alcohol

  • Alcohol-Dicyclomine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

There is limited information regarding Dicyclomine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.


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