Hyoscyamine

Overview

Hyoscyamine (Levsin®) is an anticholinergic (antimuscarinic) agent and the levo-isomer of atropine. Although its use in veterinary medicine is limited, it may be considered in dogs for managing symptomatic bradycardia or atrioventricular (AV) block when pacemaker implantation is not feasible, and for short-term treatment of hypermotile gastrointestinal disorders such as irritable bowel syndrome.

Following oral administration, hyoscyamine is rapidly and almost completely absorbed, with a duration of action of approximately 4–6 hours in humans. It is widely distributed throughout the body, penetrates the central nervous system, crosses the placenta, and is eliminated primarily unchanged in the urine after partial hepatic metabolism.

Mechanism of Action (MOA): Hyoscyamine competitively inhibits the actions of acetylcholine at muscarinic receptors in postganglionic parasympathetic effector tissues and on acetylcholine-responsive smooth muscle. Its pharmacologic effects include reduced gastrointestinal and urinary tract motility, decreased salivary and respiratory secretions, mydriasis, and an increased heart rate.

Indications

Hyoscyamine is used infrequently in veterinary medicine but may be considered in dogs as an alternative anticholinergic when muscarinic inhibition is desired. Current veterinary experience is limited, and most uses are extra-label.

• Symptomatic bradycardia and atrioventricular (AV) block: May be used as an alternative to other anticholinergic agents (e.g., glycopyrrolate) in dogs with clinically significant bradycardia or AV block when pacemaker implantation is not feasible; chronic oral therapy is indicated in symptomatic dogs that respond to an atropine response test.
• Hypermotile gastrointestinal disorders: May be used for short-term management of hypermotile GI conditions, including chronic idiopathic large bowel disease (irritable bowel syndrome), by reducing gastrointestinal motility.
• Reduction of secretions (potential use): May help decrease salivary and respiratory secretions during the perioperative period, although veterinary safety and efficacy data are limited.
• Hypersalivation and urinary tract spasm (potential use): Has been suggested for managing hypersalivation and urinary spasms, but clinical experience in veterinary patients remains limited.
• Adjunctive antiemetic use (potential use): May have a role in controlling vomiting through its anticholinergic effects; however, evidence supporting this indication in animals is limited.

Dosage (Reference)

Dog

Published veterinary dosing information for hyoscyamine is limited and applies to immediate-release oral formulations. Extended-release products may reduce dosing frequency, but no veterinary dosing data are currently available.

Cat

No doses have been established for cats.

Warnings & Precautions

Hyoscyamine should be used cautiously because of its anticholinergic effects and limited veterinary experience. Careful patient selection and monitoring are recommended, particularly in animals with underlying cardiovascular, renal, gastrointestinal, or urinary disorders.

• Hypersensitivity: Contraindicated in patients with known hypersensitivity to hyoscyamine. Animals sensitive to one belladonna alkaloid or derivative may also react to others.
• Gastrointestinal disorders: Contraindicated in patients with intestinal obstruction, toxic megacolon, intestinal atony, or severe ulcerative colitis because reduced GI motility may worsen these conditions; also do not use in patients with intestinal ileus or gastroparesis, and use extreme caution with known or suspected GI infections or GI toxin exposure.
• Glaucoma: Contraindicated in patients with narrow- or wide-angle glaucoma due to the risk of increasing intraocular pressure.
• Urinary tract obstruction: Contraindicated in patients with obstructive uropathy because urinary retention may be exacerbated.
• Cardiovascular disease: Use cautiously in patients with tachyarrhythmias, cardiac valve disease, or congestive heart failure, as anticholinergic-induced tachycardia may worsen cardiovascular compromise; do not use in patients with tachycardia, and anticholinergics are contraindicated in hypertrophic or restrictive cardiomyopathy.
• Sick sinus syndrome: In dogs with suspected disease, give parasympatholytic drugs cautiously, as they can cause tachycardias that overdrive-suppress escape rhythms, with a potential risk of asystole when the tachycardia ends.
• Unstable cardiovascular status: Based on human data, it is contraindicated during acute hemorrhage.
• Renal dysfunction: Use with caution, as reduced renal elimination may increase drug exposure.
• Other conditions: Antimuscarinic agents should be used with caution in animals with hepatic disease, hyperthyroidism, hypertension, or esophageal reflux, and in geriatric or pediatric animals.
• Myasthenia gravis: Use with extreme caution (it is a contraindication in humans), except when given to reverse adverse muscarinic effects of treatment such as pyridostigmine.
• Pregnancy and lactation: Safety has not been established in animals. Use only when the expected maternal benefit outweighs the potential risk to the fetus or nursing offspring.
• Product selection: Do not confuse hyoscyamine with hyoscine, as they are different medications.

Drug Interactions

Clinically relevant interactions with hyoscyamine are primarily related to additive anticholinergic effects, altered gastrointestinal absorption, or antagonism of drugs that enhance gastrointestinal motility. Monitor patients closely and adjust therapy when appropriate.

• Other anticholinergics (e.g., atropine, glycopyrrolate): Concurrent use may produce additive anticholinergic effects, increasing the risk of tachycardia, urinary retention, constipation, mydriasis, and reduced secretions.
• First-generation antihistamines (e.g., diphenhydramine): May enhance anticholinergic effects and increase the likelihood of adverse reactions.
• Antacids containing magnesium, aluminum, or calcium salts: May reduce the absorption of hyoscyamine; administer separately when possible.
• Ketoconazole: Hyoscyamine may decrease ketoconazole serum concentrations; administer ketoconazole at least 2 hours apart from hyoscyamine.
• Prokinetic agents (e.g., metoclopramide, cisapride): Hyoscyamine may antagonize their prokinetic effects and reduce therapeutic efficacy.
• Oral potassium chloride or potassium citrate: Anticholinergic-induced delayed gastrointestinal transit may increase the risk of gastrointestinal ulceration; this combination is contraindicated in humans.
• Alpha-2 agonists (e.g., dexmedetomidine): Giving an anticholinergic at the same time or afterwards leads to secondary tachycardia, prolonged hypertension, and cardiac arrhythmias in dogs and cats.

Side Effects & Overdose

Side Effects

Adverse effects of hyoscyamine are primarily related to its anticholinergic activity and are generally dose-dependent. Higher doses may also produce central nervous system effects.

• Mydriasis: Pupil dilation that may be accompanied by increased sensitivity to light.
• Xerostomia: Dry mouth resulting from reduced salivary secretion.
• Constipation: Decreased gastrointestinal motility may lead to constipation.
• Urinary retention: Difficulty urinating due to reduced bladder contractility.
• Tachycardia: Increased heart rate resulting from muscarinic receptor blockade.
• Xerophthalmia: Reduced tear production that may contribute to ocular dryness.
• CNS effects: High doses may cause central nervous system depression or excitation.

Overdose

Hyoscyamine overdose produces exaggerated and prolonged anticholinergic effects and may result in significant neurologic and cardiovascular complications. Management is primarily supportive.

• Tachycardia: Marked increase in heart rate due to excessive anticholinergic activity.
• CNS toxicity: Behavioral changes, depression, excitement, or seizures may occur.
• Urinary retention: Severe impairment of bladder emptying may develop.
• Reduced gastrointestinal motility: Decreased gut sounds and intestinal motility may become pronounced.
• Mydriasis: Persistent pupillary dilation is a common manifestation of toxicity.
• Management: Initiate supportive care and consider measures to reduce oral absorption following acute ingestion when appropriate; phenothiazines should not be used, as they may add to anticholinergic effects.
• Antidotal therapy: Severe anticholinergic effects may be treated with physostigmine or neostigmine under the guidance of an animal poison control center or veterinary toxicologist.
• Seizure control: Short-acting benzodiazepines or barbiturates may be used if significant CNS excitation or seizures occur.

Key Notes

Practical clinical points that may help optimize the safe and effective use of hyoscyamine in veterinary patients:

• Limited veterinary experience: Hyoscyamine is used infrequently in dogs, and published evidence supporting its efficacy and safety remains limited compared with more commonly used anticholinergics.
• More potent than atropine: As the levo-isomer of atropine, hyoscyamine produces stronger central and peripheral anticholinergic effects at equivalent doses.
• Immediate-release vs. extended-release products: Use the appropriate formulation, as immediate-release and sustained-release products have different dosing intervals and should not be interchanged on a mg-for-mg schedule.
• Sustained-release formulations: Extended-release tablets and capsules should not be split, crushed, or chewed, as this may alter drug release characteristics.
• Hydration: Ensure patients have continuous access to fresh water, particularly during prolonged therapy, to help minimize discomfort associated with reduced salivary secretions.
• Administration with food: The drug may be given with or without food. If gastrointestinal upset occurs when administered on an empty stomach, giving it with food may improve tolerance.