Drug class: Antimuscarinics/Antispasmodics
VA class: AU350
CAS number: 8007-93-0

Medically reviewed by Drugs.com on Apr 8, 2024. Written by ASHP.

Introduction

Antimuscarinic; naturally occurring mixture of tertiary amine alkaloids.

Uses for Belladonna

Peptic Ulcer Disease

Adjunct in the treatment of peptic ulcer disease; however, no conclusive data that it aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.

Has been used in combination with other drugs (e.g., phenobarbital); however, no data support superiority of combination preparations over antimuscarinics alone.

GI Motility Disorders

Treatment of functional disturbances of GI motility (e.g., irritable bowel syndrome) and neurogenic bowel disturbances; however, efficacy is limited. Use only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit.

Has been used in combination with other drugs (e.g., phenobarbital) in the treatment of functional disturbances of GI motility such as irritable bowel syndrome; however, such combined therapy lacks substantial evidence of efficacy.

Use with extreme caution, if at all, in the treatment of hypermotility and diarrhea associated with GI disorders such as acute enterocolitis.

Pain

Has been used rectally in combination with opium in patients unresponsive to nonopiate analgesics for symptomatic relief of moderate to severe pain following GU surgery and for relief of pain caused by ureteral spasm.

Parkinsonian Syndrome

Treatment of mild cases of parkinsonian syndrome or as an adjunct to other therapy; however, antimuscarinics generally have been replaced with dopaminergic drugs.

Belladonna Dosage and Administration

Administration

Administer orally or rectally.

Oral Administration

Administer orally as belladonna tincture or extract or as conventional or extended-release tablets or oral solution (elixir) containing belladonna alkaloids in fixed combination with other drugs (e.g., phenobarbital).

Belladonna extract powder used extemporaneously to prepare capsules, powders, or tablets for oral administration.

Belladonna leaf itself is not used as a therapeutic agent because of risk of overdosage of the alkaloids.

Some clinicians have preferred belladonna tincture to other antimuscarinics because it usually is the most economic and easily titrated antimuscarinic.

Rectal Administration

Moisten rectal suppositories containing belladonna and opium with water prior to rectal insertion.

Dosage

Carefully titrate dosage until therapeutic effect is achieved or adverse effects become intolerable. Higher than recommended dosage may be required for therapeutic effect. Use lowest possible effective dosage.

Pediatric Patients

General Dosage

Oral

Belladonna tincture: Usual initial dosage is 0.1 mL (0.03 mg of the alkaloids of belladonna leaf) per kg daily or 2.5 mL (0.75 mg of the alkaloids of belladonna leaf) per m² daily, given in 3 or 4 divided doses; do not exceed 3.5 mL (1.05 mg of the alkaloids of belladonna leaf) daily.

Peptic Ulcer Disease and GI Motility Disorders

Oral

Belladonna tincture: Usual initial dosage is 0.1 mL (0.03 mg of the alkaloids of belladonna leaf) per kg daily or 2.5 mL (0.75 mg of the alkaloids of belladonna leaf) per m² daily, given in 3 or 4 divided doses; do not exceed 3.5 mL (1.05 mg of the alkaloids of belladonna leaf) daily.

Belladonna alkaloids and phenobarbital (e.g., Donnatal elixir): Administer every 4–6 hours based on weight and symptoms. (See Table 1.)

Pain

Pain Following GU Surgery or Caused by Ureteral Spasm

Rectal

Adolescents ≥13 years of age: 16.2 mg of belladonna extract (0.203 mg of the alkaloids of belladonna leaf) in fixed combination with 30 or 60 mg of opium (1 suppository) once or twice daily.

Adults

General Dosage

Oral

Belladonna extract: Usual initial dosage is 15–30 mg (0.187–0.374 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

Belladonna tincture: Usual initial dosage is 0.6–1 mL (0.18–0.3 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

Peptic Ulcer Disease and GI Motility Disorders

Oral

Belladonna extract: Usual initial dosage is 15–30 mg (0.187–0.374 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

Belladonna tincture: Usual initial dosage is 0.6–1 mL (0.18–0.3 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

Immediate-release tablets or solution (elixir) containing belladonna alkaloids and phenobarbital (e.g., Donnatal): 1 or 2 tablets or 5 or 10 mL of elixir 3 or 4 times daily.

Extended-release tablets containing belladonna alkaloids and phenobarbital (Donnatal Extentabs): Usual dosage is 1 tablet every 12 hours; may administer 1 tablet every 8 hours if indicated.

Pain

Pain Following GU Surgery or Caused by Ureteral Spasm

Rectal

16.2 mg of belladonna extract (0.203 mg of the alkaloids of belladonna leaf) in fixed combination with 30 or 60 mg of opium (1 suppository) once or twice daily.

Prescribing Limits

Pediatric Patients

Belladonna tincture: Maximum 3.5 mL (1.05 mg of the alkaloids of belladonna leaf) daily.

Adults

Suppositories containing belladonna extract in fixed combination with 30 or 60 mg of opium: Maximum 64.8 mg of belladonna extract (0.812 mg of the alkaloids of belladonna leaf; equivalent to 4 suppositories) daily.

Special Populations

Hepatic Impairment

No specific hepatic dosage recommendations for belladonna.

When used in fixed combination with phenobarbital, use small initial dosage.

Avoid use of belladonna and opium suppositories in severe hepatic disease.

Renal Impairment

No specific renal dosage recommendations for belladonna.

Avoid use of belladonna and opium suppositories in severe renal disease.

Geriatric Patients

Adjust dosage based on patient tolerance and response.

Cautions for Belladonna

Contraindications

• Angle-closure glaucoma.

• Obstructive uropathy (e.g., bladder neck obstruction secondary to prostatic hypertrophy).

• Obstructive GI disease (e.g., pyloroduodenal stenosis, achalasia).

• Paralytic ileus.

• Intestinal atony (especially in geriatric or debilitated patients).

• Acute hemorrhage when cardiovascular status is unstable.

• Tachycardia secondary to cardiac insufficiency or thyrotoxicosis.

• Severe ulcerative colitis or toxic megacolon complicating ulcerative colitis.

• Myasthenia gravis (unless used to reduce adverse muscarinic effects of an anticholinesterase agent such as neostigmine).

• Some manufacturers state that belladonna is contraindicated in patients with hiatal hernia with reflux esophagitis. (See GI Effects under Cautions.)

• Known hypersensitivity to belladonna or any ingredient in the formulation.

Warnings/Precautions

Warnings

Thermoregulatory Effects

Exposure to high environmental temperatures may result in heat prostration due to decreased sweating. Increased risk of hyperthermia in patients who are febrile.

Diarrhea

May be an early sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy; in this instance, use would be inappropriate and possibly harmful.

Drowsiness and Blurred Vision

May cause drowsiness, dizziness, or blurred vision. Performance of activities requiring mental alertness and physical coordination may be impaired.

Major Toxicities

Overdosage

A curare-like action may occur (e.g., neuromuscular blockade leading to muscular weakness and possible paralysis).

General Precautions

Use of Fixed Combinations

When belladonna is used in fixed combination with phenobarbital or opium, consider cautions, precautions, and contraindications associated with the concomitant agent(s).

Concomitant Illnesses

Use with caution in patients with hyperthyroidism, autonomic neuropathy, hepatic or renal disease, CHD, CHF, cardiac arrhythmias, or hypertension.

GI Effects

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

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

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

Caution in esophageal reflux and hiatal hernia because of decreased gastric motility and lower esophageal sphincter pressure leading to gastric retention and reflux aggravation. Some manufacturers state that belladonna is contraindicated in these patients.

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. (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.

Down’s Syndrome, Spastic Paralysis, and Brain Damage

Increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect). (See Pediatric Use under Cautions.)

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether belladonna is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety of belladonna established in pediatric patients.

Safety and efficacy of belladonna extract not established in children. Manufacturer states that belladonna and opium suppositories are not recommended in children ≤12 years of age.

Children with spastic paralysis or brain damage may have increased sensitivity to antimuscarinic effects (e.g., mydriasis, positive chronotropic effect).

Infants and young children may be especially susceptible to toxic effects of anticholinergics.

Geriatric Use

Use with caution.

Geriatric patients especially susceptible to antimuscarinic effects (e.g., constipation, dry mouth, urinary retention). Mental confusion and/or excitement is especially likely in geriatric patients. Excitement, agitation, or drowsiness possible even with small dosages.

Hepatic Impairment

Use with caution in hepatic disease.

Renal Impairment

Use with caution in renal disease.

Common Adverse Effects

Drowsiness, xerostomia, tachycardia, palpitation, dizziness, nervousness, urinary hesitancy and retention, decreased sweating, constipation, increased ocular tension, photophobia, blurred vision, mydriasis.

Drug Interactions

Drugs with Anticholinergic Effects

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation). Advise of possibility of increased anticholinergic effects and monitor carefully.

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.

Specific Drugs

Belladonna Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract; however, animal studies have shown differences in the absorption rates of l-hyoscyamine and galenical preparations of belladonna.

Distribution

Extent

Not known whether belladonna is distributed into milk.

Atropine, hyoscyamine, and scopolamine cross the placenta.

Atropine and hyoscyamine readily cross the blood-brain barrier.

Elimination

Metabolism

Hydrolyzed to tropine and tropic acid.

Elimination Route

Excreted in urine and, apparently to a lesser extent, in feces.

Stability

Storage

Oral

Belladonna Leaf

Tight, light-resistant containers.

Belladonna Extract

Tight containers at ≤30°C.

Belladonna Tincture

Tight, light-resistant containers at <40°C (maintain between 15–30°C). Protect from direct sunlight and excessive heat.

Belladonna Alkaloids with Phenobarbital Elixir and Immediate- and Extended-release Tablets

Well-closed, light-resistant containers at 20–25°C. Protect from light and moisture.

Rectal

Suppositories

15–30°C. Do not refrigerate.

Actions

• Belladonna is a term applied to the various galenical preparations of the naturally occurring solanaceous alkaloids. Antimuscarinic activity results principally from the atropine (dl-hyoscyamine) content.

• 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.

• 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 because the antagonized functions principally are under the parasympathetic division of the nervous system.

• Receptors at various sites are not equally sensitive to inhibition of muscarinic effects. 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.

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

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

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

• 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).

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

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

• 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).

• 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. Little effect on IOP except with angle-closure glaucoma where IOP may increase.

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

Advice to Patients

• Potential for hyperthermia and heat prostration; avoid exposure to high environmental temperatures and avoid use when febrile.

• If rectal suppositories are prescribed, instruct patient or caregiver in the proper administration technique.

• Risk of drowsiness, dizziness, or blurred vision; use caution when driving or operating machinery until effects on individual are known.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians 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.

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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