Professional Information
Anticholinergics/Antispasmodics (Systemic)
This monograph includes information on the following:1) Anisotropine †
2) Atropine
3) Belladonna †
4) Clidinium †
5) Dicyclomine
6) Glycopyrrolate
7) Homatropine †
8) Hyoscyamine
9) Mepenzolate †
10) Methantheline †
11) Methscopolamine * †
12) Pirenzepine *
13) Propantheline
14) Scopolamine
INN:
Anisotropine †—Octatropine
Dicyclomine—Dicycloverine
Glycopyrrolate—Glycopyrronium Bromide
Methantheline †—Methanthelinium
Methscopolamine †—Hyoscine Methobromide
VA CLASSIFICATION
Anisotropine
Primary: AU305
Secondary: GA801
Atropine Oral
Primary: AU305
Secondary: GA801; GU201; AD900
Atropine Parenteral
Primary: AU305
Secondary: GA801; CV300; GU201; AD900
Belladonna
Primary: AU305
Secondary: GA801
Clidinium
Primary: AU305
Secondary: GA801
Dicyclomine
Primary: AU305
Secondary: GA801
Glycopyrrolate Oral
Primary: AU305
Secondary: GA801; GA208
Glycopyrrolate Parenteral
Primary: AU305
Secondary: GA801; CV300; GA208; AD900
Homatropine
Primary: AU305
Secondary: GA801
Hyoscyamine Oral
Primary: AU305
Secondary: GA801; GU201
Hyoscyamine Parenteral
Primary: AU305
Secondary: GA801; GU201; CV300; AD900
Mepenzolate
Primary: AU305
Secondary: GA801
Methantheline
Primary: AU305
Secondary: GA801; GU201
Methscopolamine
Primary: AU305
Secondary: GA801
Pirenzepine
Primary: AU305
Secondary: GA801
Propantheline
Primary: AU305
Scopolamine Oral
Primary: AU305
Secondary: GA801; CN550; GA609; GU201
Scopolamine Parenteral
Primary: AU305
Secondary: GA801; CV300; CN206; CN550; GA609
Scopolamine Rectal
Primary: AU305
Scopolamine Transdermal
Primary: CN550
Commonly used brand name(s): A-Spas S/L8; Anaspaz8; Banthine10; Bentyl5; Bentylol5; Buscopan14; Cantil9; Cystospaz8; Cystospaz-M8; Donnamar8; ED-SPAZ8; Formulex5; Gastrosed8; Gastrozepin12; Homapin7; Levbid8; Levsin8; Levsin/SL8; Levsinex Timecaps8; Pro-Banthine13; Propanthel13; Quarzan4; Robinul6; Robinul Forte6; Spasmoban5; Symax SL8; Symax SR8; Transderm-Scop14; Transderm-V14.
Other commonly used names are:
Dicycloverine —Dicyclomine
Glycopyrronium bromide —Glycopyrrolate
Hyoscine hydrobromide —Scopolamine
Hyoscine methobromide —Methscopolamine * †
Methanthelinium — Methantheline †
Octatropine —Anisotropine †
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
*Not commercially available in the U.S.
†Not commercially available in Canada.
Category:
Note: All of these medications have anticholinergic and, to some extent, antispasmodic actions; however, the labeled indications for specific agents may vary because of minor differences in potency and/or receptor selectivity. In general, there is a lack of specific testing and/or clinical-use data to support the indication of anticholinergics/antispasmodics in most conditions. {14} {31}
Anticholinergic—Anisotropine; * †Atropine; Belladonna; †Clidinium; †Dicyclomine; Glycopyrrolate; Homatropine; * †Hyoscyamine; Mepenzolate; †Methantheline; †Methscopolamine; * †Pirenzepine; * †Propantheline; Scopolamine;
Antispasmodic, gastrointestinal—Dicyclomine; Scopolamine Butylbromide;
Antidysmenorrheal—Belladonna; †Scopolamine Butylbromide;
Antiarrhythmic—Atropine (parenteral only); Glycopyrrolate (parenteral only); Hyoscyamine (parenteral only); Scopolamine (parenteral only);
Antidote (to cholinesterase inhibitors)—Atropine; Hyoscyamine (parenteral only);
Antidote (to muscarine)—Atropine; Hyoscyamine (parenteral only);
Antidote (to organophosphate pesticides)—Atropine;
Antispasmodic, urinary—Atropine; Scopolamine;
Cholinergic adjunct (curariform block)—Atropine (parenteral only); Glycopyrrolate (parenteral only); Hyoscyamine (parenteral only);
Anesthesia adjunct—Scopolamine (parenteral only);
Antiemetic—Scopolamine;
Antivertigo agent—Belladonna; †Scopolamine;
Antidiarrheal—Glycopyrrolate;
Indications
Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.
Accepted
Ulcer, peptic (treatment adjunct)—All anticholinergics included in this monograph, except dicyclomine and scopolamine hydrobromide, are FDA approved in conjunction with antacids or histamine H 2-receptor antagonists in the treatment of peptic ulcer, to reduce further gastric acid secretion and delay gastric emptying. However, the use of most anticholinergics as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Results with anticholinergics usually are inconsistent and transient and require high doses, which result in significant side effects. {12} Atropine {99}, belladonna, clidinium, hyoscyamine, pirenzepine {100} {101} {102} {103}, and propantheline taken orally may be used rarely. Intravenous use of hyoscyamine may be indicated for prompt relief of pain in the treatment of both the moderately severe and the severe peptic ulcer. {14} {34} {36} {41} {42} {44} {45} {48} {53} {64} {67} Anisotropine, glycopyrrolate, homatropine, mepenzolate, methantheline, and methscopolamine are generally no longer used for this indication. {97}
Bowel syndrome, irritable (treatment)—Atropine {33}, belladonna {26} {104}, [clidinium] , dicyclomine {02} {37} {104}, [glycopyrrolate ] , hyoscyamine {94} {104}, [propantheline] {104}, and [ scopolamine] {42} {97} are indicated in the treatment of irritable bowel syndrome, mainly in patients in whom other therapy, such as sedation and/or change in diet, has failed. However, results usually are inconsistent and transient and require high doses, which result in significant side effects. Anisotropine, mepenzolate, methantheline, methscopolamine, and pirenzepine are generally no longer used for this indication. {97}
Urologic disorders, symptoms of (treatment)—Oral hyoscyamine is indicated to control hypermotility in cystitis. {42} However, results of anticholinergic treatment usually are inconsistent and transient and require high doses, which result in significant side effects. {97} Atropine and scopolamine butylbromide are generally no longer used for this indication. {97}
Urinary incontinence (treatment)—[ Propantheline]1 {74} {75} {97} {105} is used in the treatment of uninhibited hypertonic neurogenic bladder to increase bladder capacity by reducing amplitude and frequency of bladder contractions. {46} Atropine and methantheline are generally no longer used for this indication. {97}
Hypersecretory conditions, gastric, in anesthesia (prophylaxis) —Parenteral glycopyrrolate is indicated as preanesthetic medication to reduce gastric acid secretion. {39} {88}
Salivation and respiratory tract secretions, excessive, in anesthesia (prophylaxis)—Oral and parenteral atropine {33} {34} {35} {89} and the parenteral forms of glycopyrrolate {39} {89} and scopolamine1 {51} are indicated as antisialagogue preanesthetic medications to prevent or reduce salivation and respiratory tract secretions. Parenteral hyoscyamine is no longer used for these indications. {97}
Arrhythmias, succinylcholine-induced (prophylaxis) or
Arrhythmias, surgical procedure-induced (prophylaxis) —The parenteral form of atropine {35} is indicated as adjunct to anesthesia to prevent reflex bradycardia, sinus arrest, and hypotension induced by succinylcholine during intubation of the trachea or produced by certain surgical manipulations. {26} Parenteral scopolamine is generally no longer used for these indications.
Arrhythmias, cardiac (treatment) or
Bradycardia, sinus (treatment)—Parenteral atropine {35} is indicated to reduce severe sinus bradycardia {83} and syncope associated with hyperactive carotid sinus reflex; and to lessen the degree of atrioventricular heart block in Type I atrioventricular (AV) conduction deficits. It is also used to treat ventricular asystole. {83} {84} {85} Parenteral atropine also is indicated as an antidote for sinus bradycardia resulting from the improper administration of a choline ester medication. {12} Parenteral hyoscyamine is generally no longer used for these indications. {97}
Arrhythmias, in anesthesia (treatment) or
Arrhythmias, in surgery (treatment)—The parenteral form of atropine is indicated to restore cardiac rate and arterial pressure when increased vagal activity has reduced pulse rate and cardiac action. Parenteral glycopyrrolate is indicated to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation. {39} Parenteral glycopyrrolate is also indicated intraoperatively to counteract drug-induced or vagal traction reflexes with the associated arrhythmias. {39} Parenteral hyoscyamine and parenteral scopolamine are generally no longer used for these indications. {97}
Toxicity, cholinesterase inhibitor (prophylaxis)—The parenteral forms of atropine {86} and glycopyrrolate {39} {92} are indicated for administration prior to or concurrently with neostigmine or pyridostigmine during reversal of nondepolarizing neuromuscular blockade to protect against the muscarinic effects of these drugs, such as bradycardia and excessive secretions. {34} {35} Parenteral hyoscyamine is generally no longer used for this indication. {97}
Toxicity, cholinesterase inhibitor (treatment)
Toxicity, muscarine (treatment) or
Toxicity, organophosphate pesticide (treatment)— Oral and parenteral atropine {33} {35} are indicated in the treatment of poisoning from cholinesterase inhibitors such as neostigmine, pilocarpine, physostigmine, and methacholine, and in the treatment of the rapid type of mushroom (muscarine) poisoning. {12} {35} Atropine is also indicated in the treatment of poisoning caused by pesticides that are organophosphate cholinesterase inhibitors, chemical warfare, and ``nerve"" gases. {03} {05} {33} Parenteral hyoscyamine is generally no longer used for these indications. {97}
Anesthesia, general, adjunct—Parenteral administration of scopolamine1 , in combination with morphine or meperidine, is indicated in preanesthesia to reduce excitement and produce amnesia. {12} {51} Scopolamine may also be used for opioid-induced respiratory depression. {73} Parenteral scopolamine1 is also indicated in conjunction with analgesics in cardiopulmonary bypass patients who cannot be deeply anesthetized because of the risk of severe hypotension or circulatory collapse. {51}
Motion sickness (prophylaxis and treatment)—Transdermal scopolamine is indicated for prophylaxis of nausea and vomiting associated with motion sickness. {50} {73} {90} {95}
Nausea and vomiting, post operative (prophylaxis) 1—Transdermal scopolamine is indicated for the prevention of nausea and vomiting associated with recovery from anesthesia and surgery, post operative nausea and vomiting (PONV).{118}
Pneumonitis, aspiration (prophylaxis)—Parenteral glycopyrrolate may provide some protection against aspiration of gastric contents during anesthesia. {06} {39}
[Asthma (treatment adjunct)]1—Inhaled atropine is indicated for the treatment of asthma in adult and pediatric patients, as part of a combination regimen. Atropine is to be used for its acute bronchodilatory effects, when ipratropium is not a feasible alternative.
{109}{110}{111}{112}{113}{114}{115}{116}
[Salivation, excessive, postsurgical (prophylaxis)]1or
[Salivation, excessive, medical condition–related (prophylaxis)]1—Transdermal scopolamine is used for short-term control of drooling in postsurgical patients and in patients with goiter or other medical conditions in whom excessive salivation becomes a social problem. {11} {15} {72}
[Salivation, excessive, in dental procedures (prophylaxis)]1—The oral forms of atropine {97}, glycopyrrolate {98} {106}, methantheline {01} {97} {106}, and propantheline {98} {106} are used to control excessive salivation that interferes with dental procedures. {01} {13} Belladonna is generally no longer used for this indication.
Anticholinergics/antispasmodics listed below are FDA (U.S.) and HPB (Canada) approved for the following indications; however, they generally have been replaced by more effective agents— • Biliary tract disorders (treatment adjunct)—Atropine, hyoscyamine, and scopolamine butylbromide. {97}
• Radiography, gastrointestinal, adjunct—Parenteral atropine and parenteral hyoscyamine. {97}
• Dysmenorrhea (treatment)—Belladonna and scopolamine butylbromide. {76}
• Enuresis, nocturnal (treatment)—Belladonna and scopolamine butylbromide. {76}
• Rhinitis, allergic, severe (treatment)—Oral hyoscyamine. {76}
Anticholinergics/antispasmodics listed below have been used for the following indications; however, they generally have been replaced by more effective agents— • [Diarrhea (treatment)]1—Glycopyrrolate. {76}
• [Parkinsonism (treatment)]1—Oral atropine, belladonna, parenteral hyoscyamine, oral hyoscyamine and scopolamine combination, and oral scopolamine. {12} {26} {42}
Unaccepted
Hyoscyamine elixir and oral solution have been used in the treatment of infant colic. {42} However, there is no conclusive evidence of effectiveness for this use. {26}
1 Not included in Canadian product labeling.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Chemical group—
Tertiary amines: Atropine, belladonna, hyoscyamine, and scopolamine.
Quaternary ammonium compounds: Anisotropine, clidinium, glycopyrrolate, homatropine, mepenzolate, methantheline, methscopolamine, and propantheline.
Molecular weight—
Anisotropine methylbromide: 362.35
Atropine: 289.37
Clidinium bromide: 432.36
Dicyclomine hydrochloride: 345.95
Glycopyrrolate: 398.34
Homatropine methylbromide: 370.29
Hyoscyamine: 289.37
Hyoscyamine sulfate: 712.85
Mepenzolate bromide: 420.35
Methantheline bromide: 420.35
Methscopolamine bromide: 398.30
Pirenzepine: 351.41
Propantheline bromide: 448.40
Scopolamine hydrobromide: 438.31
pKa—
Atropine: 9.8
Dicyclomine: 9.0 {06}
Scopolamine: 7.55–7.81
Mechanism of action/Effect:
Anticholinergic—The naturally occurring belladonna alkaloids, semisynthetic derivatives, quaternary ammonium compounds, and, to a lesser extent, the synthetic tertiary amines inhibit the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. Depending on the dose, anticholinergics may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, the smaller doses of anticholinergics inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion. {09}
Antispasmodic, gastrointestinal—Unproven. A local and direct action on smooth muscle, to reduce tone and motility of the gastrointestinal tract, has been suggested to explain the apparent gastrointestinal antispasmodic effect of the synthetic tertiary amine compounds. {06} {08}
Antidysmenorrheal—Effectiveness in relieving dysmenorrhea is due to spasmolytic action.
Antiarrhythmic—Inhibition of muscarinic actions of acetylcholine at postganglionic receptor sites present in the autonomic effector cells of the cardiac muscle, and sinoatrial and atrioventricular nodes.
Antidote (to cholinesterase inhibitors; to muscarine; to organophosphate pesticides)—Atropine and hyoscyamine antagonize the actions of cholinesterase inhibitors at muscarinic receptor sites, including increased tracheobronchial and salivary secretion, bronchoconstriction, autonomic ganglionic stimulation, and, to a moderate extent, central actions.
Cholinergic adjunct (curariform block)—Atropine and hyoscyamine antagonize the actions, such as vagal and secretory enhancing effects, of cholinesterase inhibitors used in the treatment of nondepolarizing neuromuscular blockade. {07}
Anesthesia adjunct—Scopolamine depresses the cerebral cortex; in large doses and in conjunction with analgesics, produces loss of memory.
Antiemetic—Belladonna and scopolamine act primarily by reducing the excitability of the labyrinthine receptors and by depressing conduction in the vestibular cerebellar pathway.
Antivertigo—The exact mechanism by which belladonna and scopolamine exert their antimotion sickness and antivertigo effects is unknown; however, they probably act either on the cortex or more peripherally on the maculae of the utricle and saccule.
Antidiarrheal—Glycopyrrolate may reduce the activity of the gastrocolic reflex and the excessive peristaltic activity of both the small and large bowels.
Other actions/effects:
Natural tertiary amines:
Atropine: Stimulates or depresses the central nervous system (CNS), depending on the dose; and has a more prolonged and potent action than the other belladonna alkaloids on the heart, intestine, and bronchial muscle.
Belladonna alkaloids: In parkinsonism, selectively depress certain central motor mechanisms in the CNS, controlling muscle tone and movement.
Hyoscyamine: Has actions similar to those of atropine, but is more potent in both its central and peripheral effects.
Scopolamine: Has peripheral action similar to that of atropine but, in contrast to atropine, is depressant to the CNS at therapeutic doses; it does not stimulate the medullary centers and therefore does not increase respiration or elevate blood pressure. Scopolamine has a more potent action than atropine on the sphincter muscle of the iris and the ciliary muscle of the lens, and on the secretory glands such as salivary, bronchial, and sweat glands.
Quaternary ammonium compounds, semisynthetic and synthetic:
In contrast to atropine and scopolamine, effects of these medications on the CNS are negligible. These medications are also less likely to affect the pupil or ciliary muscle of the eye. Ganglionic blockade is attributed to some increased effects of the high dosage range, and toxic doses produce neuromuscular blockade. {06} {09}
Synthetic tertiary amines:
These medications produce less prominent CNS effects than do the natural tertiary amines. {08}
Absorption:
Tertiary amines—Rapidly absorbed from gastrointestinal tract; also enter the circulation through the mucosal surfaces of the body.
Quaternary ammonium compounds—Gastrointestinal absorption is poor and irregular. Total absorption after an oral dose is about 10 to 25%.
Distribution:
Exact distribution of anticholinergics has not been fully determined. However, tertiary amines appear to be distributed throughout the entire body {12} and readily cross the blood-brain barrier, while quaternary ammonium compounds exhibit minimal passage across the blood-brain barrier and into the eye.
Atropine, belladonna, and hyoscyamine are distributed into breast milk.
Protein binding:
Atropine—Moderate.
Hyoscyamine—Moderate.
Scopolamine hydrobromide—Low.
Biotransformation:
Most anticholinergics—Hepatic, by enzymatic hydrolysis.
Half-life:
Elimination:
Atropine: 2.5 hours. {09}
Dicyclomine hydrochloride: 1.8 hours (initial phase) and 9 to 10 hours (secondary phase). {06}
Glycopyrrolate: 1.7 hours (range 0.6–4.6 hours).
Hyoscyamine: 3.5 hours. {06}
Pirenzepine—10 to 12 hours.
Propantheline bromide—1.6 (mean) hours.
Scopolamine—8 hours.
Time to peak effect:
Glycopyrrolate—Intramuscular: 30 to 45 minutes.
| Drug |
Onset of Action |
Duration of Action |
Elimination (% excreted unchanged) |
|---|---|---|---|
| Anisotropine methylbromide |
* |
||
| Atropine |
Oral: 4–6 hr Parenteral: Brief |
Renal (30–50) |
|
| Belladonna |
1–2 hr |
4 hr |
Renal (30–50 of atropine and 1 of scopolamine) |
| Clidinium bromide |
1 hr |
Up to 3 hr |
* |
| Dicyclomine hydrochloride |
* |
||
| Glycopyrrolate |
IM or SC: 15–30 min IV: 1 min |
Antisialagogue: Up to 7 hr Vagal blocking effect: 2–3 hr |
Renal |
| Homatropine |
* |
||
| Hyoscyamine sulfate |
Oral: 20–30 min Parenteral: 2–3 min |
4–6 hr |
Renal (majority) |
| Mepenzolate bromide |
Renal (3–22) |
||
| Methantheline bromide |
* |
||
| Methscopolamine bromide |
1 hr |
6–8 hr |
* |
| Pirenzepine hydrochloride |
Renal/hepatic (80–90) |
||
| Propantheline bromide |
6 hr |
Renal (<6) |
|
| Scopolamine |
Transdermal: Up to 72 hr |
Renal |
|
| Scopolamine hydrobromide |
Antisialagogue— Oral: 30–60 min Parenteral: 30 min |
Oral: 4–6 hr Parenteral: 4 hr |
Renal (1 of oral dose) (3.4 of SC dose) |
Precautions to Consider
Cross-sensitivity and/or related problems
For all anticholinergics—Patients sensitive to one belladonna alkaloid or derivative may be sensitive to the other belladonna alkaloids or derivatives also.
Pregnancy/Reproduction
Pregnancy—
For anistropine methylbromide
Problems in humans have not been documented. {31}
FDA pregnancy category not currently included in product labeling.
For atropine
Atropine crosses the placenta. Well-controlled studies in humans have not been done. Intravenous administration of atropine during pregnancy or near term may produce tachycardia in the fetus.
Studies in mice have not shown that atropine given in doses of 50 mg per kg of body weight (mg/kg) has adverse effects on the fetus.
FDA Pregnancy Category C. {34}
For belladonna
Belladonna crosses the placenta. Studies with belladonna have not been done in either animals or humans.
FDA Pregnancy Category C.
For clidinium
Adequate and well-controlled studies in humans have not been done.
Reproduction studies in rats have not shown that clidinium has adverse effects on the fetus. {01} {36}
FDA pregnancy category not currently included in product labeling.
For dicyclomine
Dicyclomine has been associated in several isolated cases with human malformations; however, in retrospective studies there has been no evidence of dicyclomine having any untoward effect on the embryo.
FDA pregnancy category not currently included in product labeling.
For glycopyrrolate
Controlled studies in humans have not been done.
Studies in rats and rabbits have not shown that glycopyrrolate causes teratogenic effects. {39} However, studies in rats have shown that rates of conception and of survival at weaning decreased in a dose-related manner with glycopyrrolate. Studies in dogs with high doses of glycopyrrolate suggest that this may be caused by a decrease in seminal secretion. {39}
FDA Pregnancy Category B. {39}
For hyoscyamine
Hyoscyamine crosses the placenta. Studies with hyoscyamine have not been done in either animals or humans. {42} Intravenous administration of hyoscyamine during pregnancy, especially near term, may produce tachycardia in the fetus.
FDA Pregnancy Category C.
For mepenzolate
Adequate and well-controlled studies in humans have not been done.
Reproduction studies in rats and rabbits have not shown that mepenzolate has adverse effects on the fetus. {01} {45}
FDA pregnancy category not currently included in product labeling.
For propantheline
Studies have not been done in either animals or humans.
FDA Pregnancy Category C. {49}
For scopolamine
Scopolamine crosses the placenta. Studies with scopolamine have not been done in either animals or humans.
FDA Pregnancy Category C.
Labor—
For scopolamine: Parenteral administration of scopolamine before the onset of labor may cause CNS depression in the neonate and may contribute to neonatal hemorrhage {108} due to reduction in vitamin K-dependent clotting factors in the neonate.
Breast-feeding
For all anticholinergics—Anticholinergics may inhibit lactation. {36} {44}
For atropine, belladonna, and hyoscyamine—These drugs are distributed into breast milk. Although amounts have not been quantified, the chronic use of these medications should be avoided during nursing since infants are usually very sensitive to the effects of anticholinergics. {01} {18}
For dicyclomine—Although a causal relationship has not been established, the use of dicyclomine in nursing mothers is not recommended, since respiratory distress has been reported in infants less than 3 months of age who ingested dicyclomine directly (not through breast milk). {01} {18}
For quaternary ammonium compounds—It is unlikely that these drugs are excreted in breast milk since they are incompletely absorbed from the gastrointestinal tract and have poor lipid solubility. {18}
Pediatrics
For all anticholinergics:
Infants and young children are especially susceptible to the toxic effects of anticholinergics.
Close supervision is recommended for infants and children with spastic paralysis or brain damage since an increased response to anticholinergics has been reported in these patients and dosage adjustments are often required.
When anticholinergics are given to children where the environmental temperature is high, there is risk of a rapid increase in body temperature because of these medications' suppression of sweat gland activity.
A paradoxical reaction characterized by hyperexcitability may occur in children taking large doses of anticholinergics.
For dicyclomine:
Respiratory symptoms, such as difficulty in breathing, shortness of breath, respiratory collapse and apnea; as well as seizures, syncope, asphyxia, pulse rate fluctuations, muscular hypotonia, and coma have been reported in some infants, 3 months old and under, with the use of dicyclomine syrup. These side effects occurred within minutes of ingestion and lasted 20 to 30 minutes. They are believed to have been caused by local irritation and/or aspiration rather than by a direct pharmacologic action.
Geriatrics
Geriatric patients may respond to usual doses of anticholinergics with excitement, agitation, drowsiness, or confusion.
Geriatric patients are especially susceptible to the anticholinergic side effects, such as constipation, dryness of mouth, and urinary retention (especially in males). If these side effects occur and continue or are severe, medication should probably be discontinued.
Caution is also recommended when anticholinergics are given to geriatric patients, because of the danger of precipitating undiagnosed glaucoma.
Memory may become severely impaired in geriatric patients, especially those who already have memory problems, with the continued use of anticholinergics since these drugs block the actions of acetylcholine, which is responsible for many functions of the brain, including memory functions. {16} {17} {18} {19}
Dental
Prolonged use of anticholinergics may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort. {01}
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Only specific interactions between anticholinergics and other oral medications have been identified in this monograph. However, because of decreased gastrointestinal motility and delayed gastric emptying, absorption of other oral medications may be decreased during concurrent use with anticholinergics. {31}
For all anticholinergics
Alkalizers, urinary, such as: {32}
Antacids, calcium- and/or magnesium-containing
Carbonic anhydrase inhibitors
Citrates
Sodium bicarbonate (urinary excretion of anticholinergics may be delayed by alkalinization of the urine, thus potentiating the anticholinergics" therapeutic and/or side effects)
» Antacids or
» Antidiarrheals, adsorbent (simultaneous use of these medications may reduce absorption of anticholinergics, resulting in decreased therapeutic effectiveness; doses of these medications should be spaced 2 or 3 hours apart from doses of anticholinergics {25} {26} {43})
» Anticholinergics or other medications with anticholinergic activity, other (see Appendix II ) (concurrent use with anticholinergics may intensify anticholinergic effects; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy {24} {45})
Antimyasthenics (concurrent use with anticholinergics may further reduce intestinal motility; therefore, caution is recommended; although atropine may be used to reduce or prevent the muscarinic effects of antimyasthenics, routine concurrent use is not recommended since the muscarinic effects may be the first signs of antimyasthenic overdose, and masking such effects with atropine may prevent early recognition of cholinergic crisis {56} {57})
» Cyclopropane (concurrent intravenous administration of anticholinergics with cyclopropane anesthesia may result in ventricular arrhythmias; however, if the anticholinergic used is glycopyrrolate, the risk is reduced if glycopyrrolate is given in increments of 100 mcg [0.1 mg] or less {01} {09} {39})
Haloperidol {34} {37} (antipsychotic effectiveness of haloperidol may be decreased in schizophrenic patients)
» Ketoconazole (anticholinergics may increase gastrointestinal pH, possibly resulting in a marked reduction in ketoconazole absorption during concurrent use with anticholinergics; patients should be advised to take these medications at least 2 hours after ketoconazole {20})
Metoclopramide (concurrent use with anticholinergics may antagonize metoclopramide's effects on gastrointestinal motility {21} {23})
Opioid (narcotic) analgesics (concurrent use with anticholinergics may result in increased risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention {61} {62})
» Potassium chloride, especially wax-matrix preparations (concurrent use with anticholinergics may increase severity of potassium chloride–induced gastrointestinal lesions {13} {27} {28})
For scopolamine (in addition to interactions listed above)
» CNS depression-producing medications, other (see Appendix II ) (concurrent use may potentiate the effects of either these medications or scopolamine, resulting in additive sedation {30})
Lorazepam, parenteral (concurrent use of scopolamine and parenteral lorazepam is reported to have no added beneficial effect and their combined effect may increase the incidence of sedation, hallucination, and irritational behavior {58})
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With diagnostic test results
For all anticholinergics:
» Gastric acid secretion test (concurrent use of anticholinergics may antagonize the effect of pentagastrin and histamine in the evaluation of gastric acid secretory function; administration of anticholinergics is not recommended during the 24 hours preceding the test )
Radionuclide gastric emptying studies (use of anticholinergics may result in delayed gastric emptying {54} {55})
For atropine (in addition to those listed for all anticholinergics) :
» Phenolsulfonphthalein (PSP) excretion test (atropine utilizes the same tubular mechanism of excretion as PSP resulting in decreased urinary excretion of PSP; concurrent use of atropine is not recommended in patients receiving PSP excretion test)
For scopolamine (in addition to those listed for all anticholinergics) :
Neuroradiological tests (residual cycloplegia and mydriasis following use of transdermal disk of scopolamine may affect results of neuroradiological tests for intracranial neoplasm, subdural hematoma, or aneurysm)
With physiology/laboratory test values
For glycopyrrolate
Serum uric acid (may be decreased in patients with hyperuricemia or gout)
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Brain damage, in children (CNS effects may be exacerbated)
» Cardiac disease, especially cardiac arrhythmias, congestive heart failure, coronary artery disease, and mitral stenosis (increase in heart rate may be undesirable)
Down"s syndrome (abnormal increase in pupillary dilation and acceleration of heart rate may occur)
» Esophagitis, reflux (decrease in esophageal and gastric motility and relaxation of lower esophageal sphincter may promote gastric retention by delaying gastric emptying and may increase gastroesophageal reflux through an incompetent sphincter)
Fever (may be increased through suppression of sweat gland activity)
» Gastrointestinal tract obstructive disease as in achalasia and pyloroduodenal stenosis (decrease in motility and tone may occur, resulting in obstruction and gastric retention {31})
» Glaucoma, angle-closure, or predisposition to (mydriatic effect resulting in increased intraocular pressure may precipitate an acute attack of angle-closure glaucoma {31})
» Glaucoma, open-angle (mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted {10} {31})
» Hemorrhage, acute, with unstable cardiovascular status (increase in heart rate may be undesirable {31})
Hepatic function impairment (decreased metabolism of anticholinergic {31})
» Hernia, hiatal, associated with reflux esophagitis (anticholinergics may aggravate condition {31})
Hypertension (may be aggravated)
Hyperthyroidism (characterized by tachycardia, which may be increased {31})
» Intestinal atony in the elderly or debilitated patient or
» Paralytic ileus (anticholinergic use may result in obstruction {31})
Lung disease, chronic, especially in infants, small children, and debilitated patients (reduction in bronchial secretion can lead to inspissation and formation of bronchial plugs)
» Myasthenia gravis {31} (condition may be aggravated because of inhibition of acetylcholine action )
Neuropathy, autonomic {31} (urinary retention and cycloplegia may be aggravated)
» Prostatic hypertrophy, nonobstructive or
» Urinary retention, or predisposition to or
» Uropathy, obstructive, such as bladder neck obstruction due to prostatic hypertrophy (urinary retention may be precipitated or aggravated {31})
» Pyloric obstruction (may be aggravated)
Renal function impairment {31} (decreased excretion may increase the risk of side effects)
Sensitivity to any belladonna alkaloids or derivatives
Spastic paralysis, in children (response to anticholinergics may be increased)
» Tachycardia {31} (may be increased)
Toxemia of pregnancy (hypertension may be aggravated)
» Ulcerative colitis {31} (large anticholinergic doses may suppress intestinal motility, possibly causing paralytic ileus; also, use may precipitate or aggravate the serious complication, toxic megacolon)
Xerostomia {31} (prolonged use may further reduce limited salivary flow)
Caution in use is also recommended in patients over 40 years of age because of the danger of precipitating undiagnosed glaucoma.
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Intraocular pressure determinations (recommended at periodic intervals, as these medications may increase the intraocular pressure by producing mydriasis)
Side/Adverse Effects
Note: When anticholinergics are given to patients, especially children, where the environmental temperature is high, there is risk of a rapid increase in body temperature because of suppression of sweat gland activity.
Infants, patients with Down"s syndrome, and children with spastic paralysis or brain damage may show an increased response to anticholinergics, thus increasing the potential for side effects.
Geriatric or debilitated patients may respond to usual doses of anticholinergics with excitement, agitation, drowsiness, or confusion.
Following use of the transdermal disk of scopolamine, a dilated and fixed pupil has been reported on the side where the disk was worn. This condition usually resolves spontaneously within a few days, but may persist for up to 2 weeks after the disk has been removed and thus may be mistaken for a sign of intracranial neoplasm, subdural hematoma, or aneurysm. To avoid extensive neuroradiological tests, instillation of 1% pilocarpine solution is recommended as an aid in the diagnosis of non-neurogenic dilation of the pupil. {04}
Table 1. Side/Adverse Effects *
| The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive: |
Legend: I=Anisotropine II=Atropine III=Belladonna IV=Clidinium |
V=Dicyclomine VI=Glycopyrrolate VII=Homatropine VIII=Hyoscyamine |
IX=Mepenzolate X=Methantheline XI=Methscopolamine |
XII=Pirenzepine XIII=Propantheline XIV=Scopolamine |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I |
II |
III |
IV |
V |
VI |
VII |
VIII |
IX |
X |
XI |
XII |
XIII |
XIV |
|
| Medical attention needed |
||||||||||||||
| Allergic reaction (skin rash or hives) |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Confusion # |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Increased intraocular pressure (eye pain) † |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Orthostatic hypotension (dizziness, feeling faint, or continuing lightheadedness) |
§ |
R |
R |
§ |
R |
§ |
§ |
R |
§ |
§ |
§ |
R |
§ |
R |
| Medical attention needed only if continuing or bothersome Bloated feeling |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Constipation |
M |
M |
M |
M |
M |
M |
M |
L |
M |
M |
M |
M |
M |
M |
| Decreased flow of breast milk |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
| Decreased salivary secretion (difficulty in swallowing) |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
L |
| Decreased sweating |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
| Difficult urination ** |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Difficulty in accommodation of the eye (blurred vision) † |
R |
L |
L |
R |
L |
R |
R |
L |
R |
R |
R |
L |
R |
L |
| Drowsiness †† |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
M |
| Dryness of mouth, nose, throat, or skin |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
M |
| False sense of well-being |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
R |
| Headache |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Lightheadedness, temporary—with parenteral administration |
U |
U |
U |
U |
R |
R |
U |
R |
U |
U |
U |
U |
U |
R |
| Loss of memory ‡‡ |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
M |
| Mydriatic effect (increased sensitivity of eyes to light) † |
R |
L |
L |
R |
L |
R |
R |
L |
R |
R |
R |
L |
R |
L |
| Nausea or vomiting |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Paradoxical reaction (trouble in sleeping) |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
R |
| Redness or other signs of irritation at injection site |
U |
M |
U |
U |
M |
M |
U |
M |
U |
U |
U |
U |
U |
M |
| Unusual tiredness or weakness |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
R |
| Medical attention needed if they occur after scopolamine is discontinued Anxiety |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
§§ |
| Irritability |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
§§ |
| Nightmares |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
§§ |
| Trouble in sleeping |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
U |
§§ |
† Quaternary ammonium compounds are fully ionized in the pH range of body fluids and possess reduced lipid solubility. Therefore, they penetrate cellular barriers less effectively and only pass across the blood-brain barrier or into the eye with difficulty. Central and ocular effects are negligible and/or less likely to occur with quaternary ammonium compounds.
‡ With quaternary ammonium compounds, difficulty in breathing, severe muscle weakness, and severe tiredness may occur because of the compounds" curare-like effects; these effects may lead to respiratory paralysis.
§ Orthostatic hypotension, due to ganglion-blocking activity, is more likely to occur with high doses of quaternary ammonium compounds.
# Confusion may occur more frequently in geriatric patients.
** Difficult urination is more likely to occur in older men and may require medical attention in patients with symptoms of prostatism.
†† More frequent with high doses of anticholinergics, but a common side effect with therapeutic doses of oral or parenteral scopolamine.
‡‡ Scopolamine, administered parenterally as preanesthetic medication and/or given in large doses, may have a temporary but detrimental effect on memory. In geriatric patients, especially those who already have memory problems, the continued use of any anticholinergic may severely impair memory.
§§ May indicate rebound reduction in rapid eye movement (REM) time.
Overdose
For specific information on the agents used in the management of overdose with anticholinergics/antispasmodics, see:
• Benzodiazepines (Systemic) monograph;
• Charcoal, Activated (Oral-Local) monograph;
• Chloral Hydrate (Systemic) monograph;
• Neostigmine Methylsulfate in Antimyasthenics (Systemic) monograph;
• Norepinephrine Bitartrate or Metaraminol Bitartrate in Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) monograph;
• Physostigmine Salicylate (Systemic) monograph; and/or
• Thiopental in Anesthetics, Barbiturate (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Blurred vision, continuing, or changes in near vision
clumsiness or unsteadiness
confusion
difficulty in breathing —may lead to respiratory paralysis with quaternary ammonium compounds because of curare-like effects
dizziness
drowsiness, severe
dryness of mouth, nose, or throat, severe
fast heartbeat
fever
hallucinations
muscle weakness, severe —may lead to respiratory paralysis with quaternary ammonium compounds because of curare-like effects
seizures
slurred speech
tiredness, severe —may lead to respiratory paralysis with quaternary ammonium compounds because of curare-like effects
unusual excitement, nervousness, restlessness, or irritability
unusual warmth, dryness, and flushing of skin
Treatment of overdose
Recommended treatment for anticholinergic overdose includes the following:
To decrease absorption:
Emesis or gastric lavage with 4% tannic acid solution.
Administration of an aqueous slurry of activated charcoal.
Specific treatment:
To reverse severe anticholinergic symptoms, slow, intravenous administration of physostigmine in doses of 0.5 to 2 mg (0.5 to 1 mg in children, up to a total dose of 2 mg), at a rate not to exceed l mg per minute; may be given in repeated doses of 1 to 4 mg as needed, up to a total dose of 5 mg in adults.
Or, neostigmine methylsulfate administered intramuscularly in doses of 0.5 to 1 mg, repeated every 2 to 3 hours; or intravenously in doses of 0.5 to 2 mg, repeated as needed.
To control excitement or delirium, administration of small doses of a short-acting barbiturate (100 mg thiopental sodium) or benzodiazepines, or rectal infusion of 2% solution of chloral hydrate.
To restore blood pressure, infusion of norepinephrine bitartrate or metaraminol.
Supportive care:
Artificial respiration with oxygen if needed for respiratory depression.
Adequate hydration.
Symptomatic treatment as necessary.
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Anticholinergics/Antispasmodics (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to any of the belladonna alkaloids or derivatives
Breast-feeding—Excreted in breast milk (except for quaternary ammonium compounds); possible inhibition of lactation
Use in children—Increased susceptibility to toxic effects of anticholinergics; increased response in infants and children with spastic paralysis or brain damage; risk of increased body temperature in hot weather; hyperexcitability (paradoxical reaction) with large doses; increased risk of respiratory depression and collapse (with dicyclomine)
Use in the elderly—Increased susceptibility to mental and other toxic effects of anticholinergics; danger of precipitating undiagnosed glaucoma; possible impairment of memory
Dental—Possible development of dental problems because of decreased salivary flow
Other medications, especially other anticholinergics, antacids, antidiarrheals, cyclopropane, ketoconazole, CNS depressants (with scopolamine), and potassium chloride
Other medical problems, especially cardiac disease, glaucoma, hemorrhage, hiatal hernia, intestinal atony or paralytic ileus, myasthenia gravis, obstruction in gastrointestinal or urinary tract, prostatic hypertrophy, reflux esophagitis, tachycardia, and ulcerative colitis
Proper use of this medication
For oral dosage forms
Taking medication 30 minutes to 1 hour before meals
For rectal dosage forms
Proper administration technique
For transdermal scopolamine
Reading patient directions
Washing and drying hands thoroughly before and after application
Applying to hairless, intact area of skin behind ear; not applying over cuts or irritations
» Importance of not taking more medication than the amount prescribed
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses
» Proper dosing
» Proper storage
Precautions while using this medication
» Suspected overdose: Getting emergency help at once
» Caution during exercise or hot weather; overheating may result in heat stroke
» Possible increased sensitivity of eyes to light
Caution about abrupt withdrawal
» Caution if blurred vision occurs
» Possible dizziness or drowsiness; caution when driving or doing things requiring alertness
Possible dizziness or lightheadedness; caution when getting up suddenly from a lying or sitting position
Possible dryness of mouth; using sugarless candy or gum, ice or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks
For scopolamine
» Avoiding use of alcohol or other CNS depressants
For oral dosage forms
Avoiding use of antacids and antidiarrheal medications within 2 or 3 hours of taking this medication
Side/adverse effects
Signs of potential side effects, especially allergic reaction, confusion, increased intraocular pressure, orthostatic hypotension (especially with high doses of quaternary ammonium compounds)
General Dosing Information
Tolerance to some of the adverse reactions may develop following continued use and/or smaller doses of anticholinergics, but effectiveness may also be reduced. {26}
Dosage adjustments are often required for infants, patients with Down's syndrome, children with brain damage or spasticity, since an increased responsiveness to anticholinergics has been reported in these patients. {26}
Geriatric and debilitated patients may respond to usual doses with excitement, agitation, drowsiness, or confusion; lower doses may be required in these patients. {26}
Anticholinergics should not be withdrawn abruptly since withdrawal-like symptoms may occur. Vomiting, malaise, sweating, transient dizziness {50}, and salivation have been reported after sudden withdrawal of large doses of scopolamine.
If scopolamine is used as antisialagogue preanesthetic medication in minor surgical procedures that do not require more than a few hours' stay in the hospital, the patient should be alerted at time of discharge about scopolamine's lingering detrimental effects on memory and motor tasks. {07}
High dosage of quaternary ammonium compounds should not be given continuously for prolonged periods, since ganglionic and skeletal neuromuscular transmission may be blocked. Stimulation of the CNS and a curare-like action may result.
For oral dosage forms only
Administration of anticholinergics 30 minutes to 1 hour before meals is recommended to maximize absorption.
For parenteral dosage forms only
Atropine, hyoscyamine, and scopolamine may be administered by intramuscular, subcutaneous, or intravenous injection.
Glycopyrrolate may be administered by intramuscular or intravenous injection.
After parenteral administration a temporary feeling of lightheadedness and local irritation may occur. {01} {09}
For transdermal dosage forms only
Transdermal application delivers reduced doses of scopolamine, which are large enough to be effective but small enough to eliminate most of the adverse effects, except drowsiness and cycloplegia.
Oral Dosage Forms
ANISOTROPINE METHYLBROMIDE TABLETS
Usual adult and adolescent dose
Anticholinergic
Oral, 50 mg three times a day, the dosage being adjusted as needed and tolerated. {01} {31}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual pediatric dose
Dosage has not been established. {06}
Strength(s) usually available
U.S.—
50 mg (Rx)[Generic]
Canada—
Not commercially available.
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.
Auxiliary labeling:
• May cause blurred vision.
Summary of Differences
Category:
Also an antidote (to cholinesterase inhibitors; to organophosphate pesticides; to muscarine) and a urinary antispasmodic. Parenteral atropine is used as an antiarrhythmic and cholinergic adjunct (curariform block).
Indications:
Also indicated for biliary tract disorders and duodenography. In preanesthesia and dental anesthesia, indicated as antisialagogue.
Pharmacology/pharmacokinetics:
Protein binding—Moderate.
Half-life (elimination)—2.5 hours.
Duration of action—Oral, 4 to 6 hours; parenteral, brief.
Elimination—Renal; 30 to 50% excreted unchanged.
Precautions:
Pregnancy—Intravenous administration may produce tachycardia in fetus.
Laboratory value alterations—May decrease excretion of phenolsulfonphthalein (PSP) during PSP excretion test.
Additional Dosing Information
See also General Dosing Information.
Doses of 0.5 to 1 mg of atropine are mildly stimulating to the CNS. Larger doses may produce mental disturbances; very large doses have depressant effect.
The fatal dose of atropine in children may be as low as 10 mg.
Oral Dosage Forms
ATROPINE SULFATE TABLETS USP
Usual adult and adolescent dose
Anticholinergic
Oral, 300 mcg (0.3 mg) to 1.2 mg every four to six hours.
Prophylaxis of excessive salivation and respiratory tract secretions, in anesthesia
Oral, 2 mg. {07}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual pediatric dose
Anticholinergic
Oral, 10 mcg (0.01 mg) per kg of body weight, not to exceed 400 mcg (0.4 mg), or 300 mcg (0.3 mg) per square meter of body surface, every four to six hours.
Strength(s) usually available
U.S.—
400 mcg (0.4 mg) (Rx)[Generic]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.
Auxiliary labeling:
• May cause blurred vision.
ATROPINE SULFATE SOLUBLE TABLETS
Usual adult and adolescent dose
Anticholinergic
Oral, 300 mcg (0.3 mg) to 1.2 mg every four to six hours.
Prophylaxis of excessive salivation and respiratory tract secretions, in anesthesia
Oral, 2 mg. {07}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual pediatric dose
Anticholinergic
Oral, 10 mcg (0.01 mg) per kg of body weight, not to exceed 400 mcg (0.4 mg), or 300 mcg (0.3 mg) per square meter of body surface, every four to six hours.
Strength(s) usually available
U.S.—
400 mcg (0.4 mg) (Rx)[Generic]
600 mcg (0.6 mg) (Rx)[Generic]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.
Auxiliary labeling:
• May cause blurred vision.
Parenteral Dosage Forms
Note: Bracketed information in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.
ATROPINE SULFATE INJECTION USP
Usual adult and adolescent dose
Anticholinergic
Intramuscular, intravenous, or subcutaneous, 400 to 600 mcg (0.4 to 0.6 mg) every four to six hours. {34}
Gastrointestinal radiography
Intramuscular, 1 mg.
Prophylaxis of excessive salivation and respiratory tract secretions, in anesthesia
Intramuscular, 200 to 600 mcg (0.2 to 0.6 mg) one-half to one hour before surgery.
Antiarrhythmic
Intravenous, 400 mcg (0.4 mg) to 1 mg every one to two hours as needed, up to a maximum of 2 mg. {34}
Cholinergic adjunct (curariform block)
Intravenous, 600 mcg (0.6 mg) to 1.2 mg administered a few minutes before or concurrently with 500 mcg (0.5 mg) to 2 mg of neostigmine methylsulfate, using separate syringes. {05}
Antidote (to cholinesterase inhibitors)
Intravenous, 2 to 4 mg initially, then 2 mg repeated every five to ten minutes until muscarinic symptoms disappear or signs of atropine toxicity appear.
Antidote (to muscarine in mushroom poisoning)
Intramuscular or intravenous, 1 to 2 mg every hour until respiratory effects subside.
Antidote (to organophosphate pesticides)
Intramuscular or intravenous, 1 to 2 mg, repeated in twenty to thirty minutes as soon as cyanosis has cleared. Continue dosage until definite improvement occurs and is maintained, sometimes for two days or more.
[Antiasthmatic ]1
Administered as an inhalation solution, diluted with saline, patients have benefited from a dose of 0.05 to 0.1 mg/kg, nebulized three to four times daily. Total dose should not exceed 2.5 mg.
{109}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual pediatric dose
Anticholinergic
Subcutaneous, 10 mcg (0.01 mg) per kg of body weight, not to exceed 400 mcg (0.4 mg) {34}, or 300 mcg (0.3 mg) per square meter of body surface, every four to six hours.
Prophylaxis of excessive salivation and respiratory tract secretions, in anesthesia or
Prophylaxis of succinylcholine- or surgical procedure–induced arrhythmias
Subcutaneous:
Children weighing up to 3 kg: 100 mcg (0.1 mg).
Children weighing 7 to 9 kg: 200 mcg (0.2 mg).
Children weighing 12 to 16 kg: 300 mcg (0.3 mg).
Children weighing 20 to 27 kg: 400 mcg (0.4 mg).
Children weighing 32 kg: 500 mcg (0.5 mg).
Children weighing 41 kg: 600 mcg (0.6 mg).
Antiarrhythmic
Intravenous, 10 to 30 mcg (0.01 to 0.03 mg) per kg of body weight.
Antidote (to cholinesterase inhibitors)
Intravenous or intramuscular, 1 mg initially, then 0.5 to 1 mg every five to ten minutes until muscarinic symptoms disappear or signs of atropine toxicity appear.
[Antiasthmatic ]1
Administered as an inhalation solution, diluted with saline, pediatric patients have benefited from a dose of 0.025 to 0.05 mg/kg, nebulized three to four times daily. Total dose should not exceed 2.5 mg.
{109}{113}{117}
Strength(s) usually available
U.S.—
50 mcg (0.05 mg) per mL (Rx)[Generic]
100 mcg (0.1 mg) per mL (Rx)[Generic]
300 mcg (0.3 mg) per mL (Rx)[Generic]
400 mcg (0.4 mg) per mL (Rx)[Generic]
500 mcg (0.5 mg) per mL (Rx)[Generic]
800 mcg (0.8 mg) per mL (Rx)[Generic]
1 mg per mL (Rx)[Generic]
Canada—
400 mcg (0.4 mg) per mL (Rx)[Generic]
600 mcg (0.6 mg) per mL (Rx)[Generic]
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.
Additional information:
The intravenous injection of atropine should be administered slowly.
Summary of Differences
Category:
Also an antidysmenorrheal and antivertigo agent.
Indications:
Also indicated in nocturnal enuresis. In dental procedures, may be used as antisialagogue.
Pharmacology/pharmacokinetics:
Onset of action—1 to 2 hours.
Duration of action—4 hours.
Elimination—Renal; 30 to 50% of atropine and 1% of scopolamine excreted unchanged.
Oral Dosage Forms
BELLADONNA TINCTURE USP
Usual adult and adolescent dose
Anticholinergic
Oral, 180 to 300 mcg (0.18 to 0.3 mg) three or four times a day, thirty minutes to one hour before meals and at bedtime, the dosage being adjusted as needed and tolerated.
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual pediatric dose
Anticholinergic
Oral, 9 mcg (0.009 mg) per kg of body weight or 240 mcg (0.24 mg) per square meter of body surface a day, in three or four divided doses.
Strength(s) usually available
U.S.—
300 mcg (0.3 mg) per mL (Rx)[Generic]
Note: Belladonna tincture contains 300 mcg (0.3 mg) of belladonna alkaloids (principally hyoscyamine and atropine) per mL.
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.
Auxiliary labeling:
• May cause blurred vision.
• Keep container tightly closed.
Summary of Differences
Pharmacology/pharmacokinetics:
Onset of action—1 hour.
Duration of action—Up to 3 hours.
Oral Dosage Forms
CLIDINIUM BROMIDE CAPSULES USP
Usual adult and adolescent dose
Anticholinergic
Oral, 2.5 to 5 mg three or four times a day, before meals and at bedtime {36}, the dosage being adjusted as needed and tolerated.
Note: Geriatric or debilitated patients—Oral, 2.5 mg three times a day before meals. {36}
Usual pediatric dose
Dosage has not been established.
Strength(s) usually available
U.S.—
2.5 mg (Rx) [Quarzan]
5 mg (Rx) [Quarzan]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.
Auxiliary labeling:
• May cause blurred vision.
Summary of Differences
Category:
Also gastrointestinal antispasmodic.
Indications:
Not indicated for peptic ulcer.
Pharmacology/pharmacokinetics:
Half-life (elimination)—1.8 hours (initial phase) and 9 to 10 hours (secondary phase).
Precautions:
Pediatrics—Respiratory symptoms, seizures, syncope, asphyxia, pulse rate fluctuations, muscular hypotonia, and coma reported with the use of the syrup in some infants 3 months old and under.
Oral Dosage Forms
DICYCLOMINE HYDROCHLORIDE CAPSULES USP
Usual adult and adolescent dose
Antispasmodic, gastrointestinal: Irritable bowel syndrome
Oral, 10 to 20 mg three or four times a day, the dosage being adjusted as needed and tolerated. {37}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual adult prescribing limits
Up to 160 mg daily. {37}
Usual pediatric dose
Antispasmodic, gastrointestinal
Children up to 6 years of age: Product not suitable for pediatric administration. See Dicyclomine Hydrochloride Syrup USP.
Children 6 years of age and over: Oral, 10 mg three or four times a day, the dosage being adjusted as needed and tolerated.
Strength(s) usually available
U.S.—
10 mg (Rx) [Bentyl][Generic]
20 mg (Rx)[Generic]
Canada—
10 mg (Rx) [Formulex]
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.
Auxiliary labeling:
• May cause blurred vision.
DICYCLOMINE HYDROCHLORIDE SYRUP USP
Usual adult and adolescent dose
Antispasmodic, gastrointestinal: Irritable bowel syndrome
Oral, 10 to 20 mg three or four times a day, the dosage being adjusted as needed and tolerated. {38}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual adult prescribing limits
Up to 160 mg daily. {38}
Usual pediatric dose
Antispasmodic, gastrointestinal
Children up to 6 months of age: Use is not recommended.
Children 6 months to 2 years of age: Oral, 5 to 10 mg three or four times a day, the dosage being adjusted as needed and tolerated.
Children 2 years of age and over: Oral, 10 mg three or four times a day, the dosage being adjusted as needed and tolerated.
Strength(s) usually available
U.S.—
10 mg per 5 mL (Rx) [Bentyl][Generic]
Canada—
10 mg per 5 mL (Rx) [Bentylol]
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.
Auxiliary labeling:
• May cause blurred vision.
DICYCLOMINE HYDROCHLORIDE TABLETS USP
Usual adult and adolescent dose
Antispasmodic, gastrointestinal: Irritable bowel syndrome
Oral, 10 to 20 mg three or four times a day, the dosage being adjusted as needed and tolerated. {38}
Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.
Usual adult presc