AHFS Class:

• Antimuscarinics/Antispasmodics 12:08.08

Generic Name(s):

• Hyoscyamine

• Hyoscyamine Sulfate

Hyoscyamine is a naturally occurring tertiary amine antimuscarinic.

GI Disorders

Hyoscyamine sulfate is used as an adjunct in the treatment of peptic ulcer disease. As with other antimuscarinics, there are no conclusive data from well-controlled studies that indicate that, in usually recommended dosage, hyoscyamine sulfate aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. In addition, in patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis.

Hyoscyamine sulfate is used as an adjunct in the treatment of functional GI disorders such as irritable bowel syndrome. As with other antimuscarinics, hyoscyamine sulfate has limited efficacy in the treatment of these disorders and should be used only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit. Although hyoscyamine sulfate has also been used in combination with phenobarbital in the treatment of irritable bowel syndrome, attempts to substantiate claims of efficacy for fixed combinations that include an antimuscarinic and phenobarbital have generally failed and these combinations are generally considered as lacking substantial evidence of efficacy in the treatment of this condition.

Although hyoscyamine sulfate has been used in the treatment of hypermotility and diarrhea associated with GI disorders such as ulcerative colitis, dysentery, shigellosis, and Clostridium difficile -associated diarrhea and colitis (also known as antibiotic-associated pseudomembranous colitis), the drug should be used with extreme caution, if at all, in patients with these conditions. (See Cautions: Precautions and Contraindications, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.)

Genitourinary Tract Disorders

Hyoscyamine and hyoscyamine sulfate have been used as adjunctive therapy in the management of hypermotility disorders of the lower urinary tract. Although these agents may provide symptomatic relief, the underlying cause should be determined and specifically treated. Appropriate anti-infective therapy should be initiated whenever urinary tract infection is present. Although hyoscyamine has been used in combination with methenamine and other drugs, the dose of methenamine (40.8 mg) contained in most combination preparations was inadequate for use as an anti-infective. With the exception of uninhibited or reflex neurogenic bladder, there is generally little evidence to support the use of antimuscarinics in the treatment of various genitourinary disorders. (See Uses: Genitourinary Tract Disorders, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.)

Infant Colic

Hyoscyamine sulfate oral solution (drops) and elixir have been used in the treatment of infant colic.106,109,114,117,120,121,122,123,124,126 However, there is minimal evidence from well-designed clinical studies of the efficacy of antimuscarinics in the management of this condition. Infant colic is considered a benign, self-limiting condition that tends to resolve spontaneously and not require medical treatment.

Surgery

Hyoscyamine sulfate injection has been used as a preoperative medication to inhibit salivation and excessive secretions of the respiratory tract; however, the current practice of using thiopental (no longer commercially available in the US), halothane, or similar general anesthetics that do not stimulate the production of salivary and tracheobronchial secretions has reduced the need to control excessive respiratory secretions during surgery.

Although hyoscyamine sulfate injection has been used prophylactically to reduce the volume and acidity of gastric secretions and to prevent acid-aspiration pneumonitis during surgery,107 antimuscarinics have not been shown to be effective for this use.

Hyoscyamine sulfate injection may be used to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation.107 The drug prevents cholinergic effects during surgery, such as cardiac arrhythmias, hypotension, and bradycardia, which may result from traction on viscera (with resultant vagal stimulation), stimulation of the carotid sinus, or administration of drugs (e.g., succinylcholine).

Hyoscyamine sulfate injection is administered concurrently with anticholinesterase agents (e.g., neostigmine) to block the adverse muscarinic effects of these latter agents when they are used after surgery to terminate curarization. For further discussion on the use of hyoscyamine sulfate injection in surgery, see Uses: Surgery, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.

Other Uses

Hyoscyamine sulfate injection is used as an antidote in the treatment of cholinesterase inhibitor toxicity. Hyoscyamine sulfate oral and sublingual preparations also are used in the treatment of cholinesterase inhibitor toxicity.100,106,109,110,112,113,114,116,117,119,120,121,122,123,124,126 Hyoscyamine sulfate also has been used as a drying agent in the relief of symptoms of acute rhinitis and as adjunctive therapy in the treatment of parkinsonian syndrome to reduce rigidity and tremors and to control associated sialorrhea and hyperhidrosis. For further discussion on the use of antimuscarinics in these conditions, see Uses: Other Uses, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.

Hyoscyamine sulfate injection has been used to facilitate endoscopy or hypotonic duodenography by reducing GI motility;107 however, glucagon appears to be more effective and is generally preferred in this examination. Hyoscyamine sulfate injection also has been used to increase visualization of the urinary tract in excretion urography.

Hyoscyamine sulfate has been used in conjunction with morphine or other opiates for the symptomatic relief of biliary or renal colic; however, since antimuscarinics exert only a weak biliary antispasmodic action, these drugs should not be relied on in the treatment of biliary tract disease. Hyoscyamine sulfate injection has been used to reduce pain and hypersecretion in pancreatitis; however, there is little, if any, evidence that antimuscarinics improve the prognosis of the disease. (See Uses: Other Uses, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.) Hyoscyamine sulfate injection also has been used concomitantly with a cholinesterase reactivator (e.g., pralidoxime) to reverse muscarinic effects associated with toxic exposure to anticholinesterase compounds (e.g., organophosphate pesticides); however, other antimuscarinic agents (principally atropine) are more commonly used for this purpose.128 In some patients, hyoscyamine sulfate injection may be useful in treating partial heart block associated with vagal activity.

Administration

Hyoscyamine is administered orally. Hyoscyamine sulfate is usually administered orally or sublingually. Hyoscyamine sulfate also may be administered by IV, IM, or subcutaneous injection when oral or sublingual administration is not feasible or when rapid therapeutic effect is necessary. Hyoscyamine sulfate is commercially available as conventional (immediate-release) tablets, extended-release capsules and tablets, oral solutions (drops), elixirs, sublingual tablets, orally disintegrating tablets, and injection.100,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,126

Immediate-release preparations of hyoscyamine sulfate (conventional, sublingual, or orally disintegrating tablets; oral solutions [drops]; elixirs) generally are administered orally or sublingually 3-6 times daily.100,106,114,115,116,117,118,119,120,121,122,123,126

Extended-release preparations of hyoscyamine sulfate should not be crushed or chewed.109,110 Symax^® SR and Symax^® DuoTab^® tablets should be swallowed whole,108,111 while Levbid^®110 tablets and certain generic preparations112,113 are scored and may be broken in order to titrate dosage.110,112,113 Extended-release preparations generally are administered every 12 hours,108,109,110,111,112,113,124 but preparations that are not scored may be administered every 8 hours if dosage adjustment is required.108,109,111,124 Patients should be advised that extended-release preparations may not completely disintegrate and fragments may be excreted in stools in some patients.108,109,110,113

Sublingual tablets of hyoscyamine sulfate (i.e., Levsin^®/SL, Symax^® SL, generic preparations) may be administered sublingually or orally.114,115,116,117 Certain sublingual tablets (e.g., Levsin^®/SL, certain generic preparations) also may be chewed.114,116,117 The manufacturers of Levsin^®/SL and certain generic preparations state that oral administration of the sublingual tablets results in similar pharmacologic effects as sublingual administration, although the onset may not be as rapid.114,116,117

Orally disintegrating tablets of hyoscyamine sulfate (i.e., NuLev^®, Symax^® FasTab^®, generic preparations) are administered by placing a tablet on the tongue to dissolve and be swallowed with the saliva; orally disintegrating tablets may be administered with or without water.100,118,119 Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that each 0.125-mg NuLev^®, Symax^® FasTab^®, or generic hyoscyamine sulfate (marketed by Ethex) orally disintegrating tablet contains aspartame (NutraSweet^®), which is metabolized in the GI tract to provide about 1.7, 4.5, or 0.5 mg, respectively, of phenylalanine following oral administration.100,101,102,103,104,105,119,127

Because antacids may decrease absorption of oral hyoscyamine sulfate when these drugs are administered simultaneously, most manufacturers recommend administration of hyoscyamine sulfate before meals and administration of antacids postprandially.100,106,112,114,116,117,119,120,121,122,123,124,126 One manufacturer recommends routine administration of hyoscyamine sulfate (Symax^® formulations) 30-60 minutes before meals.108,111,115,118

Hyoscyamine sulfate injection may be administered by IV, IM, or subcutaneous injection without prior dilution.107 Parenteral hyoscyamine sulfate solutions should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Dosage

Hyoscyamine Dosage

The usual adult oral dosage of hyoscyamine is 0.15-0.3 mg, given up to 4 times daily. If the drug is used in older pediatric patients, dosage should be reduced in proportion to age and weight.

Hyoscyamine Sulfate Oral and Sublingual Dosage

Dosage should be carefully titrated according to the condition, severity of symptoms, and the individual patient's response and tolerance to the drug.100,106,109,110,112,113,114,115,116,117,118,119,120,121,122,123,124,126 Geriatric patients may be more sensitive to the effects of the drug at usual adult dosages.108,111,115

The usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution or elixir) in adults and pediatric patients 12 years of age or older is 0.125-0.25 mg, given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 1.5 mg in a 24-hour period.100,106,114,116,117,118,119,120,121,122,123,126 One manufacturer (Symax^® SL) recommends an oral or sublingual dosage of 0.125-0.25 mg 3 or 4 times daily.115 Alternatively, in adults and pediatric patients 12 years of age or older, 0.375-0.75 mg every 12 hours, not to exceed a total dosage of 1.5 mg in a 24-hour period, may be given orally as extended-release capsules or tablets. If dosage adjustment is required, extended-release capsules and tablets may be administered at a dosage of 0.375 mg every 8 hours.108,109,111,124 As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.

For pediatric patients 2-11 years of age, the usual dosage of hyoscyamine sulfate (as conventional, sublingual, or orally disintegrating tablets or as an oral solution) is 31.25-125 mcg (0.03125-0.125 mg) given orally or sublingually every 4 hours or as needed, not to exceed a total dosage of 750 mcg in a 24-hour period.100,106,114,116,117,118,119,120,121,122,123,126 One manufacturer (Symax^® SL) recommends that pediatric patients 2-11 years of age receive an oral or sublingual dosage of 62.5-125 mcg (0.0625-0.125 mg) 3 or 4 times daily.115 Alternatively, some manufacturers state that pediatric patients 2-11 years of age may receive a dosage of 375 mcg (0.375 mg) every 12 hours (as extended-release capsules or tablets), not to exceed 750 mcg in a 24-hour period.108,111,124 Manufacturers of hyoscyamine sulfate elixir recommend that dosage in patients 2-11 years of age be determined based on body weight (see Table 1).122,123,126

For pediatric patients younger than 2 years of age, manufacturers of hyoscyamine sulfate oral solution (drops) recommend weight-based dosing (see Table 2).120,121,126

Hyoscyamine Sulfate Parenteral Dosage

The usual IV, IM, or subcutaneous dosage of hyoscyamine sulfate for the treatment of GI disorders in adults is 0.25-0.5 mg every 4 hours, 2-4 times daily. For the treatment of acute symptoms associated with GI disorders, a single parenteral dose of 0.25-0.5 mg may be sufficient. Dosage should be adjusted according to the individual patient's response and tolerance.

For diagnostic procedures (e.g., endoscopy, hypotonic duodenography) in adults, 0.25-0.5 mg of hyoscyamine sulfate is administered by IV, IM, or subcutaneous injection 5-10 minutes prior to the diagnostic procedure.107

As a preoperative medication in adults and pediatric patients older than 2 years of age, the usual dose of hyoscyamine sulfate is 5 mcg (0.005 mg) per kg given IV, IM, or subcutaneously 30-60 minutes prior to the anticipated time of induction of anesthesia or at the time other preanesthetic medications (e.g., opiates, sedatives) are administered. For intraoperative use to reverse drug-induced bradycardia, hyoscyamine sulfate is administered IV in 0. 125-mg increments, repeated as necessary.107

To block adverse muscarinic effects of anticholinesterase agents (i.e., neostigmine, physostigmine, pyridostigmine) when these agents are used to reverse the neuromuscular blockade produced by curariform agents, the usual IV dose of hyoscyamine sulfate in adults and pediatric patients older than 2 years of age is 0.2 mg for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered;107 hyoscyamine sulfate is administered concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent. In the presence of bradycardia, hyoscyamine sulfate should be given IV before the anticholinesterase agent to increase the pulse rate to about 80 beats/minute.

For the treatment of muscarinic toxicity resulting from exposure to anticholinesterase compounds (e.g., organophosphate pesticides), the usual initial adult dose of hyoscyamine sulfate is 1-2 mg, preferably administered IV. Additional 1-mg doses may be administered IM or IV every 3-10 minutes until muscarinic signs and symptoms subside and repeated if they reappear. Up to 25 mg of the drug may be required during the first 24 hours of therapy. Subsequently, 0.5-1 mg may be administered orally at intervals of several hours as maintenance therapy until signs and symptoms completely subside. A cholinesterase reactivator (e.g., pralidoxime) is administered concomitantly with antimuscarinic therapy.

Pharmacokinetics

Since hyoscyamine is one of the optical isomers comprising atropine, the pharmacokinetics of hyoscyamine ( l -hyoscyamine) and atropine ( dl -hyoscyamine) are generally considered similar. It has not been fully determined whether any stereoselective pharmacokinetic handling occurs with hyoscyamine isomers; however, following IV administration of atropine in one study, decline in plasma concentrations did not appear to be stereoselective.

Absorption

Hyoscyamine is completely absorbed from the GI tract following oral or sublingual administration.100,106,108,109,110,112,113,114,115,116,117,118,119,120,121,122,123,124,126 Food does not appear to affect absorption of the drug.

Hyoscyamine sulfate extended-release capsules (i.e., Levsinex^® Timecaps^®109 , generic preparations124 ) and extended-release tablets (i.e., Levbid^®,110 generic preparations112,113 ) are formulated to release 0.375 mg of the drug at a controlled and predictable rate for a 12-hour period,109,110,112,113,124 whereas bilayer extended-release tablets (i.e., Symax^® DuoTab^®) are formulated to release 0.125 mg of hyoscyamine sulfate immediately and 0.25 mg over 8-12 hours.108 The relative bioavailability of hyoscyamine sulfate extended-release capsules or tablets that are formulated to release the drug at a controlled and predictable rate for a 12-hour period reportedly is about 81 or 92%, respectively, that of the conventional tablets of the drug;112,124 peak blood concentrations of hyoscyamine occur in 2.5-5 or about 4 hours following administration of these extended-release capsule or tablet formulations, respectively.109,110,112,113,124

The commercially available extended-release capsules (Levsinex^® Timecaps^®) contain small beads of hyoscyamine sulfate which are surrounded by a porous membrane that permits fluids to enter and dissolve the drug; the manufacturer states that 0.375 mg of drug is delivered from a capsule at an approximate rate of 0.125 mg/4 hours. In a crossover study comparing extended-release capsules and conventional tablets, bioavailability (as determined by area under the plasma concentration-time curve) during the first 4 hours after administration of a single 0.375-mg dose as extended-release capsules was about 43% that of a single 0.125-mg dose as conventional tablets when the data were corrected for difference in dose.

Following parenteral administration of hyoscyamine sulfate, the drug has an onset of action of 2-3 minutes; peak pharmacologic action occurs within 15-30 minutes and persists for up to 4 hours. Following oral administration of hyoscyamine sulfate conventional tablets, the drug has an onset of action of 20-30 minutes. When hyoscyamine sulfate conventional tablets are chewed or administered sublingually or when the drug is administered orally as an elixir or solution, the drug has an onset of action of 5-20 minutes. Oral administration of the sublingual tablets results in similar pharmacologic effects as sublingual administration, although the onset may not be as rapid.114,116,117 Pharmacologic action peaks within 30-60 minutes and persists for about 4 hours when hyoscyamine sulfate is administered orally as conventional tablets, elixir, or solution or sublingually as conventional tablets or when conventional tablets are chewed. Following oral administration of hyoscyamine sulfate extended-release capsules, the drug has an onset of action of about 20-30 minutes; pharmacologic action peaks within 40-90 minutes and persists for about 12 hours.

Distribution

Hyoscyamine is well distributed throughout the body. The drug crosses the blood-brain barrier. Small quantities of the drug distribute into milk and are found in placental tissues. Hyoscyamine is about 50% bound to plasma proteins.

Elimination

Hyoscyamine has a plasma elimination half-life of about 2-3.5 hours in individuals with normal renal function.100,106,107,108,109,110,112,113,114,116,117,119,120,121,122,123,124,126 A plasma elimination half-life of about 5-7 or 7-9 hours has been reported following administration of extended-release capsules or tablets, respectively.109,110,112,113,124 Studies using IM atropine indicate that elimination of hyoscyamine may be biphasic and that the elimination half-life (determined by urinary excretion) in the terminal phase may be 12.5 hours or longer. Elimination of hyoscyamine is prolonged in individuals with renal dysfunction.

Hyoscyamine is partly metabolized in the liver to tropic acid, tropine, and hyoscyamine glucuronide, but most of a dose is excreted in urine unchanged within 12 hours after administration.100,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,126 In studies using atropine ( dl -hyoscyamine), approximately 30-50% of a dose was excreted in urine unchanged. In a crossover study comparing single-dose administration of extended-release capsules of hyoscyamine and administration of 3 doses of conventional tablets at 4-hour intervals, urinary excretion during the first 24 hours for extended-release capsules was about 80% that for conventional tablets.

Chemistry and Stability

Chemistry

Hyoscyamine is a naturally occurring tertiary amine antimuscarinic. Hyoscyamine is one of the principal alkaloid components of belladonna. During the extraction of belladonna, a racemic mixture of dl -hyoscyamine (atropine) is formed. Hyoscyamine and its hydrobromide and sulfate salts are the l -isomer. The antimuscarinic activity of atropine results principally from hyoscyamine, which has approximately twice the antimuscarinic potency of atropine. l -Hyoscyamine is 8-50 times as potent in central (CNS) antimuscarinic activity as the d -isomer.

Hyoscyamine occurs as a white, crystalline powder, is freely soluble in alcohol and in dilute acids and slightly soluble in water, and is sensitive to light. Hyoscyamine sulfate occurs as white, odorless crystals or as a crystalline powder and is deliquescent and sensitive to light. Hyoscyamine sulfate has solubilities of approximately 2 g/mL in water and 200 mg/mL in alcohol at 25°C.

Hyoscyamine sulfate injection is a sterile solution of the drug in water for injection and has a pH of 3-6.5 which may have been adjusted with hydrochloric acid. Hyoscyamine sulfate elixir and oral solution (drops) have a pH of 3.5-4.5; the elixir and oral solution (drops) also contain 20 and 5% alcohol, respectively.

Stability

Since hyoscyamine sulfate is one of the optical isomers comprising atropine sulfate, physical and/or chemical compatibility information on atropine sulfate generally applies to hyoscyamine sulfate. Specialized references should be consulted for specific compatibility information about atropine sulfate. Preparations of hyoscyamine and hyoscyamine sulfate generally should be stored at a controlled room temperature between 15-30°C.100,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,126 Hyoscyamine sulfate orally disintegrating tablets should be protected from moisture.100,119 At least one manufacturer states that hyoscyamine sulfate is stable under variable light conditions.

Additional Information

For further information on the chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, and dosage and administration of hyoscyamine, see the Antimuscarinics/Antispasmodics General Statement 12:08.08. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

100. Schwarz Pharma. NuLev^® (hyoscyamine sulfate) orally disintegrating tablets. Milwaukee, WI; 2005 Sep.

101. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA . 1985; 254:400-2. [PubMed 2861297]

102. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm . 1984; 9:26,28-30.

103. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist . 1983; 48:54993-5. (lDIS 178728)

104. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist . 1983; 48:31376-82. (IDIS 172957)

105. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther . 1982; 24:1-2. [PubMed 7054648]

106. Schwarz Pharma. Levsin^® (hyoscyamine sulfate) tablets prescribing information. Milwaukee, WI; 2004 Sep.

107. Schwarz Pharma. Levsin^® (hyoscyamine sulfate) injection prescribing information. Milwaukee, WI; 2003 Sep.

108. Capellon Pharmaceuticals, Ltd. Symax^® DuoTab (hyoscyamine sulfate) biphasic tablets prescribing information. Fort Worth, TX; 2006 Feb.

109. Schwarz Pharma. Levsinex^® Timecaps^® (hyoscyamine sulfate) extended-release capsules prescribing information. Milwaukee, WI; 2004 Sep.

110. Schwarz Pharma. Levbid^® (hyoscyamine sulfate) extended-release tablets prescribing information. Milwaukee, WI; 2004 Sep.

111. Capellon Pharmaceuticals, Ltd. Symax^® SR (hyoscyamine sulfate) tablets prescribing information. Fort Worth, TX; 2005 Jan.

112. Ethex Corporation. Hyoscyamine sulfate extended-release tablets prescribing information. St. Louis, MO; 2000 Oct.

113. Kremers Urban. Hyoscyamine sulfate extended-release tablets prescribing information. Mequon, WI; 2004 Aug.

114. Schwarz Pharma. Levbid^®/SL (hyoscyamine sulfate) tablets prescribing information. Milwaukee, WI; 2004 Sep.

115. Capellon Pharmaceuticals, Ltd. Symax^® SL (hyoscyamine sulfate) tablets prescribing information. Fort Worth, TX; 2003 May.

116. Ethex Corporation. Hyoscyamine sulfate sublingual tablets prescribing information. St. Louis, MO; 1998 Nov.

117. Kremers Urban. Sublingual hyoscyamine sulfate tablets prescribing information. Mequon, WI; 2004 Aug.

118. Capellon Pharmaceuticals, Ltd. Symax^® FasTab (hyoscyamine sulfate) tablets prescribing information. Fort Worth, TX; 2003 Nov.

119. Ethex Corporation. Hyoscyamine sulfate orally disintegrating tablets prescribing information. St. Louis, MO; 2005 Jul.

120. Schwarz Pharma. Levsin^® drops (hyoscyamine sulfate) oral solution prescribing information. Milwaukee, WI; 2005 Mar.

121. Kremers Urban. Hyoscyamine sulfate oral solution prescribing information. Mequon, WI; 2005 Mar.

122. Schwarz Pharma. Levsin^® (hyoscyamine sulfate) elixir prescribing information. Milwaukee, WI; 2005 Mar.

123. Kremers Urban. Hyoscyamine sulfate elixir prescribing information. Mequon, WI; 2005 Mar.

124. Ethex Corporation. Hyoscyamine sulfate extended-release capsules prescribing information. St. Louis, MO; 1999 Feb.

125. Schwarz Pharma, Milwaukee, WI: Personal communication.

126. Silarx Pharmaceuticals, Inc. Hyosyne^® (hyoscyamine sulfate) oral drops and Hyosyne^® (hyoscyamine sulfate) elixir prescribing information. Spring Valley, NY; 1998 Jul.

127. Capellon Pharmaceuticals, Ltd., Ft. Worth, TX: Personal communication.

128. Clark F. Insecticides: organic phosphorus compounds and carbamates. In: Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank's toxicologic emergenices. 7th ed. New York: McGraw-Hill; 2002;1346-65.