Hyoscine

Hyoscine is a Muscarinic Acetylcholine Receptor Antagonist belonging to Anticholinergic agent.

Hyoscine is anticholinergic effects indicated for the treatment of nausea and vomiting associated with motion sickness and postoperative nausea and vomiting.

Hyoscine tertiary salts are readily absorbed from the gastrointestinal tract while the quaternary salts are poorly absorbed. The bioavailability is about 8% via oral route. The time taken to reach peak plasma concentration is within 24 hours via (transdermal), as hydrobromide is approximately 20 minutes (via IM), and 15 minutes (via Subcutaneously). Hyoscine tertiary salts crosses blood-brain barrier and the placenta, enters breast milk. Volume of distribution as butylbromide is 128 L. Plasma protein binding of butylbromide is approximately 4%, to albumin. Hyoscine is primarily metabolized in the liver mainly via conjugation.

Hyoscine shows side effects like Disorientation, dry mouth, drowsiness, dilated pupils, dizziness, sweating, sore throat.

Hyoscine is available in the form of Injectable solution, Oral tablet, and transdermal patch.

Hyoscine is available in India, US, Germany, France, Russia, China, Italy, Spain, Canada, Australia.

Hyoscine belongs to the Anticholinergic agent acts as a Muscarinic Acetylcholine Receptor Antagonist.

Hyoscine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands and the CNS; increases cardiac output, dries secretions, antagonizes histamine and serotonin; at usual recommended doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate).

The Onset of action of Hyoscine is about ≤15 minutes (injectable solution), 6 to 8 hours (transdermal) and 1 hour (oral).

The Duration of action of Hyoscine is approximately 72 hour (transdermal), 4-8 hours (IM), 4-6 hours (oral), ≥2 hours (IV).

The Tmax of Hyoscine is approximately ~2 hours (oral), ~20 minutes (IM), ~5 minutes (IV) and ~15 minutes (Subcutaneous).

Hyoscine is available in the form of Injectable solution, Oral tablet, and transdermal patch.

Hyoscine tablet is taken orally, transdermal patch externally applied and injectable solution is given via intravenous or intramuscular route.

Hyoscine is anticholinergic effects indicated for the treatment of nausea and vomiting associated with motion sickness and postoperative nausea and vomiting.

Hyoscine is a Muscarinic Acetylcholine Receptor Antagonist belonging to Anticholinergic agent.

Hyoscine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the CNS; increases cardiac output, dries secretions, antagonizes histamine and serotonin; at usual recommended doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate).

Hyoscine is approved for use in the following clinical indications

• Gastrointestinal/genitourinary spasm
• Malignant bowel obstruction, inoperable
• Motion sickness, prevention
• Postoperative nausea and/or vomiting, prevention
• Sialorrhea
• Terminal airway secretions
• Chronic drooling

• Gastrointestinal/genitourinary spasm

Oral: 10 to 20 mg 3 to 5 times/day as needed; maximum: 60 mg/day.

IM/IV/SUBCUTANEOUS: 10 to 20 mg once; if needed, may repeat at intervals of ≥30 minutes; maximum: 100 mg/day.

• Malignant bowel obstruction, inoperable

SUBCUTANEOUS: Initial: 20 mg once followed by 60 mg over 24 hours as a continuous Subcutaneous infusion.

• Motion sickness, prevention

Transdermal: Apply 1 patch (1 mg/3 days) behind ear at least 4 hours prior to required antiemetic effect for use up to 72 hours; if needed for >72 hours, remove old patch and place new one behind another ear. If symptoms are not adequately controlled with use of 1 patch, may consider using 2 patches.

• Postoperative nausea and/or vomiting, prevention

Transdermal: Apply 1 patch (1 mg/3 days) behind ear at least 1 to 2 hours prior to anesthesia or night before and remove 24 hours after procedure.

• Sialorrhea

Transdermal: Apply 1 patch (1 mg/3 days) behind ear; after 3 days, remove old patch and place new one behind another ear.

• Terminal airway secretions

Adult Dose:

Transdermal: Apply 1 patch (1 mg/3 days) behind ear for up to 72 hours; if needed for >72 hours, remove old patch and place new one behind another ear.

SUBCUTANEOUS: 20 mg every 4 to 6 hours as needed. Alternatively, administer 20 mg once followed by a continuous Subcutaneous infusion of 20 to 60 mg over 24 hours.

Pediatric Dose:

Children <2 years: Transdermal: Apply ¹/₄ patch the evening before surgery.

Children ≥2 to 6 years: Transdermal: Apply ¹/₂ patch the evening before surgery.

Children ≥6 to 12 years: Transdermal: Apply ¹/₂ to 1 patch the evening before surgery.

Children ≥12 years and Adolescents: Transdermal: Apply 1 patch the evening before surgery.

• Chronic drooling

Children ≥3 years and Adolescents: Transdermal: Initial: Apply ¹/₄ patch every 3 days for 1 week; may titrate to effect (control of secretions) by increasing by ¹/₄ patch every 7 days as tolerated. Maximum dose: 1 patch applied every 3 days.

Hyoscine is available in various strengths as 1.5 mg; 1 mg/72 hour; 1 mg/mL; 0.4 mg/mL; 0.4 mg.

Hyoscine is contraindicated in patients with

• Glaucoma
• obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy);
• obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis)
• paralytic ileus, intestinal atony of elderly or debilitated patients
• unstable cardiovascular status in acute hemorrhage
• severe ulcerative colitis
• toxic megacolon complicating ulcerative colitis
• myasthenia gravis.

• Anaphylaxis

Anaphylaxis including episodes of shock has been reported following parenteral administration; observe for signs/symptoms of hypersensitivity following parenteral administration. Patients with a history of allergies or asthma may be at increased risk of hypersensitivity reactions.

• Bradycardia (paradoxical)

Lower doses (0.1mg) may have vagal mimetic effects (eg, increase vagal tone causing paradoxical bradycardia); these effects are likely mediated by blockade of muscarinic receptors at the level of the brain.

• Cardiovascular disease

Use with caution in patients with coronary artery disease, tachyarrhythmias, heart failure, or hypertension; evaluate tachycardia prior to administration.

• Gastrointestinal (GI) obstruction

Use with caution in patients with GI obstruction; when used for the treatment of smooth muscle spasm of the GI tract avoid continuous (daily) or prolonged use without evaluating source of abdominal pain. Patients should be instructed to report persistent or worsening abdominal pain with or without other symptoms (eg, nausea/vomiting, irregular bowel movements, bloody stool, hypotension).

• Genitourinary (GU) disease/obstruction

Use with caution in patients with GU obstruction, prostatic hyperplasia, or urinary retention; when used for the treatment of smooth muscle spasm of the GU tract, avoid continuous (daily) or prolonged use without evaluating source of the spasm.

• Glaucoma

Use transdermal product with caution in patients with open-angle glaucoma; may increase intraocular pressure; adjust glaucoma therapy as necessary.

• Hepatic impairment

Use with caution in patients with hepatic impairment.

• Hiatal hernia

Use with caution in patients with hiatal hernia with reflux esophagitis.

• Hyperthyroidism

Use caution in patients with hyperthyroidism; may have increased risk for arrhythmias.

• Parkinson disease

Adverse events (including dizziness, headache, nausea, vomiting) may occur following abrupt discontinuation in patients with Parkinson disease.

• Psychosis

Use with caution in patients with a history of psychosis; may exacerbate condition.

• Renal impairment

Use with caution in patients with renal impairment.

• Seizure disorders

Use with caution in patients with a history of seizure disorder; may exacerbate condition.

• Ulcerative colitis

Use with caution in patients with ulcerative colitis; may precipitate/aggravate toxic megacolon.

Avoid consumption of alcohol, it may enhance the effects of CNS depressant which worsen the side effect of Hyoscine.

Hyoscine is excreted in human milk. Caution should be exercised when hyoscine is administered to a nursing woman.

Pregnancy Category C

Animal reproduction studies have not been conducted with hyoscine. It is also not known whether hyoscine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hyoscine should be given to a pregnant woman only if clearly needed.

• Common

Xerostomia, Dizziness, drowsiness, agitation, confusion, mydriasis, visual impairment, Pharyngitis.

• Rare

Hypotension, Diaphoresis, erythema of skin, skin irritation, skin rash, Nausea , Dysuria, urinary retention, Application-site burning, Acute psychosis, amnesia, ataxia, delirium, delusion, disorientation, disturbance in attention, fatigue, hallucination, headache, insomnia, memory impairment, paranoid ideation, restlessness, seizure, speech disturbance, vertigo, Amblyopia, angle-closure glaucoma, blurred vision, dry eye syndrome, eye pruritus, eyelid pain (irritation).

• Drugs Causing Central Nervous System (CNS) Adverse Reactions

The concurrent use of hyoscine with other drugs that cause CNS adverse reactions of drowsiness, dizziness, or disorientation (e.g., sedatives, hypnotics, opiates, anxiolytics and alcohol) or have anticholinergic properties (e.g., other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants) may potentiate the effects of hyoscine. Either Hyoscine or the interacting drug should be chosen, depending on the importance of the drug to the patient. If the interacting drug cannot be avoided, monitor patients for CNS adverse reactions.

• Anticholinergic Drugs

Concomitant use of Hyoscine with other drugs having anticholinergic properties may increase the risk of CNS adverse reactions, intestinal obstruction and/or urinary retention. Consider more frequent monitoring during treatment with Hyoscine in patients receiving anticholinergic drugs.

• Oral Drugs Absorbed in the Stomach

Hyoscine, as an anticholinergic, may delay gastric and upper gastrointestinal motility and, therefore, the rate of absorption of other orally administered drugs. Monitor patients for modified therapeutic effect of concomitant orally administered drugs with a narrow therapeutic index.

• Interaction with Gastric Secretion Test

Scopolamine will interfere with the gastric secretion test. Discontinue Hyoscine 10 days prior to testing.

The common side effects of Hyoscine include the following

• Common side effects

Disorientation, dry mouth, drowsiness, dilated pupils, dizziness, sweating, sore throat.

• Rare side effects

Rash, redness, eye pain, redness, or discomfort; blurred vision; seeing halos or coloured images, agitation, seeing things or hearing voices that do not exist (hallucinating), confusion, believing things that are not true, not trusting others or feeling that others want to hurt you, difficulty speaking, seizure, painful or difficulty urinating, stomach pain, nausea, or vomiting.

• Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with Hyoscine. It is also not known whether Hyoscine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hyoscine should be given to a pregnant woman only if clearly needed.

• Nursing Mothers

Hyoscine is excreted in human milk. Caution should be exercised when hyoscine is administered to a nursing woman.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Pediatric patients are particularly susceptible to the adverse reactions of scopolamine, including mydriasis, hallucinations, amblyopia and drug withdrawal syndrome. Neurologic and psychiatric adverse reactions, such as hallucinations, amblyopia and mydriasis have also been reported.

• Geriatric Use

Reported clinical experience has not identified differences in safety between patients aged 65 and over and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Symptoms: CNS stimulation, tachycardia, arrhythmia, urinary retention, coma, respiratory depression.

Management: Symptomatic and supportive treatment. Empty stomach immediately via gastric lavage or induced emesis. Short acting benzodiazepines or barbiturate may be given to control CNS stimulation.

Pharmacodynamic

Hyoscine is an anticholinergic belladonna alkaloid that, through competitive inhibition of muscarinic receptors, affects parasympathetic nervous system function and acts on smooth muscles that respond to acetylcholine but lack cholinergic innervation. Formulated as a patch, Hyoscine is released continuously over three days and remains detectable in urine over a period of 108 hours. Hyoscine is contraindicated in angle-closure glaucoma and should be used with caution in patients with open-angle glaucoma due to Hyoscine ability to increase intraocular pressure. Also, Hyoscine exhibits several neuropsychiatric effects: exacerbated psychosis, seizures, seizure-like, and other psychiatric reactions, and cognitive impairment; Hyoscine may impair the ability of patients to operate machinery or motor vehicles, play underwater sports, or perform any other potentially hazardous activity.

Pharmacokinetics

Absorption

Hyoscine tertiary salts are readily absorbed from the gastrointestinal tract while the quaternary salts are poorly absorbed. The bioavailability is about 8% via oral route. The time taken to reach peak plasma concentration is within 24 hours via (transdermal), as hydrobromide is approximately 20 minutes (via IM), and 15 minutes (via Subcutaneously).

• Distribution

Hyoscine tertiary salts crosses blood-brain barrier and the placenta, enters breast milk. Volume of distribution as butylbromide is 128 L. Plasma protein binding of butylbromide is approximately 4%, to albumin.

• Metabolism and Excretion

Hyoscine is primarily metabolized in the liver mainly via conjugation. The half-life of Hyoscine differs depending on the route. Intravenous, oral, and intramuscular administration have similar half-lives of 68.7 ± 1.0, 63.7 ± 1.3, and 69.1 ±8/0 min, respectively. The half-life is greater with subcutaneous administration at 213 min. Following removal of the transdermal patch system, scopolamine plasma concentrations decrease in a log-linear fashion with a half-life of 9.5 hours.

• https://www.mims.com/india/drug/info/hyoscine?type=full&mtype=generic
• https://www.rxlist.com/levsin-drug.htm#overdosage
• https://www.uptodate.com/contents/scopolamine-hyoscine-drug-information?search=hyoscine&source=panel_search_result&selectedTitle=1~80&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://go.drugbank.com/articles/A7905
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• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/017874s043s044lbl.pdf