VA Class:AU350

AHFS Class:

• Antimuscarinics/Antispasmodics 12:08.08

Generic Name(s):

• Belladonna

Belladonna is a term applied to the various galenical preparations of the naturally occurring solanaceous alkaloids with antimuscarinic activity that results principally from the atropine content.

GI Disorders

Belladonna tincture is preferred by some clinicians to other antimuscarinics because it is usually the most economical and most easily titrated of the currently available antimuscarinics.

Belladonna is used as an adjunct in the treatment of peptic ulcer disease. Belladonna has also been used in combination with other drugs (e.g., phenobarbital) as an adjunct in the treatment of peptic ulcer disease; however, there are no data that support the superiority of combination preparations over antimuscarinics alone. As with other antimuscarinics, there are no conclusive data from well-controlled studies which indicate that, in usually recommended dosage, belladonna aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers. In addition, in patients with gastric ulcer, antimuscarinics may delay gastric emptying and result in antral stasis. With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition. Current epidemiologic and clinical evidence supports a strong association between gastric infection with Helicobacter pylori and the pathogenesis of duodenal and gastric ulcers, and the American College of Gastroenterology (ACG), the National Institutes of Health (NIH), and most clinicians currently recommend that all patients with initial or recurrent duodenal or gastric ulcer and documented H. pylori infection receive anti-infective therapy for treatment of the infection. For a more complete discussion of H. pylori infection, including details about the efficacy of various regimens and rationale for drug selection, see Uses: Helicobacter pylori Infection, in Clarithromycin 8:12.12.92.

Belladonna is used in the treatment of functional disturbances of GI motility such as irritable bowel syndrome and in the treatment of neurogenic bowel disturbances. As with other antimuscarinics, belladonna has limited efficacy in the treatment of these disorders and should be used only if other measures (e.g., diet, sedation, counseling, amelioration of environmental factors) have been of little or no benefit. Although belladonna has been used in combination with phenobarbital for the treatment of functional disturbances of GI motility such as irritable bowel syndrome, attempts to substantiate claims of efficacy for fixed combinations that include an antimuscarinic and phenobarbital have generally failed and these combinations are generally considered as lacking substantial evidence of efficacy in the treatment of this condition.

Although belladonna has been used in the treatment of hypermotility and diarrhea associated with GI disorders such as acute enterocolitis, the drug should be used with extreme caution, if at all, in patients with these conditions. (See Cautions: Precautions and Contraindications, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.)

Other Uses

Belladonna has been used in the symptomatic treatment of parkinsonian syndrome. Although antimuscarinics continue to be used as initial therapy in mild cases of parkinsonian syndrome or as adjunctive therapy to other agents, antimuscarinics have generally been replaced with dopaminergic drugs (e.g., levodopa, bromocriptine). Antimuscarinics may be especially useful in the treatment of excessive salivation associated with parkinsonian syndrome.

Belladonna has been used in the treatment of pancreatitis; however, there is little, if any, evidence that antimuscarinics improve the prognosis of the disease. (See Uses: Other Uses, in the Antimuscarinics/Antispasmodics General Statement 12:08.08.) Belladonna has also been used in the treatment of dysmenorrhea, nausea and vomiting of pregnancy, and nocturnal enuresis; however, the safety and efficacy of belladonna in the management of such conditions have not been established.

Rectal suppositories containing belladonna and opium have been used following genitourinary surgery for relief of moderate to severe pain unresponsive to non-opiate analgesics and for relief of pain caused by ureteral spasm. Rectal suppositories containing belladonna in combination with other drugs have been used for temporary relief of pain and itching of hemorrhoids and for the treatment of proctitis associated with ulcerative colitis; however, the efficacy of the drug in these disorders has not been established.

Because belladonna has been used medicinally for hundreds of years, it may continue to be used on rare occasions for the treatment of conditions for which there is little more than anecdotal claims of efficacy (e.g., topical ointments and plasters for the treatment of arthralgias and myalgias, inhalation of fumes from burning belladonna powder for the treatment of bronchitis, topical plasters to relieve breast engorgement associated with lactation). The use of belladonna for any of these conditions should be discouraged.

Administration

Belladonna tincture is administered orally. Belladonna extract powder is used extemporaneously to prepare capsules, powders, or tablets for oral administration. Belladonna extract powder may be administered rectally in the form of suppositories. Rectal suppositories containing belladonna and opium should be moistened with water prior to insertion in the rectum. When suppositories are to be self-administered by the patient, the patient should be instructed in the methods for proper rectal administration.

Dosage

Oral Dosage

As with other antimuscarinics, higher than recommended dosage of belladonna preparations may be required for therapeutic effect. Dosage should be carefully titrated until therapeutic effect is achieved or adverse effects become intolerable, using the lowest possible effective dosage.

Belladonna Extract

The usual initial adult dosage of belladonna extract is 15-30 mg (0.187-0.374 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

Safety and efficacy of belladonna extract in children have not been established.

Belladonna Tincture

The usual initial adult dosage of belladonna tincture is 0.6-1 mL (0.18-0.3 mg of the alkaloids of belladonna leaf) 3 or 4 times daily.

The usual initial dosage of belladonna tincture in children 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. The total dosage of belladonna tincture in children should not exceed 3.5 mL (1.05 mg of the alkaloids of belladonna leaf) daily.

Rectal Dosage

The usual adult dosage of suppositories containing powdered belladonna extract and powdered opium is 16.2 mg of belladonna extract (0.203 mg of the alkaloids of belladonna leaf) once or twice daily. Safety and efficacy of suppositories containing powdered belladonna extract and powdered opium in children have not been established.

For a complete discussion on cautions, precautions, and contraindications associated with belladonna, see Cautions in the Antimuscarinics/Antispasmodics General Statement 12:08.08.

Pharmacokinetics

Belladonna, like other tertiary amine antimuscarinics, is well absorbed from the GI tract. However, animal studies have shown differences in the absorption rates of l -hyoscyamine and galenical preparations of belladonna. In the isolated rat ileum, l -hyoscyamine was absorbed fastest, fresh leaf extracts were absorbed at an intermediate rate, and extracts from older belladonna leaves and roots were absorbed at a slower rate. Specific information on the rate of absorption of belladonna in humans is not available.

Little information is available on the distribution, metabolism, and excretion of belladonna. One manufacturer states that approximately 33% of an oral dose of belladonna is excreted unchanged via the kidneys. Belladonna is hydrolyzed to tropine and tropic acid, the derivatives of which are then excreted in urine and, apparently to a lesser extent, in feces.

Chemistry and Stability

Chemistry

Belladonna is a term applied to the various galenical preparations of the naturally occurring solanaceous alkaloids.

Belladonna Leaf

Belladonna leaf (belladonna herb, deadly nightshade leaf) is derived from the dried leaf and flowering or fruiting top of Atropa belladonna Linne (Fam. Solanaceae). Belladonna leaf contains several alkaloids, principally l -hyoscyamine (which probably racemizes to atropine during extraction) and scopolamine, and yields not less than 0.35% w/w alkaloids. Belladonna leaf is used in the preparation of belladonna extract, belladonna extract tablets, and belladonna tincture; the alkaloid content of these preparations is expressed in terms of the alkaloids of belladonna leaf. The pharmacologic activity of belladonna results principally from its atropine ( dl -hyoscyamine) content. Belladonna leaf itself is not used as a therapeutic agent because of the risk of overdosage of the alkaloids.

Powdered belladonna leaf is light olive brown to moderate olive green in color and occurs as separate microcrystals, dark-gray crystal cells, cuticular striping of the epidermal cells, vessels with ellipsoidal bordered pits, fibers of the stem, and occasional hairs and pollen grains. When the powder contains belladonna fruits, rosette aggregates of calcium oxalate and fragments of the seed are present. The presence of hairs with a papillose cuticle or raphides of calcium oxalate indicates adulteration. When moistened, belladonna leaf has a slight, somewhat tobacco-like odor and a somewhat bitter and acrid taste.

Belladonna Extract

Belladonna extract is prepared from belladonna leaf by two methods of extraction and occurs in either a pilular or powdered form; both forms contain approximately 1.25% w/w alkaloids. Belladonna extract is used in extemporaneous compounding of various dosage forms (e.g., capsules, suppositories, ointments); the pilular extract is preferred for suppositories and ointments, while the powdered extract is preferred for capsules, powders, or tablets.

Powdered belladonna extract is a fine grayish-green powder.

Belladonna Tincture

Belladonna tincture is a clear, olive- to dark-green hydroalcoholic solution which is prepared from belladonna leaf and contains approximately 0.03% w/v alkaloids.

Other Forms of Belladonna

Other forms (e.g., belladonna root) and official foreign preparations (e.g., belladonna green extract, belladonna syrup, belladonna glycerin) exist which vary in alkaloid content. Specialized references should be consulted for specific information on these forms and preparations; care should be taken not to confuse the specific recommendations for use (e.g., dosages) for each of these.

Stability

Belladonna Leaf

Belladonna leaf should be stored in well-closed containers and protected from exposure to direct sunlight; powdered belladonna leaf should be stored in light-resistant containers.

Belladonna Extract

Belladonna extract should be stored in tight containers and at a temperature not exceeding 30°C.

Belladonna Tincture

Belladonna tincture should be stored in tight, light-resistant containers and protected from direct sunlight and excessive heat. The tincture should be stored at a temperature less than 40°C, preferably between 15-30°C; freezing should be avoided.

Additional Information

For further information on the chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, and dosage and administration of belladonna, see the Antimuscarinics/Antispasmodics General Statement 12:08.08.

Only references cited for selected revisions after 1984 are available electronically.

100. Food and Drug Administration. FDA takes action to halt marketing of unapproved ergotamine— Companies ordered to cease manufacturing and distribution of illegal drugs to treat migraine headaches. FDA News. March 1, 2007. From FDA website. [Web]

101. Food and Drug Administration. Ergotamine tartrate. Rockville, MD; 2007 Mar 2. From FDA website. [Web]

102. Food and Drug Administration. Warning letters for ergotamine-containing drug products (issued February 26, 2007). From FDA web site. [Web]