Limitations on Dosing:

Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines.1,2,3 If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted. Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture, indicative of fibrosing colonopathy, in children less than 12 years of age [see Warnings and Precautions (5.1) ]. Patients currently receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Use of ULTRESA in children is limited by the available capsule dosage strengths and their ability to provide the recommended dose based on age and weight. Attempting to divide the capsule contents in small fractions to deliver small doses of lipase is not recommended.

3 DOSAGE FORMS AND STRENGTHSThe active ingredient in ULTRESA eva luated in clinical trials is lipase. ULTRESA is dosed by lipase units. Other active ingredients include protease and amylase.

ULTRESA is available in 3 color coded delayed-release capsule strengths. Each ULTRESA delayed-release capsule strength contains the specified amounts of lipase, protease, and amylase as follows:

◦13,800 USP units of lipase; 27,600 USP units of protease; 27,600 USP units of amylase delayed-release capsules have a white cap printed with “13800UL” and yellow body printed with “AXCA” in black.
◦20,700 USP units of lipase; 41,400 USP units of protease; 41,400 USP units of amylase delayed-release capsules have a gray cap printed with “20700UL” and white body printed with “AXCA” in black.
◦23,000 USP units of lipase; 46,000 USP units of protease; 46,000 USP units of amylase delayed-release capsules have a light gray cap printed with “23000UL” and yellow body printed with “AXCA” in black.
4 CONTRAINDICATIONSNone.

5 WARNINGS AND PRECAUTIONS5.1 Fibrosing ColonopathyFibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4, 5 Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture in children less than 12 years of age.1 Patients with fibrosin