ULTRASE® (pancrelipase) Capsules are orally administered and contain 250 mg of enteric-coated microspheres of porcine pancreatic enzyme concentrate, predominantly pancreatic lipase, amylase, and protease.

Each ULTRASE® Capsule contains:

Lipase .................................................. 4,500 U.S.P. Units
Amylase .................................................. 20,000 U.S.P. Units
Protease .................................................. 25,000 U.S.P. Units

Inactive ingredients: povidone, talc, sugar, methacrylic acid copolymer (Type C), triethyl citrate, simethicone emulsion.

Last updated on RxList: 1/20/2009

ULTRASE® (pancrelipase) Capsules are indicated for patients with partial or complete exocrine pancreatic insufficiency caused by:

• Cystic fibrosis (CF)
• Chronic pancreatitis due to alcohol use or other causes
• Surgery (pancreatico-duodenectomy or Whipple's procedure, with or without Wirsung duct injection, total pancreatectomy)
• Obstruction (pancreatic and biliary duct lithiasis, pancreatic and duodenal neoplasms, ductal stenosis)
• Other pancreatic disease (hereditary, post traumatic and allograft pancreatitis, hemochromatosis, Shwachman's Syndrome, lipomatosis, hyperparathyroidism)
• Poor mixing (Billroth II gastrectomy, other types of gastric bypass surgery, gastrinoma)

Pancrelipase capsules are effective in controlling steatorrhea.^1-9

The enzymatic activity of ULTRASE® (pancrelipase) Capsules is expressed in U.S.P. units. 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 microspheres 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 FIBROSIS¹²

1. Patients should be receiving optimal diet for age and clinical status, recognizing that those with failure to thrive or malnutrition require additional calories and other nutrients for catch-up growth.
2. Nutrition assessment should be a part of routine clinical evaluations.
3. Initial dosing of pancreatic enzyme supplements should begin with 500 lipase U/kg/meal using enteric-coated microsphere products.
4. Patients should be reassessed 2-4 weeks after initiation of therapy. The following items should be assessed:
   • Clinical status, e.g., abdominal symptoms and exam;
   • Nutritional intake and growth (height, weight, head circumference);
   • Character of stools - greasy, oily (for information, not for decision making);
   • Quantitative 72-hour fecal fat when indicated but not less than annually (perform on a normal diet for age);
   • Fat soluble vitamin measures.
5. Corollaries to dosing suggestions:
   1. Dose may be altered in a stepwise fashion according to the response of the patient (see 4. above).
   2. Dose approaching 2,000 lipase U/kg/meal would indicate the need for further investigation (see below). Patients presently on higher doses should be reevaluated; either immediately decrease the dose or titrate down to a lower dose range at, or below, 2,000 lipase U/kg/meal. Doses > 6,000 lipase U/kg/meal have been associated with colonic strictures.
   3. Pancreatic supplements mixed with applesauce or other acidic food substances should be administered immediately, not stored.
   4. Enteric-coated microspheres should not be crushed.
   5. Enzyme doses (as lipase U/kg/meal) tend to decrease with advancing age.
   6. Patients should accept only product brands prescribed by their physician.
   7. Adjustment of dosage is the responsibility of the physician. Patients should be advised not to adjust doses without consulting their physician. Changes in product or dosage may require an adjustment period.
   8. Complaints transmitted by phone should be investigated thoroughly before dose is adjusted. If indicated, this investigation should include 72-hour fecal fat testing.
   9. Pancreatic supplements should be stored in a cool, dry place and checked regularly for expiration date.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

ULTRASE® (pancrelipase) Capsules

Gelatin capsules (opaque white and opaque white), imprinted “ULTRASE”. Bottles of 100 (NDC 58914-045-10).

Store at controlled room temperature, between 15°C and 25°C (59°F and 77°F), in a dry place. Do not refrigerate.

REFERENCES

1. Delchier JC, Vidon N, et al. Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations. Aliment Pharmacol Therap. 1991;5:365-378.

2. Duhamel JP, Vidailhet M, et al. Étude multicentrique comparative d'une nouvelle présentation de pancréatine en microgranules gastrorésistants dans I'insuffisance pancréatique exocrine de la mucoviscidose chez l'enfant. Ann Pediatr. 1988;35:69-74.

3. Dutta SK, Tilley DK. The pH-sensitive enteric-coated pancreatic enzyme preparations: an evaluation of therapeutic efficacy in adult patients with pancreatic insufficiency. J Clin Gastroenterol. 1983;5:51-54.

4. Dutta SK, Rubin J, Harvey J. Comparative evaluation of the therapeutic efficacy of a pH-sensitive enteric-coated pancreatic enzyme preparation with conventional pancreatic enzyme therapy in the treatment of exocrine pancreatic insufficiency. Gastroenterol. 1983;84:476-482.

5. Gouerou H, Dain MP, et al. Alipase versus nonenteric-coated enzymes in pancreatic insufficiency. Int J Pancreatol. 1989;5:45-50.

6. Mischler EH, Parrell S, et al. Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis. Am J Dis Child. 1982;136:1060-1063.

7. Salen G, Prakash A. Evaluation of enteric-coated microspheres for enzyme replacement therapy in adults with pancreatic insufficiency. Cur Ther Res. 1979;25:650-656.

8. Schneider MU, Knoll-Ruzicka ML, et al. Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhea in chronic pancreatitis. Hepatogastroenterol. 1985;32:97-102.

9. Halgreen H, Thorsgaard Pedersen N, Worning H. Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis. Scand J Gastroenterol. 1986;21:104-108.

12. Cystic Fibrosis Foundation Conference on Pancreatic Enzyme Supplementation in the Context of Fibrosing Colonopathy; Washington, D.C., March 23-24, 1995.

REV. June 2008. Marketed as ULTRASE® by: AXCAN PHARMA US, INC. 22 Inverness Center, Parkway, Birmingham, AL 35242 USA. www.axcan.com. ULTRASE® is manufactured by Eurand International, Milan, Italy using its DIFFUCAPS® technology for Axcan Pharma US, Inc., 22 Inverness Center Parkway, Birmingham, Alabama 35242 USA. FDA revision date: n/a

Last updated on RxList: 1/16/2009

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.

Colonic strictures have been reported in cystic fibrosis patients treated with both high- and lower-strength enzyme supplements.¹⁰ 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.¹¹

“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.

1. In whom should one consider the diagnosis of fibrosing colonopathy?
   1. Patients with cystic fibrosis who have evidence of partial or complete obstruction, bloody diarrhea or chylous ascites.
   2. Patients who have two of the following three symptoms:
      • abdominal pain
      • ongoing diarrhea
      • poor weight gain

ESPECIALLY if they have:

• taken > 6,000 lipase U/kg/meal
• age less than twelve years
• history of meconium ileus
• prior intestinal surgery
• history of recurrent DIOS
• “inflammatory bowel disease”¹²

No information provided.

REFERENCES

10. Smyth RL, van Velzen D, et al. Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes. The Lancet. 1994; 343:85-86.

11. Lands L, Zinman R, et al. Pancreatic function testing in meconium disease in CF: two case reports. J Ped Gastroenterol and Nut. 1988; 7:276-279.

12. Cystic Fibrosis Foundation Conference on Pancreatic Enzyme Supplementation in the Context of Fibrosing Colonopathy; Washington, D.C., March 23-24, 1995.

Last updated on RxList: 1/20/2009

Should hypersensitivity occur, discontinue medication and treat symptomatically.

General

TO PROTECT ENTERIC COATING, MICROSPHERES MUST NOT BE CRUSHED OR CHEWED. Where swallowing of capsules is difficult, they may be opened and the microspheres 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 microsphere 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® (pancrelipase) Capsules, has been reported to act as a teratogen in rat embryo cultures. However, the copolymer enteric-coating of ULTRASE® (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® (pancrelipase) Capsules. It is not known whether ULTRASE® (pancrelipase) Capsules can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ULTRASE® (pancrelipase) Capsules should be given to a pregnant woman only if the potential benefit outweighs the potential risk to the fetus.

Nursing Mothers

It is not known whether ULTRASE® (pancrelipase) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ULTRASE® (pancrelipase) Capsules are administered to a nursing mother.

Last updated on RxList: 1/16/2009

No information provided.

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.

Last updated on RxList: 1/16/2009

ULTRASE® (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.

Last updated on RxList: 1/16/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 1/28/2005

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PANCRELIPASE ENTERIC-COATED CAPSULE - ORAL

(pan-kreh-LIP-aze)

COMMON BRAND NAME(S): Creon, Pancrease, Pancron, Protilase, Ultrase, Zymase

USES: This medication contains digestive enzymes to help break down and digest fats, starch, and proteins in food. It is used in conditions where the pancreas cannot make or does not release enough digestive enzymes into the small intestines to digest the food (e.g., chronic pancreatitis, cystic fibrosis, cancer of the pancreas, post-pancreatectomy, post-gastrointestinal bypass surgery).

HOW TO USE: Take this medication by mouth with meals and snacks as directed by your doctor. Swallow the capsule whole. If swallowing is difficult, then the capsule may be opened and the contents mixed in a small amount of liquid or soft food that does not need to be chewed (e.g., applesauce). Do not mix the contents of the capsule with alkaline food or liquid (e.g., milk, ice cream, tea). Consult your doctor or pharmacist for more information about what foods/liquids to avoid when mixing. Swallow the food or liquid right away, making sure not to chew the medication. Drink a glass of water or juice after swallowing the food to make sure all the medication is swallowed. Do not save the medication mixture for later.

Dosage is based on your medical condition, diet, and response to therapy.

Drink plenty of fluids while taking this medication unless your doctor tells you otherwise.

Use this medication regularly to get the most benefit from it. Take it with every meal or snack.

If your doctor has recommended that you follow a special diet, it is very important to follow the diet to get the most benefit from this medication.

Do not change brands or dosage forms of pancrelipase without consulting your doctor or pharmacist. Different products may contain different amounts of the digestive enzymes.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Diarrhea, constipation, abdominal pain/cramps, nausea, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe constipation, severe stomach/abdominal discomfort, frequent/painful urination, joint pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking pancrelipase, tell your doctor or pharmacist if you are allergic to it; or to pork protein; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: sudden/severe swelling of the pancreas (acute pancreatitis), sudden worsening of long-term disease of the pancreas.

Before using this medication, tell your doctor or pharmacist your medical history.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medications because very serious interactions may occur: acarbose, miglitol.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting pancrelipase.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this product with others.

MISSED DOSE: If you miss a dose, take the next dose with your next meal or snack as directed. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.