bentyl
Generic Name: (
dicyclomine hydrochloride)
Dosage Type: capsule bentyl
Generic Name: (
dicyclomine hydrochloride)
Dosage Type: tablet bentyl
Generic Name: (
dicyclomine hydrochloride)
Dosage Type: syrup bentyl
Generic Name: (
dicyclomine hydrochloride)
Dosage Type: injection Organization: Axcan Scandipharm Inc.
DESCRIPTION
BENTYL is an antispasmodic and anticholinergic (antimuscarinic)
agent available in the following 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 syrup for oral use contains 10 mg dicyclomine hydrochloride USP
in each 5 mL (1 teaspoonful). BENTYL syrup also contains inactive ingredients:
citric acid, D&C Red No. 33, FD&C Blue No. 1, FD&C Red No. 40,
FD&C Yellow No. 6, flavors, glucose, methylparaben, propylene glycol,
propylparaben, saccharin sodium, and water.
- BENTYL injection is a sterile, pyrogen-free, aqueous solution for intramuscular
injection (NOT FOR INTRAVENOUS USE).
Ampule. 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.
Chemically, BENTYL (dicyclomine hydrochloride)
is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethyl ester, hydrochloride
with the following chemical structure:
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.
CLINICAL PHARMACOLOGY
Dicyclomine relieves smooth muscle spasm of the gastrointestinal
tract. Animal studies indicate that this action is achieved via a dual mechanism:
(1) a specific anticholinergic effect (antimuscarinic) at the acetylcholine-receptor
sites with approximately 1/8 the milligram potency of atropine (in
vitro, guinea pig ileum); and (2) a direct effect upon smooth muscle
(musculotropic) as evidenced by dicyclomines antagonism of bradykinin- and
histamine-induced spasms of the isolated guinea pig ileum. 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 (BaCI2)-induced
intestinal spasm while atropine was at least 200 times more potent against
effects of ACh than BaCI2. 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.
In
man, dicyclomine is rapidly absorbed after oral administration, reaching peak
values within 60-90 minutes. The principal route of elimination 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 concentration 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. Mean volume of distribution
for a 20 mg oral dose is approximately 3.65 L/kg suggesting extensive distribution
in tissues.
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 q.i.d.) demonstrated a favorable clinical response
compared with 55% treated with placebo (p<.05). In these trials most
of the side effects were typically anticholinergic in nature (see table) and
were reported by 61% of the patients.
|
Side Effect
|
Dicyclomine
Hydrochloride
(40
mg q.i.d.)
%
|
Placebo
%
|
|
Dry Mouth
|
33
|
5
|
|
Dizziness
|
29
|
2
|
|
Blurred Vision
|
27
|
2
|
|
Nausea
|
14
|
6
|
|
Light-Headedness
|
11
|
3
|
|
Drowsiness
|
9
|
1
|
|
Weakness
|
7
|
1
|
|
Nervousness
|
6
|
2
|
Nine percent (9%) of patients were discontinued from the
drug 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.
(See ADVERSE REACTIONS.)
INDICATIONS AND USAGE
For the treatment of functional bowel/irritable bowel syndrome.
CONTRAINDICATIONS
- Obstructive uropathy
- Obstructive disease of the gastrointestinal tract
- Severe ulcerative colitis (See PRECAUTIONS)
- Reflux esophagitis
- Unstable cardiovascular status in acute hemorrhage
- Glaucoma
- Myasthenia gravis
- Evidence of prior hypersensitivity to dicyclomine hydrochloride or other
ingredients of these formulations
- Infants less than 6 months of age (See WARNINGS and PRECAUTIONS: Information for Patients.)
- Nursing Mothers (See WARNINGS and PRECAUTIONS: Information for Patients.)
WARNINGS
In the presence of a high environmental temperature, heat
prostration can occur with drug use (fever and heat stroke due to decreased
sweating). If symptoms occur, the drug should be discontinued and supportive
measures instituted.
Diarrhea may be an early symptom
of incomplete intestinal obstruction, especially in patients with ileostomy
or colostomy. In this instance, treatment with this drug would be inappropriate
and possibly harmful.
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 performing hazardous work while taking this drug.
Psychosis
has been reported in sensitive individuals given anticholinergic drugs. CNS
signs and symptoms include confusion, disorientation, short-term memory loss,
hallucinations, dysarthria, ataxia, coma, euphoria, decreased anxiety, fatigue,
insomnia, agitation and mannerisms, and inappropriate affect.
These
CNS signs and symptoms usually resolve within 12 to 24 hours after discontinuation
of the drug.
There are reports that administration
of dicyclomine hydrochloride syrup to infants has been followed by serious
respiratory symptoms (dyspnea, shortness of breath, breathlessness, respiratory
collapse, apnea, asphyxia), seizures, syncope, pulse rate fluctuations, muscular
hypotonia, and coma. Death has been reported. No causal relationship between
these effects observed in infants and dicyclomine administration has been
established. BENTYL IS CONTRAINDICATED IN INFANTS LESS THAN 6 MONTHS OF AGE
AND IN NURSING MOTHERS. (See CONTRAINDICATIONS and PRECAUTIONS: Nursing Mothers and Pediatric Use.)
Safety and efficacy of dicyclomine
hydrochloride in pediatric patients have not been established.
PRECAUTIONS
General
Use with caution in patients with:
- Autonomic neuropathy
- Hepatic or renal disease
- Ulcerative colitis-large doses may suppress intestinal motility to the
point of producing a paralytic ileus and the use of this drug may precipitate
or aggravate the serious complication of toxic megacolon (see CONTRAINDICATIONS)
- Hyperthyroidism
- Hypertension
- Coronary heart disease
- Congestive heart failure
- Cardiac tachyarrhythmia
- Hiatal hernia (see CONTRAINDICATIONS: Reflux esophagitis)
- Known or suspected prostatic hypertrophy.
Investigate any tachycardia before administration of dicyclomine
hydrochloride, since it may increase the heart rate.
With
overdosage, a curare-like action may occur (i.e., neuromuscular blockade leading
to muscular weakness and possible paralysis).
Information For Patients
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 this drug.
BENTYL is contraindicated in
infants less than 6 months of age and in nursing mothers. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: Nursing Mothers and Pediatric Use.)
In
the presence of a high environmental temperature, heat prostration can occur
with drug use (fever and heat stroke due to decreased sweating). If symptoms
occur, the drug should be discontinued and a physician contacted.
Drug Interactions
The following agents may increase certain actions or side
effects of anticholinergic drugs: 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.
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. (See also CONTRAINDICATIONS.)
Anticholinergic
agents may affect gastrointestinal absorption of various drugs, such as slowly
dissolving dosage forms of digoxin; increased serum digoxin concentration
may result. Anticholinergic drugs may antagonize the effects of drugs that
alter gastrointestinal motility, such as metoclopramide. Because antacids
may interfere with the absorption of anticholinergic agents, simultaneous
use of these drugs should be avoided. 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
There are no known human data on long-term potential for
carcinogenicity or mutagenicity.
Long-term studies
in animals to determine carcinogenic potential are not known to have been
conducted. In studies in rats at doses of up to 100 mg/kg/day, BENTYL produced
no deleterious effects on breeding, conception, or parturition.
Pregnancy
Teratogenic Effects. Pregnancy Category B.
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 impaired fertility or harm to the
fetus due to dicyclomine. Epidemiologic studies in pregnant women with products
containing dicyclomine hydrochloride (at doses up to 40 mg/day) have not shown
that dicyclomine increases the risk of fetal abnormalities if administered
during the first trimester of pregnancy. There are, however, no adequate
and well-controlled studies in pregnant women at the recommended doses (80-160
mg/day). Because animal reproduction studies are not always predictive of
human response, BENTYL as indicated for functional bowel/irritable bowel
syndrome should be used during pregnancy only if clearly needed.
Nursing Mothers
Since dicyclomine hydrochloride has been reported to be excreted
in human milk, BENTYL IS CONTRAINDICATED IN NURSING MOTHERS. (See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS: Pediatric Use and ADVERSE REACTIONS.)
Pediatric Use
(See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS: Nursing Mothers.)
BENTYL IS CONTRAINDICATED IN INFANTS LESS THAN 6 MONTHS OF AGE.
Safety and effectiveness in pediatric patients have not been established.
Geriatric 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, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (See DOSAGE AND ADMINISTRATION)
This 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. 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.
ADVERSE REACTIONS
Controlled clinical trials have provided frequency information
for reported adverse effects of dicyclomine hydrochloride listed in a decreasing
order of frequency. (See CLINICAL
PHARMACOLOGY.)
Not
all of the following adverse reactions have been reported with dicyclomine
hydrochloride. Adverse reactions are included here that have been reported
for pharmacologically similar drugs with anticholinergic/antispasmodic action.
Gastrointestinal: dry mouth, nausea, vomiting,
constipation, bloated feeling, abdominal pain, taste loss, anorexia
Central Nervous System: dizziness, light-headedness,
tingling, headache, drowsiness, weakness, nervousness, numbness, mental confusion
and/or excitement (especially in elderly persons), dyskinesia, lethargy, syncope,
speech disturbance, insomnia
Ophthalmologic: blurred vision, diplopia, mydriasis, cycloplegia, increased ocular
tension
Dermatologic/Allergic: rash, urticaria, itching, and other dermal manifestations; severe
allergic reaction or drug idiosyncrasies including anaphylaxis
Genitourinary: urinary hesitancy, urinary retention
Cardiovascular: tachycardia, palpitations
Respiratory: dyspnea, apnea, asphyxia (see WARNINGS)
Other: decreased sweating, nasal stuffiness or
congestion, sneezing, throat congestion, impotence, suppression of lactation
(see PRECAUTIONS: Nursing Mothers)
With the injectable
form, there may be temporary sensation of light-headedness. Some local irritation
and focal coagulation necrosis may occur following the I.M. injection of the
drug.
DRUG ABUSE AND DEPENDENCE
Abuse of and/or dependence on dicyclomine for anticholinergic
effects have been rarely reported.
OVERDOSAGE
Signs and Symptoms
The
signs and symptoms of overdosage are headache; nausea; vomiting; blurred vision;
dilated pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty
in swallowing; and CNS stimulation. A curare-like action may occur (i.e.,
neuromuscular blockade leading to muscular weakness and possible paralysis).
A
37-year-old female 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 QID) for four days.
These events resolved after discontinuing the dicyclomine.
Oral LD50
The
acute oral LD50 of the drug is 625 mg/kg in mice.
Minimum Human Lethal Dose/Maximum Human Dose Recorded
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), the blood concentrations
of drug were 200, 220, and 505 ng/mL, respectively.
Dialysis
It is
not know if BENTYL is dialyzable.
Treatment
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.
DOSAGE AND ADMINSTRATION
DOSAGE MUST BE ADJUSTED TO INDIVIDUAL PATIENT NEEDS (See CLINICAL
PHARMACOLOGY.)
Adults-Oral . The only oral dose clearly shown to be effective is 160 mg per
day (in 4 equally divided doses). Since this dose is associated with a significant
incidence of side effects, it is prudent to begin with 80 mg per day (in 4
equally divided doses). Depending upon the patients response during the
first week of therapy, the dose should be increased to 160 mg per 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.
Adults-Intramuscular Injection. NOT FOR INTRAVENOUS USE.
The intramuscular dosage form is to be used
temporarily when the patient cannot take oral medication. Intramuscular injection
is about twice as bioavailable as oral dosage forms; consequently, the recommended
intramuscular dose is 80 mg daily (in 4 equally divided doses). Oral dicyclomine
hydrochloride should be started as soon as possible and the intramuscular
form should not be used for periods longer than 1 or 2 days.
ASPIRATE
THE SYRINGE BEFORE INJECTING TO AVOID INTRAVASUCLAR INJECTION, SINCE THROMBOSIS
MAY OCCUR IF THE DRUG IS INADVERTENTLY INJECTED INTRAVASCULARLY. Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit.
Elderly: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. (See PRECAUTIONS Geriatric Use)
HOW SUPPLIED
10 mg blue capsules, imprinted BENTYL 10, NDC 58914-012-10: bottles of 100. Store at room temperature, preferably below 86°F (30°C).
20 mg compressed, light blue, round tablets, debossed BENTYL 20, NDC 58914-013-10: bottles of 100. To prevent fading, avoid exposure to direct sunlight. Store at room temperature, preferably below 86°F (30°C).
10 mg/5 mL pink syrup, NDC 58914-015-16: 16 ounce bottle.
Store at room temperature, preferably below 86°F (30°C). Protect from excessive heat.
20 mg/2 mL (10 mg/mL) injection (for intramuscular use only, NOT FOR INTRAVENOUS USE) NDC 58914-080-52: Boxes of five 20 mg/2
mL ampules (10 mg/mL).
Store at room temperature, preferably below 86°F (30°C). Protect from freezing.
Rx only
Rev. March 2005
Bentyl Capsules, Bentyl Tablets and Bentyl Syrup Manufactured by:
Patheon Pharmaceuticals Inc.
Cincinnati, OH 45215
Bentyl Injection Manufactured by:
Akorn Inc.
Decatur, IL 62522
Manufactured for:
Axcan Scandipharm Inc.
Birmingham, AL 35242
www.axcan.com
| Bentyl (dicyclomine hydrochloride) |
|
|
|
|
|
|
|
|
| Bentyl (dicyclomine hydrochloride) |
|
|
|
|
|
|
|
|
| Bentyl (dicyclomine hydrochloride) |
|
|
|
|
|
|
|
|
| Bentyl (dicyclomine hydrochloride) |
|
|
|
|
|
|
|
|
Revised: 10/2006Axcan Scandipharm Inc.