Scopolamine

Class: Antimuscarinics/Antispasmodics
VA Class: AU350
CAS Number: 51-34-3
Brands: Scopace, Transderm Scop

Antimuscarinic; naturally occurring tertiary amine.

Uses for Scopolamine

Motion Sickness

Prevention of motion-induced nausea and vomiting; considered most effective drug for this use.

Oral or IM administration usually reserved for patients exposed to short periods of intense motion or those highly susceptible to motion because these routes have short duration of effect and high incidence of adverse effects.

Transdermal administration is effective and has fewer adverse effects and increased duration compared with oral administration.

Postoperative Nausea and Vomiting

Used transdermally for prevention of nausea and vomiting associated with recovery from anesthesia and surgery, but efficacy is equivocal.

Surgery

Has been used preoperatively to inhibit salivation and excessive respiratory tract secretions, but use of general anesthetics (e.g., thiopental [no longer commercially available in the US], halothane) that do not stimulate secretions has reduced the need for this use.

Used preoperatively and in obstetrics in conjunction with analgesics or sedatives to produce tranquilization and amnesia; however, benzodiazepines may be preferred.

Has greater sedative, antisecretory (e.g., on respiratory secretions), and antiemetic effects than atropine; however, less effective than atropine in preventing intraoperative cholinergic effects (e.g., cardiac arrhythmias, hypotension, bradycardia).

Parkinsonian Syndrome

Has been used for symptomatic treatment of parkinsonian syndrome; however, antimuscarinincs generally have been replaced with dopaminergic drugs.

Scopolamine Dosage and Administration

Administration

Administer orally or by IM, direct IV, or sub-Q injection; also may administer percutaneously by topical application of a transdermal system (Transderm Scop).

When administered orally or IM for the prevention of motion sickness, generally administer 1 hour (range: 0.5–1.5 hours) before anticipated exposure to motion.

When used preoperatively, administer 30–60 minutes prior to the anticipated time of induction of anesthesia or at the same time other preanesthetic medications (e.g., opiates, sedatives) are administered, since scopolamine may cause behavioral changes in patients with pain or anxiety. (See CNS Effects under Cautions.)

Transdermal Administration

To prevent motion sickness, apply at least 4 hours (e.g., 4–24 hours) before anticipated exposure to motion.

To prevent postoperative nausea and vomiting, apply the evening before scheduled surgery.

For use in cesarean section, apply 1 hour prior to surgery to minimize exposure of the fetus to the drug.

Transdermal system should not be cut; only one transdermal system should be worn at any time.

Prior to administration, wipe area behind the ear with a clean, dry tissue to ensure it is dry.

To expose adhesive surface, peel and discard the clear plastic protective strip prior to administration; avoid finger contact with exposed adhesive layer to prevent contamination of the fingers with scopolamine.

Apply to dry, hairless area of skin behind the ear (postauricular) by firmly pressing the system with the adhesive side touching the skin.

If the system becomes dislodged during the intended period of use (up to 72 hours), remove it and replace with another system at a different postauricular site.

Generally not affected by limited exposure to water (e.g., during bathing or swimming).

Dosage

Tablets and injection: Available as scopolamine hydrobromide; dosage expressed in terms of the salt.

Pediatric Patients

Usual Dosage

IM, IV, Sub-Q

Children 6 month to 3 years of age: 0.1–0.15 mg

Children 3–6 years of age: 0.2–0.3 mg

Motion Sickness

Sub-Q

Usually 0.006 mg/kg (6 mcg/kg).

Postoperative Nausea and Vomiting

Sub-Q

Usually 0.006 mg/kg (6 mcg/kg).

Adults

Usual Dosage

Oral

0.4–0.8 mg.

IM, IV, Sub-Q

0.32–0.65 mg; may be repeated 3 or 4 times daily if necessary.

Motion Sickness

Oral

Initially, 0.25–0.8 mg 1 hour before exposure to motion; subsequently, 0.25–0.8 mg 3 times daily as needed and tolerated.

IM, IV, Sub-Q

Usually 0.32–0.65 mg; may be repeated 3 or 4 times daily if necessary.

Alternatively, 0.2–1 mg.

Transdermal

Usually, one scopolamine system applied ≥4 hours prior to anticipated exposure to motion.

May use for up to 72 hours if necessary or may remove during the 72-hour period when an antiemetic effect is no longer required.

When necessary to continue beyond 72 hours, remove the initially applied system and place another system behind the ear at a different site.

Postoperative Nausea and Vomiting

Transdermal

Apply one transdermal system the evening before scheduled surgery.

For cesarean section, apply 1 hour prior to surgery to minimize exposure of the infant to the drug.

Allow patch to remain in place for 24 hours following surgery, then remove and discard.

Surgery

Obstetric Anmesia or Preoperative Sedation

IM, IV, Sub-Q

Usually 0.32–0.65 mg.

Inhibition of Salivation

IM, IV, Sub-Q

Usually 0.32–0.65 mg. Alternatively, 0.2–0.6 mg has been suggested.

Amnestic Effect

IM, IV, Sub-Q

Usually 0.32–0.65 mg.

Sedative or Tranquilizing Effect

IM, IV, Sub-Q

Usually 0.6 mg.

Cautions for Scopolamine

Contraindications

• Angle-closure glaucoma.
• Prostatic hypertrophy and obstructive uropathy (urinary bladder neck obstruction caused by prostatic hypertrophy). (See GU Effects under Cautions.)
• Obstructive GI disease (e.g., pyloroduodenal stenosis, achalasia). (See GI Effects under Cautions.)
• Repeated administration in those with chronic lung disease. (See Respiratory Effects under Cautions.)
• Paralytic ileus.
• Tachycardia secondary to cardiac insufficiency or thyrotoxicosis.
• Known idiosyncratic reaction to anticholinergic drugs.
• Known hypersensitivity to scopolamine, other belladonna alkaloid, barbiturates, or any ingredient or component in the formulation or administration system.

Warnings/Precautions

Warnings

CNS Effects

Possible adverse CNS effects, including CNS depression, manifested as drowsiness, euphoria, amnesia, fatigue, and dreamless sleep; disorientation; confusion; memory disturbances; and dizziness. Excitement, restlessness, hallucinations, or delirium may paradoxically occur, especially when scopolamine is used in the presence of severe pain. May result in impairment of performance of activities requiring mental alertness, physical coordination, or visual acuity (e.g., operating machinery, driving a motor vehicle).

Use caution with underwater sports participation; warn patients about possible disorientation.

Use with caution in patients with autonomic neuropathy.

Ocular Effects

Possible increased intraocular pressure; monitor open-angle glaucoma therapy and adjust as necessary.

Idiosyncratic Reaction

Excessive susceptibility to the effects of scopolamine occurs rarely. Toxic symptoms may occur with therapeutic doses.

Most serious idiosyncratic reaction is acute toxic psychosis (e.g., confusion, agitation, rambling speech, hallucinations, paranoid behavior, delusions). Other manifestations may include marked CNS disturbances (e.g., complete disorientation, active delirium), somnolence, dilated pupils, accelerated pulse rate, and dryness of the mouth with a husky quality of the voice.

Idiosyncratic reaction usually is reversed by physostigmine.

Withdrawal of Therapy

Possible drug withdrawal symptoms (e.g., nausea, vomiting, headache, dizziness, disturbances of equilibrium) following discontinuance of the transdermal system; usually do not appear until ≥24 hours after system removal.

Withdrawal symptoms must be distingushed from overdosage signs and symptoms. Mental confusion and dizziness may be observed with both withdrawal and acute toxicity. Scopolamine withdrawal is suggested by bradycardia, headache, nausea, abdominal cramps, and sweating, while tachyarrhythmias, dry skin, and decreased bowel sounds occur with acute toxicity.

General Precautions

Cardiovascular Effects

Possible tachycardia; use with caution in patients with tachyarrhythmias, CHF, CAD, or hyperthyroidism.

GI Effects

Possible decreased GI motility. Use with caution if pyloric or intestinal obstruction is suspected.

Down Syndrome, Spastic Paralysis, and Brain Damage

Possible increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).

Respiratory Effects

Systemically administered antimuscarinics may reduce bronchial secretions and may lead to inspissation and formation of bronchial plugs in debilitated patients with chronic pulmonary disease; use with caution in such patients.

GU Effects

Antimuscarinics decrease the tone and amplitude of contractions of the ureters and bladder. In patients with uninhibited or reflex neurogenic bladder, the amplitude and frequency of uninhibited contractions are reduced and bladder capacity is increased.

Possible urinary retention in patients with urinary obstruction. Use with caution in patients with partial obstructive uropathy. Use contraindicated in patients with obstructive uropathy (urinary bladder neck obstruction caused by prostatic hypertrophy).

Seizure or Psychosis

Scopolamine may aggravate seizures or psychosis; use with caution in patients with a history of these conditions.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy of scopolamine hydrobromide tablets or scopolamine transdermal system not established.

Generally use antimuscarinics with caution; children are particularly susceptible to adverse effects of belladonna alkaloids.

Do not use scopolamine transdermal system in children since it is not known if the system will release an amount of drug that could cause serious adverse effects.

Geriatric Use

Use with caution; possible increased incidence of mental confusion and other adverse CNS effects compared with younger adults. (See CNS Effects under Cautions.)

Hepatic Impairment

Use with caution; possible increased incidence of adverse CNS effects. (See CNS Effects under Cautions.) Tablets contraindicated.

Renal Impairment

Use with caution; possible increased incidence of adverse CNS effects. (See CNS Effects under Cautions.) Tablets contraindicated.

Common Adverse Effects

With transdermal therapy, dry mouth, drowsiness, dizziness, blurred vision, mydriasis.

With oral therapy, dry mouth, dry skin, drowsiness, flushing, tachycardia, urinary retention, mydriasis.

With parenteral therapy, dry mouth, dry skin, anhidrosis, tachycardia, urinary retention, mydriasis.

Interactions for Scopolamine

Orally Administered Drugs

Potential pharmacokinetic interaction (altered GI absorption of various drugs): Antimuscarinics may inhibit GI motility, delay gastric emptying, and prolong GI transit time.

Specific Drugs

Drug	Interaction	Comments
Amantadine	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Antacids	Possible decreased absorption of antimuscarinic	Administer oral scopolamine at least 1 hour before antacids
Antiarrhythmic agents (quinidine, disopyramide, procainamide)	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Antidepressants, tricyclic	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Antihistamine agents (meclizine)	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Antiparkinsonian agents	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Belladonna alkaloids	Possible additive anticholinergic effects	Use concomitantly with extra caution
Corticosteroids	Possible increased intraocular pressure
CNS depressants (e.g., sedatives, tranquilizers, alcohol)	Possible increased CNS depressive effects (see CNS Effects under Cautions.)	Use concomitantly with caution
Glutethimide	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Ketoconazole	Possible decreased ketoconazole absorption	If concomitant therapy is necessary, give antimuscarinic at least 2 hours after ketoconazole
Levodopa	Possible increased gastric metabolism of levodopa and decreased levodopa absorption in the small intestine	Toxicity may result from increased levodopa absorption if antimuscarinic is discontinued without a concomitant reduction in levodopa dosage
Meperidine	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Phenothiazines	Possible additive anticholinergic adverse effects	Use concomitantly with caution
Potassium chloride	Antimuscarinics may potentiate potassium chloride's local GI mucosal effects	Use antimuscarinics cautiously with potassium chloride preparations (especially wax-matrix preparations), monitor carefully for evidence of GI mucosal lesions
Skeletal muscle relaxants	Possible additive anticholinergic adverse effects	Use concomitantly with caution

Scopolamine Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract, principally from the upper small intestine.

Rapidly absorbed following IM or sub-Q injection.

Well absorbed percutaneously.

Onset

Antiemetic effect occurs within 15–30 minutes following IM administration.

Transdermal system is designed to provide antiemetic effect in about 4 hours after application.

Inhibition of salivation occurs within 30 minutes to 1 hour after oral administration, peaks within 1–2 hours.

Inhibition of salivation occurs within 30 minutes after IM administration, peaks within 1 hour.

Amnesia occurs within 10 minutes following IV administration, peaks between 50–80 minutes.

Duration

Antiemetic effect persists for about 4 hours following IM administration.

After application, transdermal system is designed to provide antiemetic effect for up to 72 hours.

Inhibition of salivation persists for up to 4–6 hours after oral or IM administration.

Amnesia persists for at least 120 minutes following IV administration.

Mydriasis persists for up to 8 hours following IM administration.

Distribution

Extent

Not fully characterized; apparently crosses the blood-brain barrier since the drug causes CNS effects.

Scopolamine crosses the placenta and is distributed into milk.

Plasma Protein Binding

Apparently reversibly bound to plasma proteins.

Elimination

Metabolism

Not fully determined; thought to be almost completely metabolized (principally by conjugation) in the liver.

Elimination Route

Principally in urine as metabolites.

Half-life

Following transdermal application, average elimination half-life was 9.5 hours.

Stability

Storage

Oral

Soluble Tablets

15–30°C.

Parenteral

Injection

15–30°C; protect from light.

Topical

Transdermal System

20–25°C.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility

Scopolamine is readily racemized in the presence of dilute alkali. Scopolamine hydrobromide solutions are incompatible with alkalies.

Consult specialized references for specific compatibility information since the compatibility of admixtures with scopolamine hydrobromide injection depends on several factors (e.g., concentration of the drugs, resulting pH, temperature).

A haze may form within 1 hour when scopolamine hydrobromide injection is mixed with methohexital sodium solutions.

Admixture CompatibilityHID

Compatible

Meperidine HCl

Oxycodone HCI

Succinylcholine chloride

Y-Site CompatibilityHID

Compatible

Fentanyl citrate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Methadone HCl

Morphine sulfate

Potassium chloride

Propofol

Sufentanil citrate

Vitamin B complex with C

 

Compatibility in Syringe (physically compatible for at least 15 minutes)a

Compatible

Atropine sulfate

Butorphanol tartrate

Chlorpromazine HCl

Cimetidine HCl

Dimenhydrinate

Diphenhydramine HCl

Droperidol

Fentanyl citrate

Glycopyrrolate

Hydromorphone HCl

Hydroxyzine HCl

Meperidine HCl

Metoclopramide HCl

Midazolam HCl

Morphine sulfate

Nalbuphine HCl

Pentazocine lactate

Pentobarbital sodium

Perphenazine

Prochlorperazine edisylate

Promethazine HCl

Ranitidine HCl

Sufentanil Citrate

Thiopental sodium

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.
• At usual doses, principally antagonizes cholinergic stimuli at muscarinic receptors and has little or no effect on cholinergic stimuli at nicotinic receptors.
• Generally more potent than atropine in its antimuscarinic action on the iris, ciliary body, and certain secretory (salivary, bronchial, sweat) glands, and less potent than atropine in its antimuscarinic action on the heart and on bronchial and intestinal smooth muscle.
• Apparently corrects some central imbalance of acetylcholine and norepinephrine that may occur in patients with motion sickness. Antimuscarinics may block the transmission of cholinergic impulses from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center; these effects result in prevention of motion-induced nausea and vomiting.
• 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.
• Also have been referred to as parasympatholytics since the antagonized functions principally are under the parasympathetic division of the nervous system.
• Receptors at various sites are not equally sensitive to inhibitory effects of antimuscarinics, and degree of inhibition at each site is dose dependent. 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. 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.

Advice to Patients

• Importance of patients reporting serious adverse reactions promptly.
• Risk of drowsiness, dizziness, blurred vision; avoid activities requiring mental alertness and/or visual acuity (e.g., driving, operating machinery, hazardous work) until effects on individual are known.
• Importance of using caution with underwater sports participation because of possible disorientation.
• For transdermal therapy, carefully instruct patient about use of transdermal scopolamine; importance of providing patient a copy of manufacturer's patient information.
• Importance of patient (or individual assisting the patient) thoroughly washing hands with soap and water after handling transdermal system (e.g., initial application, removal) and to wash the application site thoroughly after removing the system, since contamination of the fingers and subsequent contact with the eyes may result in cycloplegia (i.e., mydriasis and blurred vision).
• Importance of proper transdermal system disposal, including keeping it out of the reach of children or pets.
• Importance of removing the transdermal system and contacting clinician if pain and reddening of eyes accompanied by dilated pupils occur.
• Importance of removing the transdermal system if difficulty in urinating occurs.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs , and any concomitant illnesses.
• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

 

Scopolamine
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Transdermal System	approximately 1 mg/72 hours (1.5 mg/2.5 cm2)	Transderm Scop	Novartis

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

Scopolamine Hydrobromide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, soluble	0.4 mg	Scopace	Hope
Bulk	Powder*
Parenteral	Injection	0.4 mg/mL*	Scopolamine Hydrobromide Injection (with parabens)	Abraxis