Brand names: Anaspaz, Cystospaz, Hyosyne, Levbid, Levsin, ... show all 8 brands Levsinex, NuLev, Symax
Drug class: Antimuscarinics/Antispasmodics

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

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

Uses for Hyoscyamine

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 [no longer commercially available in the US], 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 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

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

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).

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

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.^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126} CNS manifestations include confusion, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, coma,^{107 112 116 119 124 126} euphoria, anxiety, fatigue, insomnia, agitation and mannerisms, and inappropriate affect.^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126}

Mental confusion and/or excitement, especially in geriatric patients.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

CNS manifestations usually resolve within 12–48 hours after drug is discontinued.^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126}

General Precautions

Concomitant Illnesses

Use with caution in patients with autonomic neuropathy, hyperthyroidism, CHD, CHF, cardiac arrhythmias, hypertension, renal disease, or hiatal hernia associated with reflux esophagitis.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126 b}

Cardiac Tachyarrhythmia

Investigate any tachycardia before administration since antimuscarinics may increase heart rate.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

GI Precautions

Extreme caution in known or suspected GI infections because of decreased GI motility and retention of causative organism and/or toxins.^b

Extreme caution in mild to moderate ulcerative colitis because of suppressed intestinal motility and resultant paralytic ileus and toxic megacolon.^b

Caution in gastric ulcer because of delayed gastric emptying and possible antral stasis.^b

Caution in esophageal reflux and hiatal hernia because of decreased gastric motility and lower esophageal sphincter pressure leading to gastric retention and reflux aggravation.^b

Oropharyngeal or Dental Effects

Long-term use of antimuscarinics may decrease or inhibit salivary flow, thus contributing to development of caries, periodontal disease, oral candidiasis, and discomfort.^{108 111 115 118}

GU Disturbances

Extreme caution in patients with partial obstructive uropathy because of decreased tone and amplitude of contractions of ureters and bladder and resultant urinary retention.^b (See Contraindications under Cautions.)

Respiratory Effects

Caution with systemically administered antimuscarinics in debilitated patients with chronic pulmonary disease because a reduction in bronchial secretions may lead to inspissation and formation of bronchial plugs.^b

Down’s Syndrome, Spastic Paralysis, and Brain Damage

Increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).^{108 111 115 118 b} (See Pediatric Use under Cautions.)

Phenylketonuria

NuLev, Symax FasTab, and generic hyoscyamine sulfate (marketed by Ethex) orally disintegrating tablets contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 1.7, 4.5, and 0.5 mg, respectively, of phenylalanine per 0.125-mg tablet.^{100 101 102 103 104 105 119 127}

Specific Populations

Pregnancy

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

Lactation

Distributed into milk.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126} Caution if used in nursing women.^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126}

Pediatric Use

Manufacturer states that use of Symax DuoTab, Symax FasTab, Symax SL, or Symax SR is not recommended in pediatric patients <2 years of age.^{108 111 115 118}

Infants and children with spastic paralysis or brain damage may have increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).^{108 111 115 118 b} Close supervision recommended, and dosage adjustments often required.^{108 111 115 118}

Infants and young children especially susceptible to toxic effects of antimuscarinics.^{108 111 115 118} Paradoxical reaction (characterized by hyperexcitability) may occur with large doses of antimuscarinics.^{108 111 115 118}

Geriatric Use

Reported clinical experience has not identified differences in safety relative to younger adults.^{100 106 109 110 113 114 116 117 120 121 122 123 124}

Hyoscyamine is substantially eliminated by the kidneys.^{100 106 109 110 113 114 116 117 120 121 122 123 124} Select dosage with caution 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 Patients under Dosage and Administration.) Monitoring of renal function may be useful.^{100 106 109 110 113 114 117 120 121 122 123}

Geriatric patients especially susceptible to antimuscarinic effects (e.g., constipation, dry mouth, urinary retention [particularly male patients]); if these adverse effects occur, persist, or are severe, consider discontinuance of drug.^{108 111 115 118 b} Possible excitement, agitation, drowsiness, or confusion at usual dosages.^{108 111 115 118}

Antimuscarinics may precipitate undiagnosed glaucoma; use with caution in geriatric patients.^{108 111 115 118}

Continued use of antimuscarinics may severely impair memory, particularly in geriatric patients who already have memory problems.^{108 111 115 118}

Hepatic Impairment

Use with caution in hepatic disease.^b

Renal Impairment

Use with caution in renal disease.^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126 b} Substantially excreted by the kidneys.^{100 106 107 108 109 110 111 112 113 114 116 117 118 120 121 122 123 124 126} Possible increased risk of adverse effects.^{100 106 109 110 113 114 117 120 121 122 123}

Common Adverse Effects

Most adverse effects are manifestations of pharmacologic effects at muscarinic-cholinergic receptors and usually are reversible when therapy is discontinued.^b

Severity and frequency of adverse effects are dose related and individual intolerance varies greatly; adverse effects occasionally may be obviated by a reduction in dosage but this also may eliminate potential therapeutic effects.^b

Adverse effects include dry mouth, urinary hesitancy and retention, blurred vision, tachycardia, palpitations, mydriasis, increased ocular tension, loss of taste, headache, nervousness, drowsiness, weakness, fatigue, dizziness, insomnia, nausea, vomiting, impotence, constipation, bloated feeling, abdominal pain, diarrhea, allergic reactions or drug idiosyncrasies, urticaria and other dermal manifestations, ataxia, speech disturbance, mental confusion and/or excitement (especially in geriatric patients), short-term memory loss, hallucinations, and decreased sweating.^{100 106 109 110 113 114 116 117 120 121 122 123 b}

Drug Interactions

Drugs with Anticholinergic Effects

Possible additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation).^{100 106 107 109 110 112 113 114 116 117 119 120 121 122 123 124 126 b} Inform patient of this possibility.^b

Effects on GI Absorption of Drugs

By inhibiting the motility of the GI tract and prolonging GI transit time, antimuscarinics have the potential to alter GI absorption of various drugs.^{108 111 115 118 b}

Specific Drugs

Hyoscyamine Pharmacokinetics

Absorption

Pharmacokinetics of hyoscyamine (l-hyoscyamine) and atropine (dl-hyoscyamine) generally considered similar.^a

Bioavailability

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}

Extended-release capsules (Levsinex Timecaps,¹⁰⁹ generic preparations¹²⁴ ) and extended-release tablets (Levbid,¹¹⁰ generic preparations^{112 113} ) 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} Relative bioavailability reportedly is about 81 or 92%, respectively, that of the conventional tablets.^{112 124} Peak blood concentrations 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}

Bilayer extended-release tablets (i.e., Symax DuoTab) are formulated to release 0.125 mg of hyoscyamine sulfate immediately and the remaining 0.25 mg over 8–12 hours.¹⁰⁸

Onset

Time to onset and peak pharmacologic action depends on formulation and route of administration (see Table 7).^a Oral administration of sublingual tablets results in similar pharmacologic effects as sublingual administration, although onset may not be as rapid.^{114 116 117}

Duration

Immediate-release hyoscycamine sulfate preparations: Pharmacologic action generally persists for about 4 hours.^a

Hyoscyamine sulfate extended-release capsules: Pharmacologic action persists for about 12 hours.^a

Hyoscyamine sulfate injection: Pharmacologic action persists for up to 4 hours.^a

Food

Food does not appear to affect absorption.^a

Distribution

Extent

Well distributed throughout the body.^{100 106 107 108 109 110 112 113 114 115 116 117 118 119 120 121 122 123 124 126 a}

Crosses the blood-brain barrier.^{100 106 107 108 109 110 112 113 114 116 117 118 119 120 121 122 123 124 126 a}

Small quantities are distributed into milk and are found in placental tissues.^{100 106 107 108 109 110 112 113 114 115 116 117 118 119 120 121 122 123 124 126 a}

Plasma Protein Binding

Approximately 50%.^a

Elimination

Metabolism

Partly metabolized in the liver to tropic acid, tropine, and hyoscyamine glucuronide.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

Elimination Route

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}

Half-life

Immediate-release preparations: About 2–3.5 hours in individuals with normal renal function.^{100 106 114 116 117 119 120 121 122 123 126}

Extended-release capsules: About 5–7 hours.^{109 124}

Extended-release tablets: About 7–9 hours.^{110 113}

Elimination may be biphasic; elimination half-life (determined by urinary excretion) in the terminal phase may be ≥12.5 hours.^a

Special Populations

Elimination is prolonged in individuals with renal dysfunction.^a

Stability

Storage

Oral

Conventional Tablets and Sublingual Tablets

15–30°C.^{106 114 115 116 117}

Oral Solution (Drops) and Elixir

20–25°C (may be exposed to 15–30°C).^{120 121 122 123}

Orally Disintegrating Tablets

Tight, light resistant containers at 20–25°C (may be exposed to 15–30°C).^{100 118 119} Protect from moisture.^{100 119}

Extended-release Capsules and Tablets

15–30°C.^{109 110 111 112 113 124}

Parenteral

Injection

15–30°C.¹⁰⁷

Actions

• Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic cholinergic nerves and, to a lesser extent, on smooth muscles that lack cholinergic innervation.^{100 106 107 108 109 110 112 113 114 116 117 119 120 121 122 123 124 126 b} At usual doses, principally antagonizes cholinergic stimuli at muscarinic receptors and has little or no effect on cholinergic stimuli at nicotinic receptors.^{100 106 107 108 109 110 112 113 114 116 117 119 120 121 122 123 124 126 b}

• Antimuscarinics also have been referred to as anticholinergics (cholinergic blocking agents), but this term is appropriate only when it describes the antagonism of cholinergic stimuli at any cholinergic receptor, whether muscarinic or nicotinic.^b

• Also have been referred to as parasympatholytics because the antagonized functions principally are under the parasympathetic division of the nervous system.^b

• Receptors at various sites are not equally sensitive to inhibition of muscarinic effects.^b Relative sensitivity of physiologic functions (proceeding from the most sensitive) is as follows: secretions of the salivary, bronchial, and sweat glands; pupillary dilation, ocular accommodation, and heart rate; contraction of the detrusor muscle of the bladder and smooth muscle of the GI tract; and gastric secretion and motility.^b Doses used to decrease gastric secretions are likely to cause dryness of the mouth (xerostomia) and interfere with visual accommodation, and possibly cause difficulty in urinating.^b

• Various antisecretory effects in the GI tract, including reduction of salivation (producing xerostomia) and gastric secretions (only partial reduction in gastric acid secretion).^b Prolonged inhibitory effects on the motility of the esophagus, stomach, duodenum, jejunum, ileum, and colon.^b

• Relaxes lower esophageal sphincter with a resultant decrease in lower esophageal sphincter pressure.^b

• Decreases the tone and amplitude of contractions of the ureters and bladder.^b May cause urinary retention (e.g., in patients with urinary obstruction).^b

• Can reverse reflex vagal cardiac slowing or asystole such as that induced by inhalation of irritant vapors or by vagal stimulation (e.g., carotid sinus stimulation, pressure on the eyeball).^b

• May cause cutaneous vasodilation, especially at toxic doses (atropine flush).^b

• Reduces secretions from the nose, mouth, pharynx, and bronchi.^b Relaxes smooth muscles of the bronchi and bronchioles with a resultant decrease in airway resistance.^b

• Stimulates the medulla and higher cerebral centers and exhibits CNS effects similar to those produced by antimuscarinics used in the treatment of parkinsonian syndrome (e.g., trihexyphenidyl).^b

• Blocks the responses of the sphincter muscle of the iris and the ciliary muscle of the lens to cholinergic stimulation, producing mydriasis and cycloplegia and a resultant decrease in ocular accommodation.^b Little effect on IOP except with angle-closure glaucoma where IOP may increase.^b

• Reduces the volume of perspiration by inhibiting sweat-gland secretions.^b May suppress sweating sufficiently to increase body temperature.^b

Advice to Patients

• Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery or performing hazardous work if such effects occur.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

• Risk of heat prostration, fever, or heat stroke secondary to decreased sweating; caution when febrile, exercising, or when exposed to high environmental temperatures.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

• Extended-release preparations may not completely disintegrate, and fragments may be excreted in stools.^{108 109 110 113}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126}

• Importance of informing patients of other important precautionary information.^{100 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 126} (See Cautions.)

Additional Information

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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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