Hyoscyamine Sulfate

Class: Antimuscarinics/Antispasmodics
VA Class: AU350
CAS Number: 101-31-5
Brands: Anaspaz, Cystospaz, Hyosyne, Levbid, Levsin, Levsinex, NuLev, Symax

Introduction

Antimuscarinic; a naturally occurring tertiary amine; one of the optical isomers (the l-isomer) constituting atropine (d,l-hyoscyamine).^a

Uses for Hyoscyamine Sulfate

GI Disorders

Adjunct in the treatment of peptic ulcer disease;^a however, no conclusive data that it aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. In patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis.^a

Adjunct in the treatment of functional GI disorders such as irritable bowel syndrome;^{100 106 107 108 109 110 112 113 114 115 116 117 118 119 120 121 122 123 124 126 a} however, efficacy is limited.^a Use only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit.^a Also has been used in combination with phenobarbital in the treatment of irritable bowel syndrome; however, such combined therapy lacks substantial evidence of efficacy.^a

Use with caution, if at all, 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).^a

GU Disorders

Adjunctive therapy in the management of hypermotility disorders of the lower urinary tract.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 a} May provide symptomatic relief, but the underlying cause should be determined and specifically treated.^a

With the exception of uninhibited or reflex neurogenic bladder, there is generally little evidence to support use of antimuscarinics in the treatment of various GU disorders.^a

Infant Colic

Treatment of infant colic;^{106 109 114 117 120 121 122 123 124 126} however, minimal evidence of efficacy with antimuscarinics.^a Infant colic is considered a benign, self-limiting condition that tends to resolve spontaneously and not require medical treatment.^a

Surgery

Has been used to inhibit salivation and excessive secretions of the respiratory tract;^{107 a} however, current surgical practice (e.g., using thiopental, halothane, or similar general anesthetics that do not stimulate salivary and tracheobronchial secretions) has reduced the need to control excessive respiratory secretions during surgery.^a

Has been used prophylactically to reduce volume and acidity of gastric secretions and to prevent acid-aspiration pneumonitis during surgery; however, antimuscarinics not shown to be effective for this use.¹⁰⁷

May be used to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation, thus preventing cholinergic effects during surgery (e.g., cardiac arrhythmias, hypotension, bradycardia) secondary to visceral traction (resulting in vagal stimulation), carotid sinus stimulation, or concomitant drugs (e.g., succinylcholine).^{107 a}

Used to block adverse muscarinic effects of anticholinesterase agents that are used after surgery to terminate curarization.^a

Cholinesterase Inhibitor Toxicity

Used parenterally as an antidote in the treatment of cholinesterase inhibitor toxicity.^a

Also used orally or sublingually in the treatment of cholinesterase inhibitor toxicity.^{100 106 109 110 112 113 114 116 117 119 120 121 122 123 124 126}

Pesticide Poisoning

Concomitantly with a cholinesterase reactivator (pralidoxime chloride) to reverse muscarinic effects associated with toxic exposure to anticholinesterase compounds (e.g., organophosphate pesticides).^a However, other antimuscarinics (principally atropine) are used more commonly.¹²⁸

Radiographic Uses

Facilitation of endoscopy or hypotonic duodenography by reducing GI motility;¹⁰⁷ however, glucagon appears to be more effective and generally is preferred.^a

Has been used to increase visualization of the urinary tract in excretion urography.^a

Biliary Disorders

Do not rely on antimuscarinics for relief of biliary tract disorders (e.g., combined with opiates for biliary colic) because of weak biliary antispasmodic action.^a

Pancreatitis

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.^a

Acute Rhinitis

Has been used as a drying agent in the relief of symptoms of acute rhinitis.^a

Parkinsonian Syndrome

Adjunctive therapy in the treatment of parkinsonian syndrome to reduce rigidity and tremors and to control associated sialorrhea and hyperhidrosis.^a

Renal Colic

Has been used in conjunction with morphine or other opiates for the symptomatic relief of renal colic.^a

Heart Block

May be useful in some patients in the treatment of partial heart block associated with vagal activity.^a

Hyoscyamine Sulfate Dosage and Administration

Administration

Administer hyoscyamine orally.^a

Administer hyoscyamine sulfate orally, sublingually, or by sub-Q, IM, or IV injection.^a

Oral Administration

Immediate-release Preparations

Conventional tablets, elixir, oral solution (drops), orally disintegrating tablets, and sublingual tablets generally administered orally 3–6 times daily.^{100 106 114 116 117 118 119 120 121 122 123 126} One manufacturer (Symax FasTab, Symax SL) recommends administration 30–60 minutes before meals.^{115 118}

Place orally disintegrating tablet on the tongue, allow it to disintegrate, then swallow with or without water.^{100 118 119}

Certain sublingual tablets (Levsin/SL, certain generic preparations) may be chewed.^{114 116 117}

Oral administration of sublingual tablets results in similar pharmacologic effects as sublingual administration, but onset may not be as rapid.^{114 116 117}

Extended-release Preparations

Do not crush or chew extended-release preparations.^{109 110}

Administer Levbid extended-release tablets (or generic preparations) orally every 12 hours; tablets are scored and may be broken to titrate dosage.^{110 112 113}

Administer extended-release capsules (Levsinex Timecaps, generic preparations), Symax SR extended-release tablets, and Symax DuoTab bilayer extended-release tablets orally every 12 hours; swallow capsules or tablets whole; may adjust dosage by reducing dosing interval to 8 hours.^{108 109 111 124} One manufacturer (Symax DuoTab, Symax SR) recommends administration 30–60 minutes before meals.^{108 111}

Sublingual Administration

Sublingual tablets generally administered 3–6 times daily.^{114 116 117} One manufacturer (Symax SL) recommends administration 30–60 minutes before meals and at bedtime.¹¹⁵

Parenteral Administration

Administer by sub-Q, IM, or IV injection without prior dilution.¹⁰⁷

Dosage

Available as hyoscyamine and hyoscyamine sulfate; dosage of hyoscyamine sulfate expressed in terms of the salt.^{106 107 108 109 110 111 112 113 114 115 116 118 120 121 122 123 124 126}

Titrate dosage carefully according to the condition, severity of symptoms, and the individual patient’s response and tolerance to the drug.^{100 106 109 110 114 115 116 117 118 119 120 121 122 123 126} Higher than recommended dosage may be required for therapeutic effect.^a Use lowest possible effective dosage.^a

Pediatric Patients

General Hyoscyamine Sulfate Dosage (for GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity)

See GU Disorders dosage section for hyoscyamine dosage for GU disorders.

Oral

Recommended dosages of hyoscyamine sulfate vary by age and/or formulation (see Tables 1–4).

Using the dropper provided by the manufacturer, which is calibrated to deliver approximately 32 drops/mL.¹²⁵

Table 1. Usual Dosages of Hyoscyamine Sulfate (as Oral Solution [Drops]) for Management of GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity in Pediatric Patients <2 Years of Age120121126

Body Weight	Usual Dosage	Maximum Dosage in a 24-hour Period
3.4 kg (7.5 lb)	4 drops (15.63 mcg) every 4 hours or as needed	24 drops (93.75 mcg)
5 kg (11 lb)	5 drops (19.53 mcg) every 4 hours or as needed	30 drops (117.19 mcg)
7 kg (15 lb)	6 drops (23.44 mcg) every 4 hours or as needed	36 drops (140.63 mcg)
10 kg (22 lb)	8 drops (31.25 mcg) every 4 hours or as needed	48 drops (187.5 mcg)

Table 2. Usual Dosages of Hyoscyamine Sulfate for Management of GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity in Children 2–11 Years of Age100106108111114115116117118119120121124126

Formulation(s)	Usual Dosage	Maximum Dosage in a 24-hour Period
Conventional tablets, orally disintegrating tablets, or sublingual tablets	62.5–125 mcg every 4 hours or as needed100 106 114 116 117 118 119 Symax SL: 62.5–125 mcg 3 or 4 times daily given 30–60 minutes before meals and at bedtime115	750 mcg100 106 114 116 117 118 119 120 121 126
Elixir	Weight-based dosing (see Table 3)122 123
Oral solution (drops)	31.25–125 mcg every 4 hours or as needed120 121 126	750 mcg120 121 126
Bilayer extended-release tablets, extended-release capsules, extended-release tablets	375 mcg every 12 hours108 111 124	750 mcg108 109 110 111 112 113 124

Table 3. Weight-based Dosing of Hyoscyamine Sulfate (as Elixir) for Management of GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity in Children 2–11 Years of Age122123125126

Body Weight	Usual Dosage	Maximum Dosage in a 24-hour Period
10 kg (22 lb)	1.25 mL (31.25 mcg) every 4 hours or as needed	7.5 mL (187.5 mcg)
20 kg (44 lb)	2.5 mL (62.5 mcg) every 4 hours or as needed	15 mL (375 mcg)
40 kg (88 lb)	3.75 mL (93.75 mcg) every 4 hours or as needed	22.5 mL (562.5 mcg)
50 kg (110 lb)	5 mL (125 mcg) every 4 hours or as needed	30 mL (750 mcg)

Table 4. Usual Dosages of Hyoscyamine Sulfate for Management of GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity in Children ≥12 Years of Age100106108109110111112113114115116117118119120121124126

Formulation(s)	Usual Dosage	Maximum Dosage in a 24-hour Period
Conventional tablets, elixir, oral solution (drops), orally disintegrating tablets, sublingual tablets	0.125–0.25 mg every 4 hours or as needed100 106 114 116 117 118 119 120 121 122 123 126 Symax SL tablets: 0.125–0.25 mg 3 or 4 times daily given 30–60 minutes before meals and at bedtime115	1.5 mg100 106 114 116 117 118 119 120 121 122 123 126
Bilayer extended-release tablets, extended-release capsules, extended-release tablets	0.375–0.75 mg every 12 hours.108 109 110 111 112 113 124 Alternatively, may adjust dosage to 0.375 mg every 8 hours as needed108 109 111 124	1.5 mg108 109 110 111 112 113 124

Sublingual

Children 2–11 years of age: 62.5–125 mcg (0.0625–0.125 mg) hyoscyamine sulfate every 4 hours or as needed, not to exceed 750 mcg in a 24-hour period.^{114 116 117} For Symax SL tablets, 62.5–125 mcg 3 or 4 times daily given 30–60 minutes before meals and at bedtime.¹¹⁵

Children ≥12 years of age: 0.125–0.25 mg hyoscyamine sulfate every 4 hours or as needed, not to exceed 1.5 mg in a 24-hour period.^{114 116 117} For Symax SL tablets, 0.125–0.25 mg 3 or 4 times daily given 30–60 minutes before meals and at bedtime.¹¹⁵

GU Disorders

Oral

Hyoscyamine: In older pediatric patients, reduce dosage (compared with adult dosage) in proportion to age and weight.^a (See Adults under Dosage and Administration.)

Hyoscyamine sulfate: See General Hyoscyamine Sulfate Dosage section.

Sublingual

See General Hyoscyamine Sulfate Dosage section.

Infant Colic

Oral

Children <2 years of age: Dosage of hyoscyamine sulfate based on weight (see Table 5).^{120 121 126}

Using the dropper provided by the manufacturer, which is calibrated to deliver approximately 32 drops/mL.¹²⁵

Table 5. Usual Dosages of Hyoscyamine Sulfate (as Oral Solution [Drops]) for Management of Infant Colic in Pediatric Patients <2 Years of Age120121126

Body Weight	Usual Dosage	Maximum Dosage in a 24-hour Period
3.4 kg (7.5 lb)	4 drops (15.63 mcg) every 4 hours or as needed	24 drops (93.75 mcg)
5 kg (11 lb)	5 drops (19.53 mcg) every 4 hours or as needed	30 drops (117.19 mcg)
7 kg (15 lb)	6 drops (23.44 mcg) every 4 hours or as needed	36 drops (140.63 mcg)
10 kg (22 lb)	8 drops (31.25 mcg) every 4 hours or as needed	48 drops (187.5 mcg)

Surgery

Preoperatively to Decrease Secretions and Block Cardiac Vagal Reflexes

IV, IM, or Sub-Q

Children >2 years of age: 5 mcg/kg (0.005 mg/kg) hyoscyamine sulfate given 30–60 minutes before anesthesia or concurrently with other preanesthetic medications (e.g., opiates, sedatives).^{107 a}

Reversal of Drug-induced Bradycardia

IV

Children >2 years of age: 0.125 mg hyoscyamine sulfate; repeat as necessary.¹⁰⁷

Muscarinic Blockade during Anticholinesterase Reversal of Curariform Neuromuscular Blockade

IV

Children >2 years of age: 0.2 mg hyoscyamine sulfate for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered.¹⁰⁷

Administer concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent.^a

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to about 80 bpm.^a

Adults

General Hyoscyamine Sulfate Dosage (for GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity)

See GI Disorders dosage section for parenteral hyoscyamine sulfate dosage for GI disorders and see GU Disorders dosage section for hyoscyamine dosage for GU disorders.

Oral

Recommended dosages of hyoscyamine sulfate vary by formulation (see Table 6).

Table 6. Usual Dosages of Hyoscyamine Sulfate for Management of GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity in Adults100106108109110111112113114115116117118119120121124126

Formulation(s)	Usual Dosage	Maximum Dosage in a 24-hour Period
Conventional tablets, elixir, oral solution (drops), orally disintegrating tablets, sublingual tablets	0.125–0.25 mg every 4 hours or as needed100 106 114 116 117 118 119 120 121 122 123 126 Symax SL tablets: 0.125–0.25 mg 3 or 4 times daily given 30–60 minutes before meals and at bedtime115	1.5 mg100 106 114 116 117 118 119 120 121 122 123 126
Bilayer extended-release tablets, extended-release capsules, extended-release tablets	0.375–0.75 mg every 12 hours.108 109 110 111 112 113 124 Alternatively, may adjust dosage to 0.375 mg every 8 hours as needed108 109 111 124	1.5 mg108 109 110 111 112 113 124

Sublingual

0.125–0.25 mg hyoscyamine sulfate every 4 hours or as needed, not to exceed 1.5 mg in a 24-hour period.^{114 116 117}

Symax SL tablets: 0.125–0.25 mg hyoscyamine sulfate 3 or 4 times daily given 30–60 minutes before meals and at bedtime.¹¹⁵

GI Disorders

Oral

See General Hyoscyamine Sulfate Dosage section.

Sublingual

See General Hyoscyamine Sulfate Dosage section.

IV, IM, or Sub-Q

0.25–0.5 mg hyoscyamine sulfate every 4 hours, 2–4 times daily; for acute symptoms, a single parenteral dose of 0.25–0.5 mg may be sufficient.^a Adjust dosage according to individual patient’s response and tolerance.^a

GU Disorders

Oral

Hyoscyamine: 0.15–0.3 mg up to 4 times daily.^a

Hyoscyamine sulfate: See General Hyoscyamine Sulfate Dosage section.

Sublingual

See General Hyoscyamine Sulfate Dosage section.

Surgery

Preoperatively to Decrease Secretions and Block Cardiac Vagal Reflexes

IV, IM, or Sub-Q

5 mcg/kg (0.005 mg/kg) hyoscyamine sulfate given 30–60 minutes before anesthesia or concurrently with other preanesthetic medications (e.g., opiates, sedatives).^{107 a}

Reversal of Drug-induced Bradycardia

IV

0.125 mg hyoscyamine sulfate; repeat as necessary.¹⁰⁷

Muscarinic Blockade during Anticholinesterase Reversal of Curariform Neuromuscular Blockade

IV

0.2 mg hyoscyamine sulfate for each 1 mg of neostigmine methylsulfate or the equivalent dose of physostigmine salicylate or pyridostigmine bromide administered.¹⁰⁷

Administer concurrently with (but in a separate syringe) or a few minutes before the anticholinesterase agent.^a

If bradycardia is present, administer before the anticholinesterase agent to increase pulse to about 80 bpm.^a

Pesticide Poisoning

Organophosphate Anticholinesterase Pesticides

Initial dose preferably should be administered IV.^a

A cholinesterase reactivator (pralidoxime) is administered concomitantly.^a

IV or IM, then Oral

Initially, 1–2 mg hyoscyamine sulfate IV.^a May administer additional 1-mg doses IV or IM every 3–10 minutes until muscarinic signs and symptoms disappear; up to 25 mg may be required during first 24 hours.^a Subsequently, administer 0.5–1 mg hyoscyamine sulfate orally at intervals of several hours (maintenance therapy) until signs and symptoms completely subside.^a

Radiographic Uses

Endoscopy or Hypotonic Duodenography

IV, IM, or Sub-Q

0.25–0.5 mg hyoscyamine sulfate 5–10 minutes prior to the diagnostic procedure.¹⁰⁷

Prescribing Limits

Pediatric Patients

GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity

Oral or Sublingual

Pediatric patients <2 years of age receiving hyoscyamine sulfate oral solution (drops): In a 24-hour period, maximum 24 drops (93.75 mcg) in infants weighing 3.4 kg, 30 drops (117.19 mcg) in infants weighing 5 kg, 36 drops (140.63 mcg) in infants weighing 7 kg, or 48 drops (187.5 mcg) in infants weighing 10 kg.^{120 121 126}

Children 2–11 years of age: Maximum 750 mcg hyoscyamine sulfate in a 24-hour period.^{100 106 108 111 114 115 116 117 118 119 120 121 124 126} For weight-based dosing using elixir, in a 24-hour period, maximum 7.5 mL (187.5 mcg) in children weighing 10 kg, 15 mL (375 mcg) in children weighing 20 kg, 22.5 mL (562.5 mcg) in children weighing 40 kg, or 30 mL (750 mcg) in children weighing 50 kg.¹²⁵

Children ≥12 years of age: Maximum 1.5 mg hyoscyamine sulfate in a 24-hour period.^{100 106 108 109 110 111 112 113 114 115 116 117 118 119 120 121 124 126}

Infant Colic

Oral

Pediatric patients <2 years of age receiving hyoscyamine sulfate oral solution (drops): In a 24-hour period, maximum 24 drops (93.75 mcg) in infants weighing 3.4 kg, 30 drops (117.19 mcg) in infants weighing 5 kg, 36 drops (140.63 mcg) in infants weighing 7 kg, or 48 drops (187.5 mcg) in infants weighing 10 kg.^{120 121 126}

Adults

GI/GU/Biliary Disorders, Renal Colic, Acute Rhinitis, Parkinsonian Syndrome, or Cholinesterase Inhibitor Toxicity

Oral or Sublingual

Maximum 1.5 mg hyoscyamine sulfate in a 24-hour period.^{100 106 108 109 110 111 112 113 114 115 116 117 118 119 120 121 124 126}

Special Populations

Geriatric Patients

Geriatric patients may be more sensitive to drug’s effects at usual adult dosages.^{108 115}

Select dosage with caution, usually starting at low end of dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^{100 106 109 110 112 113 114 116 117 120 121 122 123 124} (See Geriatric Use under Cautions.)

Cautions for Hyoscyamine Sulfate

Contraindications

• 
  

  Angle-closure glaucoma.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Obstructive uropathy (e.g., bladder neck obstruction secondary to prostatic hypertrophy).^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Obstructive GI disease (e.g., achalasia, pyloroduodenal stenosis).^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Paralytic ileus.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Intestinal atony (especially in geriatric or debilitated patients).^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Acute hemorrhage when cardiovascular status is unstable.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Tachycardia secondary to cardiac insufficiency or thyrotoxicosis.^b

  
  


• 
  

  Severe ulcerative colitis or toxic megacolon complicating ulcerative colitis.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

  
  


• 
  

  Myasthenia gravis^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126} (unless used to reduce adverse muscarinic effects of an anticholinesterase agent such as neostigmine).^b

  
  


• 
  

  Myocardial ischemia.^{108 111 115 118}

  
  

Warnings/Precautions

Warnings

Thermoregulatory Effects

Exposure to high environmental temperatures may result in heat prostration (fever and heat stroke due to decreased sweating).^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b} Increased risk of hyperthermia in patients who are febrile.^b

Diarrhea

May be an early sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy; in this instance, use of hyoscyamine would be inappropriate and possibly harmful.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

Drowsiness and Blurred Vision

May cause drowsiness, dizziness, or blurred vision.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b} Performance of activities requiring mental alertness and physical coordination may be impaired.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

CNS Effects

Psychosis in patients with increased sensitivity to antimuscarinic drugs.^{100 106 107}