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

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

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.

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.

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

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

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.

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