Summary of 
FDA Information:



 
 
  FOI Summary; NADA 042-841 (supplement); Amforol® (Kanamycin, pectin, bismuth subcarbonate, activated attapulgite); re: revised formulation for 
Amforol®, without aminopentamide hydrogen sulfate; Feburary 21, 1991
--Editor's abstract
I. GENERAL INFORMATION

NADA Number: 042-841

Sponsor:

Fort Dodge Laboratories
Division of 
American Home Products
800 5th Street NW
Ford Dodge, IA 50501-0518

Generic Name: Kanamycin, pectin, bismuth subcarbonate, activated attapulgite (aluminum magnesium silicate)

Trade Name: Amforol® Veterinary Oral Tablets

Marketing Status: Rx

Effect of 
Supplement:

This supplement provides for 
a revised formulation for 
Amforol® Veterinary Oral Tablets without aminopentamide hydrogen sulfate.
The following issues are addressed:

A. Dose of 
aminopentamide in original formulation

B. Rationale for 
removing aminopentamide

C. Safety and 
efficacy of 
new formulation

II. DOSE OF AMINOPENTAMIDE IN ORIGINAL FORMULATION

Aminopentamide is an antispasmodic and 
anticholinergic agent which 
reduces peristalsis thereby reducing propulsive activity.
The amount of 
aminopentamide in Amforol's original formulation was 
0.033 mg per tablet, only 1/6 to 1/12 of 
the dose recommended when 
aminopentamide alone is given orally to the dog.

III. RATIONALE FOR REMOVING AMINOPENTAMIDE

In recent years, clinicians have modified their recommendations for 
the treatment of 
acute non-specific diarrhea. Published literature now suggests that the 
use of 
antispasmodics / anticholinergics is not indicated in the 
routine treatment of 
small animals with diarrhea.
They may produce intractable diarrhea due to ileus.

In cases of 
spasmodic diarrhea, antispasmodics / anticholinergics may result in a therapeutic benefit. However, the 
use of 
anticholinergics should be restricted to documented cases of 
spasmodic diarrhea since their routine use in other types of 
diarrhea may impair normal motility.
The following references suggest that anticholinergic drugs like aminopentamide may be contraindicated in the 
routine management of 
diarrhea.
A . Wilson, R. C.: Antimotility drugs used in treatment of 
diarrhea. JAVMA, 180:776-777, 1982.

B. Strombeck, D. R.: Management of 
diarrhea: Motility modifiers and 
adjunct therapy. IN, Current Veterinary Therapy, VII, 1980.

C. Chiapella A. M.: Treatment of 
Intestinal Disease. IN, The Veterinary Clinics of 
North America, 567-584, August 1983.

D. Reves R., et al: Failure to Demonstrate Effectiveness of 
an Anticholinergic Drug in the 
Symptomatic Treatment of 
Acute Travelers Diarrhea. 5:223-227, 1983.

IV. EFFICACY OF NEW FORMULATION

The removal of 
aminopentamide hydrogen sulfate which 
was 
present at subtherapeutic levels will not 
have an adverse effect on the product's efficacy.
The new formulation provides:

Kanamycin, a broad-spectrum antibiotic
Pectin
Attapulgite (aluminum magnesium silicate), an activated clay mineral 
Bismuth subcarbonate

The following references support the efficacy of 
the reformulated product:

Federal Register Vol. 51, 161 38-49, No. 83 (4/30/86)

Federal Register Vol. 35, 11707, No. 141 (7/22/70)

Dekker, W. and 
K. Reisma, Treatment of 
Duodenal Ulcers with Bismuth, Annals of 
Clinical Research, Vol. 11, pp. 94-97, 1979.

V. SAFETY OF NEW FORMULATION

Kanamycin sulfate

Orally administered kanamycin sulfate is generally considered to be poorly absorbed systemically through intact intestinal mucosa, although the possibility of 
increased absorption through ulcerated or 
denuded areas should be considered especially when 
the dose is increased.

Dogs, particularly those weighing less than 5 pounds, should be observed for 
systemic nephrotoxic and 
ototoxic side effects due to systemic absorption of 
kanamycin sulfate from 
ulcerated areas following oral administration. Since orally administered kanamycin sulfate is not expected to reach therapeutic levels, Amforol should not be prescribed for 
treating Salmonella septicemia.
A "Contraindication" appears on the labeling as follows:

"Amforol is contraindicated in treatment of 
Salmonella septicemias."

Bismuth subcarbonate

Orally administered bismuth subcarbonate is an insoluble salt and 
generally not absorbed in significant amounts.
There is documentation of 
systemic absorption from 
an ulcerated gastrointestinal tract.

Systemically available bismuth has been associated with hepatopathy, nephropathy and 
neurotoxicity in humans.
The neurotoxic syndrome has been characterized by lack of 
energy, muscle twitching, confusion, convulsions and 
coma.

Winship, K.
A ."Toxicity of 
Bismuth Salts" Adv. Drug React. Ac. Pois. Rev. 2 1983 103-121.

Hoffman, R. S. et al "Bismuth Absorption and 
Myotonic Encephalopathies After Bismuth Subsalicylate Therapy" Vet Hum Toxicol 31 (4) Aug. 1989.

An adverse reaction reported central nervous system disfunction in two dogs after use of 
Amforol Suspension at the 
recommended dose.
The "Side Effects" section of 
the labeling includes:

"The bismuth subcarbonate in Amforol (Veterinary Oral Tablets) may produce darkening of 
the tongue and 
stools which 
can be confused with melena. Prolonged exposure to orally administered bismuth salts has been associated with encephalopathies in other species. Signs may include lack of 
energy, muscle twitching, confusion, convulsions and 
comas."

Activated attapulgite (aluminum magnesium silicate) and 
pectin when 
orally administered have not been reported to produce toxicity.

See the original FOI for 
additional information.

VI. AGENCY CONCLUSIONS

Removal of 
aminopentamide increases the safety of 
Amforol.
The reformulation is supported by substantial evidence of 
safety and 
effectiveness as found in the 
veterinary and 
human medical literature.
The effectiveness of 
the reformulated product is also based on data in the 
original approval human monographs for 
antidiarrheal products and 
NAS/NRC reviews.
The data meet the requirements of 
Section 512 of 
the Act and 
Section 514.111 of 
the implementing regulations.
The data demonstrate that the 
product when 
used according to the approved labeling is safe and 
effective for 
the treatment of 
bacterial enteritis caused by susceptible strains of 
E. coli, Salmonella, Shigella, Alcaligenes faecalis, Proteus spp. and 
Staphylococcus aureus.
This product must be dispensed under 
a prescription because the expertise of 
a veterinarian is necessary for 
the diagnosis of 
etiologies causing enteritis.
A veterinarian's expertise is also needed to monitor response to treatment and 
to detect and 
treat adverse reactions if they occur.

Under section 512(c)(2)(F)(iii) of 
the Federal Food, Drug, and 

Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(iii), this change in the 
drug product does not qualify for 
exclusivity because new clinical or 
field investigations were 
not required for 
approval.