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, ergotamine) 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.
Used in combination with other drugs (e.g., ergotamine, phenobarbital) in the treatment of recurrent, throbbing headaches.
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.
Menopausal Disorders
Has been used in combination with other drugs (e.g., ergotamine, phenobarbital) in the management of exaggerated autonomic response and nervous tension in menopausal disorders (e.g., hot flushes [flashes], sweats, restlessness, insomnia); however, such combined therapy lacks substantial evidence of efficacy.
Dosage and Administration
Administration
Oral Administration
Administer orally or rectally.
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., ergotamine, 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.)
Initial Pediatric Dosage of Belladonna Alkaloids and Phenobarbital (e.g., Donnatal® elixir)
Body Weight
Dose Every 4 Hours
Dose Every 6 Hours
4.5 kg
0.5 mL
0.75 mL
9.1 kg
1 mL
1.5 mL
13.6 kg
1.5 mL
2 mL
22.7 kg
2.5 mL
3.75 mL
34 kg
3.75 mL
5 mL
45.4 kg
5 mL
7.5 mL
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.
l-Alkaloids of belladonna in fixed combination with ergotamine and phenobarbital: Usual initial dosage is 0.2 mg of l-alkaloids (1 tablet) twice daily, given in the morning and at night.
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.
Headache
Oral
l-Alkaloids of belladonna in fixed combination with ergotamine and phenobarbital: Usual initial dosage is 0.2 mg of l-alkaloids (1 tablet) twice daily, given in the morning and at night.
Prescribing Limits
Pediatric Patients
Belladonna tincture: Maximum 3.5 mL (1.05 mg of the alkaloids of belladonna leaf) daily.
Adults
l-Alkaloids of belladonna in fixed combination with ergotamine and phenobarbital: Limit dosage to 16 tablets weekly because of ergotamine content.
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 fixed-combination tablets containing l-alkaloids of belladonna, ergotamine, and phenobarbital in hepatic impairment. Avoid use of belladonna and opium suppositories in severe hepatic disease.
Renal Impairment
No specific renal dosage recommendations for belladonna.
Avoid use of fixed-combination tablets containing l-alkaloids of belladonna, ergotamine, and phenobarbital in renal impairment. Avoid use of belladonna and opium suppositories in severe renal disease.
Geriatric Patients
Adjust dosage based on patient tolerance and response.
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, ergotamine, or opium, consider cautions, precautions, and contraindications associated with the concomitant agent(s).
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 and of the l-alkaloids in fixed combination with phenobarbital and ergotamine 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.
Slowed GI transit potentiates adverse GI effects of oral potassium chloride (especially wax-matrix tablets)
Caution if used concomitantly; monitor for possible GI mucosal lesions
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 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.
On February 26, 2007, FDA warned 20 firms that manufacture or distribute unapproved drug preparations containing ergotamine tartrate (including unapproved preparations containing ergotamine tartrate in fixed combination with belladonna and phenobarbital) of the agency’s intention to take enforcement action (e.g., seizure, injunction, other judicial proceeding) against all firms attempting to manufacture or distribute such preparations after April 27, 2007, or August 25, 2007, respectively, without an approved new drug application (NDA). Unapproved preparations manufactured or distributed before these dates may still be found on pharmacy shelves for a short period of time. Manufacturers' labelings for most of these unapproved preparations omit critical drug interaction warnings, and the preparations have not undergone FDA review of safety, efficacy, quality, and labeling.
Belladonna
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Bulk
Leaf*
USP (with at least 0.35% w/w of the alkaloids)
Oral
Tincture*
0.3 mg of the alkaloids of belladonna leaf per mL with alcohol 67%
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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