Donnatal is a combination medication that provides natural belladonna alkaloids in a specific fixed ratio combined with phenobarbital to provide peripheral anticholinergic/antispasmodic action and mild sedation. Donnatal is manufactured for Concordia Pharmaceuticals by IriSys, LLC. It is available as tablets and 5 mL elixir. Active ingredients are listed as: phenobarbital (16.2 mg), hyoscyamine sulfate (0.1037 mg), atropine sulfate (0.0194 mg), and scopolamine hydrobromide (0.0065 mg). The latter two ingredients are found in plants of the family Solanaceae, such as belladonna. Indication
Based on a review of this drug by the National Academy of Sciences–National Research Council and/or other information, FDA has classified the indications as follows: "possibly" effective: For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. May also be useful as adjunctive therapy in the treatment of duodenal ulcer. History
Clinical Research with Combinations of Belladonna Alkaloids and Phenobarbital
Clinical studies have been performed on different combinations of belladonna alkaloids and phenobarbital over the last 70 years. For example, Steigmann et al. evaluated a combination of 0.25 mg belladonna alkaloids and 50 mg phenobarbital on gastrointestinal symptoms in 93 patients. The population included 33 IBS patients. Eighteen out of 33 patients reported complete relief of symptoms and 13 reported fair response with partial relief within 24 hours. Only 2 IBS patients reported no response.
After 1 day, patients exhibited significant improvement in day and night pain as well as clinician global evaluation when taking Donnatal® tablets and belladonna alkaloids, but the phenobarbital group also was statistically better for day and night pain, and the placebo group for day pain. Females taking Donnatal® tablets were 4 times more likely to experience weeks free of daytime pain compared to phenobarbital alone and twice as likely to experience weeks free of nighttime pain compared to belladonna alkaloids. Only the phenobarbital group demonstrated a significant change in pain type compared to belladonna alkaloids at the end of the study with an approximate 48% response rate. Patients on Donnatal® tablets, belladonna alkaloids, and placebo all had non-significant (p > 0.149) shifts to dull pain, 39.5%, 52.3%, and 40.4%, respectively compared to belladonna alkaloids eline. Males also showed a greater response for pain free-weeks on phenobarbital in comparison to Donnatal® tablets. All groups demonstrated an improvement in bowel movement frequency. FDA status
Donnatal® is considered part of the DESI drug category and currently is listed as one of 14 drugs still under evaluation by the FDA. In response to FDA questions about Donnatal® efficacy, A. H. Robins Co. filed abbreviated new drug applications for Donnatal® tablets (ANDA 86-676), capsules (ANDA 86-677), and Elixir (ANDA 86-661). These ANDAs, with the exception of the capsule formulation, are still in force today and the FDA has not changed the review status of Donnatal® as being conditionally approved for its indication.