Scopolamine

Scopolamine, also known as hyoscine hydrobromide, is a naturally occurring tertiary amine antimuscarinic with stronger central effects than atropine. It is used to prevent motion sickness and postoperative nausea and vomiting, and to dry secretions in palliative care. It must not be confused with hyoscine butylbromide, a quaternary antispasmodic with different doses and no central action.

Classification. Antimuscarinic; non-selective; tertiary amine; centrally acting.

Mechanism. Blocks muscarinic receptors in the vestibular nuclei and vomiting centre, reducing vestibular input to the vomiting reflex; peripherally reduces salivary and bronchial secretions.

Pharmacodynamics. Sedation, amnesia and, at higher doses or in older adults, delirium. Less effect on heart rate than atropine; low doses can slow the heart.

Pharmacokinetics. Oral bioavailability about 10 to 15%. Hepatic metabolism, including by CYP3A4, with a short elimination half life. Transdermal delivery gives steady plasma levels over 72 hours, with onset of effect about 4 to 6 hours after application.

Motion sickness, adult.

• Transdermal patch delivering about 1 mg over 72 hours, one patch behind the ear at least 4 hours before travel (5 to 6 hours where feasible). Replace every 72 hours if needed; one patch at a time.

• Oral 300 micrograms 30 minutes before travel, repeated every 6 hours if needed. Maximum 900 micrograms in 24 hours.

Motion sickness, children (oral). 4 to 10 years: 75 to 150 micrograms; over 10 years: 150 to 300 micrograms; 30 minutes before travel, repeated every 6 hours, maximum 3 doses in 24 hours. Patch use is not licensed in children in most markets.

Postoperative nausea and vomiting prophylaxis, adult. One patch the evening before surgery, removed 24 hours after surgery. For caesarean delivery, apply 1 hour before surgery to limit newborn exposure.

Terminal respiratory secretions, adult palliative care. 400 micrograms SC every 4 hours as needed; continuous SC infusion 1.2 to 2 mg over 24 hours; maximum 2.4 mg in 24 hours. Sedation can be useful in the agitated dying patient; glycopyrrolate is preferred when the patient is alert.

Clozapine induced hypersalivation, adult (off label). 300 micrograms orally up to three times daily; watch for added anticholinergic burden and constipation.

Contraindications. Angle closure glaucoma; hypersensitivity; obstructive uropathy and paralytic ileus; myasthenia gravis.

Warnings. Confusion, hallucinations and delirium, mainly in older adults, children and those with kidney or liver impairment. Can lower the seizure threshold. Withdrawal after several days of patch use: nausea, dizziness, headache and imbalance, starting 24 hours after removal. Drowsiness impairs driving and machine work. Touching the eye after handling a patch causes unilateral dilated pupil and blurred vision, which can be mistaken for a neurological emergency.

Adverse effects. Dry mouth (most common), drowsiness, blurred vision, dilated pupils, dizziness, urinary retention, constipation, confusion, tachycardia or bradycardia, local skin irritation.

Interactions. Additive sedation with alcohol, opioids, benzodiazepines and sedating antihistamines. Additive anticholinergic effects with tricyclic antidepressants, antipsychotics including clozapine, and other antimuscarinics. Opposes metoclopramide and domperidone. Strong CYP3A4 inhibitors can raise levels.

Special groups.

• Pregnancy: limited data; avoid regular use; patch use at caesarean is accepted practice.

• Breastfeeding: passes into milk; short courses acceptable with infant monitoring for drowsiness and feeding problems.

• Children: oral doses by age; more prone to toxicity.

• Older adults: avoid where possible because of delirium, falls and urinary retention.

• Kidney and liver impairment: no defined adjustment; use lowest dose and watch for central effects.

Overdose. Antimuscarinic toxidrome with prominent delirium; supportive care, benzodiazepines; physostigmine for severe delirium where QRS is normal.

Formulations. Transdermal patch (about 1 mg over 72 hours); tablets 150 and 300 micrograms; injection 400 micrograms/mL.

Patch application. Apply to clean, dry, hairless skin behind one ear. Wash hands after handling. Replace if it falls off. Remove before MRI scanning, because some patches contain metal and can cause burns. Fold used patches sticky side in before disposal.

Monitoring. Sedation, confusion, urinary retention and bowel habit, especially in older adults. Palliative: secretion score and comfort every 4 hours.

Common prescribing errors. Confusing hyoscine hydrobromide with hyoscine butylbromide; leaving a patch in place before MRI; using it for vomiting from causes other than motion or surgery; using it in older adults when glycopyrrolate would do.