DICYCLOMINE HYDROCHLORIDE- dicyclomine hydrochloride injection, solution

United States - English - NLM (National Library of Medicine)

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Active ingredient:
DICYCLOMINE HYDROCHLORIDE (UNII: CQ903KQA31) (DICYCLOMINE - UNII:4KV4X8IF6V)
Available from:
Fresenius Kabi USA, LLC
Administration route:
INTRAMUSCULAR
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Dicyclomine hydrochloride is indicated for the treatment of patients with functional bowel/irritable bowel syndrome. Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age [see Use in Specific Populations ( 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 - 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 Pre
Product summary:
  Dicyclomine Hydrochloride Injection, USP is supplied as: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from freezing.
Authorization status:
Abbreviated New Drug Application
Authorization number:
63323-842-02, 63323-842-21

DICYCLOMINE HYDROCHLORIDE- dicyclomine hydrochloride injection, solution

Fresenius Kabi USA, LLC

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DICYCLOMINE HYDROCHLORIDE

INJECTION safely and effectively. See full prescribing information for DICYCLOMINE HYDROCHLORIDE

INJECTION.

DICYCLOMINE HYDROCHLORIDE injection, for intramuscular use

Initial U.S. Approval: 1950

INDICATIONS AND USAGE

Dicyclomine hydrochloride is an antispasmodic and anticholinergic (antimuscarinic) agent indicated for the treatment of

functional bowel/irritable bowel syndrome ( 1)

DOSAGE AND ADMINISTRATION

Dosage for Dicyclomine hydrochloride must be adjusted to individual patient needs. ( 2)

If a dose is missed, patients should continue the normal dosing schedule. ( 2)

Intramuscular in adults (2.2):

Intramuscular administration recommended no longer than 1 or 2 days when patients cannot take oral administration

Recommended dose: 10 mg to 20 mg four times a day

DOSAGE FORMS AND STRENGTHS

Dicyclomine Hydrochloride Injection, USP 20 mg per 2 mL (10 mg per mL) ( 3)

CONTRAINDICATIONS

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)

WARNINGS AND PRECAUTIONS

For Intramuscular injection only; should not be administered by any other route. Intravenous injection may result in

thrombosis or thrombophlebitis and injection site reactions ( 5.1)

Cardiovascular conditions: worsening of conditions ( 5.2)

Peripheral and central nervous system: heat prostration can occur with drug use (fever and heat stroke due to

decreased sweating); drug should be discontinued and supportive measures instituted ( 5.3)

Psychosis and delirium have been reported in patients sensitive to anticholinergic drugs (such as elderly patients

and/or in patients with mental illness): signs and symptoms resolve within 12 to 24 hours after discontinuation of

dicyclomine hydrochloride ( 5.3)

Myasthenia Gravis: overdose may lead to muscular weakness and paralysis. Dicyclomine hydrochloride should be

given to patients with myasthenia gravis only to reduce adverse muscarinic effects of an anticholinesterase ( 5.4)

Incomplete intestinal obstruction: diarrhea may be an early symptom especially in patients with ileostomy or

colostomy. Treatment with dicyclomine hydrochloride would be inappropriate and possibly fatal ( 5.5)

Salmonella dysenteric patients: due to risk of toxic megacolon ( 5.6)

Ulcerative colitis: Dicyclomine hydrochloride should be used with caution in these patients; large doses may suppress

intestinal motility or aggravate the serious complications of toxic megacolon ( 5.7)

Prostatic hypertrophy: Dicyclomine Hydrochloride Injection should be used with caution in these patients; may lead to

urinary retention ( 5.8)

Hepatic and renal disease: should be used with caution ( 5.9)

Geriatric: use with caution in elderly who may be more susceptible to dicyclomine hydrochloride adverse events ( 5.10)

ADVERSE REACTIONS

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 Fresenius Kabi USA, LLC, at 1-800-551-7176 or FDA at

1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Antiglaucoma agents: anticholinergics antagonize antiglaucoma agents and may increase intraocular pressure ( 7)

Anticholinergic agents: may affect the gastrointestinal absorption of various drugs; may also increase certain actions or

side effects of other anticholinergic drugs ( 7)

Antacids: interfere with the absorption of anticholinergic agents ( 7)

USE IN SPECIFIC POPULATIONS

Pregnancy: use only if clearly needed ( 8.1)

Pediatric Use: Safety and effectiveness not established ( 8.4)

Hepatic and renal impairment: caution must be taken with patients with significantly impaired hepatic and renal function

( 8.6)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 5/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.2 Intramuscular Dosage and Administration in Adults

2.3 Preparation for Intramuscular Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Inadvertent Intravenous Administration

5.2 Cardiovascular Conditions

5.3 Peripheral and Central Nervous System

5.4 Myasthenia Gravis

5.5 Intestinal Obstruction

5.6 Toxic Dilatation of Intestinemegacolon

5.7 Ulcerative Colitis

5.8 Prostatic Hypertrophy

5.9 Hepatic and Renal Disease

5.10 Geriatric Population

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

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

Action

7 DRUG INTERACTIONS

7.1 Antiglaucoma Agents

7.2 Other Drugs with Anticholinergic Activity

7.3 Other Gastrointestinal Motility Drugs

7.4 Effect of Antacids

7.5 Effect on Absorption of Other Drugs

7.6 Effect on Gastric Acid Secretion

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

17.1 Inadvertent Intravenous Administration

17.2 Use in Infants

17.3 Use in Nursing Mothers

17.4 Peripheral and Central Nervous System

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Dicyclomine hydrochloride is indicated for the treatment of patients with functional bowel/irritable

bowel syndrome.

2 DOSAGE AND ADMINISTRATION

Dosage must be adjusted to individual patient needs.

2.2 Intramuscular Dosage and Administration in Adults

Dicyclomine hydrochloride intramuscular injection must be administered via intramuscular route only.

Do not administer by any other route.

The recommended intramuscular dose is 10 mg to 20 mg four times a day [see Clinical Pharmacology (

12)] . 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.

2.3 Preparation for Intramuscular Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to

Sections or subsections omitted from the full prescribing information are not listed.

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.

3 DOSAGE FORMS AND STRENGTHS

Dicyclomine Hydrochloride Injection, USP 20 mg per 2 mL (10 mg per mL)

4 CONTRAINDICATIONS

Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age [see Use in Specific

Populations ( 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

5 WARNINGS AND PRECAUTIONS

5.1 Inadvertent Intravenous Administration

Dicyclomine hydrochloride solution is for intramuscular administration only. Do not administer by any

other route. Inadvertent intravenous administration may result in thrombosis, thrombophlebitis, and

injection site reactions such as pain, edema, skin color change, and reflex sympathetic dystrophy

syndrome [see Adverse Reactions ( 6.2)] .

5.2 Cardiovascular Conditions

Dicyclomine hydrochloride needs to be used with caution in conditions characterized by

tachyarrhythmia such as thyrotoxicosis, congestive heart failure and in cardiac surgery, where they may

further accelerate the heart rate. Investigate any tachycardia before administration of dicyclomine

hydrochloride. Care is required in patients with coronary heart disease, as ischemia and infarction may

be worsened, and in patients with hypertension [see Adverse Reactions ( 6.3)] .

5.3 Peripheral and Central Nervous System

The peripheral effects of dicyclomine hydrochloride are a consequence of their inhibitory effect on

muscarinic receptors of the autonomic nervous system. They include dryness of the mouth with

difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of the pupils

(mydriasis) with loss of accommodation (cycloplegia) and photophobia, flushing and dryness of the

skin, transient bradycardia followed by tachycardia, with palpitations and arrhythmias, and difficulty in

micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to

constipation [see Adverse Reactions ( 6)] .

In the presence of high environmental temperature heat prostration can occur with drug use (fever and

heat stroke due to decreased sweating). It should also be used cautiously in patients with fever. If

symptoms occur, the drug should be discontinued and supportive measures instituted. Because of the

inhibitory effect on muscarinic receptors within the autonomic nervous system, caution should be taken

in patients with autonomic neuropathy. Central nervous system (CNS) signs and symptoms include

confusional state, disorientation, amnesia, hallucinations, dysarthria, ataxia, coma, euphoria, fatigue,

insomnia, agitation and mannerisms, and inappropriate affect.

Psychosis and delirium have been reported in sensitive individuals (such as elderly patients and/or in

patients with mental illness) given anticholinergic drugs. These CNS signs and symptoms usually

resolve within 12 to 24 hours after discontinuation of the drug.

Dicyclomine hydrochloride may produce drowsiness, dizziness 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 dicyclomine hydrochloride.

5.4 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 [see Contraindications ( 4)] .

5.5 Intestinal Obstruction

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 [see Contraindications ( 4)] .

Rarely development of Ogilvie’s syndrome (colonic pseudo-obstruction) has been reported. Ogilvie’s

syndrome is a clinical disorder with signs, symptoms, and radiographic appearance of an acute large

bowel obstruction but with no evidence of distal colonic obstruction

5.6 Toxic Dilatation of Intestinemegacolon

Toxic dilatation of intestine and intestinal perforation is possible when anticholinergic agents are

administered in patients with Salmonella dysentery.

5.7 Ulcerative Colitis

Caution should be taken in patients with 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 Adverse Reactions ( 6.3)] . Dicyclomine hydrochloride is

contraindicated in patients with severe ulcerative colitis [see Contraindications ( 4)] .

5.8 Prostatic Hypertrophy

Dicyclomine hydrochloride should be used with caution in patients with known or suspected prostatic

enlargement, in whom prostatic enlargement may lead to urinary retention [see Adverse Reactions ( 6.3)] .

5.9 Hepatic and Renal Disease

Dicyclomine hydrochloride should be used with caution in patients with known hepatic and renal

impairment.

5.10 Geriatric Population

Dicyclomine hydrochloride should be used with caution in elderly who may be more susceptible to its

adverse effects.

6 ADVERSE REACTIONS

The pattern of adverse effects seen with dicyclomine is mostly related to its pharmacological actions at

muscarinic receptors [see 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)] .

and central nervous system symptoms [see Warnings and Precautions ( 5.2, 5.3)] .

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

Dizziness

Vision blurred

Nausea

Somnolence

Asthenia

Nervousness

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.

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 dicyclomine hydrochloride.

6.3 Adverse Reactions Reported with Similar Drugs with Adverse 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 hydrochloride.

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 hydrochloride 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 hydrochloride: 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

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

hydrochloride, 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 hydrochloride 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.

8.3 Nursing Mothers

Dicyclomine hydrochloride 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 dicyclomine hydrochloride, 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 [see Use

in Specific Populations ( 8.4)] .

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Dicyclomine hydrochloride is contraindicated in infants less than 6 months of age [see Contraindications

( 4)] . 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.

8.5 Geriatric Use

Clinical studies of dicyclomine hydrochloride 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.

8.6 Renal Impairment

Effects of renal impairment on PK, safety and efficacy of dicyclomine hydrochloride have not been

studied. Dicyclomine hydrochloride 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. Dicyclomine

hydrochloride should be administered with caution in patients with renal impairment.

8.7 Hepatic Impairment

Effects of renal impairment on PK, safety and efficacy of dicyclomine hydrochloride have not been

studied. Dicyclomine hydrochloride should be administered with caution in patients with hepatic

impairment.

10 OVERDOSAGE

In case of an overdose, patients should contact a physician, poison control center (1-800-222-1222), or

emergency room.

The signs and symptoms of overdosage include: headache; nausea; vomiting; blurred vision; dilated

pupils; hot, dry skin; dizziness; dryness of the mouth; difficulty in swallowing; and CNS stimulation

including convulsion. A curare-like action may occur (i.e., neuromuscular blockade leading to muscular

weakness and possible paralysis).

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 LD

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 1,500 mg in an adult, each of whom survived. In

three of the infants who died following administration of dicyclomine hydrochloride [see Warnings and

Precautions ( 5.1)] , the blood concentrations of drug were 200, 220, and 505 ng/mL.

It is not known if dicyclomine hydrochloride is dialyzable.

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.

11 DESCRIPTION

Dicyclomine Hydrochloride Injection,USP is an antispasmodic and anticholinergic (antimuscarinic)

agent available in the following dosage form:

Dicyclomine Hydrochloride Injection, USP is a sterile, pyrogen-free, aqueous solution for

intramuscular injection (NOT FOR INTRAVENOUS USE) supplied as a vial 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.

Dicyclomine hydrochloride is [bicyclohexyl]-1-carboxylic acid, 2-(diethylamino) ethyl ester,

hydrochloride and the following structural formula:

C

H

NO

·HCl M. W. 345.95

Dicyclomine Hydrochloride Injection, USP 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dicyclomine relieves smooth muscle spasm of the gastrointestinal tract. Animal studies indicate that this

action is achieved via a dual mechanism:

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

a direct effect upon smooth muscle (musculotropic) as evidenced by dicyclomine’s 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 (BaCl

)-induced

intestinal spasm while atropine was at least 200 times more potent against effects of ACh than BaCl

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.

12.2 Pharmacodynamics

Dicyclomine hydrochloride 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.

12.3 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

extensive distribution in tissues.

Elimination

The metabolism of dicyclomine was not studied. The principal route of excretion is via the urine

19

35

2

(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.

13 NONCLINICAL TOXICOLOGY

13.1 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.

14 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).

16 HOW SUPPLIED/STORAGE AND HANDLING

Dicyclomine Hydrochloride Injection, USP is supplied as:

Product Code Unit of Sale

Strength

Each

842102

NDC 63323-842-02

Packaged in carton of 5

20 mg per 2 mL

(10 mg per mL)

NDC 63323-842-21

2 mL Single-Dose Vial

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Protect from freezing.

17 PATIENT COUNSELING INFORMATION

17.1 Inadvertent Intravenous Administration

Dicyclomine Hydrochloride Injection is for intramuscular administration only. Do not administer by any

other route. Inadvertent administration may result in thrombosis or thrombophlebitis, and injection site

such as pain, edema, skin color change and even reflex sympathetic dystrophy syndrome [see Adverse

Reactions ( 6.2)] .

17.2 Use in Infants

Inform parents and caregivers not to administer dicyclomine hydrochloride in infants less than 6 months

of age [see Use in Specific Populations ( 8.4)] .

17.3 Use in Nursing Mothers

Advise lactating women that dicyclomine hydrochloride should not be used while breastfeeding their

infants [see Use in Specific Populations (8.3, 8.4)].

17.4 Peripheral and Central Nervous System

In the presence of a high environmental temperature, heat prostration can occur with dicyclomine

In the presence of a high environmental temperature, heat prostration can occur with dicyclomine

hydrochloride use (fever and heat stroke due to decreased sweating). If symptoms occur, the drug

should be discontinued and a physician contacted. Dicyclomine hydrochloride 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

dicyclomine hydrochloride [see Warnings and Precautions (5.3)].

Manufactured for:

www.fresenius-kabi.com/us

Made in India

451546

Issued: May 2019

PACKAGE LABEL - PRINCIPAL DISPLAY - Dicyclomine Hydrochloride 20 mg Vial Label

NDC 63323-842-21

Dicyclomine Hydrochloride Injection, USP

20 mg per 2 mL (10 mg per mL)

For Intramuscular Use Only

2 mL Single-Dose Vial Rx only

PACKAGE LABEL - PRINCIPAL DISPLAY - Dicyclomine Hydrochloride 20 mg Vial Carton

Panel

NDC 63323-842-02 842102

Dicyclomine Hydrochloride Injection, USP

20 mg per 2 mL (10 mg per mL)

For Intramuscular Use Only

5 x 2 mL

Single-Dose Vials Rx only

DICYCLOMINE HYDROCHLORIDE

dicyclomine hydrochloride injection, solution

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 3323-8 42

Route of Administration

INTRAMUSCULAR

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DICYCLO MINE HYDRO CHLO RIDE (UNII: CQ9 0 3KQA31) (DICYCLOMINE -

UNII:4KV4X8 IF6 V)

DICYCLOMINE

HYDROCHLORIDE

10 mg

in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

WATER (UNII: 0 59 QF0 KO0 R)

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:6 3323-8 42-

5 in 1 CARTON

0 9 /12/20 19

1

NDC:6 3323-8 42-

2 mL in 1 VIAL, SINGLE-DOSE; Type 0 : No t a Co mbinatio n

Pro duc t

Fresenius Kabi USA, LLC

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA210 257

0 9 /12/20 19

Labeler -

Fresenius Kabi USA, LLC (608775388)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Caplin Steriles Limited

6 50 7446 70

analysis(6 3323-8 42) , manufacture(6 3323-8 42) , pack(6 3323-8 42)

Revised: 7/2019

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