ULTRASE® MT (pancrelipase) Capsules are orally administered capsules containing enteric-coated minitablets of porcine pancreatic enzyme concentrate, predominantly pancreatic lipase, amylase, and protease.
Each ULTRASE ® MT12 Capsule contains:
Lipase 12,000 U.S.P. Units
Amylase 39,000 U.S.P. Units
Protease 39,000 U.S.P. Units
Each ULTRASE ® MT18 Capsule contains:
Lipase 18,000 U.S.P. Units
Amylase 58,500 U.S.P. Units
Protease 58,500 U.S.P. Units
Each ULTRASE ® MT20 Capsule contains:
Lipase 20,000 U.S.P. Units
Amylase 65,000 U.S.P. Units
Protease 65,000 U.S.P. Units
ULTRASE® MT (pancrelipase) Capsules contain an amount of pancrelipase equivalent to but not more than 125% of the labeled lipase activity expressed in U.S.P. Units.
Inactive ingredients: hydrogenated castor oil, silicon dioxide, sodium carboxymethylcellulose, magnesium stearate, microcrystalline cellulose, methacrylic acid copolymer (Type C), talc, simethicone, triethyl citrate, iron oxides and titanium oxide.
ULTRASE® MT (pancrelipase) Capsules are designed to prevent inactivation by gastric acid thereby resulting in the delivery of high levels of biologically active enzymes into the duodenum. The enzymes catalyze the hydrolysis of fats into glycerol and fatty acids, starch into dextrins and sugars, and protein into proteoses and derived substances.
ULTRASE® MT (pancrelipase) Capsules are indicated for patients with partial or complete exocrine pancreatic insufficiency caused by:
Pancrelipase capsules are contraindicated in patients known to be hypersensitive to pork protein. Pancrelipase capsules are contraindicated in patients with acute pancreatitis or with acute exacerbations of chronic pancreatic diseases.
Should hypersensitivity occur, discontinue medication and treat symptomatically.
TO PROTECT ENTERIC COATING, MINITABLETS MUST NOT BE CRUSHED OR CHEWED. Where swallowing of capsules is difficult, they may be opened and the minitablets added to a small quantity of a soft food (e.g. applesauce, gelatin, etc.) that does not require chewing, and swallowed immediately. Contact of the minitablet with foods having a pH greater than 5.5 can dissolve the protective enteric shell.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate carcinogenic potential. Methacrylic acid, a minor component of the methacrylic acid copolymer enteric-coating contained in ULTRASE® MT (pancrelipase) Capsules, has been reported to act as a teratogen in rat embryo cultures. However, ULTRASE® MT (pancrelipase) Capsules have been shown to contain <0.001% of methacrylic acid, and the mammalian teratology studies in the rat and rabbit were negative.
The copolymer enteric-coating of ULTRASE® MT (pancrelipase) Capsules was not mutagenic by the Ames test, and it did not produce chromosome damage in a test for unscheduled DNA synthesis in rat hepatocytes.
Pregnancy : Category C.
Animal reproduction studies have not been conducted with ULTRASE® MT (pancrelipase) Capsules. It is not known whether ULTRASE® MT (pancrelipase) Capsules can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ULTRASE® MT (pancrelipase) Capsules should be given to a pregnant woman only if the potential benefit outweighs the potential risk to the fetus.
It is not known whether ULTRASE® MT (pancrelipase) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ULTRASE® MT (pancrelipase) Capsules are administered to a nursing mother.
The most frequently reported adverse reactions to products containing pancrelipase are gastrointestinal in nature. Less frequently, allergic-type reactions have also been observed.
Extremely high doses of exogenous pancreatic enzymes have been associated with hyperuricosuria and hyperuricemia when the preparations given were pancrelipase in powdered or capsule form, or pancreatin in tablet form.
In two clinical studies with ULTRASE® MT in 193 patients with cystic fibrosis, the adverse events described were all gastrointestinal in nature and may actually represent symptoms of the underlying disease, such as abdominal pain/cramps (5.7%), diarrhea (3.6%), and greasy stools and flatulence (1.5% each). In a postmarketing trial with another enteric-coated formulation, 160 adverse events occurred in the 15,711 patients (0.97%) evaluated. 10 The most frequent events reported were diarrhea, skin reaction, and abdominal discomfort (0.2% each).
Colonic strictures have been reported in cystic fibrosis patients treated with both high- and lower-strength enzyme supplements. 11 A causal relationship has not been established. The possibility of bowel stricture should be considered if symptoms suggestive of gastrointestinal obstruction occur. Since impaired fluid secretion may be a factor in the development of intestinal obstruction, care should be taken to maintain adequate hydration, particularly in warm weather. 12
"Fibrosing colonopathy" is a term used to describe a condition seen in patients with CF who have taken high amounts of pancreatic enzyme supplements (>6,000 lipase U/kg/meal). At its most advanced, this condition leads to colonic strictures.
The enzymatic activity of ULTRASE® MT (pancrelipase) Capsules is expressed in U.S.P. units. Each capsule contains the labeled amount of lipase activity and an overage of not more than 25%.
The smallest effective dose should be used. Dosage should be adjusted according to the severity of the exocrine pancreatic insufficiency. Begin therapy with one or two capsules with meals or snacks and adjust dosage according to symptoms. The number of capsules or capsule strength given with meals and/or snacks should be estimated by assessing which dose minimizes steatorrhea and maintains good nutritional status. Dosages should be adjusted according to the response of the patient. Where swallowing of capsules is difficult, they may be opened and the minitablets added to a small quantity of a soft food (e.g. applesauce, gelatin, etc.) that does not require chewing, and swallowed immediately.
It is recommended that the total dose of pancrelipase being ingested for a meal or snack be dispersed equally (with fluids) before, during, and after the meal or snack.
SUGGESTIONS FOR THE USE OF PANCREATIC ENZYMES IN CYSTIC FIBROSIS 13
ULTRASE ® MT12 (pancrelipase) Capsules
Gelatin capsules (white and yellow), imprinted "ULTRASE MT12". Bottles of 100 (NDC 58914-002-10).
ULTRASE ® MT18 (pancrelipase) Capsules
Gelatin capsules (gray and white), imprinted "ULTRASE MT18". Bottles of 100 (NDC 58914-018-10).
ULTRASE ® MT20 (pancrelipase) Capsules
Gelatin capsules (light gray and yellow), imprinted "ULTRASE MT20". Bottles of 100 (NDC 58914-004-10), and bottles of 500 (NDC 58914-004-50).
Store at controlled room temperature, between 15°C and 25°C (59°F and 77°F), in a dry place. Do not refrigerate.
Marketed as ULTRASE® MT by:
Axcan Scandipharm Inc.
22 Inverness Center Parkway
Birmingham, AL 35242
Rev. 4/00. Printed in U.S.A.
ULTRASE® is a registered trademark of Axcan Scandipharm Inc. Manufactured by Eurand International, Milan, Italy, using its EURAND MINITABS® technology for Axcan Scandipharm Inc.